BLK

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

Basic information

Region (hg38): 8:11486894-11564599

Links

ENSG00000136573 ∙ NCBI:640 ∙ OMIM:191305 ∙ HGNC:1057 ∙ Uniprot:P51451 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

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
• systemic lupus erythematosus (Supportive), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

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 ClinVar and linked to the BLK gene.

• not_provided (217 variants)
• Maturity-onset_diabetes_of_the_young_type_11 (84 variants)
• not_specified (73 variants)
• BLK-related_disorder (26 variants)
• Systemic_lupus_erythematosus (25 variants)
• Monogenic_diabetes (12 variants)
• Maturity_onset_diabetes_mellitus_in_young (2 variants)

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. These statistics are base on transcript: NM_000001715.3. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			9	54	6	69
missense	2		141	22	2	167
nonsense			1			1
start loss						0
frameshift			4			4
splice donor/acceptor (+/-2bp)			2	1		3
Total	2	0	157	77	8

Highest pathogenic variant AF is 6.8421167e-7

GnomAD

Source: gnomAD

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: 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

	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