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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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C2CD4A
C2 calcium dependent domain containing 4A
Chromosome 15 · 15q22.2
NCBI Gene: 145741Ensembl: ENSG00000198535.5HGNC: HGNC:33627UniProt: Q8NCU7
15PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
regulation of vascular permeability involved in acute inflammatory responsepositive regulation of acute inflammatory responseregulation of cell adhesionnucleustype 2 diabetes mellituspreeclampsiadiabetic eye diseaseresponse to radiation
✦AI Summary

C2CD4A is a nuclear protein with diverse cellular functions, most notably in glucose homeostasis and transcriptional regulation. In pancreatic β cells, C2CD4A functions as a transcriptional coregulator of the glycolytic pathway, regulating glycolytic genes and repressing β cell 'disallowed' genes such as lactate dehydrogenase A 1. The protein is controlled by FoxO1 superenhancers and localizes partially to the plasma membrane under Ca2+ control, with binding partners including secretory-granule-localized PTPRN2/phogrin 2. Genetic variants in the VPS13C-C2CD4A-C2CD4B locus are associated with type 2 diabetes susceptibility across multiple ethnic populations 34. The diabetes risk allele increases C2CD4A expression through enhanced NFAT-mediated islet enhancer activity 4. Beyond metabolic function, C2CD4A plays roles in cancer biology, where it inhibits p53 signaling by promoting p53 ubiquitination and degradation, contributing to colorectal cancer progression 5. The gene is also upregulated in invasive pituitary adenomas and serves as a protective factor against lung cancer in Chinese populations 67. These findings establish C2CD4A as a multifunctional protein involved in metabolic regulation, transcriptional control, and cancer pathogenesis.

Sources cited
1
C2CD4A functions as a transcriptional coregulator of the glycolytic pathway in β cells and represses β cell 'disallowed' genes
PMID: 31527256
2
C2CD4A localizes partially to the plasma membrane under Ca2+ control and binds to PTPRN2/phogrin
PMID: 33492421
3
The C2CD4A-C2CD4B locus is associated with type 2 diabetes susceptibility
PMID: 20818381
4
Diabetes risk variants increase C2CD4A expression through NFAT-mediated enhancer activity
PMID: 29625024
5
C2CD4A inhibits p53 signaling by promoting p53 ubiquitination and degradation in colorectal cancer
PMID: 34656159
6
C2CD4A is upregulated in invasive gonadotrophic pituitary adenomas
PMID: 36750863
7
C2CD4A variants serve as protective factors against lung cancer in Chinese populations
PMID: 35212842
Disease Associationsⓘ20
type 2 diabetes mellitusOpen Targets
0.27Weak
preeclampsiaOpen Targets
0.25Weak
diabetic eye diseaseOpen Targets
0.22Weak
response to radiationOpen Targets
0.22Weak
diabetes mellitusOpen Targets
0.20Weak
diabetic retinopathyOpen Targets
0.16Weak
Abnormality of the skeletal systemOpen Targets
0.16Weak
type 2 diabetes nephropathyOpen Targets
0.16Weak
open-angle glaucomaOpen Targets
0.15Weak
diabetic neuropathyOpen Targets
0.15Weak
glaucomaOpen Targets
0.14Weak
Parkinson diseaseOpen Targets
0.13Weak
systemic lupus erythematosusOpen Targets
0.13Weak
Esophageal atresiaOpen Targets
0.11Weak
pyloric stenosisOpen Targets
0.11Weak
premature birthOpen Targets
0.11Weak
metabolic syndromeOpen Targets
0.10Weak
morbid obesityOpen Targets
0.10Suggestive
ovarian dysfunctionOpen Targets
0.08Suggestive
Romano-Ward syndromeOpen Targets
0.08Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
C2CD4BShared pathway80%RND1Protein interaction78%UNC79Protein interaction72%NALCNProtein interaction72%CYTIPShared pathway50%CBLL2Shared pathway50%
Tissue Expression6 tissues
Liver
100%
Brain
84%
Bone Marrow
63%
Lung
36%
Ovary
14%
Heart
0%
Gene Interaction Network
Click a node to explore
C2CD4AC2CD4BRND1UNC79NALCNCYTIPCBLL2
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q8NCU7
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.96LoF Tolerant
pLIⓘ
0.01Tolerant
Observed/Expected LoF3.61 [0.78–1.96]
RankingsWhere C2CD4A stands among ~20K protein-coding genes
  • #15,504of 20,598
    Most Researched15
  • #17,759of 17,882
    Most Constrained (LOEUF)1.96
Genes detectedC2CD4A
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Identification of
PMID: 31527256
Proc Natl Acad Sci U S A · 2019
1.00
2
Identification and gene expression profiling of human gonadotrophic pituitary adenoma stem cells.
PMID: 36750863
Acta Neuropathol Commun · 2023
0.90
3
Sexually dimorphic roles for the type 2 diabetes-associated C2cd4b gene in murine glucose homeostasis.
PMID: 33492421
Diabetologia · 2021
0.80
4
The novel circSLC6A6/miR-1265/C2CD4A axis promotes colorectal cancer growth by suppressing p53 signaling pathway.
PMID: 34656159
J Exp Clin Cancer Res · 2021
0.70
5
A Common Type 2 Diabetes Risk Variant Potentiates Activity of an Evolutionarily Conserved Islet Stretch Enhancer and Increases C2CD4A and C2CD4B Expression.
PMID: 29625024
Am J Hum Genet · 2018
0.60