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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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SHC3
SHC adaptor protein 3
Chromosome 9 · 9q22.1
NCBI Gene: 53358Ensembl: ENSG00000148082.10HGNC: HGNC:18181UniProt: Q92529
56PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
nucleoplasmprotein bindingphosphotyrosine residue bindingplasma membranesmoking initiationsubstance abuseattention deficit hyperactivity disorderpreeclampsia
✦AI Summary

SHC3 (Src homology and collagen homology 3) is a neuronal signaling adapter protein that couples activated receptor tyrosine kinases to downstream intracellular pathways 1. In the central nervous system, SHC3 functions primarily in growth factor receptor signaling, particularly in neurons 1. Mechanistically, SHC3 operates as a multiprotein scaffold that interacts with various signaling molecules. It binds activated growth factor receptors (including ErbB2) and transduces signals through interactions with FAK, MVP, AP complexes, and other effectors 2345. SHC3 undergoes tyrosine phosphorylation upon activation and modulates downstream kinase cascades including MEK/ERK and AKT pathways 634. Clinically, SHC3 dysregulation associates with multiple malignancies and psychiatric disease. Genetic variants in SHC3 show significant association with schizophrenia susceptibility in the Han Chinese population 1. In cancer, SHC3 is frequently amplified or overexpressed in glioblastomas, ependymomas, hepatocellular carcinomas, and breast cancers 2647. Elevated SHC3 promotes drug resistance through MDR1/P-glycoprotein upregulation and enhances tumor stemness, metastasis, and glucose adaptation 3745. These findings identify SHC3 as a potential therapeutic target in both cancer and neuropsychiatric disorders.

Sources cited
1
SHC3 is an adaptor protein expressed predominantly in mature CNS neurons; genetic variants associated with schizophrenia susceptibility
PMID: 32933237
2
SHC3 expression increases with cell density in glioblastoma cells through FAK activation
PMID: 25062668
3
SHC3 and EDG3 are co-amplified in ependymomas; SHC3 undergoes tyrosine phosphorylation indicating activation
PMID: 19748727
4
SHC3 overexpression promotes breast cancer drug resistance via ErbB2/COX2/MDR1 axis activation
PMID: 36880347
5
SHC3 promotes HCC stemness and chemoresistance by stabilizing β-catenin and increasing MDR1 expression
PMID: 33723262
6
SHC3 overexpression in HCC promotes MEK/ERK activation through MVP interaction and drives metastasis
PMID: 29330146
7
SHC3 increases during glucose starvation in glioblastoma and mediates glucose uptake through GLUT trafficking via AP and PARP1 interactions
PMID: 32443613
8
SHC3 phosphorylates and stabilizes RasGRP1, promoting Ras/c-Jun activation in hepatocellular carcinoma
PMID: 37646951
Disease Associationsⓘ20
smoking initiationOpen Targets
0.39Weak
substance abuseOpen Targets
0.31Weak
attention deficit hyperactivity disorderOpen Targets
0.30Weak
preeclampsiaOpen Targets
0.25Weak
multinodular goiterOpen Targets
0.17Weak
hepatocellular carcinomaOpen Targets
0.09Suggestive
colorectal carcinomaOpen Targets
0.09Suggestive
breast cancerOpen Targets
0.08Suggestive
neoplasmOpen Targets
0.06Suggestive
nephrotic syndromeOpen Targets
0.05Suggestive
schizophreniaOpen Targets
0.04Suggestive
experimental autoimmune encephalomyelitisOpen Targets
0.04Suggestive
colorectal adenocarcinomaOpen Targets
0.03Suggestive
neuroblastomaOpen Targets
0.03Suggestive
Crohn's diseaseOpen Targets
0.02Suggestive
colorectal cancerOpen Targets
0.02Suggestive
ependymomaOpen Targets
0.02Suggestive
thyroid neoplasmOpen Targets
0.02Suggestive
cancerOpen Targets
0.02Suggestive
Parkinson diseaseOpen Targets
0.02Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
EGFRProtein interaction100%ABL1Protein interaction99%NTRK1Protein interaction99%FGRProtein interaction99%HCKProtein interaction99%NTRK2Protein interaction99%
Tissue Expression6 tissues
Brain
100%
Lung
14%
Heart
5%
Liver
2%
Ovary
2%
Bone Marrow
0%
Gene Interaction Network
Click a node to explore
SHC3EGFRABL1NTRK1FGRHCKNTRK2
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q92529
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.42Moderately Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.27 [0.18–0.42]
RankingsWhere SHC3 stands among ~20K protein-coding genes
  • #8,132of 20,598
    Most Researched56
  • #2,227of 17,882
    Most Constrained (LOEUF)0.42 · top quartile
Genes detectedSHC3
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Cell density modulates SHC3 expression and survival of human glioblastoma cells through Fak activation.
PMID: 25062668
J Neurooncol · 2014
1.00
2
Positive Association of Human SHC3 Gene with Schizophrenia in a Northeast Chinese Han Population.
PMID: 32933237
Psychiatry Investig · 2020
0.90
3
EDG3 and SHC3 on chromosome 9q22 are co-amplified in human ependymomas.
PMID: 19748727
Cancer Lett · 2010
0.80
4
Shc3 facilitates breast cancer drug resistance by interacting with ErbB2 to initiate ErbB2/COX2/MDR1 axis.
PMID: 36880347
Cancer Med · 2023
0.70
5
Shc3 promotes hepatocellular carcinoma stemness and drug resistance by interacting with β-catenin to inhibit its ubiquitin degradation pathway.
PMID: 33723262
Cell Death Dis · 2021
0.60