Information on ALPK1
Basic details
Alt. symbols: Lak | FLJ22670 | KIAA1527
Approved name: alpha kinase 1
Alt. names: lymphocyte alpha-kinase
Location: 4q25: 112285509 - 112442621 (+)
Gene type: protein_coding, 19 transcripts.
Scores: LoFtool: 0.955000 | pLI: 0.00000010 | LOEUF: 0.929
Normal function
ALPK1 encodes a Ser/Thr alpha-kinase that detects bacterial pathogen-associated molecular pattern metabolites (PAMPs) to initiate an innate immune response involving pro-inflammatory NF-kappaB signaling (PMID: 28877472, 28222186, 30111836). It has also been implicated in apical protein transport by mediating phosphorylation of unconventional myosin MYO1A (PMID: 15883161), as well as in ciliogenesis (PMID: 30967659).
Dysfunction and disease
Heterozygous GOF mutations in ALPK1 are associated with ROSAH (Retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache) syndrome [OMIM: 614979], an AD disorder featuring childhood-onset reduced vision associated with papilledema, low-grade ocular inflammation unresponsive to immunosuppression and progressive deterioration of visual acuity. Patients also show anhidrosis, splenomegaly, chronic mild pancytopenia that may be exacerbated during infections, migraine-like headaches often accompanied by episodic fevers with back and joint pains, dental and/or nail issues, and variable renal impairment (PMID: 22307799, 30967659, 31939038). Peripheral smears frequently show leukopenia with reactive lymphocytosis, while bone marrow is normocellular with trilineage hematopoiesis and relative erythroid hyperplasia. Immunophenotyping performed on 2 Chinese patients found elevated inflammatory markers and serum TNF-alpha levels, as well as reduced CD19+ B cell counts and low IgM in one patient (PMID: 31939038). For further details, see GeneReviews: https://www.ncbi.nlm.nih.gov/books/NBK604494/ [Load More]
[Reviewed by Xiao P. Peng on 2024-07-29 01:01:50]
Associated conditions
| Acronym | Condition's_name | MOI | Mode_of_action |
OMIM_ID | No.cases |
|---|---|---|---|---|---|
ROSAH |
ROSAH syndrome | AD |
Gain of Function | 614979 |
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 ALPK1
| Name | ENSEMBL_ID | LRG_ID | CCDS_ID | MANE | Transcript.type | Exons | Canonical | CDS_length | REFSEQ_ID |
|---|---|---|---|---|---|---|---|---|---|
| 205 | ENST00000504176.6 | CCDS58923 | protein_coding | 15 | No | 5203 | NM_001253884 | ||
| 219 | ENST00000650871.1 | CCDS3697 | Select | protein_coding | 16 | Yes | 5399 | NM_001102406,NM_025144 |
Published variants
Found 0 variants
| Var.name | Exon/Intron | cDNA_pos. | CDS_change | Prot.change | Var.type | Var.class. | Patients |
|---|
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 | - | |
| - | Cryptic splicing | - | Unreported or not recorded in our DB. |
| - | Uniparental disomy | - | Unreported or not recorded in our DB. |
| - | Mosaicism | - | 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 ALPK1
| ID | Year | Title | Journal | PMID | Variants |
|---|