HomeAboutRankingsData Sources
© 2026 GeneE
🧬
GeneE
50 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
ⓘGeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
SHC1
SHC adaptor protein 1
Chromosome 1 · 1q21.3
NCBI Gene: 6464Ensembl: ENSG00000160691.20HGNC: HGNC:10840UniProt: P29353
591PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Hub Gene
RESEARCH IMPACT
Highly Studied
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
phosphotyrosine residue bindinginsulin receptor bindinginsulin-like growth factor receptor bindingneurotrophin TRKA receptor bindingcancerDecreased total leukocyte countCrohn's diseaseinflammatory bowel disease
✦AI Summary

SHC1 encodes a signaling adapter protein that plays critical roles in growth factor signaling, cellular stress responses, and aging processes. The gene produces multiple isoforms, with p46Shc and p52Shc functioning as initiators of the Ras signaling cascade by coupling activated receptor tyrosine kinases to downstream pathways through GRB2/SOS recruitment 1. The p66Shc isoform serves a distinct function in oxidative stress responses and longevity regulation, mediating endothelial dysfunction across various pathological conditions including hyperlipidemia, diabetes, and aging 2. SHC1 acts downstream of p53 during stress responses, promoting intracellular oxidant elevation and apoptosis 3. The protein demonstrates clinical significance as a biomarker, with upregulation observed across multiple cancer types and association with poor prognosis 4. In gastric cancer, SHC1 recruitment to HER2 activates MAPK and PI3K pathways, while its binding partner SHCBP1 regulates mitotic processes 1. Additionally, SHC1 serves as a therapeutic target, with microRNA 452 regulation maintaining cellular homeostasis during carcinogenesis 5. A longevity-associated polymorphism (Met410Val) has been identified, suggesting potential links between SHC1 variants and human lifespan 6.

Sources cited
1
SHC1 couples activated receptor tyrosine kinases to Ras signaling cascade and is recruited to HER2 for MAPK/PI3K pathway activation
PMID: 33990570
2
p66Shc isoform mediates endothelial dysfunction in pathological conditions including hyperlipidemia, diabetes, and aging
PMID: 30918103
3
SHC1 acts downstream of p53 during stress responses, promoting oxidant elevation and apoptosis
PMID: 40569566
4
SHC1 upregulation is observed across multiple cancer types and associated with poor prognosis
PMID: 35601500
5
MicroRNA 452 regulates SHC1 expression to maintain cellular homeostasis during carcinogenesis
PMID: 37523129
6
Met410Val polymorphism in SHC1 shows potential association with human longevity
PMID: 15036421
Disease Associationsⓘ20
cancerOpen Targets
0.61Moderate
Decreased total leukocyte countOpen Targets
0.32Weak
Crohn's diseaseOpen Targets
0.28Weak
inflammatory bowel diseaseOpen Targets
0.28Weak
neurodegenerative diseaseOpen Targets
0.25Weak
osteoarthritisOpen Targets
0.24Weak
colorectal carcinomaOpen Targets
0.16Weak
pancreatic carcinomaOpen Targets
0.15Weak
neoplasmOpen Targets
0.11Weak
breast cancerOpen Targets
0.10Suggestive
lung cancerOpen Targets
0.10Suggestive
lung adenocarcinomaOpen Targets
0.10Suggestive
glioblastoma multiformeOpen Targets
0.08Suggestive
infectionOpen Targets
0.08Suggestive
nonpapillary renal cell carcinomaOpen Targets
0.08Suggestive
familial amyotrophic lateral sclerosisOpen Targets
0.06Suggestive
Charcot-Marie-Tooth disease type 1AOpen Targets
0.06Suggestive
neuronopathy, distal hereditary motor, type 5COpen Targets
0.06Suggestive
urinary bladder carcinomaOpen Targets
0.06Suggestive
X-linked Charcot-Marie-Tooth disease type 2Open Targets
0.06Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
AP2A2Protein interaction100%EGFRProtein interaction100%FGFR1Protein interaction100%FGFR3Protein interaction100%FGFR2Protein interaction100%FGFR4Protein interaction100%
Tissue Expression6 tissues
Lung
100%
Liver
68%
Ovary
59%
Heart
45%
Bone Marrow
35%
Brain
20%
Gene Interaction Network
Click a node to explore
SHC1AP2A2EGFRFGFR1FGFR3FGFR2FGFR4
PROTEIN STRUCTURE
Preparing viewer…
PDB4XWX · 1.87 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.70LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.51 [0.38–0.70]
RankingsWhere SHC1 stands among ~20K protein-coding genes
  • #402of 20,598
    Most Researched591 · top 5%
  • #5,379of 17,882
    Most Constrained (LOEUF)0.70
Genes detectedSHC1
Sources retrieved50 papers
Response time—
📄 Sources
50▼
1
Hyperactivation of HER2-SHCBP1-PLK1 axis promotes tumor cell mitosis and impairs trastuzumab sensitivity to gastric cancer.
PMID: 33990570
Nat Commun · 2021
1.00
2
MicroRNA 452 regulates SHC1 expression in human colorectal cancer and colitis.
PMID: 37523129
Genes Genomics · 2023
0.90
3
Serial analysis of gene expression reveals differential expression between endometriosis and normal endometrium. Possible roles for AXL and SHC1 in the pathogenesis of endometriosis.
PMID: 19055724
Reprod Biol Endocrinol · 2008
0.84
4
Chromosome locations of genes encoding human signal transduction adapter proteins, Nck (NCK), Shc (SHC1), and Grb2 (GRB2).
PMID: 7806213
Genomics · 1994
0.82
5
Identification and validation of SHC1 and FGFR1 as novel immune-related oxidative stress biomarkers of non-obstructive azoospermia.
PMID: 39391879
Front Endocrinol (Lausanne) · 2024
0.80