SHC2
protein-codingSHC adaptor protein 2, the group of SH2 domain containing
Gene summary
Predicted to enable receptor tyrosine kinase binding activity. Predicted to be involved in cell surface receptor protein tyrosine kinase signaling pathway. Predicted to be located in cytosol. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Jul 2025]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~44.4 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 SHC2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_012435.3. 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 | 6 | |||
| missense | 139 | 2 | 141 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 145 | 5 | 0 | 150 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_036567.2 | 12 | MANE Select | |
| Ensembl | ENSP00000264554.4 | 12 | MANE Select | |
| RefSeq | NP_001373985.1 | 11 | Standard | |
| Ensembl | ENSP00000465764.3 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Chronic myeloid leukemia - Homo sapiens (human)
- Gastric cancer - Homo sapiens (human)
- Focal adhesion - Homo sapiens (human)
- Relaxin signaling pathway - Homo sapiens (human)
- VEGF signaling pathway - Homo sapiens (human)
Biological Process
- MAPK cascade
- activation of MAPK activity
- Ras protein signal transduction
- vascular endothelial growth factor receptor signaling pathway
Molecular Function
- Ras guanyl-nucleotide exchange factor activity
- protein binding
- receptor tyrosine kinase binding
Cellular Component
- cellular_component
- cytosol
- plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000264554
- Coding exons
- 12
- Length
- 44414
- Individuals with no LoFs
- 124490
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 57
- Defined
- 124547
- p
- 0.000229
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.274 | 277 | 290 | 0.955 | 0.0000200 | 3653 |
| Missense (PolyPhen) | 138 | 157.48 | 0.87632 | 1576 | ||
| Synonymous | -0.203 | 138 | 135 | 1.02 | 0.0000110 | 1250 |
| Loss of Function | 0.312 | 22 | 23.6 | 0.931 | 0.00000128 | 274 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00035 | 0.00032 | rare |
| Latino/Admixed American | 0.00061 | 0.00055 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00051 | 0.00050 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00017 | 0.00015 | rare |
| South Asian | 0.00020 | 0.00020 | rare |
| Other | 0.00017 | 0.00017 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Signaling adapter that couples activated growth factor receptors to signaling pathway in neurons. Involved in the signal transduction pathways of neurotrophin-activated Trk receptors in cortical neurons (By similarity). {ECO:0000250}.;
Recessive Scores
- pRec
- 0.245
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.970
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |