SH2D1B
protein-codingSH2 domain containing 1B, the group of SH2 domain containing
Gene summary
By binding phosphotyrosines through its free SRC (MIM 190090) homology-2 (SH2) domain, EAT2 regulates signal transduction through receptors expressed on the surface of antigen-presenting cells (Morra et al., 2001 [PubMed 11689425]).[supplied by OMIM, Mar 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~16.9 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to SH2D1B variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_053282.5. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 0 | |||||
| missense | 18 | 18 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 19 | 0 | 0 | 19 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_444512.2 | 4 | MANE Select | |
| Ensembl | ENSP00000356906.2 | 4 | MANE Select | |
| Ensembl | ENSP00000522090.1 | 3 | Standard | |
| Ensembl | ENSP00000522090.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Natural killer cell mediated cytotoxicity - Homo sapiens (human)
- Immune System
- Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
- Adaptive Immune System
Biological Process
- adaptive immune response
- leukocyte activation involved in immune response
- positive regulation of natural killer cell mediated immunity
- innate immune response
- positive regulation of innate immune response
Molecular Function
- protein binding
- protein binding, bridging
Cellular Component
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000367929
- Coding exons
- 4
- Length
- 16873
- Individuals with no LoFs
- 125686
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 60
- Defined
- 125747
- p
- 0.000243
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.319 | 63 | 70.5 | 0.893 | 0.00000359 | 856 |
| Missense (PolyPhen) | 18 | 23.058 | 0.78063 | 275 | ||
| Synonymous | -0.393 | 30 | 27.4 | 1.10 | 0.00000151 | 240 |
| Loss of Function | 1.30 | 4 | 7.95 | 0.503 | 5.20e-7 | 84 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0021 | 0.0021 | notable |
| Latino/Admixed American | 0.00020 | 0.00020 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000097 | 0.000088 | rare |
| South Asian | 0.00016 | 0.00016 | rare |
| Other | 0.00049 | 0.00049 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Cytoplasmic adapter regulating receptors of the signaling lymphocytic activation molecule (SLAM) family such as CD84, SLAMF1, LY9 and CD244 (PubMed:11689425). In SLAM signaling seems to cooperate with SH2D1A/SAP. Plays a role in regulation of effector functions of natural killer (NK) cells by controlling signal transduction through CD244/2B4 without effecting its tyrosine phosphorylation; downstream signaling involves PLCG1 and ERK activation (PubMed:24687958). Activation of SLAMF7-mediated NK cell function does not effect receptor tyrosine phosphorylation but distal signaling (By similarity). In the context of NK cell- mediated cytotoxicity does not enhance conjugate formation with target cells but stimulates polarization of the microtubule- organizing center and cytotoxic granules toward the NK cell synapse (PubMed:24687958). Negatively regulates CD40-induced cytokine production in dendritic cells downstream of SLAM family receptors probably by inducing activation of the PI3K pathway to inhibit p38 MAPK and JNK activation (By similarity). {ECO:0000250|UniProtKB:O35324, ECO:0000269|PubMed:11689425, ECO:0000269|PubMed:24687958, ECO:0000305|PubMed:21219180}.;
Recessive Scores
- pRec
- 0.147
Intolerance Scores
- LoFtool
- 0.565
- RVIS EVS
- 0.37
- RVIS percentile EVS
- 74.95
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.455
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |