BLNK B cell linker [Homo sapiens (human)] - Gene

Summary

Official Symbol: BLNKprovided by HGNC
Official Full Name: B cell linkerprovided by HGNC
Primary source: HGNC:HGNC:14211
See related: Ensembl:ENSG00000095585 MIM:604515; AllianceGenome:HGNC:14211
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: bca; AGM4; BASH; LY57; SLP65; BLNK-S; SLP-65
Summary: This gene encodes a cytoplasmic linker or adaptor protein that plays a critical role in B cell development. This protein bridges B cell receptor-associated kinase activation with downstream signaling pathways, thereby affecting various biological functions. The phosphorylation of five tyrosine residues is necessary for this protein to nucleate distinct signaling effectors following B cell receptor activation. Mutations in this gene cause hypoglobulinemia and absent B cells, a disease in which the pro- to pre-B-cell transition is developmentally blocked. Deficiency in this protein has also been shown in some cases of pre-B acute lymphoblastic leukemia. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, May 2012]
Expression: Broad expression in spleen (RPKM 11.8), lymph node (RPKM 11.8) and 20 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 10q24.1

Exon count:: 17

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	10	NC_000010.11 (96189171..96271569, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	10	NC_060934.1 (97068476..97150877, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	10	NC_000010.10 (97948927..98031326, complement)

Chromosome 10 - NC_000010.11 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?

ErbB2/Her2-dependent downregulation of a cell death-promoting protein BLNK in breast cancer cells is required for 3D breast tumor growth.
Title: ErbB2/Her2-dependent downregulation of a cell death-promoting protein BLNK in breast cancer cells is required for 3D breast tumor growth.
Silencing BLNK protects against interleukin-1beta-induced chondrocyte injury through the NF-kappaB signaling pathway.
Title: Silencing BLNK protects against interleukin-1β-induced chondrocyte injury through the NF-κB signaling pathway.
C/EBPbeta induces B-cell acute lymphoblastic leukemia and cooperates with BLNK mutations.
Title: C/EBPβ induces B-cell acute lymphoblastic leukemia and cooperates with BLNK mutations.
Involvement of Blnk and Foxo1 in tumor suppression in BCRABL1transformed proB cells.
Title: Involvement of Blnk and Foxo1 in tumor suppression in BCR‑ABL1‑transformed pro‑B cells.
Prognostic value of B-cell linker protein in colorectal cancer.
Title: Prognostic value of B-cell linker protein in colorectal cancer.
Further delineation of primary B cell immunodeficiency caused by novel variants of the BLNK gene in two Chinese patients.
Title: Further delineation of primary B cell immunodeficiency caused by novel variants of the BLNK gene in two Chinese patients.
vesicular signaling scaffolds are required for B cell activation indicates that vesicles may deliver preassembled signaling cargo to sites of BCR activation.
Title: Macromolecular assembly of the adaptor SLP-65 at intracellular vesicles in resting B cells.
early Ca(2+) fluxing provides feed-forward signal amplification by promoting anchoring of the PLCgamma2 C2 domain to phospho-SLP65.
Title: Cutting edge: feed-forward activation of phospholipase Cγ2 via C2 domain-mediated binding to SLP65.
up-regulation of BLNK is associated with RUNX1 mutations in cytogenetically normal acute myeloid leukemia.
Title: RUNX1 mutations in cytogenetically normal acute myeloid leukemia are associated with a poor prognosis and up-regulation of lymphoid genes.
Live cell imaging and co-immunoprecipitation experiments confirmed that both SLP65 and CIN85 are both required for the onset and progression phases of B-cell antigen receptor signal transduction.
Title: The B-cell antigen receptor signals through a preformed transducer module of SLP65 and CIN85.

Submit: New GeneRIF Correction See all GeneRIFs (23)

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
Agammaglobulinemia 4, autosomal recessive MedGen: C3150752 OMIM: 613502 GeneReviews: Not available	Compare labs

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D10S1562 (e-PCR)
- UniSTS:71719

RH103510 (e-PCR)
- UniSTS:97835

SHGC-148592 (e-PCR)
- UniSTS:176482

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables SH2 domain binding	IDA Inferred from Direct Assay more info	PubMed
enables enzyme binding	IPI Inferred from Physical Interaction more info	PubMed
enables lipid binding	IDA Inferred from Direct Assay more info	PubMed
enables lipid binding	IMP Inferred from Mutant Phenotype more info	PubMed
enables molecular condensate scaffold activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables phospholipase binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein kinase binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein tyrosine kinase binding	IPI Inferred from Physical Interaction more info	PubMed
enables signaling adaptor activity	IDA Inferred from Direct Assay more info	PubMed
enables transmembrane receptor protein tyrosine kinase adaptor activity	TAS Traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
involved_in B cell differentiation	NAS Non-traceable Author Statement more info	PubMed
involved_in B cell receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in B cell receptor signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cell surface receptor protein tyrosine kinase signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in humoral immune response	TAS Traceable Author Statement more info	PubMed
involved_in inflammatory response	TAS Traceable Author Statement more info	PubMed
involved_in intracellular signal transduction	IBA Inferred from Biological aspect of Ancestor more info
involved_in intracellular signal transduction	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of gene expression	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytosol	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	TAS Traceable Author Statement more info
located_in intracellular membrane-bounded organelle	IDA Inferred from Direct Assay more info
located_in membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	IDA Inferred from Direct Assay more info
located_in plasma membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: B-cell linker protein

Names: B cell adaptor containing SH2 domain; B-cell activation; B-cell adapter containing a SH2 domain protein; B-cell adapter containing a Src homology 2 domain protein; Src homology 2 domain-containing leukocyte protein of 65 kDa; Src homology [SH2] domain-containing leukocyte protein of 65 kD; cytoplasmic adapter protein

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_007575.1 RefSeqGene

Range

9994..89872

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_21

mRNA and Protein(s)

NM_001114094.2 → NP_001107566.1 B-cell linker protein isoform 2

See identical proteins and their annotated locations for NP_001107566.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an in-frame exon in the mid-coding region compared to variant 1, resulting in a shorter isoform (2, also known as BLNK-s) compared to isoform 1.

Source sequence(s)

AC021037, AF068181, AI307343, BC018906, DA045252

Consensus CDS

CCDS44464.1

UniProtKB/TrEMBL

Q2MD52

Related

ENSP00000360218.2, ENST00000371176.7

Conserved Domains (1) summary

cd09929
Location:313 → 431

SH2_BLNK_SLP-76; Src homology 2 (SH2) domain found in B-cell linker (BLNK) protein and SH2 domain-containing leukocyte protein of 76 kDa (SLP-76)
NM_001258440.2 → NP_001245369.1 B-cell linker protein isoform 3

See identical proteins and their annotated locations for NP_001245369.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) lacks an in-frame exon in the 3' coding region compared to variant 1, resulting in a shorter isoform (3) compared to isoform 1.

Source sequence(s)

AC021037, AI307343, AM180337, DA045252

Consensus CDS

CCDS58091.1

UniProtKB/TrEMBL

Q2MD50

Related

ENSP00000397487.2, ENST00000413476.6

Conserved Domains (1) summary

cl15255
Location:336 → 402

SH2; Src homology 2 (SH2) domain
NM_001258441.2 → NP_001245370.1 B-cell linker protein isoform 4

See identical proteins and their annotated locations for NP_001245370.1

Status: REVIEWED

Description

Transcript Variant: This variant (4) lacks two in-frame exons in the mid- and 3' coding regions compared to variant 1, resulting in a shorter isoform (4) compared to isoform 1.

Source sequence(s)

AC021037, AI307343, AM180332, DA045252

Consensus CDS

CCDS91311.1

UniProtKB/TrEMBL

Q2MD50, Q2MD54

Related

ENSP00000512506.1, ENST00000696253.1

Conserved Domains (1) summary

cl15255
Location:313 → 379

SH2; Src homology 2 (SH2) domain
NM_001258442.2 → NP_001245371.1 B-cell linker protein isoform 5

See identical proteins and their annotated locations for NP_001245371.1

Status: REVIEWED

Description

Transcript Variant: This variant (5) lacks 3 in-frame exons in the mid- and 3' coding regions, and uses alternate in-frame donor and acceptor splice sites compared to variant 1, resulting in a shorter isoform (5) compared to isoform 1.

Source sequence(s)

AC021037, AI307343, AM180327, DA045252

Consensus CDS

CCDS73171.1

UniProtKB/TrEMBL

A0A8Q3WLN9, F5GXS1, Q2MD59

Related

ENSP00000391924.3, ENST00000427367.6

Conserved Domains (1) summary

cl15255
Location:231 → 297

SH2; Src homology 2 (SH2) domain
NM_013314.4 → NP_037446.1 B-cell linker protein isoform 1

See identical proteins and their annotated locations for NP_037446.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longest isoform (1).

Source sequence(s)

AC021037, AF068180, AI307343, BC018906, DA045252

Consensus CDS

CCDS7446.1

UniProtKB/Swiss-Prot

O75498, O75499, Q2MD49, Q8WV28

UniProtKB/TrEMBL

B3KNL5

Related

ENSP00000224337.6, ENST00000224337.10

Conserved Domains (2) summary

cd09929
Location:336 → 454

SH2_BLNK_SLP-76; Src homology 2 (SH2) domain found in B-cell linker (BLNK) protein and SH2 domain-containing leukocyte protein of 76 kDa (SLP-76)

PHA03132
Location:41 → 231

PHA03132; thymidine kinase; Provisional

RNA

NR_047680.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (6) lacks an internal exon compared to variant 1. It is represented as non-coding because the use of the 5'-most translational start codon (with a strong Kozak signal), as used in variant 1, renders this transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AC021037, AI307343, BC018906, BC110298, DA045252
NR_047681.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (7) lacks two internal exons, and uses an alternate donor splice site at another internal exon compared to variant 1. It is represented as non-coding because the use of the 5'-most translational start codon (with a strong Kozak signal), as used in variant 1, renders this transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AC021037, AI307343, AM180338, BC018906, DA045252
NR_047682.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (8) lacks two internal exons compared to variant 1. It is represented as non-coding because the use of the 5'-most translational start codon (with a strong Kozak signal), as used in variant 1, renders this transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AC021037, AI307343, AM180339, BC018906, DA045252
NR_047683.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (9) lacks two consecutive internal exons and another internal exon compared to variant 1. It is represented as non-coding because the use of the 5'-most translational start codon (with a strong Kozak signal), as used in variant 1, renders this transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AC021037, AI307343, AM180340, BC018906, DA045252