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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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SHC4
SHC adaptor protein 4
Chromosome 15 · 15q21.1
NCBI Gene: 399694Ensembl: ENSG00000185634.12HGNC: HGNC:16743UniProt: F5H5M1
25PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingplasma membranereceptor tyrosine kinase bindingcell surface receptor protein tyrosine kinase signaling pathwaytype 1 diabetes mellitusbenign neoplasm of eyeAbruptio Placentaetooth disease
✦AI Summary

SHC4 (SHC adaptor protein 4) is a signaling adaptor protein that functions as a key regulator in both developmental and pathological processes. Primary function: SHC4 activates Ras-dependent and Ras-independent migratory pathways and regulates receptor tyrosine kinase signaling 1. Mechanism: SHC4 interacts with Src kinase and maintains its autophosphorylated activation state, which activates β-catenin independent of canonical Wnt signaling, subsequently upregulating metastasis-associated genes CD44 and MMP7 1. Additionally, SHC4 enhances mesenchymal stem cell migration and hematopoietic niche establishment 2. Disease relevance: SHC4 is upregulated in triple-negative breast cancer (TNBC) with high expression correlating to poor prognosis and increased metastatic potential 1. SHC4 regulates BDNF-induced MAPK activation and has been associated with depressive symptoms severity in bipolar disorder 3. SHC4 is also implicated in prostate cancer progression through regulation of extracellular vesicle secretion 4, and differentially methylated regions of SHC4 associate with general psychopathology in childhood 5. Clinical significance: SHC4 represents a potential prognostic marker and therapeutic target in TNBC 1, with targeting its interaction with Src kinase offering a novel therapeutic strategy for aggressive cancers.

Sources cited
1
SHC4 is upregulated in TNBC, promotes metastasis by binding Src kinase and activating β-catenin independent of Wnt signaling, upregulating CD44 and MMP7
PMID: 38052369
2
SHC4 overexpression promotes migratory ability of mesenchymal stem cells and facilitates their engraftment into decellularized bone
PMID: 36290460
3
SHC4 is associated with depressive symptoms severity in bipolar disorder and regulates BDNF-induced MAPK activation
PMID: 30149091
4
SHC4 regulates extracellular vesicle secretion from prostate cancer cells, contributing to cancer progression
PMID: 32494663
5
DNA methylation at SHC4 locus associates with general psychopathology factor in childhood and has been implicated in multiple psychiatric disorders
PMID: 36385171
Disease Associationsⓘ20
type 1 diabetes mellitusOpen Targets
0.39Weak
benign neoplasm of eyeOpen Targets
0.33Weak
Abruptio PlacentaeOpen Targets
0.33Weak
tooth diseaseOpen Targets
0.30Weak
SplenomegalyOpen Targets
0.28Weak
KeloidOpen Targets
0.27Weak
goiterOpen Targets
0.25Weak
placenta praeviaOpen Targets
0.23Weak
uterine disorderOpen Targets
0.21Weak
kidney diseaseOpen Targets
0.19Weak
melanomaOpen Targets
0.09Suggestive
hepatocellular carcinomaOpen Targets
0.08Suggestive
neoplasmOpen Targets
0.05Suggestive
posterior cortical atrophyOpen Targets
0.03Suggestive
neuroblastomaOpen Targets
0.03Suggestive
gliomaOpen Targets
0.03Suggestive
triple-negative breast cancerOpen Targets
0.03Suggestive
prostate cancerOpen Targets
0.02Suggestive
acute lung injuryOpen Targets
0.01Suggestive
ataxia telangiectasiaOpen Targets
0.01Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
SHC2Shared pathway100%SH2D6Shared pathway100%GRB2Protein interaction100%EGFRProtein interaction100%FGRProtein interaction99%HCKProtein interaction99%
Tissue Expression6 tissues
Heart
100%
Brain
75%
Ovary
15%
Liver
15%
Lung
14%
Bone Marrow
3%
Gene Interaction Network
Click a node to explore
SHC4SHC2SH2D6GRB2EGFRFGRHCK
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q6S5L8
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.72LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.54 [0.41–0.72]
RankingsWhere SHC4 stands among ~20K protein-coding genes
  • #13,062of 20,598
    Most Researched25
  • #5,520of 17,882
    Most Constrained (LOEUF)0.72
Genes detectedSHC4
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Low molecular weight fucoidan fraction ameliorates inflammation and deterioration of skin barrier in fine-dust stimulated keratinocytes.
PMID: 33220376
Int J Biol Macromol · 2021
1.00
2
Human Keratinocyte UVB-Protective Effects of a Low Molecular Weight Fucoidan from
PMID: 32326316
Antioxidants (Basel) · 2020
0.90
3
SHC4 orchestrates β-catenin pathway-mediated metastasis in triple-negative breast cancer by promoting Src kinase autophosphorylation.
PMID: 38052369
Cancer Lett · 2024
0.80
4
Identification of the Factor That Leads Human Mesenchymal Stem Cell Lines into Decellularized Bone.
PMID: 36290460
Bioengineering (Basel) · 2022
0.70
5
DNA methylation and general psychopathology in childhood: an epigenome-wide meta-analysis from the PACE consortium.
PMID: 36385171
Mol Psychiatry · 2023
0.60