Information on NLRP3

Basic details

Alt. symbols: C1orf7 | CIAS1 | DFNA34 | AGTAVPRL | AII | AVP | FCAS | FCU | NALP3 | PYPAF1 | MWS | CLR1.1

Approved name: NLR family pyrin domain containing 3
Alt. names: cold autoinflammatory syndrome 1, deafness, autosomal dominant 34 | Cryopyrin, nucleotide-binding oligomerization domain, leucine rich repeat and pyrin domain containing 3

Location: 1q44: 247332331 - 247449108 (+)
Gene type: protein_coding, 11 transcripts.

Scores: LoFtool: 0.003510 | pLI: 0.44726268 | LOEUF: 0.519

HGNC: 16400

NCBI: 114548, RefSeq: NG_007509.2

Ensembl: ENSG00000162711.19

LRG_197 | Status: public

OMIM: 606416

Expression | ProteinAtlas

Normal function

The NLRP3 inflammasome is primarily expressed in myeloid cells and its importance to host defenses is reflected in its many complex levels of regulation, including by reactive oxygen species, calcium signaling, phosphorylation, ubiquitylation, prenylation, SUMOylation and microRNAs. The NLRP3 gene encodes the NACHT, LRR and PYD domains-containing protein 3 (NALP3), also known as cryopyrin. Cryopyrin is a nucleotide-binding domain and leucine-rich repeat containing (NLR) protein, cytosolic sensors that initiate and regulate the immune system's response to injury, toxins, or invasion by microorganisms. Cryopyrin recognizes bacterial particles, extracellular ATP, chemicals such as asbestos, silica, and uric acid crystals, and compounds released by injured cells. Once activated, cryopyrin and associated proteins assemble into inflammasomes, which are required to activate signaling cascades resulting in pro-inflammatory cytokine (i.e. IL-1beta, IL-18) production and pyroptosis.

Dysfunction and disease

Heterozygous NLRP3 GOF mutations are associated with various conditions grouped under the term Cryopyrinopathies (Cryopyrin-associated periodic syndrome or CAPS), or NLRP3-associated auto-inflammatory disease (NLRP3-AID). These conditions all present with cold-induced urticaria as a hallmark feature, but fall along a clinical continuum from milder FCAS (familial cold autoinflammatory syndrome) [OMIM:120100] to MWS (Muckle-Wells syndrome) [OMIM:191900] to severe NOMID (neonatal-onset multisystem inflammatory disease) or CINCA (chronic infantile neurological cutaneous and articular) syndrome [OMIM:607115] (PMID: 32546426). Patient cells spontaneously secrete high levels of IL-1beta, consistent with the spectacular therapeutic response that patients presenting with all three CAPS phenotypes have shown to IL-1 inhibition. However, CNS damage and SNHL may be irreversible despite therapy, especially if there is a long delay in treatment initiation after symptom onset. NOMID/CINCA is associated with systemic inflammation that is chronic and persistent, whereas flares in FCAS or MWS are triggered by cold temperature and humidity. FCAS is characterized by a delay in the onset of symptoms (minutes to hours) following cold exposure. Attacks are short-lived and involve fever, chills, arthritis/arthralgias, myalgias, headache, conjunctivitis, in addition to urticaria and swelling of the extremities. MWS is characterized by sensorineural hearing loss (SNHL) and the potential for SAA amyloidosis if untreated, in addition to attacks featuring ocular inflammation, fever, headache, and less commonly arthritis/arthralgias. NOMID/CINCA presents in the first days of life with TORCH-like craniofacial findings of frontal bossing and saddle-nose deformity along with manifestations of neurological (i.e. CNS lesions, chronic meningitis), cutaneous (diffuse non-pruritic urticarial rash), and articular (progressive deforming arthropathy, particularly of the knee) inflammation (PMID: 27927236, 31077002). The majority of disease-associated mutations are missense changes affecting exons 3 and 4, thus affecting the NACHT domain or nearby residues (PMID: 28191008). Those located around the ATP-binding pocket are usually inherited de novo and cause constitutive inflammasome activation, leading to the severe phenotypes of NOMID/CINCA, while others may destabilize interdomain interactions and lower the threshold for NLRP3 activation, leading to FCAS or MWS (PMID: 31189953). Several missense mutations in the autoinhibitory LRR domains have been identified in patients with late-onset symptoms, hearing loss and atypical presentations (PMID: 20131254, 15334500, 12032915) or even isolated SNHL [OMIM:617772] (PMID: 28847925). Moreover, recurrent low penetrance missense variants in multiple domains have also been identified, with patients showing more fever and gastrointestinal symptoms than “typical” CAPS patients and intermediate cellular phenotypes between wild-type and highly penetrant NLRP3 mutations on functional inflammasome studies (PMID: 28692792). Thus far, only one CAPS-associated mutation has been identified in the pyrin domain (PYD) of NLRP3 - specifically, a missense change in a MWS patient that increased its interaction with the PYD of ASC (apoptosis-associated speck-like protein) (PMID: 28229991). Of note, another rare exon 1 variant (Asp21His) affecting the PYD has been identified in Finnish families diagnosed with keratoendotheliitis fugax hereditaria, a cond [Load More]

[Reviewed by Xiao P. Peng on 2022-06-21 16:21:52]

Associated conditions

Acronym Condition's_name MOI Mode_of_actionwww icon OMIM_ID No.cases
CINCA CINCA syndrome ADdict. icon 607115www icon 0 (0 fams)
DFNA34 Deafness 34, with or without inflammation ADdict. icon 617772www icon 0 (0 fams)
MWS Muckle-Wells syndrome ADdict. icon 191900www icon 0 (0 fams)
FCAS1 Familial cold inflammatory syndrome 1 ADdict. icon 120100www icon 0 (0 fams)
KEFH Keratoendothelitis fugax hereditaria ADdict. icon 148200www icon 0 (0 fams)
CPP Cryopyrinopathy Sodict. icon Gain of Function - 0 (0 fams)

Please mind that full curation (inclusion of all published patients) of this gene has not started yet. Please contact us if you want to volunteer.

Transcripts of NLRP3

Name ENSEMBL_ID LRG_ID CCDS_ID MANE Transcript.type Exons Canonical CDS_length REFSEQ_ID
202 ENST00000348069.7 protein_coding 7 No 3824 NM_183395
201 ENST00000336119.8 Select protein_coding 10 Yes 4187 NM_001079821,NM_001243133,NM_004895
203 ENST00000366496.7 protein_coding 8 No 3995 NM_001127461
205 ENST00000391827.3 protein_coding 9 No 4242 NM_001127462
210 ENST00000697350.1 protein_coding 10 No XM_047443534

Published variants

Found 532 variants

Var.name Exon/Intron cDNA_pos. CDS_change Prot.change Var.type Var.class. Patients
T4A EX2 779 c.10A>G p.Thr4Ala missense_variant Likely Benign 0
R5C EX2 782 c.13C>T p.Arg5Cys missense_variant Uncertain significance 0
R5H EX2 783 c.14G>A p.Arg5His missense_variant Uncertain significance 0
D19H EX2 824 c.55G>C p.Asp19His missense_variant Pathogenic 0
H26Y EX2 845 c.76C>T p.His26Tyr missense_variant Pathogenic 0
L27V EX2 848 c.79T>G p.Leu27Val missense_variant Likely Pathogenic 0
D29V EX2 855 c.86A>T p.Asp29Val missense_variant Uncertain significance 0
P32S EX2 863 c.94C>T p.Pro32Ser missense_variant Likely Benign 0
I37L EX2 878 c.109A>C p.Ile37Leu missense_variant Likely Benign 0
P38S EX2 881 c.112C>T p.Pro38Ser missense_variant Likely Benign 0
P38R EX2 882 c.113C>G p.Pro38Arg missense_variant Likely Benign 0
P40S EX2 887 c.118C>T p.Pro40Ser missense_variant Uncertain significance 0
Q43* EX2 896 c.127C>T p.Gln43Ter stop_gained Uncertain significance 0
T44R EX2 900 c.131C>G p.Thr44Arg missense_variant Uncertain significance 0
A47S EX2 908 c.139G>T p.Ala47Ser missense_variant Uncertain significance 0
H49R EX2 915 c.146A>G p.His49Arg missense_variant Pathogenic 0
L52V EX2 923 c.154C>G p.Leu52Val missense_variant Uncertain significance 0
I57V EX2 938 c.169A>G p.Ile57Val missense_variant Likely Pathogenic 0
I57M EX2 940 c.171C>G p.Ile57Met missense_variant Uncertain significance 0
D58N EX2 941 c.172G>A p.Asp58Asn missense_variant Likely Pathogenic 0
N60S EX2 948 c.179A>G p.Asn60Ser missense_variant Uncertain significance 0
A65G EX2 963 c.194C>G p.Ala65Gly missense_variant Likely Benign 0
M68T EX2 972 c.203T>C p.Met68Thr missense_variant Uncertain significance 0
V70M EX2 977 c.208G>A p.Val70Met missense_variant Likely Benign 0
V70L EX2 977 c.208G>C p.Val70Leu missense_variant Likely Benign 0
I72N EX2 984 c.215T>A p.Ile72Asn missense_variant Uncertain significance 0
A74T EX2 989 c.220G>A p.Ala74Thr missense_variant Uncertain significance 0
A75E EX2 993 c.224C>A p.Ala75Glu missense_variant Uncertain significance 0
A75V EX2 993 c.224C>T p.Ala75Val missense_variant Likely Benign 0
K84R EX2 1020 c.251A>G p.Lys84Arg missense_variant Likely Benign 0
R87K EX2 1029 c.260G>A p.Arg87Lys missense_variant Likely Benign 0
D88Y EX2 1031 c.262G>T p.Asp88Tyr missense_variant Likely Benign 0
P90L EX2 1038 c.269C>T p.Pro90Leu missense_variant Likely Benign 0
R98G EX3 1061 c.292C>G p.Arg98Gly missense_variant Likely Benign 0
R98C EX3 1061 c.292C>T p.Arg98Cys missense_variant Likely Benign 0
R98H EX3 1062 c.293G>A p.Arg98His missense_variant Likely Benign 0
S100L EX3 1068 c.299C>T p.Ser100Leu missense_variant Likely Pathogenic 0
N101K EX3 1072 c.303T>A p.Asn101Lys missense_variant Likely Benign 0
S110N EX3 1098 c.329G>A p.Ser110Asn missense_variant Likely Benign 0
M116L EX3 1115 c.346A>T p.Met116Leu missense_variant Likely Benign 0
M116I EX3 1117 c.348G>A p.Met116Ile missense_variant Likely Pathogenic 0
G117S EX3 1118 c.349G>A p.Gly117Ser missense_variant Likely Pathogenic 0
E120* EX3 1127 c.358G>T p.Glu120Ter stop_gained Uncertain significance 0
E120D EX3 1129 c.360G>C p.Glu120Asp missense_variant Likely Benign 0
S123L EX3 1137 c.368C>T p.Ser123Leu missense_variant Likely Benign 0
I127L EX3 1148 c.379A>C p.Ile127Leu missense_variant Likely Benign 0
I127V EX3 1148 c.379A>G p.Ile127Val missense_variant Likely Benign 0
C128S EX3 1151 c.382T>A p.Cys128Ser missense_variant Likely Benign 0
C128S EX3 1152 c.383G>C p.Cys128Ser missense_variant Likely Benign 0
K129R EX3 1155 c.386A>G p.Lys129Arg missense_variant Likely Benign 0
R135C EX4 1172 c.403C>T p.Arg135Cys missense_variant Likely Benign 0
R135H EX4 1173 c.404G>A p.Arg135His missense_variant Likely Benign 0
K137N EX4 1180 c.411G>T p.Lys137Asn missense_variant Likely Benign 0
K140R EX4 1188 c.419A>G p.Lys140Arg missense_variant Likely Benign 0
S144N EX4 1200 c.431G>A p.Ser144Asn missense_variant Likely Benign 0
C148G EX4 1211 c.442T>G p.Cys148Gly missense_variant Likely Benign 0
C148Y EX4 1212 c.443G>A p.Cys148Tyr missense_variant Likely Benign 0
I149T EX4 1215 c.446T>C p.Ile149Thr missense_variant Uncertain significance 0
R155C EX4 1232 c.463C>T p.Arg155Cys missense_variant Likely Benign 0
S159I EX4 1245 c.476G>T p.Ser159Ile missense_variant Likely Benign 0
N163S EX4 1257 c.488A>G p.Asn163Ser missense_variant Likely Benign 0
R168* EX4 1271 c.502C>T p.Arg168Ter stop_gained Likely Benign 0
R168Q EX4 1272 c.503G>A p.Arg168Gln missense_variant Likely Benign 0
R170S EX4 1277 c.508C>A p.Arg170Ser missense_variant Likely Benign 0
R170C EX4 1277 c.508C>T p.Arg170Cys missense_variant Likely Benign 0
R170H EX4 1278 c.509G>A p.Arg170His missense_variant Likely Pathogenic 0
I172T EX4 1284 c.515T>C p.Ile172Thr missense_variant Pathogenic 0
K173E EX4 1286 c.517A>G p.Lys173Glu missense_variant Likely Benign 0
H175Y EX4 1292 c.523C>T p.His175Tyr missense_variant Likely Benign 0
R176W EX4 1295 c.526C>T p.Arg176Trp missense_variant Likely Benign 0
S177N EX4 1299 c.530G>A p.Ser177Asn missense_variant Likely Benign 0
E182Q EX4 1313 c.544G>C p.Glu182Gln missense_variant Likely Benign 0
E182V EX4 1314 c.545A>T p.Glu182Val missense_variant Likely Benign 0
G189S EX4 1334 c.565G>A p.Gly189Ser missense_variant Likely Benign 0
K190R EX4 1338 c.569A>G p.Lys190Arg missense_variant Likely Benign 0
K192R EX4 1344 c.575A>G p.Lys192Arg missense_variant Likely Benign 0
T193K EX4 1347 c.578C>A p.Thr193Lys missense_variant Likely Benign 0
T193M EX4 1347 c.578C>T p.Thr193Met missense_variant Likely Benign 0
S196N EX4 1356 c.587G>A p.Ser196Asn missense_variant Likely Benign 0
P200T EX4 1367 c.598C>A p.Pro200Thr missense_variant Likely Benign 0
M203T EX4 1377 c.608T>C p.Met203Thr missense_variant Likely Benign 0
E204K EX4 1379 c.610G>A p.Glu204Lys missense_variant Likely Benign 0
E204G EX4 1380 c.611A>G p.Glu204Gly missense_variant Likely Benign 0
F207L EX4 1388 c.619T>C p.Phe207Leu missense_variant Uncertain significance 0
D210N EX4 1397 c.628G>A p.Asp210Asn missense_variant Uncertain significance 0
D211N EX4 1400 c.631G>A p.Asp211Asn missense_variant Likely Benign 0
D211G EX4 1401 c.632A>G p.Asp211Gly missense_variant Likely Benign 0
H213R EX4 1407 c.638A>G p.His213Arg missense_variant Likely Benign 0
S214Y EX4 1410 c.641C>A p.Ser214Tyr missense_variant Likely Benign 0
E215G EX4 1413 c.644A>G p.Glu215Gly missense_variant Likely Benign 0
Q223P EX4 1437 c.668A>C p.Gln223Pro missense_variant Uncertain significance 0
A225S EX4 1442 c.673G>T p.Ala225Ser missense_variant Likely Benign 0
A225V EX4 1443 c.674C>T p.Ala225Val missense_variant Likely Benign 0
T231I EX4 1461 c.692C>T p.Thr231Ile missense_variant Uncertain significance 0
A234T EX4 1469 c.700G>A p.Ala234Thr missense_variant Likely Benign 0
M237L EX4 1478 c.709A>C p.Met237Leu missense_variant Likely Benign 0
M237L EX4 1478 c.709A>T p.Met237Leu missense_variant Likely Benign 0
L239M EX4 1484 c.715T>A p.Leu239Met missense_variant Likely Benign 0
L239F EX4 1486 c.717G>T p.Leu239Phe missense_variant Likely Benign 0
A242T EX4 1493 c.724G>A p.Ala242Thr missense_variant Uncertain significance 0
A242K EX4 1493-1494 c.724_725delinsAA p.Ala242Lys missense_variant Uncertain significance 0
A242E EX4 1494 c.725C>A p.Ala242Glu missense_variant Uncertain significance 0
A242V EX4 1494 c.725C>T p.Ala242Val missense_variant Uncertain significance 0
S243L EX4 1497 c.728C>T p.Ser243Leu missense_variant Uncertain significance 0
Q248R EX4 1512 c.743A>G p.Gln248Arg missense_variant Likely Benign 0
L254M EX4 1529 c.760C>A p.Leu254Met missense_variant Likely Benign 0
F255Lfs*49 EX4 1532-1533 c.763_764del p.Phe255LeufsTer49 frameshift_variant Likely Benign 0
I257F EX4 1538 c.769A>T p.Ile257Phe missense_variant Pathogenic 0
I257N EX4 1539 c.770T>A p.Ile257Asn missense_variant Uncertain significance 0
C259W EX4 1546 c.777T>G p.Cys259Trp missense_variant Pathogenic 0
R260W EX4 1547-1549 c.778_780delinsTGG p.Arg260Trp missense_variant Pathogenic 0
R260Q EX4 1548 c.779G>A p.Arg260Gln missense_variant Likely Pathogenic 0
R260P EX4 1548 c.779G>C p.Arg260Pro missense_variant Pathogenic 0
R260L EX4 1548 c.779G>T p.Arg260Leu missense_variant Pathogenic 0
V262A EX4 1554 c.785T>C p.Val262Ala missense_variant Pathogenic 0
V262G EX4 1554 c.785T>G p.Val262Gly missense_variant Pathogenic 0
L264V EX4 1559 c.790C>G p.Leu264Val missense_variant Pathogenic 0
L264F EX4 1559 c.790C>T p.Leu264Phe missense_variant Pathogenic 0
L264H EX4 1560 c.791T>A p.Leu264His missense_variant Pathogenic 0
L264P EX4 1560 c.791T>C p.Leu264Pro missense_variant Pathogenic 0
L264R EX4 1560 c.791T>G p.Leu264Arg missense_variant Pathogenic 0
V265M EX4 1562 c.793G>A p.Val265Met missense_variant Likely Benign 0
T266P EX4 1565 c.796A>C p.Thr266Pro missense_variant Pathogenic 0
Q267R EX4 1569 c.800A>G p.Gln267Arg missense_variant Likely Benign 0
D280N EX4 1607 c.838G>A p.Asp280Asn missense_variant Likely Benign 0
P281A EX4 1610 c.841C>G p.Pro281Ala missense_variant Likely Benign 0
P283L EX4 1617 c.848C>T p.Pro283Leu missense_variant Likely Benign 0
I288M EX4 1633 c.864C>G p.Ile288Met missense_variant Likely Benign 0
V289M EX4 1634 c.865G>A p.Val289Met missense_variant Likely Benign 0
R294K EX4 1650 c.881G>A p.Arg294Lys missense_variant Likely Benign 0
M299V EX4 1664 c.895A>G p.Met299Val missense_variant Likely Benign 0
D300H EX4 1667 c.898G>C p.Asp300His missense_variant Uncertain significance 0
G301S EX4 1670 c.901G>A p.Gly301Ser missense_variant Likely Benign 0
G301C EX4 1670 c.901G>T p.Gly301Cys missense_variant Uncertain significance 0
G301D EX4 1671 c.902G>A p.Gly301Asp missense_variant Pathogenic 0
F302C EX4 1674 c.905T>G p.Phe302Cys missense_variant Pathogenic 0
F302L EX4 1675 c.906C>A p.Phe302Leu missense_variant Pathogenic 0
F302L EX4 1675 c.906C>G p.Phe302Leu missense_variant Pathogenic 0
D303N EX4 1676 c.907G>A p.Asp303Asn missense_variant Pathogenic 0
D303H EX4 1676 c.907G>C p.Asp303His missense_variant Pathogenic 0
D303A EX4 1677 c.908A>C p.Asp303Ala missense_variant Pathogenic 0
D303G EX4 1677 c.908A>G p.Asp303Gly missense_variant Pathogenic 0
E304K EX4 1679 c.910G>A p.Glu304Lys missense_variant Pathogenic 0
E304D EX4 1681 c.912G>C p.Glu304Asp missense_variant Pathogenic 0
L305M EX4 1682 c.913C>A p.Leu305Met missense_variant Pathogenic 0
L305P EX4 1683 c.914T>C p.Leu305Pro missense_variant Likely Pathogenic 0
Q306K EX4 1685 c.916C>A p.Gln306Lys missense_variant Pathogenic 0
Q306E EX4 1685 c.916C>G p.Gln306Glu missense_variant Pathogenic 0
G307S EX4 1688 c.919G>A p.Gly307Ser missense_variant Pathogenic 0
G307R EX4 1688 c.919G>C p.Gly307Arg missense_variant Pathogenic 0
G307Vfs*5 EX4 1689-1695 c.920_926del p.Gly307ValfsTer5 frameshift_variant Likely Pathogenic 0
G307D EX4 1689 c.920G>A p.Gly307Asp missense_variant Pathogenic 0
G307V EX4 1689 c.920G>T p.Gly307Val missense_variant Pathogenic 0
F309Y EX4 1695 c.926T>A p.Phe309Tyr missense_variant Likely Pathogenic 0
F309S EX4 1695 c.926T>C p.Phe309Ser missense_variant Pathogenic 0
E311K EX4 1700 c.931G>A p.Glu311Lys missense_variant Pathogenic 0
H312P EX4 1704 c.935A>C p.His312Pro missense_variant Pathogenic 0
I313L EX4 1706 c.937A>C p.Ile313Leu missense_variant Likely Benign 0
I313V EX4 1706 c.937A>G p.Ile313Val missense_variant Likely Benign 0
I313T EX4 1707 c.938T>C p.Ile313Thr missense_variant Likely Benign 0
G314R EX4 1709 c.940G>A p.Gly314Arg missense_variant Uncertain significance 0
P315L EX4 1713 c.944C>T p.Pro315Leu missense_variant Likely Benign 0
D319N EX4 1724 c.955G>A p.Asp319Asn missense_variant Uncertain significance 0
K322E EX4 1733 c.964A>G p.Lys322Glu missense_variant Uncertain significance 0
A323V EX4 1737 c.968C>T p.Ala323Val missense_variant Likely Benign 0
E324K EX4 1739 c.970G>A p.Glu324Lys missense_variant Uncertain significance 0
R325W EX4 1742 c.973C>T p.Arg325Trp missense_variant Likely Benign 0
R325Q EX4 1743 c.974G>A p.Arg325Gln missense_variant Likely Benign 0
G326E EX4 1746 c.977G>A p.Gly326Glu missense_variant Pathogenic 0
G326A EX4 1746 c.977G>C p.Gly326Ala missense_variant Uncertain significance 0
G326V EX4 1746 c.977G>T p.Gly326Val missense_variant Likely Benign 0
L329V EX4 1754 c.985C>G p.Leu329Val missense_variant Likely Benign 0
S331N EX4 1761 c.992G>A p.Ser331Asn missense_variant Likely Pathogenic 0
S331R EX4 1762 c.993C>A p.Ser331Arg missense_variant Pathogenic 0
S332G EX4 1763 c.994A>G p.Ser332Gly missense_variant Uncertain significance 0
S332N EX4 1764 c.995G>A p.Ser332Asn missense_variant Uncertain significance 0
I334V EX4 1769 c.1000A>G p.Ile334Val missense_variant Pathogenic 0
K337N EX4 1780 c.1011G>C p.Lys337Asn missense_variant Uncertain significance 0
E341K EX4 1790 c.1021G>A p.Glu341Lys missense_variant Uncertain significance 0
T347I EX4 1809 c.1040C>T p.Thr347Ile missense_variant Pathogenic 0
T348M EX4 1812 c.1043C>T p.Thr348Met missense_variant Pathogenic 0
P350L EX4 1818 c.1049C>T p.Pro350Leu missense_variant Uncertain significance 0
V351M EX4 1820 c.1051G>A p.Val351Met missense_variant Pathogenic 0
V351L EX4 1820 c.1051G>C p.Val351Leu missense_variant Pathogenic 0
V351L EX4 1820 c.1051G>T p.Val351Leu missense_variant Pathogenic 0
A352T EX4 1823 c.1054G>A p.Ala352Thr missense_variant Pathogenic 0
A352S EX4 1823 c.1054G>T p.Ala352Ser missense_variant Pathogenic 0
A352V EX4 1824 c.1055C>T p.Ala352Val missense_variant Pathogenic 0
L353P EX4 1827 c.1058T>C p.Leu353Pro missense_variant Likely Pathogenic 0
E354D EX4 1831 c.1062G>T p.Glu354Asp missense_variant Pathogenic 0
K355T EX4 1833 c.1064A>C p.Lys355Thr missense_variant Pathogenic 0
K355R EX4 1833 c.1064A>G p.Lys355Arg missense_variant Likely Pathogenic 0
K355N EX4 1834 c.1065A>C p.Lys355Asn missense_variant Pathogenic 0
H358R EX4 1842 c.1073A>G p.His358Arg missense_variant Pathogenic 0
L359V EX4 1844 c.1075T>G p.Leu359Val missense_variant Pathogenic 0
L359W EX4 1845 c.1076T>G p.Leu359Trp missense_variant Pathogenic 0
L360Q EX4 1848 c.1079T>A p.Leu360Gln missense_variant Uncertain significance 0
R364W EX4 1859 c.1090C>T p.Arg364Trp missense_variant Uncertain significance 0
H365Y EX4 1862 c.1093C>T p.His365Tyr missense_variant Likely Benign 0
I368L EX4 1871 c.1102A>C p.Ile368Leu missense_variant Uncertain significance 0
L369M EX4 1874 c.1105C>A p.Leu369Met missense_variant Likely Benign 0
A374D EX4 1890 c.1121C>A p.Ala374Asp missense_variant Pathogenic 0
K375E EX4 1892 c.1123A>G p.Lys375Glu missense_variant Likely Benign 0
E378K EX4 1901 c.1132G>A p.Glu378Lys missense_variant Likely Benign 0
S385P EX4 1922 c.1153T>C p.Ser385Pro missense_variant Likely Benign 0
S385A EX4 1922 c.1153T>G p.Ser385Ala missense_variant Likely Benign 0
D386E EX4 1927 c.1158T>A p.Asp386Glu missense_variant Likely Benign 0
E387K EX4 1928 c.1159G>A p.Glu387Lys missense_variant Likely Benign 0
A392E EX4 1944 c.1175C>A p.Ala392Glu missense_variant Likely Benign 0
A393G EX4 1947 c.1178C>G p.Ala393Gly missense_variant Uncertain significance 0
S395G EX4 1952 c.1183A>G p.Ser395Gly missense_variant Likely Benign 0
L396V EX4 1955 c.1186C>G p.Leu396Val missense_variant Likely Benign 0
I397T EX4 1959 c.1190T>C p.Ile397Thr missense_variant Likely Benign 0
N400Y EX4 1967 c.1198A>T p.Asn400Tyr missense_variant Pathogenic 0
E401K EX4 1970 c.1201G>A p.Glu401Lys missense_variant Likely Benign 0
T405P EX4 1982 c.1213A>C p.Thr405Pro missense_variant Pathogenic 0
M406V EX4 1985 c.1216A>G p.Met406Val missense_variant Pathogenic 0
M406T EX4 1986 c.1217T>C p.Met406Thr missense_variant Pathogenic 0
M406I EX4 1987 c.1218G>A p.Met406Ile missense_variant Pathogenic 0
F408S EX4 1992 c.1223T>C p.Phe408Ser missense_variant Likely Benign 0
L411M EX4 2000 c.1231C>A p.Leu411Met missense_variant Pathogenic 0
L411V EX4 2000 c.1231C>G p.Leu411Val missense_variant Likely Benign 0
L411F EX4 2000-2002 c.1231_1233delinsTTT p.Leu411Phe missense_variant Pathogenic 0
W414L EX4 2010 c.1241G>T p.Trp414Leu missense_variant Likely Pathogenic 0
V416M EX4 2015 c.1246G>A p.Val416Met missense_variant Uncertain significance 0
V416L EX4 2015 c.1246G>T p.Val416Leu missense_variant Likely Benign 0
E425A EX4 2043 c.1274A>C p.Glu425Ala missense_variant Likely Benign 0
T433A EX4 2066 c.1297A>G p.Thr433Ala missense_variant Likely Benign 0
T433I EX4 2067 c.1298C>T p.Thr433Ile missense_variant Pathogenic 0
K435E EX4 2072 c.1303A>G p.Lys435Glu missense_variant Pathogenic 0
K435N EX4 2074 c.1305G>C p.Lys435Asn missense_variant Pathogenic 0
K435N EX4 2074 c.1305G>T p.Lys435Asn missense_variant Pathogenic 0
T436- EX4 2075-2077 c.1312_1314del p.Thr438del inframe_deletion Pathogenic 0
T436P EX4 2075 c.1306A>C p.Thr436Pro missense_variant Pathogenic 0
T436A EX4 2075 c.1306A>G p.Thr436Ala missense_variant Pathogenic 0
T436N EX4 2076 c.1307C>A p.Thr436Asn missense_variant Pathogenic 0
T436I EX4 2076 c.1307C>T p.Thr436Ile missense_variant Pathogenic 0
T438- EX4 2081-2083 c.1312_1314del p.Thr438del inframe_deletion Pathogenic 0
A439T EX4 2084 c.1315G>A p.Ala439Thr missense_variant Pathogenic 0
A439P EX4 2084 c.1315G>C p.Ala439Pro missense_variant Pathogenic 0
A439V EX4 2085 c.1316C>T p.Ala439Val missense_variant Likely Pathogenic 0
Y441H EX4 2090 c.1321T>C p.Tyr441His missense_variant Pathogenic 0
Y441C EX4 2091 c.1322A>G p.Tyr441Cys missense_variant Pathogenic 0
V442I EX4 2093 c.1324G>A p.Val442Ile missense_variant Likely Benign 0
F443L EX4 2098 c.1329C>G p.Phe443Leu missense_variant Pathogenic 0
F444V EX4 2099 c.1330T>G p.Phe444Val missense_variant Pathogenic 0
L445F EX4 2102 c.1333C>T p.Leu445Phe missense_variant Likely Benign 0
R452Q EX4 2124 c.1355G>A p.Arg452Gln missense_variant Likely Benign 0
G454E EX4 2130 c.1361G>A p.Gly454Glu missense_variant Likely Benign 0
S455N EX4 2133 c.1364G>A p.Ser455Asn missense_variant Likely Benign 0
S455R EX4 2134 c.1365C>A p.Ser455Arg missense_variant Likely Benign 0
E457D EX4 2140 c.1371G>T p.Glu457Asp missense_variant Uncertain significance 0
H458Q EX4 2143 c.1374C>A p.His458Gln missense_variant Likely Benign 0
G459C EX4 2144 c.1375G>T p.Gly459Cys missense_variant Likely Benign 0
G459A EX4 2145 c.1376G>C p.Gly459Ala missense_variant Likely Benign 0
C461Y EX4 2151 c.1382G>A p.Cys461Tyr missense_variant Likely Benign 0
A462T EX4 2153 c.1384G>A p.Ala462Thr missense_variant Likely Benign 0
H463Y EX4 2156 c.1387C>T p.His463Tyr missense_variant Uncertain significance 0
L464I EX4 2159 c.1390C>A p.Leu464Ile missense_variant Likely Benign 0
C468R EX4 2171 c.1402T>C p.Cys468Arg missense_variant Uncertain significance 0
S469F EX4 2175 c.1406C>T p.Ser469Phe missense_variant Uncertain significance 0
N477K EX4 2200 c.1431C>A p.Asn477Lys missense_variant Pathogenic 0
K479N EX4 2206 c.1437A>T p.Lys479Asn missense_variant Uncertain significance 0
I480F EX4 2207 c.1438A>T p.Ile480Phe missense_variant Pathogenic 0
D486N EX4 2225 c.1456G>A p.Asp486Asn missense_variant Uncertain significance 0
R488W EX4 2231 c.1462A>T p.Arg488Trp missense_variant Likely Benign 0
R488K EX4 2232 c.1463G>A p.Arg488Lys missense_variant Likely Benign 0
N489K EX4 2236 c.1467T>A p.Asn489Lys missense_variant Likely Benign 0
Q493R EX4 2247 c.1478A>G p.Gln493Arg missense_variant Likely Benign 0
A495V EX4 2253 c.1484C>T p.Ala495Val missense_variant Likely Benign 0
D496N EX4 2255 c.1486G>A p.Asp496Asn missense_variant Likely Benign 0
D496V EX4 2256 c.1487A>T p.Asp496Val missense_variant Uncertain significance 0
S498C EX4 2262 c.1493C>G p.Ser498Cys missense_variant Uncertain significance 0
R502G EX4 2273 c.1504A>G p.Arg502Gly missense_variant Likely Benign 0
Q507R EX4 2289 c.1520A>G p.Gln507Arg missense_variant Likely Benign 0
S517R EX4 2320 c.1551C>G p.Ser517Arg missense_variant Uncertain significance 0
F518L EX4 2321 c.1552T>C p.Phe518Leu missense_variant Uncertain significance 0
I519T EX4 2325 c.1556T>C p.Ile519Thr missense_variant Likely Benign 0
M521L EX4 2330 c.1561A>C p.Met521Leu missense_variant Likely Benign 0
M521L EX4 2330 c.1561A>T p.Met521Leu missense_variant Likely Benign 0
M521K EX4 2331 c.1562T>A p.Met521Lys missense_variant Pathogenic 0
M521T EX4 2331 c.1562T>C p.Met521Thr missense_variant Pathogenic 0
T522S EX4 2333 c.1564A>T p.Thr522Ser missense_variant Pathogenic 0
T522S EX4 2334 c.1565C>G p.Thr522Ser missense_variant Pathogenic 0
F523Y EX4 2337 c.1568T>A p.Phe523Tyr missense_variant Pathogenic 0
F523C EX4 2337 c.1568T>G p.Phe523Cys missense_variant Pathogenic 0
F523L EX4 2338 c.1569C>A p.Phe523Leu missense_variant Pathogenic 0
F523L EX4 2338 c.1569C>G p.Phe523Leu missense_variant Pathogenic 0
E525K EX4 2342 c.1573G>A p.Glu525Lys missense_variant Pathogenic 0
E525V EX4 2343 c.1574A>T p.Glu525Val missense_variant Pathogenic 0
M530V EX4 2357 c.1588A>G p.Met530Val missense_variant Uncertain significance 0
K538E EX4 2381 c.1612A>G p.Lys538Glu missense_variant Likely Benign 0
T542M EX4 2394 c.1625C>T p.Thr542Met missense_variant Likely Benign 0
V544I EX4 2399 c.1630G>A p.Val544Ile missense_variant Likely Benign 0
V544L EX4 2399 c.1630G>C p.Val544Leu missense_variant Likely Benign 0
P545A EX4 2402 c.1633C>G p.Pro545Ala missense_variant Likely Benign 0
S547C EX4 2408 c.1639A>T p.Ser547Cys missense_variant Likely Benign 0
R548C EX4 2411 c.1642C>T p.Arg548Cys missense_variant Likely Benign 0
R548H EX4 2412 c.1643G>A p.Arg548His missense_variant Likely Benign 0
L549V EX4 2414 c.1645T>G p.Leu549Val missense_variant Likely Benign 0
R554* EX4 2429 c.1660C>T p.Arg554Ter stop_gained Uncertain significance 0
R554Q EX4 2430 c.1661G>A p.Arg554Gln missense_variant Likely Benign 0
V556M EX4 2435 c.1666G>A p.Val556Met missense_variant Uncertain significance 0
T557A EX4 2438 c.1669A>G p.Thr557Ala missense_variant Likely Benign 0
L559- EX4 2444-2446 c.1677_1679del p.Leu560del inframe_deletion Uncertain significance 0
Y563N EX4 2456 c.1687T>A p.Tyr563Asn missense_variant Pathogenic 0
Y563C EX4 2457 c.1688A>G p.Tyr563Cys missense_variant Pathogenic 0
G564S EX4 2459 c.1690G>A p.Gly564Ser missense_variant Pathogenic 0
G564D EX4 2460 c.1691G>A p.Gly564Asp missense_variant Pathogenic 0
K565E EX4 2462 c.1693A>G p.Lys565Glu missense_variant Pathogenic 0
F566Y EX4 2466 c.1697T>A p.Phe566Tyr missense_variant Pathogenic 0
F566L EX4 2467 c.1698C>A p.Phe566Leu missense_variant Pathogenic 0
E567K EX4 2468 c.1699G>A p.Glu567Lys missense_variant Pathogenic 0
E567Q EX4 2468 c.1699G>C p.Glu567Gln missense_variant Pathogenic 0
E567A EX4 2469 c.1700A>C p.Glu567Ala missense_variant Pathogenic 0
E567G EX4 2469 c.1700A>G p.Glu567Gly missense_variant Pathogenic 0
K568N EX4 2473 c.1704G>C p.Lys568Asn missense_variant Pathogenic 0
G569R EX4 2474 c.1705G>A p.Gly569Arg missense_variant Pathogenic 0
G569R EX4 2474 c.1705G>C p.Gly569Arg missense_variant Pathogenic 0
G569E EX4 2475 c.1706G>A p.Gly569Glu missense_variant Pathogenic 0
G569A EX4 2475 c.1706G>C p.Gly569Ala missense_variant Pathogenic 0
G569V EX4 2475 c.1706G>T p.Gly569Val missense_variant Pathogenic 0
Y570N EX4 2477 c.1708T>A p.Tyr570Asn missense_variant Pathogenic 0
Y570H EX4 2477 c.1708T>C p.Tyr570His missense_variant Pathogenic 0
Y570C EX4 2478 c.1709A>G p.Tyr570Cys missense_variant Pathogenic 0
Y570F EX4 2478 c.1709A>T p.Tyr570Phe missense_variant Pathogenic 0
L571V EX4 2480 c.1711T>G p.Leu571Val missense_variant Pathogenic 0
L571F EX4 2482 c.1713G>C p.Leu571Phe missense_variant Pathogenic 0
L571F EX4 2482 c.1713G>T p.Leu571Phe missense_variant Pathogenic 0
I572F EX4 2483 c.1714A>T p.Ile572Phe missense_variant Pathogenic 0
F573S EX4 2487 c.1718T>C p.Phe573Ser missense_variant Pathogenic 0
F579Y EX4 2505 c.1736T>A p.Phe579Tyr missense_variant Likely Benign 0
L581V EX4 2510 c.1741C>G p.Leu581Val missense_variant Uncertain significance 0
T587I EX4 2529 c.1760C>T p.Thr587Ile missense_variant Pathogenic 0
K593E EX4 2546 c.1777A>G p.Lys593Glu missense_variant Likely Benign 0
S595G EX4 2552 c.1783A>G p.Ser595Gly missense_variant Pathogenic 0
I598F EX4 2561 c.1792A>T p.Ile598Phe missense_variant Pathogenic 0
S599T EX4 2564 c.1795T>A p.Ser599Thr missense_variant Likely Benign 0
Q600* EX4 2567 c.1798C>T p.Gln600Ter stop_gained Uncertain significance 0
Q600R EX4 2568 c.1799A>G p.Gln600Arg missense_variant Likely Pathogenic 0
R603G EX4 2576 c.1807A>G p.Arg603Gly missense_variant Uncertain significance 0
L604Q EX4 2580 c.1811T>A p.Leu604Gln missense_variant Likely Benign 0
E605V EX4 2583 c.1814A>T p.Glu605Val missense_variant Likely Benign 0
I610T EX4 2598 c.1829T>C p.Ile610Thr missense_variant Uncertain significance 0
K613N EX4 2608 c.1839A>T p.Lys613Asn missense_variant Likely Benign 0
S624R EX4 2641 c.1872C>G p.Ser624Arg missense_variant Likely Pathogenic 0
E627Q EX4 2648 c.1879G>C p.Glu627Gln missense_variant Pathogenic 0
E627G EX4 2649 c.1880A>G p.Glu627Gly missense_variant Likely Pathogenic 0
E627D EX4 2650 c.1881A>T p.Glu627Asp missense_variant Pathogenic 0
Y630F EX4 2658 c.1889A>T p.Tyr630Phe missense_variant Uncertain significance 0
C631W EX4 2662 c.1893T>G p.Cys631Trp missense_variant Pathogenic 0
L632F EX4 2665 c.1896G>T p.Leu632Phe missense_variant Pathogenic 0
Y633* EX4 2668 c.1899C>G p.Tyr633Ter stop_gained Uncertain significance 0
M635L EX4 2672 c.1903A>T p.Met635Leu missense_variant Likely Benign 0
M635T EX4 2673 c.1904T>C p.Met635Thr missense_variant Likely Pathogenic 0
Q636E EX4 2675 c.1906C>G p.Gln636Glu missense_variant Pathogenic 0
Q636R EX4 2676 c.1907A>G p.Gln636Arg missense_variant Likely Benign 0
E638K EX4 2681 c.1912G>A p.Glu638Lys missense_variant Likely Benign 0
F640V EX4 2687 c.1918T>G p.Phe640Val missense_variant Uncertain significance 0
V641M EX4 2690 c.1921G>A p.Val641Met missense_variant Uncertain significance 0
D646Y EX4 2705 c.1936G>T p.Asp646Tyr missense_variant Likely Benign 0
D646G EX4 2706 c.1937A>G p.Asp646Gly missense_variant Likely Benign 0
Y647N EX4 2708 c.1939T>A p.Tyr647Asn missense_variant Likely Benign 0
F648L EX4 2713 c.1944C>A p.Phe648Leu missense_variant Uncertain significance 0
P649S EX4 2714 c.1945C>T p.Pro649Ser missense_variant Likely Benign 0
P649R EX4 2715 c.1946C>G p.Pro649Arg missense_variant Likely Benign 0
P649L EX4 2715 c.1946C>T p.Pro649Leu missense_variant Uncertain significance 0
I651T EX4 2721 c.1952T>C p.Ile651Thr missense_variant Uncertain significance 0
N654D EX4 2729 c.1960A>G p.Asn654Asp missense_variant Likely Benign 0
N654S EX4 2730 c.1961A>G p.Asn654Ser missense_variant Likely Benign 0
T657N EX4 2739 c.1970C>A p.Thr657Asn missense_variant Likely Benign 0
M659K EX4 2745 c.1976T>A p.Met659Lys missense_variant Likely Pathogenic 0
M659R EX4 2745 c.1976T>G p.Met659Arg missense_variant Pathogenic 0
M662V EX4 2753 c.1984A>G p.Met662Val missense_variant Likely Benign 0
M662T EX4 2754 c.1985T>C p.Met662Thr missense_variant Pathogenic 0
F666V EX4 2765 c.1996T>G p.Phe666Val missense_variant Uncertain significance 0
C671S EX4 2781 c.2012G>C p.Cys671Ser missense_variant Likely Benign 0
R673W EX4 2786 c.2017C>T p.Arg673Trp missense_variant Likely Benign 0
R673Q EX4 2787 c.2018G>A p.Arg673Gln missense_variant Likely Benign 0
L677V EX4 2798 c.2029C>G p.Leu677Val missense_variant Likely Benign 0
L677P EX4 2799 c.2030T>C p.Leu677Pro missense_variant Likely Pathogenic 0
L679V EX4 2804 c.2035C>G p.Leu679Val missense_variant Likely Benign 0
H683Y EX4 2816 c.2047C>T p.His683Tyr missense_variant Likely Benign 0
H683R EX4 2817 c.2048A>G p.His683Arg missense_variant Likely Benign 0
N684D EX4 2819 c.2050A>G p.Asn684Asp missense_variant Likely Benign 0
E688K EX4 2831 c.2062G>A p.Glu688Lys missense_variant Pathogenic 0
E690K EX4 2837 c.2068G>A p.Glu690Lys missense_variant Pathogenic 0
E690Q EX4 2837 c.2068G>C p.Glu690Gln missense_variant Likely Pathogenic 0
E690* EX4 2837 c.2068G>T p.Glu690Ter stop_gained Uncertain significance 0
K694N EX4 2851 c.2082G>C p.Lys694Asn missense_variant Likely Benign 0
G696V EX4 2856 c.2087G>T p.Gly696Val missense_variant Likely Benign 0
R697* EX4 2858 c.2089C>T p.Arg697Ter stop_gained Uncertain significance 0
R697Q EX4 2859 c.2090G>A p.Arg697Gln missense_variant Likely Benign 0
L699F EX4 2864 c.2095C>T p.Leu699Phe missense_variant Likely Benign 0
D700N EX4 2867 c.2098G>A p.Asp700Asn missense_variant Likely Benign 0
M701T EX4 2871 c.2102T>C p.Met701Thr missense_variant Likely Benign 0
Q703K EX4 2876 c.2107C>A p.Gln703Lys missense_variant Likely Benign 0
Q703H EX4 2878 c.2109G>T p.Gln703His missense_variant Likely Benign 0
P707Q EX4 2889 c.2120C>A p.Pro707Gln missense_variant Likely Benign 0
S710C EX4 2898 c.2129C>G p.Ser710Cys missense_variant Likely Benign 0
H711L EX4 2901 c.2132A>T p.His711Leu missense_variant Likely Benign 0
H711Q EX4 2902 c.2133T>A p.His711Gln missense_variant Likely Benign 0
H711H EX4 2902 c.2133T>C p.His711= synonymous_variant Likely Benign 0
A712S EX4 2903 c.2134G>T p.Ala712Ser missense_variant Likely Benign 0
C714R EX4 2909 c.2140T>C p.Cys714Arg missense_variant Likely Benign 0
C714S EX4 2910 c.2141G>C p.Cys714Ser missense_variant Likely Benign 0
V719M EX5 2924 c.2155G>A p.Val719Met missense_variant Likely Benign 0
N720T EX5 2928 c.2159A>C p.Asn720Thr missense_variant Likely Benign 0
L723I EX5 2936 c.2167C>A p.Leu723Ile missense_variant Likely Pathogenic 0
S726T EX5 2946 c.2177G>C p.Ser726Thr missense_variant Likely Benign 0
R729W EX5 2954 c.2185C>T p.Arg729Trp missense_variant Likely Benign 0
S738R EX5 2983 c.2214C>A p.Ser738Arg missense_variant Likely Benign 0
S738R EX5 2983 c.2214C>G p.Ser738Arg missense_variant Likely Benign 0
S740N EX5 2988 c.2219G>A p.Ser740Asn missense_variant Likely Benign 0
L746F EX5 3005 c.2236C>T p.Leu746Phe missense_variant Likely Benign 0
D748E EX5 3013 c.2244C>G p.Asp748Glu missense_variant Likely Benign 0
S750P EX5 3017 c.2248T>C p.Ser750Pro missense_variant Likely Benign 0
G752E EX5 3024 c.2255G>A p.Gly752Glu missense_variant Likely Benign 0
D753N EX5 3026 c.2257G>A p.Asp753Asn missense_variant Likely Benign 0
G755R EX5 3032 c.2263G>A p.Gly755Arg missense_variant Likely Pathogenic 0
G755R EX5 3032 c.2263G>C p.Gly755Arg missense_variant Likely Pathogenic 0
G755A EX5 3033 c.2264G>C p.Gly755Ala missense_variant Likely Pathogenic 0
R757K EX5 3039 c.2270G>A p.Arg757Lys missense_variant Likely Benign 0
R757T EX5 3039 c.2270G>C p.Arg757Thr missense_variant Likely Benign 0
V758A EX5 3042 c.2273T>C p.Val758Ala missense_variant Likely Benign 0
T762M EX5 3054 c.2285C>T p.Thr762Met missense_variant Likely Benign 0
P766L EX5 3066 c.2297C>T p.Pro766Leu missense_variant Likely Benign 0
G767S EX5 3068 c.2299G>A p.Gly767Ser missense_variant Likely Benign 0
R771W EX5 3080 c.2311C>T p.Arg771Trp missense_variant Uncertain significance 0
W774C EX6 3091 c.2322G>T p.Trp774Cys missense_variant Likely Benign 0
L775M EX6 3092 c.2323T>A p.Leu775Met missense_variant Likely Benign 0
R777C EX6 3098 c.2329C>T p.Arg777Cys missense_variant Likely Benign 0
R777H EX6 3099 c.2330G>A p.Arg777His missense_variant Likely Benign 0
G779D EX6 3105 c.2336G>A p.Gly779Asp missense_variant Likely Benign 0
G779V EX6 3105 c.2336G>T p.Gly779Val missense_variant Likely Benign 0
L780I EX6 3107 c.2338C>A p.Leu780Ile missense_variant Likely Benign 0
S781L EX6 3111 c.2342C>T p.Ser781Leu missense_variant Uncertain significance 0
C785R EX6 3122 c.2353T>C p.Cys785Arg missense_variant Uncertain significance 0
D787N EX6 3128 c.2359G>A p.Asp787Asn missense_variant Likely Benign 0
S793G EX6 3146 c.2377A>G p.Ser793Gly missense_variant Likely Benign 0
Q796P EX6 3156 c.2387A>C p.Gln796Pro missense_variant Likely Benign 0
Q796R EX6 3156 c.2387A>G p.Gln796Arg missense_variant Likely Benign 0
L798M EX6 3161 c.2392C>A p.Leu798Met missense_variant Likely Benign 0
L798V EX6 3161 c.2392C>G p.Leu798Val missense_variant Likely Benign 0
E800V EX6 3168 c.2399A>T p.Glu800Val missense_variant Likely Benign 0
A807T EX6 3188 c.2419G>A p.Ala807Thr missense_variant Likely Benign 0
G809S EX6 3194 c.2425G>A p.Gly809Ser missense_variant Likely Benign 0
G812A EX6 3204 c.2435G>C p.Gly812Ala missense_variant Likely Benign 0
V818L EX6 3221 c.2452G>T p.Val818Leu missense_variant Likely Benign 0
L820P EX6 3228 c.2459T>C p.Leu820Pro missense_variant Uncertain significance 0
C825F EX6 3243 c.2474G>T p.Cys825Phe missense_variant Uncertain significance 0
N826H EX6 3245 c.2476A>C p.Asn826His missense_variant Likely Benign 0
L830I EX6 3257 c.2488C>A p.Leu830Ile missense_variant Likely Benign 0
L837P EX7 3279 c.2510T>C p.Leu837Pro missense_variant Uncertain significance 0
A840E EX7 3288 c.2519C>A p.Ala840Glu missense_variant Likely Benign 0
C841G EX7 3290 c.2521T>G p.Cys841Gly missense_variant Likely Benign 0
C842F EX7 3294 c.2525G>T p.Cys842Phe missense_variant Uncertain significance 0
D844Y EX7 3299 c.2530G>T p.Asp844Tyr missense_variant Likely Benign 0
A846P EX7 3305 c.2536G>C p.Ala846Pro missense_variant Uncertain significance 0
T851I EX7 3321 c.2552C>T p.Thr851Ile missense_variant Likely Benign 0
T856N EX7 3336 c.2567C>A p.Thr856Asn missense_variant Likely Benign 0
R857K EX7 3339 c.2570G>A p.Arg857Lys missense_variant Likely Benign 0
Y859H EX7 3344 c.2575T>C p.Tyr859His missense_variant Likely Benign 0
Y859S EX7 3345 c.2576A>C p.Tyr859Ser missense_variant Likely Benign 0
Y859C EX7 3345 c.2576A>G p.Tyr859Cys missense_variant Likely Benign 0
V860M EX7 3347 c.2578G>A p.Val860Met missense_variant Likely Benign 0
E862Q EX7 3353 c.2584G>C p.Glu862Gln missense_variant Likely Benign 0
A864V EX7 3360 c.2591C>T p.Ala864Val missense_variant Likely Benign 0
G866R EX7 3365 c.2596G>A p.Gly866Arg missense_variant Likely Benign 0
A871T EX7 3380 c.2611G>A p.Ala871Thr missense_variant Likely Benign 0
A877G EX7 3399 c.2630C>G p.Ala877Gly missense_variant Likely Benign 0
K878E EX7 3401 c.2632A>G p.Lys878Glu missense_variant Likely Benign 0
P880S EX7 3407 c.2638C>T p.Pro880Ser missense_variant Likely Benign 0
G888G EX8 3433 c.2664G>T p.Gly888= splice_region_variant Likely Benign 0
V890L EX8 3437 c.2668G>T p.Val890Leu missense_variant Likely Benign 0
V890A EX8 3438 c.2669T>C p.Val890Ala missense_variant Likely Benign 0
G893A EX8 3447 c.2678G>C p.Gly893Ala missense_variant Likely Benign 0
L894F EX8 3449 c.2680C>T p.Leu894Phe missense_variant Likely Benign 0
S896P EX8 3455 c.2686T>C p.Ser896Pro missense_variant Likely Benign 0
A901V EX8 3471 c.2702C>T p.Ala901Val missense_variant Likely Benign 0
S904L EX8 3480 c.2711C>T p.Ser904Leu missense_variant Likely Benign 0
T908I EX8 3492 c.2723C>T p.Thr908Ile missense_variant Likely Benign 0
N909D EX8 3494 c.2725A>G p.Asn909Asp missense_variant Uncertain significance 0
N911S EX8 3501 c.2732A>G p.Asn911Ser missense_variant Likely Benign 0
T913R EX8 3507 c.2738C>G p.Thr913Arg missense_variant Likely Benign 0
T913M EX8 3507 c.2738C>T p.Thr913Met missense_variant Likely Benign 0
L915R EX8 3513 c.2744T>G p.Leu915Arg missense_variant Uncertain significance 0
R918Q EX8 3522 c.2753G>A p.Arg918Gln missense_variant Likely Benign 0
G919D EX8 3525 c.2756G>A p.Gly919Asp missense_variant Likely Benign 0
T921A EX8 3530 c.2761A>G p.Thr921Ala missense_variant Likely Benign 0
G923R EX8 3536 c.2767G>A p.Gly923Arg missense_variant Likely Benign 0
D924E EX8 3541 c.2772C>G p.Asp924Glu missense_variant Likely Benign 0
K928N EX8 3553 c.2784A>C p.Lys928Asn missense_variant Likely Benign 0
L935W EX8 3573 c.2804T>G p.Leu935Trp missense_variant Likely Benign 0
H936R EX8 3576 c.2807A>G p.His936Arg missense_variant Likely Benign 0
D938N EX8 3581 c.2812G>A p.Asp938Asn missense_variant Likely Benign 0
K940R EX8 3588 c.2819A>G p.Lys940Arg missense_variant Likely Benign 0
V943L EX8 3596 c.2827G>C p.Val943Leu missense_variant Likely Benign 0
D947E EX9 3610 c.2841C>A p.Asp947Glu missense_variant Likely Benign 0
T952K EX9 3624 c.2855C>A p.Thr952Lys missense_variant Likely Benign 0
T952M EX9 3624 c.2855C>T p.Thr952Met missense_variant Likely Benign 0
H954Y EX9 3629 c.2860C>T p.His954Tyr missense_variant Likely Benign 0
S960T EX9 3647 c.2878T>A p.Ser960Thr missense_variant Likely Benign 0
L962F EX9 3653 c.2884C>T p.Leu962Phe missense_variant Likely Benign 0
T964Sfs*16 EX9 3658-3665 c.2889_2896delinsTTCCACACTTTC p.Thr964SerfsTer16 frameshift_variant Likely Pathogenic 0
S966G EX9 3665 c.2896A>G p.Ser966Gly missense_variant Likely Benign 0
Q967H EX9 3670 c.2901G>C p.Gln967His missense_variant Likely Benign 0
S968G EX9 3671 c.2902A>G p.Ser968Gly missense_variant Likely Benign 0
S968R EX9 3673 c.2904C>A p.Ser968Arg missense_variant Likely Benign 0
R970* EX9 3677 c.2908C>T p.Arg970Ter stop_gained Likely Benign 0
K971T EX9 3681 c.2912A>C p.Lys971Thr missense_variant Likely Benign 0
S973G EX9 3686 c.2917A>G p.Ser973Gly missense_variant Likely Benign 0
N976H EX9 3695 c.2926A>C p.Asn976His missense_variant Likely Benign 0
L982V EX9 3713 c.2944C>G p.Leu982Val missense_variant Likely Benign 0
V984D EX9 3720 c.2951T>A p.Val984Asp missense_variant Likely Benign 0
M986I EX9 3727 c.2958G>A p.Met986Ile missense_variant Likely Benign 0
C988S EX9 3732 c.2963G>C p.Cys988Ser missense_variant Likely Benign 0
Q994H EX9 3751 c.2982G>C p.Gln994His missense_variant Likely Benign 0
C996S EX9 3756 c.2987G>C p.Cys996Ser missense_variant Likely Benign 0
S1004P EX10 3779 c.3010T>C p.Ser1004Pro missense_variant Likely Pathogenic 0
S1004F EX10 3780 c.3011C>T p.Ser1004Phe missense_variant Likely Benign 0
E1005* EX10 3782 c.3013G>T p.Glu1005Ter stop_gained Likely Benign 0
Y1007C EX10 3789 c.3020A>G p.Tyr1007Cys missense_variant Likely Benign 0
K1013E EX10 3806 c.3037A>G p.Lys1013Glu missense_variant Likely Benign 0
A1015V EX10 3813 c.3044C>T p.Ala1015Val missense_variant Likely Benign 0
L1016F EX10 3817 c.3048A>C p.Leu1016Phe missense_variant Likely Benign 0
P1024L EX10 3840 c.3071C>T p.Pro1024Leu missense_variant Likely Benign 0
T1027I EX10 3849 c.3080C>T p.Thr1027Ile missense_variant Likely Benign 0
V1028Gfs*4 EX10 3850-3851 c.3082dup p.Val1028GlyfsTer4 frameshift_variant Likely Pathogenic 0
E1031Q EX10 3860 c.3091G>C p.Glu1031Gln missense_variant Likely Benign 0
P1032T EX10 3863 c.3094C>A p.Pro1032Thr missense_variant Likely Benign 0
P1032H EX10 3864 c.3095C>A p.Pro1032His missense_variant Likely Benign 0

Please mind that full curation (inclusion of all published variants) of this gene has not started yet. Please contact us if you want to volunteer.

Diagnostic pitfalls & paradigms

Considerations to take into account when analyzing this gene

Year Paradigm ⓘ PMID Notes
- Regions of Homology -
2015Mosaicism24326009
2015Mosaicism25239704
2017Mosaicism29163488[somatic]
2015Mosaicism25988971[somatic]
2016Mosaicism27273849[somatic]
2014Mosaicism24431285[somatic]
2010Mosaicism20131270[somatic]
2011Mosaicism21702021[somatic]
2012Mosaicism22279087[somatic]
2019Mosaicism30273710[somatic]
2017Mosaicism28916543[somatic]
-Cryptic splicing-Unreported or not recorded in our DB.
-Uniparental disomy-Unreported or not recorded in our DB.
-Incomplete penetrance-Unreported or not recorded in our DB.
-Di-/oligo-genic inheritance-Unreported or not recorded in our DB.
-Somatic reversion-Unreported or not recorded in our DB.

References linked to variants in NLRP3

ID Year Title Journal PMID Variants
560 2015 Diagnosis of cryopyrin-associated periodic syndrome: challen... Exp. Rev. Clin. Immunol. 25979514 1
561 2015 Clinical features and genetic background of the periodic fev... Mediat. of Inflamm. 25821352 1
1380 2024 Mechanisms of NLRP3 activation and inhibition elucidated by ... Seth Masters' lab 141218163 534

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