BLK

Chr 8

BLK proto-oncogene, Src family tyrosine kinase

Also known as: MODY11

NCBI Gene: 640 ENSG00000136573 UniProt: P51451

The BLK protein is a nonreceptor tyrosine kinase that regulates B-cell receptor signaling and B-lymphocyte development, and also stimulates insulin synthesis and secretion in pancreatic beta cells. Mutations cause maturity-onset diabetes of the young type 11 (MODY11), which follows autosomal dominant inheritance. This gene shows very low constraint against loss-of-function variants (pLI near zero), suggesting the pathogenic variants likely act through alternative mechanisms.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt

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]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtMaturity-onset diabetes of the young 11

Clinical highlights

Gene–disease validity (ClinGen)

Refuted · monogenic diabetes · AD · ClinGen 2023

evidence has disproved this relationship

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.17

LOEUF

Multiple*

Mechanism· predicted

📖

GeneReview available — BLK

Authoritative clinical overview · Recommended first read

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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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 OE?0.82 (0.59–1.17)

0≤0.351.4

Missense OE?1.31 (1.20–1.42)

0≤0.61.4

Synonymous OE?1.40

0≤1.21.6

LoF obs/exp: 23 / 27.9Missense obs/exp: 390 / 298.7Syn Z: -3.61

Background carrier burden — how many people carry a rare variant somewhere in BLK?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 55

888 rare PASS variants

Rare truncating (LoF)

1 in 820

145 rare PASS variants

Rare synonymous (reference)

1 in 70

366 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for BLK. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 90	1 in 1,100
South Asian	~43k	1 in 62	1 in 570
Remaining (unassigned)	~30k	1 in 59	1 in 910
European (Finnish)	~27k	1 in 130	1 in 3,300
Admixed American	~22k	1 in 58	1 in 1,000
African / African American	~21k	1 in 41	1 in 730
East Asian	~20k	1 in 82	1 in 330
Ashkenazi Jewish	~13k	1 in 140	≈ 1 in 3,300
Middle Eastern	~2,884	1 in 67	1 in 480

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 12 coding exons well covered in gnomAD exomes and genomes.? see exons ↓