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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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SH2D3C
SH2 domain containing 3C
Chromosome 9 · 9q34.11
NCBI Gene: 10044Ensembl: ENSG00000095370.21HGNC: HGNC:16884UniProt: B4DG32
33PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
cytosolprotein bindingJNK cascadecell adhesionneurodegenerative diseaseGenu valgumGenu varumneoplasm
✦AI Summary

SH2D3C (SH2 domain containing 3C) is an adaptor protein located on chromosome 9.11-q34.13 that contains both an SH2 domain and a Ras GEF-like domain, classifying it as a novel SH2-containing protein (NSP3) 1. The protein is involved in regulation of cell adhesion, migration, and tissue organization through its interactions with signaling proteins 1. SH2D3C localizes to the cytosol and membrane ruffles, where it binds to DPP3 (dipeptidyl peptidase 3) via its C-terminal Ras GEF-like domain 1. Functionally, SH2D3C participates in cellular stress responses and the JNK signaling cascade, with evidence suggesting involvement in the BCAR1/CAS-mediated JNK activation pathway. Clinically, SH2D3C has emerged as a significant biomarker across multiple disease contexts: it is overexpressed in Gram-positive bacterial sepsis in preterm infants 2, correlates with poor prognosis in acute myeloid leukemia 3, participates in myocardial ischemia-reperfusion injury responses 4, and serves as a potential diagnostic biomarker for Sjögren's syndrome based on alternative splicing patterns 5. Additionally, SH2D3C shows methylation changes associated with fetal development 6, and inclusion in prognostic models for head and neck squamous cell carcinoma 7.

Sources cited
1
SH2D3C is an adaptor protein with SH2 and Ras GEF-like domains involved in regulation of adhesion, migration, and tissue organization; binds DPP3 through C-terminal domain; localizes to cytosol and membrane ruffles
PMID: 37762480
2
SH2D3C is overexpressed in Gram-positive bacterial sepsis in preterm infants and correlates with gene expression profiles discriminating sepsis types
PMID: 33767373
3
SH2D3C expression correlates with poor prognosis in acute myeloid leukemia and is associated with VAV family genes in AML pathogenesis
PMID: 34894858
4
SH2D3C is significantly enriched in cellular response to stress and plays critical regulatory roles in myocardial ischemia-reperfusion injury
PMID: 30657634
5
SH2D3C alternative splicing isoforms serve as potential diagnostic biomarkers for Sjögren's syndrome linked to immune infiltration
PMID: 40100583
6
SH2D3C gene shows methylation status changes associated with fetal growth and development
PMID: 24731722
7
SH2D3C is included in an 8-gene macrophage-related gene prognostic model for head and neck squamous cell carcinoma
PMID: 38688945
8
SH2D3C is part of the SH2D3C locus at human chromosome 9q34.11-q34.13, paralogous to other SH2D family loci
PMID: 14654988
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.52Moderate
Genu valgumOpen Targets
0.17Weak
Genu varumOpen Targets
0.17Weak
neoplasmOpen Targets
0.08Suggestive
lung cancerOpen Targets
0.08Suggestive
isolated agammaglobulinemiaOpen Targets
0.07Suggestive
infectionOpen Targets
0.06Suggestive
ICF syndromeOpen Targets
0.06Suggestive
autoimmune diseaseOpen Targets
0.06Suggestive
pulmonary fibrosisOpen Targets
0.05Suggestive
classic Hodgkin lymphomaOpen Targets
0.05Suggestive
Hodgkins lymphomaOpen Targets
0.05Suggestive
BENTA diseaseOpen Targets
0.05Suggestive
severe combined immunodeficiency due to CARD11 deficiencyOpen Targets
0.05Suggestive
hyper-IgM syndrome type 3Open Targets
0.05Suggestive
combined immunodeficiency with skin granulomasOpen Targets
0.05Suggestive
lung adenocarcinomaOpen Targets
0.05Suggestive
severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positiveOpen Targets
0.05Suggestive
T-B+ severe combined immunodeficiency due to JAK3 deficiencyOpen Targets
0.05Suggestive
immunodeficiency 73c with defective neutrophil chemotaxis and hypogammaglobulinemiaOpen Targets
0.05Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
SRCProtein interaction100%PRSS57Protein interaction100%EIF4G1Protein interaction99%IRF3Protein interaction93%SPECC1Protein interaction91%PPP1CAProtein interaction88%
Tissue Expression6 tissues
Lung
100%
Heart
44%
Bone Marrow
26%
Brain
18%
Liver
8%
Ovary
8%
Gene Interaction Network
Click a node to explore
SH2D3CSRCPRSS57EIF4G1IRF3SPECC1PPP1CA
PROTEIN STRUCTURE
Preparing viewer…
PDB3T6G · 2.50 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.52Moderately Constrained
pLIⓘ
0.91Intolerant
Observed/Expected LoF0.37 [0.27–0.52]
RankingsWhere SH2D3C stands among ~20K protein-coding genes
  • #11,406of 20,598
    Most Researched33
  • #3,217of 17,882
    Most Constrained (LOEUF)0.52 · top quartile
Genes detectedSH2D3C
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Identification and characterization of human FNBP1L gene in silico.
PMID: 14654988
Int J Mol Med · 2004
1.00
2
Identification of SH2 Domain-Containing Protein 3C as a Novel, Putative Interactor of Dipeptidyl Peptidase 3.
PMID: 37762480
Int J Mol Sci · 2023
0.90
3
LncRNA-mRNA competing endogenous RNA network depicts transcriptional regulation in ischaemia reperfusion injury.
PMID: 30657634
J Cell Mol Med · 2019
0.80
4
Characterization of macrophages in head and neck squamous cell carcinoma and development of MRG-based risk signature.
PMID: 38688945
Sci Rep · 2024
0.70
5
Transcriptome profiles discriminate between Gram-positive and Gram-negative sepsis in preterm neonates.
PMID: 33767373
Pediatr Res · 2022
0.60