BLK

BLK proto-oncogene, Src family tyrosine kinase, the group of Src family tyrosine kinases|SH2 domain containing

Basic information

Region (hg38): 8:11486893-11564599

Links

ENSG00000136573NCBI:640OMIM:191305HGNC:1057Uniprot:P51451AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

  • 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: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Maturity-onset diabetes of the young, type 11ADGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingEndocrine19667185

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the BLK gene.

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
9
clinvar
39
clinvar
7
clinvar
55
missense
93
clinvar
13
clinvar
106
nonsense
2
clinvar
2
start loss
0
frameshift
3
clinvar
3
inframe indel
0
splice donor/acceptor (+/-2bp)
1
clinvar
1
clinvar
2
splice region
2
6
1
9
non coding
21
clinvar
40
clinvar
58
clinvar
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)361456
8-11494063-G-A Maturity onset diabetes mellitus in young Likely benign (Jun 14, 2016)361457
8-11494109-G-A Maturity onset diabetes mellitus in young Uncertain significance (Jun 14, 2016)361458
8-11494118-A-C Maturity onset diabetes mellitus in young Uncertain significance (Jun 14, 2016)361459
8-11494145-T-C Maturity onset diabetes mellitus in young Likely benign (Jun 14, 2016)361460
8-11494152-C-A Maturity onset diabetes mellitus in young Benign/Likely benign (Jun 01, 2023)361461
8-11494153-G-A Maturity onset diabetes mellitus in young Uncertain significance (Jun 14, 2016)361462
8-11494218-G-A Maturity onset diabetes mellitus in young Uncertain significance (Jun 14, 2016)361463
8-11494289-C-G Maturity onset diabetes mellitus in young Likely benign (Jun 14, 2016)361464
8-11494326-C-T Maturity onset diabetes mellitus in young Uncertain significance (Jun 14, 2016)361465
8-11494384-C-T Maturity onset diabetes mellitus in young Uncertain significance (Jun 14, 2016)361466
8-11494390-C-T Maturity-onset diabetes of the young type 11 Uncertain significance (Jan 13, 2018)361467
8-11494392-G-A Maturity-onset diabetes of the young type 11 Uncertain significance (Jan 12, 2018)911925
8-11494403-C-T Maturity-onset diabetes of the young type 11 Benign (Jan 12, 2018)361468
8-11494428-G-T Maturity-onset diabetes of the young type 11 Benign (Jan 13, 2018)361469
8-11494469-C-T Maturity-onset diabetes of the young type 11 Uncertain significance (Jan 13, 2018)361470
8-11494517-G-A Maturity-onset diabetes of the young type 11 Uncertain significance (Mar 30, 2018)908999
8-11494546-C-T Maturity-onset diabetes of the young type 11 Uncertain significance (Jan 13, 2018)909000
8-11494547-A-G Maturity-onset diabetes of the young type 11 Benign (Jan 13, 2018)361471
8-11494584-T-C Maturity onset diabetes mellitus in young Uncertain significance (Jun 14, 2016)361472
8-11542946-T-G Benign (Mar 31, 2019)1271417
8-11542970-C-A Benign (Aug 30, 2018)1252213
8-11543119-C-G Maturity-onset diabetes of the young type 11 • Systemic lupus erythematosus Benign (Jul 14, 2021)1192422
8-11543141-G-A Benign (Aug 30, 2018)1293437
8-11543171-G-A Maturity-onset diabetes of the young type 11 • Systemic lupus erythematosus Benign (Jul 14, 2021)1192423

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
BLKprotein_codingprotein_codingENST00000259089 1270604
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
8.35e-140.13012563601121257480.000445
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense-1.883902991.310.00001763244
Missense in Polyphen161118.071.36361319
Synonymous-3.611821301.400.00000848985
Loss of Function0.8602327.90.8240.00000145308

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0008470.000836
Ashkenazi Jewish0.002580.00258
East Asian0.0007230.000707
Finnish0.00004650.0000462
European (Non-Finnish)0.0003710.000360
Middle Eastern0.0007230.000707
South Asian0.0002370.000229
Other0.0004890.000489

dbNSFP

Source: dbNSFP

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

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

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