SH2D3C
protein-codingSH2 domain containing 3C, the group of SH2 domain containing|NSP adaptor proteins
Gene summary
This gene encodes an adaptor protein and member of a cytoplasmic protein family involved in cell migration. The encoded protein contains a putative Src homology 2 (SH2) domain and guanine nucleotide exchange factor-like domain which allows this signaling protein to form a complex with scaffolding protein Crk-associated substrate. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2011]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~40.4 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 SH2D3C variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_170600.3. 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 | 3 | 3 | 1 | 7 | ||
| missense | 97 | 7 | 104 | |||
| nonsense | 2 | 2 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 104 | 10 | 1 | 115 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_733745.1 | 12 | MANE Select | |
| Ensembl | ENSP00000317817.8 | 12 | MANE Select | |
| RefSeq | NP_001136003.1 | 8 | Standard | |
| RefSeq | NP_001136004.1 | 8 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- TCR
Biological Process
- JNK cascade
- small GTPase mediated signal transduction
- positive regulation of signal transduction
- positive regulation of peptidyl-serine phosphorylation
Molecular Function
- SH3/SH2 adaptor activity
- guanyl-nucleotide exchange factor activity
- protein binding
Cellular Component
- cytoplasm
- membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000314830
- Coding exons
- 12
- Length
- 40425
- Individuals with no LoFs
- 125713
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 35
- Defined
- 125748
- p
- 0.000139
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.95 | 415 | 543 | 0.765 | 0.0000345 | 5543 |
| Missense (PolyPhen) | 155 | 247.48 | 0.62631 | 2494 | ||
| Synonymous | 0.514 | 215 | 225 | 0.956 | 0.0000145 | 1803 |
| Loss of Function | 3.41 | 12 | 33.2 | 0.362 | 0.00000177 | 383 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00049 | 0.00025 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0.00010 | 0.000099 | rare |
| East Asian | 0.00049 | 0.00049 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00016 | 0.00016 | rare |
| South Asian | 0.000098 | 0.000098 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Eph receptor-binding protein which may be a positive regulator of TCR signaling. Binding to BCAR1 is required to induce membrane ruffling and promote EGF-dependent cell migration (By similarity). {ECO:0000250}.;
Recessive Scores
- pRec
- 0.123
Intolerance Scores
- LoFtool
- 0.757
- RVIS EVS
- -0.64
- RVIS percentile EVS
- 16.71
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.911
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |