BLK

Chr 8AD

BLK proto-oncogene, Src family tyrosine kinase

Also known as: MODY11

NCBI Gene: 640ENSG00000136573UniProt: P51451

This gene encodes a nonreceptor tyrosine-kinase of the src family of proto-oncogenes that are typically involved in cell proliferation and differentiation. The protein has a role in B-cell receptor signaling and B-cell development. The protein also stimulates insulin synthesis and secretion in response to glucose and enhances the expression of several pancreatic beta-cell transcription factors. [provided by RefSeq, Aug 2010]

Primary Disease Associations & Inheritance

Maturity-onset diabetes of the young, type 11MIM #613375
AD
5
Active trials
66
Pathogenic / LP
491
ClinVar variants
38
Pubs (1 yr)
-1.9
Missense Z
1.17
LOEUF
Clinical Summary— BLK
🧬
Gene-Disease Validity (ClinGen)
monogenic diabetes · ADRefuted

Refuted — evidence has disproved this relationship

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
66 Pathogenic / Likely Pathogenic· 200 VUS of 491 total submissions
💊
Clinical Trials
5 active or recruiting trials — potential therapeutic options may be available
📖
GeneReview available — BLK
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.17LOEUF
pLI 0.000
Z-score 0.86
OE 0.82 (0.59–1.17)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-1.88Z-score
OE missense 1.31 (1.20–1.42)
390 obs / 298.7 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.82 (0.59–1.17)
0≤0.351.4
Missense OE1.31 (1.20–1.42)
0≤0.61.4
Synonymous OE1.40
0≤1.21.6
LoF obs/exp: 23 / 27.9Missense obs/exp: 390 / 298.7Syn Z: -3.61
GOFDN
DN
0.7130th %ile
GOF
0.73top 25%
LOF
0.3551th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

491 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic61
Likely Pathogenic5
VUS200
Likely Benign137
Benign69
Conflicting19
61
Pathogenic
5
Likely Pathogenic
200
VUS
137
Likely Benign
69
Benign
19
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
2
59
0
61
Likely Pathogenic
0
0
5
0
5
VUS
7
151
35
7
200
Likely Benign
1
11
63
62
137
Benign
0
1
65
3
69
Conflicting
—19
Total816522772491

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

BLK · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients