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7 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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C2CD2
C2 calcium dependent domain containing 2
Chromosome 21 · 21q22.3
NCBI Gene: 25966Ensembl: ENSG00000157617.18HGNC: HGNC:1266UniProt: Q9Y426
23PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
nucleuscytosolmembranechronic primary adrenal insufficiencyAbnormal blistering of the skinalcohol drinkingcorneal neovascularization
✦AI Summary

C2CD2 is a calcium-dependent lipid transporter localized to the endoplasmic reticulum (ER) that functions at ER-plasma membrane (PM) junctions. As a phospholipid transporter containing a C2 domain, C2CD2 mediates non-vesicular lipid transfer between the ER and PM 1. The protein forms complexes with band 4.1 family members and cell adhesion molecules like SynCAM 1, enriching ER-PM junctions at cell-cell contact sites 2. Unlike its brain-enriched paralog TMEM24, C2CD2 displays lower sensitivity to calcium-induced dissociation from the PM, suggesting tissue-specific regulatory properties 1. C2CD2-containing ER-PM junctions may participate in adaptive responses to cell contact-dependent signaling, particularly relevant in neurons where these structures are abundant 2. Genome-wide association studies have implicated C2CD2 variants in diverse phenotypes including hand grip strength, gait speed in older adults, childhood obesity through DNA methylation-mediated mechanisms, and gut microbiota composition, though effect sizes are small and replication has been inconsistent 3456. A C2CD2-TFF1 in-frame fusion transcript was identified in breast cancer 7. These findings suggest C2CD2 participates in fundamental cellular functions with modest contributions to complex traits.

Sources cited
1
C2CD2 is an ER protein functioning as a phospholipid transporter and PM tether that forms complexes with band 4.1 and cell adhesion molecules at ER-PM junctions
PMID: 39158698
2
C2CD2 is a calcium-dependent lipid transporter with lower calcium sensitivity than its paralog TMEM24, displaying tissue-specific regulatory differences
PMID: 30819882
3
C2CD2 was identified in gene-based GWAS analyses for hand grip strength, though results were not replicated in independent cohort
PMID: 25637336
4
C2CD2 genetic variants (rs928874, rs1788355) were significantly associated with gait speed in elderly individuals but not replicated in independent study
PMID: 29158487
5
C2CD2 CpG methylation mediates associations between prenatal EDC exposure and elevated childhood BMI
PMID: 38986426
6
C2CD2 locus was significantly associated with gut microbiota diversity measures in GWAS of Japanese population
PMID: 33208821
7
C2CD2-TFF1 in-frame fusion transcript was validated in breast cancer samples
PMID: 26227178
Disease Associationsⓘ20
chronic primary adrenal insufficiencyOpen Targets
0.31Weak
Abnormal blistering of the skinOpen Targets
0.21Weak
alcohol drinkingOpen Targets
0.21Weak
corneal neovascularizationOpen Targets
0.09Suggestive
hypoparathyroidism, familial isolated, 2Open Targets
0.06Suggestive
intestinal hypomagnesemia 1Open Targets
0.05Suggestive
Primary hypomagnesemia with secondary hypocalcemiaOpen Targets
0.05Suggestive
pseudohypoparathyroidism type 2Open Targets
0.05Suggestive
22q11.2 deletion syndromeOpen Targets
0.04Suggestive
Familial isolated hypoparathyroidismOpen Targets
0.04Suggestive
familial isolated hyperparathyroidismOpen Targets
0.04Suggestive
hyperparathyroidismOpen Targets
0.04Suggestive
familial isolated hypoparathyroidism due to agenesis of parathyroid glandOpen Targets
0.04Suggestive
adamantinomaOpen Targets
0.03Suggestive
blue diaper syndromeOpen Targets
0.03Suggestive
ulna metaphyseal dysplasia syndromeOpen Targets
0.03Suggestive
thyroid diseaseOpen Targets
0.03Suggestive
breast cancerOpen Targets
0.00Suggestive
Dravet syndromeOpen Targets
0.00Suggestive
acneOpen Targets
0.00Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
ARHGAP10Protein interaction82%ARHGAP26Protein interaction72%C2CD2LCo-mentioned in literature29%
Tissue Expression6 tissues
Ovary
100%
Liver
43%
Heart
42%
Lung
35%
Brain
28%
Bone Marrow
23%
Gene Interaction Network
Click a node to explore
C2CD2ARHGAP10ARHGAP26C2CD2L
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt Q9Y426
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.92LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.70 [0.54–0.92]
RankingsWhere C2CD2 stands among ~20K protein-coding genes
  • #13,378of 20,598
    Most Researched23
  • #8,510of 17,882
    Most Constrained (LOEUF)0.92
Genes detectedC2CD2
Sources retrieved7 papers
Response time—
📄 Sources
7▼
1
A complex of the lipid transport ER proteins TMEM24 and C2CD2 with band 4.1 at cell-cell contacts.
PMID: 39158698
J Cell Biol · 2024
1.00
2
Genetics of hand grip strength in mid to late life.
PMID: 25637336
Age (Dordr) · 2015
0.86
3
Prenatal EDC exposure, DNA Methylation, and early childhood growth: A prospective birth cohort study.
PMID: 38986426
Environ Int · 2024
0.71
4
Lipid transporter TMEM24/C2CD2L is a Ca
PMID: 30819882
Proc Natl Acad Sci U S A · 2019
0.57
5
Genome-wide association studies and heritability analysis reveal the involvement of host genetics in the Japanese gut microbiota.
PMID: 33208821
Commun Biol · 2020
0.43