BLK BLK proto-oncogene, Src family tyrosine kinase [Homo sapiens (human)] - Gene

Summary

Official Symbol: BLKprovided by HGNC
Official Full Name: BLK proto-oncogene, Src family tyrosine kinaseprovided by HGNC
Primary source: HGNC:HGNC:1057
See related: Ensembl:ENSG00000136573 MIM:191305
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: MODY11
Summary: 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]
Expression: Biased expression in lymph node (RPKM 18.9), spleen (RPKM 13.7) and 4 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 8p23.1

Exon count:: 15

Annotation release	Status	Assembly	Chr	Location
109.20201120	current	GRCh38.p13 (GCF_000001405.39)	8	NC_000008.11 (11493991..11564599)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	8	NC_000008.10 (11351521..11422108)

Chromosome 8 - NC_000008.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Polymorphisms of BLK are associated with renal disorder in patients with systemic lupus erythematosus.
Title: Polymorphisms of BLK are associated with renal disorder in patients with systemic lupus erythematosus.
This is the first study showing an association of BLK rs2736340T/C and rs13277113A/G and BANK1 R61H with susceptibility to SLE in a Latin-American population. In addition, some BLK and BANK1 interactions were associated with susceptibility to SLE.
Title: BLK and BANK1 polymorphisms and interactions are associated in Mexican patients with systemic lupus erythematosus.
The results suggest that this is the first study to disclose a possible association of genetic variants of BLK with susceptibility to GD, HT and AITD, and the diversity of AmiA levels.
Title: Associations of secreted phosphoprotein 1 and B lymphocyte kinase gene polymorphisms with autoimmune thyroid disease.
Study demonstrates the functional consequences of rare and low frequency missense variants in the interacting proteins BLK and BANK1, which are present alone, or in combination, in a substantial proportion of lupus patients. The rare variants found in patients, but not those found exclusively in controls, impair suppression of IRF5 and type-I IFN in human B cell lines.
Title: Functional rare and low frequency variants in BLK and BANK1 contribute to human lupus.
our results indicated that the BLK rs13277113 polymorphism was involved in the genetic background of RA in Chinese population and the association of BANK1 rs3733197 polymorphism with RA was dependent on the genotype of BLK rs13277113 polymorphism, highlighting B-cell response implicated in the pathogenesis of RA.
Title: Interaction analysis between BLK rs13277113 polymorphism and BANK1 rs3733197 polymorphism, MMEL1/TNFRSF14 rs3890745 polymorphism in determining susceptibility to rheumatoid arthritis.
present study suggests a novel association between specific TNFSF4 and BLK gene polymorphisms and allergic rhinitis risk.
Title: Association between TNFSF4 and BLK gene polymorphisms and susceptibility to allergic rhinitis.
This meta-analysis confirms that polymorphisms in the BLK alleles rs13277113 A/G, rs2736340 T/C, and rs2248932 T/C are associated with susceptibility to SLE in Caucasian and Asian populations.
Title: Association between BLK polymorphisms and susceptibility to SLE : A meta-analysis.
Confirm the association of rs548234/ATG5, rs2736340/BLK and rs10516487/BANK1 with systemic lupus erythematosus in Chinese Han and reinforced our hypothesis of their epistasis effect in regulating B-cell signaling in SLE.
Title: Gene-gene interaction of ATG5, ATG7, BLK and BANK1 in systemic lupus erythematosus.
ur study provides evidence that human BLK is a true proto-oncogene capable of inducing tumors, and we demonstrate a novel BLK activity-dependent tumor model suitable for studies of BLK-driven lymphomagenesis and screening of novel BLK inhibitors in vivo.
Title: A novel BLK-induced tumor model.
rs13277113 GA genotype of BLK is more frequent in Systemic Lupus Erythematosus patients and may have a role in low gene expression and increased flares
Title: BLK pathway-associated rs13277113 GA genotype is more frequent in SLE patients and associated with low gene expression and increased flares.

Submit: New GeneRIF Correction See all GeneRIFs (57)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
A genome-wide association study identifies three new risk loci for Kawasaki disease. GeneReviews: Not available
A systemic sclerosis and systemic lupus erythematosus pan-meta-GWAS reveals new shared susceptibility loci. GeneReviews: Not available
Association of systemic lupus erythematosus with C8orf13-BLK and ITGAM-ITGAX. GeneReviews: Not available
Differential genetic associations for systemic lupus erythematosus based on anti-dsDNA autoantibody production. GeneReviews: Not available
Genetic variants near TNFAIP3 on 6q23 are associated with systemic lupus erythematosus. GeneReviews: Not available
Genetics of rheumatoid arthritis contributes to biology and drug discovery. GeneReviews: Not available
Genome-wide analysis of polymorphisms associated with cytokine responses in smallpox vaccine recipients. GeneReviews: Not available
Genome-wide association study in a Chinese Han population identifies nine new susceptibility loci for systemic lupus erythematosus. GeneReviews: Not available
Genome-wide association study of chronic periodontitis in a general German population. GeneReviews: Not available
Genome-wide association study of rheumatoid arthritis in Koreans: population-specific loci as well as overlap with European susceptibility loci. GeneReviews: Not available
Genome-wide pathway analysis of genome-wide association studies on systemic lupus erythematosus and rheumatoid arthritis. GeneReviews: Not available
Maturity-onset diabetes of the young, type 11 MedGen: C3150618 OMIM: 613375 GeneReviews: Maturity-Onset Diabetes of the Young Overview	Compare labs
Meta-analysis followed by replication identifies loci in or near CDKN1B, TET3, CD80, DRAM1, and ARID5B as associated with systemic lupus erythematosus in Asians. GeneReviews: Not available
REL, encoding a member of the NF-kappaB family of transcription factors, is a newly defined risk locus for rheumatoid arthritis. GeneReviews: Not available
Two new susceptibility loci for Kawasaki disease identified through genome-wide association analysis. GeneReviews: Not available

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Replication interactions

Interaction	Pubs
Knockdown of B lymphoid tyrosine kinase (BLK) by siRNA inhibits the early stages of HIV-1 replication in 293T cells infected with VSV-G pseudotyped HIV-1	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

GDB:462442 (e-PCR)
- UniSTS:157494

G60355 (e-PCR)
- UniSTS:137611

D8S1695 (e-PCR), detects polymorphism
- UniSTS:2975

SHGC-82225 (e-PCR)
- UniSTS:103120

Homology

Homologs of the BLK gene: The BLK gene is conserved in chimpanzee, dog, cow, mouse, rat, chicken, zebrafish, and frog.
Orthologs from Annotation Pipeline: 247 organisms have orthologs with human gene BLK
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
ATP binding	IEA Inferred from Electronic Annotation more info
non-membrane spanning protein tyrosine kinase activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
non-membrane spanning protein tyrosine kinase activity	IDA Inferred from Direct Assay more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info	PubMed
protein tyrosine kinase activity	IDA Inferred from Direct Assay more info	PubMed
signaling receptor binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed

Process	Evidence Code	Pubs
B cell receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
Fc receptor mediated stimulatory signaling pathway	IBA Inferred from Biological aspect of Ancestor more info	PubMed
cell differentiation	IBA Inferred from Biological aspect of Ancestor more info	PubMed
cellular response to DNA damage stimulus	IBA Inferred from Biological aspect of Ancestor more info	PubMed
dendritic cell differentiation	IBA Inferred from Biological aspect of Ancestor more info	PubMed
innate immune response	IBA Inferred from Biological aspect of Ancestor more info	PubMed
intracellular signal transduction	TAS Traceable Author Statement more info	PubMed
negative regulation of B cell proliferation	IBA Inferred from Biological aspect of Ancestor more info	PubMed
negative regulation of mast cell proliferation	IBA Inferred from Biological aspect of Ancestor more info	PubMed
neuron projection development	IBA Inferred from Biological aspect of Ancestor more info	PubMed
peptidyl-tyrosine autophosphorylation	IBA Inferred from Biological aspect of Ancestor more info	PubMed
peptidyl-tyrosine phosphorylation	IDA Inferred from Direct Assay more info	PubMed
platelet degranulation	IBA Inferred from Biological aspect of Ancestor more info	PubMed
positive regulation of dendritic cell apoptotic process	IBA Inferred from Biological aspect of Ancestor more info	PubMed
positive regulation of insulin secretion	IMP Inferred from Mutant Phenotype more info	PubMed
regulation of B cell apoptotic process	IBA Inferred from Biological aspect of Ancestor more info	PubMed
regulation of B cell receptor signaling pathway	IBA Inferred from Biological aspect of Ancestor more info	PubMed
regulation of B cell receptor signaling pathway	TAS Traceable Author Statement more info
regulation of cell population proliferation	IBA Inferred from Biological aspect of Ancestor more info	PubMed
regulation of mast cell degranulation	IBA Inferred from Biological aspect of Ancestor more info	PubMed
regulation of platelet aggregation	IBA Inferred from Biological aspect of Ancestor more info	PubMed
tolerance induction to self antigen	IBA Inferred from Biological aspect of Ancestor more info	PubMed
transmembrane receptor protein tyrosine kinase signaling pathway	IBA Inferred from Biological aspect of Ancestor more info	PubMed

Component	Evidence Code	Pubs
cytosol	TAS Traceable Author Statement more info
extrinsic component of cytoplasmic side of plasma membrane	IBA Inferred from Biological aspect of Ancestor more info	PubMed

General protein information

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Preferred Names: tyrosine-protein kinase Blk

Names: B lymphoid tyrosine kinase; BLK nonreceptor tyrosine kinase; b lymphocyte kinase; p55-Blk

NP_001317394.1

EC 2.7.10.2

NP_001706.2

EC 2.7.10.2

XP_011542126.1

EC 2.7.10.2

XP_011542127.1

EC 2.7.10.2

XP_011542129.1

EC 2.7.10.2

XP_011542130.1

EC 2.7.10.2

XP_011542131.1

EC 2.7.10.2

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_023543.2 RefSeqGene

Range

5376..75588

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001330465.2 → NP_001317394.1 tyrosine-protein kinase Blk isoform 2

Status: REVIEWED

Source sequence(s)

AC022239, AF131216

Consensus CDS

CCDS83251.1

UniProtKB/TrEMBL

E9PJX5

Related

ENSP00000433663.1, ENST00000529894.1
NM_001715.3 → NP_001706.2 tyrosine-protein kinase Blk isoform 1

See identical proteins and their annotated locations for NP_001706.2

Status: REVIEWED

Source sequence(s)

BC007371, BC018703, BC032413, BQ057058

Consensus CDS

CCDS5982.1

UniProtKB/Swiss-Prot

P51451

UniProtKB/TrEMBL

Q05D26

Related

ENSP00000259089.4, ENST00000259089.9

Conserved Domains (3) summary

cd10371
Location:120 → 219

SH2_Src_Blk; Src homology 2 (SH2) domain found in B lymphoid kinase (Blk)

cd12009
Location:62 → 115

SH3_Blk; Src homology 3 domain of Blk Protein Tyrosine Kinase

cl21453
Location:233 → 496

PKc_like; Protein Kinases, catalytic domain

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.20201120

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p13 Primary Assembly

Genomic

NC_000008.11 Reference GRCh38.p13 Primary Assembly

Range

11493991..11564599

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011543824.1 → XP_011542126.1 tyrosine-protein kinase Blk isoform X1

See identical proteins and their annotated locations for XP_011542126.1

Conserved Domains (4) summary

cd10371
Location:120 → 219

SH2_Src_Blk; Src homology 2 (SH2) domain found in B lymphoid kinase (Blk)

cd12009
Location:62 → 115

SH3_Blk; Src homology 3 domain of Blk Protein Tyrosine Kinase

pfam07714
Location:241 → 516

Pkinase_Tyr; Protein tyrosine kinase

cl21453
Location:233 → 522

PKc_like; Protein Kinases, catalytic domain
XM_011543827.1 → XP_011542129.1 tyrosine-protein kinase Blk isoform X2

Conserved Domains (4) summary

cd10371
Location:49 → 148

SH2_Src_Blk; Src homology 2 (SH2) domain found in B lymphoid kinase (Blk)

pfam07714
Location:170 → 445

Pkinase_Tyr; Protein tyrosine kinase

cl17036
Location:1 → 44

SH3; Src Homology 3 domain superfamily

cl21453
Location:162 → 451

PKc_like; Protein Kinases, catalytic domain
XM_011543828.3 → XP_011542130.1 tyrosine-protein kinase Blk isoform X3

Conserved Domains (3) summary

cd10371
Location:120 → 219

SH2_Src_Blk; Src homology 2 (SH2) domain found in B lymphoid kinase (Blk)

cd12009
Location:62 → 115

SH3_Blk; Src homology 3 domain of Blk Protein Tyrosine Kinase

cl21453
Location:232 → 256

PKc_like; Protein Kinases, catalytic domain
XM_011543829.3 → XP_011542131.1 tyrosine-protein kinase Blk isoform X4

Conserved Domains (3) summary

cd10371
Location:120 → 219

SH2_Src_Blk; Src homology 2 (SH2) domain found in B lymphoid kinase (Blk)

cd12009
Location:62 → 115

SH3_Blk; Src homology 3 domain of Blk Protein Tyrosine Kinase

cl21453
Location:232 → 256

PKc_like; Protein Kinases, catalytic domain
XM_011543825.3 → XP_011542127.1 tyrosine-protein kinase Blk isoform X1

See identical proteins and their annotated locations for XP_011542127.1

Conserved Domains (4) summary

cd10371
Location:120 → 219

SH2_Src_Blk; Src homology 2 (SH2) domain found in B lymphoid kinase (Blk)

cd12009
Location:62 → 115

SH3_Blk; Src homology 3 domain of Blk Protein Tyrosine Kinase

pfam07714
Location:241 → 516

Pkinase_Tyr; Protein tyrosine kinase

cl21453
Location:233 → 522

PKc_like; Protein Kinases, catalytic domain