BLNK (B cell linker)

Gene

• Entrez ID: 29760
• Gene name: B cell linker
• Gene symbol: BLNK
• Synonyms (NCBI Gene): AGM4, BASH, BLNK-S, LY57, SLP-65, SLP65, bca
• Chromosome: 10
• Chromosome location: 10q24.1
• 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 function

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs1554906579	C>-	Pathogenic	Non coding transcript variant, splice acceptor variant, coding sequence variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT029539	hsa-miR-26b-5p	Microarray	19088304
MIRT821970	hsa-miR-1302	CLIP-seq
MIRT821971	hsa-miR-3122	CLIP-seq
MIRT821972	hsa-miR-3199	CLIP-seq
MIRT821973	hsa-miR-371-5p	CLIP-seq
MIRT821974	hsa-miR-371b-5p	CLIP-seq
MIRT821975	hsa-miR-3913-5p	CLIP-seq
MIRT821976	hsa-miR-4298	CLIP-seq
MIRT821977	hsa-miR-4670-3p	CLIP-seq
MIRT821978	hsa-miR-513c	CLIP-seq
MIRT821979	hsa-miR-514b-5p	CLIP-seq
MIRT821973	hsa-miR-371-5p	CLIP-seq
MIRT821974	hsa-miR-371b-5p	CLIP-seq
MIRT1942949	hsa-miR-4428	CLIP-seq
MIRT821978	hsa-miR-513c	CLIP-seq
MIRT821979	hsa-miR-514b-5p	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0005068	Function	Transmembrane receptor protein tyrosine kinase adaptor activity	TAS	9697839
GO:0005515	Function	Protein binding	IPI	9697839, 16912232, 16969585, 21822214, 21930792, 24728074
GO:0005737	Component	Cytoplasm	IBA
GO:0005737	Component	Cytoplasm	IEA
GO:0005829	Component	Cytosol	IDA	9697839
GO:0005829	Component	Cytosol	TAS
GO:0005886	Component	Plasma membrane	IDA
GO:0005886	Component	Plasma membrane	IEA
GO:0005886	Component	Plasma membrane	TAS
GO:0006954	Process	Inflammatory response	TAS	9697839
GO:0006959	Process	Humoral immune response	TAS	9697839
GO:0007169	Process	Cell surface receptor protein tyrosine kinase signaling pathway	IBA
GO:0008289	Function	Lipid binding	IDA	32051419
GO:0008289	Function	Lipid binding	IMP	25140054
GO:0010628	Process	Positive regulation of gene expression	IEA
GO:0016020	Component	Membrane	IDA	9697839
GO:0016020	Component	Membrane	IEA
GO:0019899	Function	Enzyme binding	IPI	9697839
GO:0019901	Function	Protein kinase binding	IPI	11606584
GO:0030183	Process	B cell differentiation	NAS	10583958
GO:0035556	Process	Intracellular signal transduction	IBA
GO:0035556	Process	Intracellular signal transduction	IDA	9341187, 11606584
GO:0035591	Function	Signaling adaptor activity	IDA	9697839, 11606584
GO:0042113	Process	B cell activation	IEA
GO:0042169	Function	SH2 domain binding	IDA	9697839
GO:0043274	Function	Phospholipase binding	IPI	11606584
GO:0050853	Process	B cell receptor signaling pathway	IDA	9697839
GO:0050853	Process	B cell receptor signaling pathway	IMP	11606584
GO:0140693	Function	Molecular condensate scaffold activity	IMP	32051419
GO:1990782	Function	Protein tyrosine kinase binding	IPI	9697839

Other IDs

• MIM: 604515
• HGNC: 14211
• e!Ensembl: ENSG00000095585

Protein

• UniProt ID: Q8WV28
• Protein name: B-cell linker protein (B-cell adapter containing a SH2 domain protein) (B-cell adapter containing a Src homology 2 domain protein) (Cytoplasmic adapter protein) (Src homology 2 domain-containing leukocyte protein of 65 kDa) (SLP-65)
• Protein function: Functions as a central linker protein, downstream of the B-cell receptor (BCR), bridging the SYK kinase to a multitude of signaling pathways and regulating biological outcomes of B-cell function and development. Plays a role in the activation of
• PDB: 6YLU
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00017	SH2	346 → 429	SH2 domain	Domain

• Tissue specificity: TISSUE SPECIFICITY: Expressed in B-cell lineage and fibroblast cell lines (at protein level). Highest levels of expression in the spleen, with lower levels in the liver, kidney, pancreas, small intestines and colon.
• Sequence:

  MDKLNKITVPASQKLRQLQKMVHDIKNNEGGIMNKIKKLKVKAPPSVPRRDYASESPADE
  EEQWSDDFDSDYENPDEHSDSEMYVMPAEENADDSYEPPPVEQETRPVHPALPFARGEYI
  DNRSSQRHSPPFSKTLPSKPSWPSEKARLTSTLPALTALQKPQVPPKPKGLLEDEADYVV
  PVEDNDENYIHPTESSSPPPEKAPMVNRSTKPNSSTPASPPGTASGRNSGAWETKSPPPA
  APSPLPRAGKKPTTPLKTTPVASQQNASSVCEEKPIPAERHRGSSHRQEAVQSPVFPPAQ
  KQIHQKPIPLPRFTEGGNPTVDGPLPSFSSNSTISEQEAGVLCKPWYAGACDRKSAEEAL
  HRSNKDGSFLIRKSSGHDSKQPYTLVVFFNKRVYNIPVRFIEATKQYALGRKKNGEEYFG
  SVAEIIRNHQHSPLVLIDSQNNTKDSTRLKYAVKVS

• Sequence length: 456

Pathways

KEGG:

NF-kappa B signaling pathway
Osteoclast differentiation
B cell receptor signaling pathway
Epstein-Barr virus infection
Primary immunodeficiency

Reactome:

Antigen activates B Cell Receptor (BCR) leading to generation of second messengers

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Agammaglobulinemia 4, autosomal recessive	Pathogenic; Likely pathogenic	rs1554894837, rs2133946382, rs2134092983, rs2134166251, rs2493183249, rs2492841066, rs1842918742, rs1554906579, rs2083906060	RCV001385592 RCV001388635 RCV002033287 RCV000005842 RCV003020917 RCV003614861 RCV003990685 RCV000648342 RCV001253462	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
BLNK-related disorder	Likely pathogenic	rs2492954169	RCV003404229	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
ALZHEIMER DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ATTENTION DEFICIT HYPERACTIVITY DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AUTOSOMAL AGAMMAGLOBULINEMIA	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AUTOSOMAL NON-SYNDROMIC AGAMMAGLOBULINEMIA	—	Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cervical cancer	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
COLORECTAL ADENOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gastric cancer	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hepatocellular carcinoma	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lung cancer	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Nonpapillary renal cell carcinoma	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian serous cystadenocarcinoma	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SUBSTANCE ABUSE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thyroid cancer, nonmedullary, 1	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine corpus endometrial carcinoma	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Acute lymphocytic leukemia	Lymphocytic Leukemia	BEFREE	15029213, 16568084, 16636677, 16912232, 26703467		★☆☆☆☆ Found in Text Mining only
Adult Acute Lymphocytic Leukemia	Lymphocytic Leukemia	BEFREE	15029213		★☆☆☆☆ Found in Text Mining only
Agammaglobulinemia	Agammaglobulinemia	BEFREE	25893637		★☆☆☆☆ Found in Text Mining only
Agammaglobulinemia	Agammaglobulinemia	GENOMICS_ENGLAND_DG	25893637		★☆☆☆☆ Found in Text Mining only
Agammaglobulinemia	Agammaglobulinemia	Pubtator	30619340	Associate	★☆☆☆☆ Found in Text Mining only
Agammaglobulinemia	Agammaglobulinemia	CTD_human_DG			★☆☆☆☆ Found in Text Mining only
Agammaglobulinemia	Agammaglobulinemia	HPO_DG			★☆☆☆☆ Found in Text Mining only
AGAMMAGLOBULINEMIA 4, AUTOSOMAL RECESSIVE	Agammaglobulinemia	GENOMICS_ENGLAND_DG	25893637		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
AGAMMAGLOBULINEMIA 4, AUTOSOMAL RECESSIVE	Agammaglobulinemia	CLINVAR_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Agammaglobulinemia, non-Bruton type	Agammaglobulinemia	ORPHANET_DG	10583958		★☆☆☆☆ Found in Text Mining only
Alzheimer Disease	Alzheimer disease	Pubtator	40050982	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Aneuploidy	Aneuploidy	Pubtator	19018766	Inhibit	★☆☆☆☆ Found in Text Mining only
Aortic Aneurysm Abdominal	Aortic aneurysm	Pubtator	22797469	Associate	★☆☆☆☆ Found in Text Mining only
Arthritis	Arthritis	BEFREE	25893637		★☆☆☆☆ Found in Text Mining only
Arthritis	Arthritis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Autosomal agammaglobulinemia	Agammaglobulinemia	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
B-Cell Lymphomas	B-Cell Lymphoma	BEFREE	16568084, 17717600		★☆☆☆☆ Found in Text Mining only
Bladder Neoplasm	Bladder Neoplasm	BEFREE	28599664		★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Breast neoplasm	Pubtator	32841536	Associate	★☆☆☆☆ Found in Text Mining only
Bronchiectasis	Bronchiectasis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Byzanthine arch palate	High palate	HPO_DG			★☆☆☆☆ Found in Text Mining only
Carcinoma of bladder	Bladder carcinoma	BEFREE	28599664		★☆☆☆☆ Found in Text Mining only
Childhood Acute Lymphoblastic Leukemia	Lymphoblastic Leukemia	BEFREE	15029213		★☆☆☆☆ Found in Text Mining only
Chronic Lymphocytic Leukemia	Lymphocytic Leukemia	BEFREE	28130399		★☆☆☆☆ Found in Text Mining only
Chronic otitis media	Otitis media	HPO_DG			★☆☆☆☆ Found in Text Mining only
Chronic sinusitis	Sinusitis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Colon Carcinoma	Colon Carcinoma	BEFREE	14660655		★☆☆☆☆ Found in Text Mining only
Congenital arteriovenous malformation	Congenital Arteriovenous Malformation	BEFREE	30851033		★☆☆☆☆ Found in Text Mining only
Congenital Epicanthus	Congenital Epicanthus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Conjunctivitis	Conjunctivitis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Dermatitis	Dermatitis	BEFREE	25893637		★☆☆☆☆ Found in Text Mining only
Dermatitis Atopic	Atopic dermatitis	Pubtator	26817661	Associate	★☆☆☆☆ Found in Text Mining only
Diffuse Large B-Cell Lymphoma	Diffuse Lymphoma	BEFREE	24169826		★☆☆☆☆ Found in Text Mining only
Hodgkin Disease	Hodgkin disease	Pubtator	12881301, 28791394	Associate	★☆☆☆☆ Found in Text Mining only
Hypogammaglobulinemia	Hypogammaglobulinemia	CTD_human_DG			★☆☆☆☆ Found in Text Mining only
Hypoxia	Hypoxia	Pubtator	32099002	Associate	★☆☆☆☆ Found in Text Mining only
IGA Glomerulonephritis	Glomerulonephritis	BEFREE	18249037		★☆☆☆☆ Found in Text Mining only
Immunologic Deficiency Syndromes	Immunologic Deficiency Syndromes	HPO_DG			★☆☆☆☆ Found in Text Mining only
Ki-1+ Anaplastic Large Cell Lymphoma	Anaplastic Lymphoma	BEFREE	30339972		★☆☆☆☆ Found in Text Mining only
Leukemia	Leukemia	Pubtator	14993251	Associate	★☆☆☆☆ Found in Text Mining only
leukemia	Leukemia	BEFREE	16636677		★☆☆☆☆ Found in Text Mining only
Leukemia Myeloid Acute	Myeloid leukemia	Pubtator	22689681	Associate	★☆☆☆☆ Found in Text Mining only
Lymphoid leukemia	Lymphoid leukemia	BEFREE	16636677		★☆☆☆☆ Found in Text Mining only
Lymphoma	Lymphoma	LHGDN	15744341		★☆☆☆☆ Found in Text Mining only
Lymphoma	Lymphoma	BEFREE	16568084		★☆☆☆☆ Found in Text Mining only
Malabsorption Syndrome	Malabsorption Syndrome	HPO_DG			★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of urinary bladder	Urinary bladder cancer	BEFREE	28599664		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	14660655, 28470571, 30335638		★☆☆☆☆ Found in Text Mining only
Malignant tumor of colon	Colonic Neoplasms	BEFREE	14660655		★☆☆☆☆ Found in Text Mining only
Multiple Myeloma	Multiple myeloma	Pubtator	38280104	Associate	★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	16300960, 16912232, 19620627, 25820259, 31409641		★☆☆☆☆ Found in Text Mining only
Neutropenia	Neutropenia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Osteomyelitis	Osteomyelitis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Pancreatic Neoplasms	Pancreatic neoplasm	Pubtator	35934795	Stimulate	★☆☆☆☆ Found in Text Mining only
Pre B-cell acute lymphoblastic leukemia	B-cell Lymphoma	BEFREE	12761551		★☆☆☆☆ Found in Text Mining only
Precursor B-cell lymphoblastic leukemia	Lymphoblastic Leukemia	BEFREE	12761551, 15029213, 16568084, 16636677, 24582315, 25893637, 26522721		★☆☆☆☆ Found in Text Mining only
Precursor B-Cell Lymphoblastic Leukemia-Lymphoma	Lymphoblastic Leukemia	BEFREE	12761551, 16300960		★☆☆☆☆ Found in Text Mining only
Precursor Cell Lymphoblastic Leukemia Lymphoma	Lymphoblastic Leukemia	BEFREE	16568084, 16636677, 16912232, 26703467		★☆☆☆☆ Found in Text Mining only
Prostatic Neoplasms	Prostatic neoplasm	Pubtator	35742868	Associate	★☆☆☆☆ Found in Text Mining only
Pulmonary Disease Chronic Obstructive	Chronic obstructive pulmonary disease	Pubtator	32099002	Associate	★☆☆☆☆ Found in Text Mining only
Recurrent otitis media	Otitis media	HPO_DG			★☆☆☆☆ Found in Text Mining only
Sinusitis	Sinusitis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Waldenstrom Macroglobulinemia	Waldenstrom`s Macroglobulinemia	BEFREE	17252022		★☆☆☆☆ Found in Text Mining only
Waldenstrom Macroglobulinemia	Waldenstrom macroglobulinemia	Pubtator	30402490	Associate	★☆☆☆☆ Found in Text Mining only
X-linked agammaglobulinemia	Agammaglobulinemia, X-Linked	BEFREE	11206059		★☆☆☆☆ Found in Text Mining only