BLNK

B cell linker, the group of SH2 domain containing

Basic information

Region (hg38): 10:96189171-96271587

Links

ENSG00000095585

∙ NCBI:29760 ∙ OMIM:604515 ∙ HGNC:14211 ∙ Uniprot:Q8WV28 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

agammaglobulinemia 4, autosomal recessive (Moderate), mode of inheritance: AR
agammaglobulinemia 4, autosomal recessive (Strong), mode of inheritance: AR
autosomal agammaglobulinemia (Supportive), mode of inheritance: AD
agammaglobulinemia 4, autosomal recessive (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Agammaglobulinemia 4, autosomal recessive	AR	Allergy/Immunology/Infectious	Individuals can have immunodeficiency (which can involve frequent and severe infections, including reports of lethal bacterial sepsis) related to agammaglobulinemia, and antiinfectious prophylaxis (IVIG has been reported to be beneficial) and early and aggressive treatment of infections may be beneficial	Allergy/Immunology/Infectious	10583958

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the BLNK gene.

Agammaglobulinemia_4,_autosomal_recessive (309 variants)
Inborn_genetic_diseases (39 variants)
not_provided (24 variants)
BLNK-related_disorder (8 variants)
not_specified (5 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the BLNK gene is commonly pathogenic or not. These statistics are base on transcript: NM_000013314.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	79 clinvar	4 clinvar	85
missense			128 clinvar	5 clinvar	1 clinvar	134
nonsense	2 clinvar	3 clinvar				5
start loss						0
frameshift	4 clinvar	1 clinvar				5
splice donor/acceptor (+/-2bp)		4 clinvar				4
Total	6	8	130	84	5

Highest pathogenic variant AF is 0.00000410651

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
BLNK	protein_coding	protein_coding	ENST00000224337	17	79887

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.611	0.389	125731	0	17	125748	0.0000676

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.50	183	250	0.733	0.0000135	2953
Missense in Polyphen		33	65.732	0.50204		800
Synonymous	-0.178	98	95.8	1.02	0.00000622	869
Loss of Function	4.25	7	33.6	0.208	0.00000191	373

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000905	0.0000904
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.0000879	0.0000879
Middle Eastern	0.000109	0.000109
South Asian	0.00	0.00
Other	0.000326	0.000326

dbNSFP

Source: dbNSFP

Function: 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 ERK/EPHB2, MAP kinase p38 and JNK. Modulates AP1 activation. Important for the activation of NF-kappa-B and NFAT. Plays an important role in BCR-mediated PLCG1 and PLCG2 activation and Ca(2+) mobilization and is required for trafficking of the BCR to late endosomes. However, does not seem to be required for pre-BCR- mediated activation of MAP kinase and phosphatidyl-inositol 3 (PI3) kinase signaling. May be required for the RAC1-JNK pathway. Plays a critical role in orchestrating the pro-B cell to pre-B cell transition. May play an important role in BCR-induced B-cell apoptosis. {ECO:0000269|PubMed:10583958, ECO:0000269|PubMed:15270728, ECO:0000269|PubMed:16912232, ECO:0000269|PubMed:9697839}.;
Disease: DISEASE: Agammaglobulinemia 4, autosomal recessive (AGM4) [MIM:613502]: A primary immunodeficiency characterized by profoundly low or absent serum antibodies and low or absent circulating B-cells due to an early block of B-cell development. Affected individuals develop severe infections in the first years of life. {ECO:0000269|PubMed:10583958}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: Primary immunodeficiency - Homo sapiens (human);B cell receptor signaling pathway - Homo sapiens (human);Osteoclast differentiation - Homo sapiens (human);NF-kappa B signaling pathway - Homo sapiens (human);B Cell Receptor Signaling Pathway;Antigen activates B Cell Receptor (BCR) leading to generation of second messengers;Signaling by Interleukins;bcr signaling pathway;Cytokine Signaling in Immune system;B cell receptor signaling;Signaling by the B Cell Receptor (BCR);Immune System;Adaptive Immune System;BCR;BCR signaling pathway;Class I PI3K signaling events;Regulation of signaling by CBL;Interleukin-3, 5 and GM-CSF signaling (Consensus)

Recessive Scores

pRec: 0.284

Intolerance Scores

loftool: 0.0565
rvis_EVS: -0.38
rvis_percentile_EVS: 27.88

Haploinsufficiency Scores

pHI: 0.251
hipred: Y
hipred_score: 0.774
ghis: 0.592

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: S
essential_gene_gene_trap: N
gene_indispensability_pred: N
gene_indispensability_score: 0.484

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

Gene name: Blnk
Phenotype: hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); neoplasm; immune system phenotype; cellular phenotype;

Gene ontology

Biological process: inflammatory response;humoral immune response;transmembrane receptor protein tyrosine kinase signaling pathway;positive regulation of signal transduction;B cell differentiation;intracellular signal transduction
Cellular component: cytoplasm;cytosol;plasma membrane;cytoplasmic ribonucleoprotein granule
Molecular function: transmembrane receptor protein tyrosine kinase adaptor activity;SH3/SH2 adaptor activity;protein binding