BLK
Basic information
Region (hg38): 8:11486893-11564599
Links
Phenotypes
GenCC
Source:
- maturity-onset diabetes of the young type 11 (Limited), mode of inheritance: Unknown
- maturity-onset diabetes of the young (Supportive), mode of inheritance: AD
- maturity-onset diabetes of the young type 11 (Limited), mode of inheritance: AD
- monogenic diabetes (Refuted Evidence), mode of inheritance: AD
Clinical Genomic Database
Source:
Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
---|---|---|---|---|---|
Maturity-onset diabetes of the young, type 11 | AD | General | Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing | Endocrine | 19667185 |
ClinVar
This is a list of variants' phenotypes submitted to
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the BLK gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
---|---|---|---|---|---|---|
synonymous | 39 | 55 | ||||
missense | 93 | 13 | 106 | |||
nonsense | 2 | |||||
start loss | 0 | |||||
frameshift | 3 | |||||
inframe indel | 0 | |||||
splice donor/acceptor (+/-2bp) | 2 | |||||
splice region | 2 | 6 | 1 | 9 | ||
non coding | 21 | 40 | 58 | 119 | ||
Total | 0 | 0 | 129 | 93 | 65 |
Variants in BLK
This is a list of pathogenic ClinVar variants found in the BLK region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
Position | Type | Phenotype | Significance | ClinVar |
---|---|---|---|---|
8-11494062-C-T | Maturity onset diabetes mellitus in young | Uncertain significance (Jun 14, 2016) | ||
8-11494063-G-A | Maturity onset diabetes mellitus in young | Likely benign (Jun 14, 2016) | ||
8-11494109-G-A | Maturity onset diabetes mellitus in young | Uncertain significance (Jun 14, 2016) | ||
8-11494118-A-C | Maturity onset diabetes mellitus in young | Uncertain significance (Jun 14, 2016) | ||
8-11494145-T-C | Maturity onset diabetes mellitus in young | Likely benign (Jun 14, 2016) | ||
8-11494152-C-A | Maturity onset diabetes mellitus in young | Benign/Likely benign (Jun 01, 2023) | ||
8-11494153-G-A | Maturity onset diabetes mellitus in young | Uncertain significance (Jun 14, 2016) | ||
8-11494218-G-A | Maturity onset diabetes mellitus in young | Uncertain significance (Jun 14, 2016) | ||
8-11494289-C-G | Maturity onset diabetes mellitus in young | Likely benign (Jun 14, 2016) | ||
8-11494326-C-T | Maturity onset diabetes mellitus in young | Uncertain significance (Jun 14, 2016) | ||
8-11494384-C-T | Maturity onset diabetes mellitus in young | Uncertain significance (Jun 14, 2016) | ||
8-11494390-C-T | Maturity-onset diabetes of the young type 11 | Uncertain significance (Jan 13, 2018) | ||
8-11494392-G-A | Maturity-onset diabetes of the young type 11 | Uncertain significance (Jan 12, 2018) | ||
8-11494403-C-T | Maturity-onset diabetes of the young type 11 | Benign (Jan 12, 2018) | ||
8-11494428-G-T | Maturity-onset diabetes of the young type 11 | Benign (Jan 13, 2018) | ||
8-11494469-C-T | Maturity-onset diabetes of the young type 11 | Uncertain significance (Jan 13, 2018) | ||
8-11494517-G-A | Maturity-onset diabetes of the young type 11 | Uncertain significance (Mar 30, 2018) | ||
8-11494546-C-T | Maturity-onset diabetes of the young type 11 | Uncertain significance (Jan 13, 2018) | ||
8-11494547-A-G | Maturity-onset diabetes of the young type 11 | Benign (Jan 13, 2018) | ||
8-11494584-T-C | Maturity onset diabetes mellitus in young | Uncertain significance (Jun 14, 2016) | ||
8-11542946-T-G | Benign (Mar 31, 2019) | |||
8-11542970-C-A | Benign (Aug 30, 2018) | |||
8-11543119-C-G | Maturity-onset diabetes of the young type 11 • Systemic lupus erythematosus | Benign (Jul 14, 2021) | ||
8-11543141-G-A | Benign (Aug 30, 2018) | |||
8-11543171-G-A | Maturity-onset diabetes of the young type 11 • Systemic lupus erythematosus | Benign (Jul 14, 2021) |
GnomAD
Source:
Gene | Type | Bio Type | Transcript | Coding Exons | Length |
---|---|---|---|---|---|
BLK | protein_coding | protein_coding | ENST00000259089 | 12 | 70604 |
pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
---|---|---|---|---|---|---|
8.35e-14 | 0.130 | 125636 | 0 | 112 | 125748 | 0.000445 |
Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
---|---|---|---|---|---|---|
Missense | -1.88 | 390 | 299 | 1.31 | 0.0000176 | 3244 |
Missense in Polyphen | 161 | 118.07 | 1.3636 | 1319 | ||
Synonymous | -3.61 | 182 | 130 | 1.40 | 0.00000848 | 985 |
Loss of Function | 0.860 | 23 | 27.9 | 0.824 | 0.00000145 | 308 |
LoF frequencies by population
Ethnicity | Sum of pLOFs | p |
---|---|---|
African & African-American | 0.000847 | 0.000836 |
Ashkenazi Jewish | 0.00258 | 0.00258 |
East Asian | 0.000723 | 0.000707 |
Finnish | 0.0000465 | 0.0000462 |
European (Non-Finnish) | 0.000371 | 0.000360 |
Middle Eastern | 0.000723 | 0.000707 |
South Asian | 0.000237 | 0.000229 |
Other | 0.000489 | 0.000489 |
dbNSFP
Source:
- Function
- FUNCTION: Non-receptor tyrosine kinase involved in B-lymphocyte development, differentiation and signaling. B-cell receptor (BCR) signaling requires a tight regulation of several protein tyrosine kinases and phosphatases, and associated coreceptors. Binding of antigen to the B-cell antigen receptor (BCR) triggers signaling that ultimately leads to B-cell activation. Signaling through BLK plays an important role in transmitting signals through surface immunoglobulins and supports the pro-B to pre-B transition, as well as the signaling for growth arrest and apoptosis downstream of B-cell receptor. Specifically binds and phosphorylates CD79A at 'Tyr-188'and 'Tyr-199', as well as CD79B at 'Tyr-196' and 'Tyr- 207'. Phosphorylates also the immunoglobulin G receptors FCGR2A, FCGR2B and FCGR2C. With FYN and LYN, plays an essential role in pre-B-cell receptor (pre-BCR)-mediated NF-kappa-B activation. Contributes also to BTK activation by indirectly stimulating BTK intramolecular autophosphorylation. In pancreatic islets, acts as a modulator of beta-cells function through the up-regulation of PDX1 and NKX6-1 and consequent stimulation of insulin secretion in response to glucose. {ECO:0000269|PubMed:19667185, ECO:0000269|PubMed:8756631}.;
- Disease
- DISEASE: Maturity-onset diabetes of the young 11 (MODY11) [MIM:613375]: A form of diabetes that is characterized by an autosomal dominant mode of inheritance, onset in childhood or early adulthood (usually before 25 years of age), a primary defect in insulin secretion and frequent insulin-independence at the beginning of the disease. {ECO:0000269|PubMed:19667185}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Apoptosis Modulation and Signaling;B Cell Receptor Signaling Pathway;Focal Adhesion;Transcriptional regulation by RUNX1;Gene expression (Transcription);Generic Transcription Pathway;RNA Polymerase II Transcription;RUNX1 regulates transcription of genes involved in BCR signaling;BCR;CXCR4-mediated signaling events;Thromboxane A2 receptor signaling;Ephrin B reverse signaling;Class I PI3K signaling events;Transcriptional regulation by RUNX1;Glypican 1 network;Regulation of p38-alpha and p38-beta;Alpha-synuclein signaling;PDGFR-beta signaling pathway;Signaling events mediated by PTP1B;EPHA forward signaling
(Consensus)
Recessive Scores
- pRec
- 0.244
Intolerance Scores
- loftool
- 0.403
- rvis_EVS
- -0.35
- rvis_percentile_EVS
- 29.56
Haploinsufficiency Scores
- pHI
- 0.182
- hipred
- N
- hipred_score
- 0.412
- ghis
- 0.541
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.985
Gene Damage Prediction
All | Recessive | Dominant | |
---|---|---|---|
Mendelian | Medium | Medium | Medium |
Primary Immunodeficiency | Medium | Medium | Medium |
Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Blk
- Phenotype
- reproductive system phenotype; normal phenotype; hematopoietic system phenotype; immune system phenotype; hearing/vestibular/ear phenotype; endocrine/exocrine gland phenotype;
Gene ontology
- Biological process
- transmembrane receptor protein tyrosine kinase signaling pathway;cell differentiation;positive regulation of insulin secretion;intracellular signal transduction;peptidyl-tyrosine autophosphorylation;B cell receptor signaling pathway;regulation of B cell receptor signaling pathway
- Cellular component
- cytosol;extrinsic component of cytoplasmic side of plasma membrane
- Molecular function
- protein tyrosine kinase activity;non-membrane spanning protein tyrosine kinase activity;signaling receptor binding;protein binding;ATP binding