Information on BLNK
Alt. symbols: SLP65 | Ly57 | SLP-65 | BLNK-s | BASH | bca
Approved name: B cell linker
Alt. names: B-cell adapter containing a SH2 domain protein, B-cell activation, Src homology [SH2] domain-containing leukocyte protein of 65 kD, B cell adaptor containing SH2 domain
Location: 10q24.1: 96189171 - 96271587 (-)
Gene type: protein_coding, 25 transcripts.
Scores: LoFtool: 0.056500 | pLI: 0.99001110 | LOEUF: 0.391
Gene Ontology (GO)
- Molecular function:
- Cell component: cytoplasm [GO:0005737]
- Biological process: intracellular signal transduction [GO:0035556]; cell surface receptor protein tyrosine kinase signaling pathway [GO:0007169]
Normal function
The BLNK gene encodes a B-cell linker or adaptor protein that plays a critical role in B cell development. Linker or adaptor proteins provide mechanisms by which receptors can amplify and regulate downstream effector proteins. BLNK is essential for normal B-cell development (Fu et al., 1998) because it bridges B cell receptor-associated kinase activation with downstream signalling pathways. The phosphorylation of five tyrosine residues is necessary for this protein to nucleate distinct signalling effectors following B cell receptor activation.
Dysfunction and disease
Biallic mutations in BLNK have been associated with Agammaglobulinemia 4 [MIM:613502]. Homozygous splice defects in the cytoplasmic adapter protein BLNK (B cell linker protein) have been identified in patients with this type of agammaglobulinemia (no pre-B cells and no mature B cells), indicating that BLNK plays a critical role in orchestrating the pro-B cell to pre-B cell transition. Deficiency in this protein has also been shown in some cases of pre-B acute lymphoblastic leukemia. [Load More]
[Reviewed by Andrés Caballero-Oteyza on ]
Associated conditions
| Acronym | Condition's_name | MOI | Mode_of_action |
OMIM_ID | No.cases |
|---|---|---|---|---|---|
AGM4 |
Agammaglobulinemia 4 | AR |
Loss of Function | 613502 |
2 (1 fams) |
Please mind that curation (inclusion of all reported patients) of this gene has not been completed. It is currently ongoing.
Transcripts of BLNK
| Name | ENSEMBL_ID | LRG_ID | CCDS_ID | MANE | Transcript.type | Exons | Canonical | CDS_length | REFSEQ_ID |
|---|---|---|---|---|---|---|---|---|---|
| 204 | ENST00000427367.6 | CCDS73171 | protein_coding | 14 | No | 1284 | NM_001258442 | ||
| 201 | ENST00000224337.10 | 1 | CCDS7446 | Select | protein_coding | 17 | Yes | 4344 | NM_013314 |
| 203 | ENST00000413476.6 | CCDS58091 | protein_coding | 16 | No | 1599 | NM_001258440 | ||
| 202 | ENST00000371176.7 | CCDS44464 | protein_coding | 16 | No | 1715 | NM_001114094 | ||
| 211 | ENST00000696253.1 | protein_coding | No | NM_001258441 |
Published variants
Found 4 variants
| Var.name ⓘ | Exon/Intron | cDNA_pos. | CDS_change | Prot.change | Var.type | Var.class. | Patients |
|---|---|---|---|---|---|---|---|
| R282X |
EX12 | 1015 | c.844C>T | p.Arg282* | stop_gained | Pathogenic | 0 |
| EK145-146DX |
EX6 | 606-607 | c.435_436delinsT | p.Glu145Aspfs*12 | frameshift_variant | Pathogenic | 2 |
| R123X |
EX6 | 538 | c.367C>T | p.Arg123* | stop_gained | Pathogenic | 0 |
| EX1+3A>T |
IN1 | c.47+3A>T | splice_region_variant | Pathogenic | 0 |
Please mind that curation (inclusion of all reported gene variants) has not been completed. It is currently ongoing.
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 BLNK
Please mind that curation (inclusion of all relevant literature) has not been completed. It is currently ongoing.
| ID | Year | Title | Journal | PMID | Variants |
|---|---|---|---|---|---|
| 78 |
2015 | Enteroviral Infection in a Patient with BLNK Adaptor Protein... | JoCI | 25893637 |
1 |
| 81 |
2009 | Primary B cell immunodeficiencies: comparisons and contrasts... | Annu. Rev. Immunol | 19302039 |
1 |
| 82 |
1999 | An essential role for BLNK in human B cell development... | Science | 10583958 |
1 |
| 83 |
2014 | The BLNK adaptor protein has a nonredundant role in human B-... | JACI | 24582315 |
1 |