C2CD5
protein-codingC2 calcium dependent domain containing 5, the group of C2 domain containing
Gene summary
Enables calcium ion binding activity and calcium-dependent phospholipid binding activity. Involved in several processes, including insulin receptor signaling pathway; positive regulation of protein targeting to membrane; and positive regulation of vesicle fusion. Located in several cellular components, including cell cortex; cytoplasmic vesicle membrane; and ruffle membrane. [provided by Alliance of Genome Resources, Jun 2026]
- KIAA0528
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~96.0 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to C2CD5 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001286176.2. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | 2 | ||||
| missense | 108 | 2 | 110 | |||
| nonsense | 2 | 2 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 115 | 2 | 0 | 117 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001273105.1 | 26 | MANE Select | |
| Ensembl | ENSP00000388756.1 | 26 | MANE Select | |
| RefSeq | NP_001273102.1 | 27 | Standard | |
| RefSeq | NP_001273103.1 | 26 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Vesicle-mediated transport
- Membrane Trafficking
- Translocation of GLUT4 to the plasma membrane
Biological Process
- vesicle fusion
- positive regulation of glucose transmembrane transport
- positive regulation of vesicle fusion
- cellular response to insulin stimulus
- insulin receptor signaling pathway via phosphatidylinositol 3-kinase
Molecular Function
- calcium ion binding
- calcium-dependent phospholipid binding
Cellular Component
- microtubule organizing center
- cytosol
- plasma membrane
- cell cortex
- cytoplasmic vesicle membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000333957
- Coding exons
- 24
- Length
- 95964
- Individuals with no LoFs
- 125673
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 75
- Defined
- 125748
- p
- 0.000298
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.68 | 353 | 526 | 0.671 | 0.0000262 | 6525 |
| Missense (PolyPhen) | 48 | 104.29 | 0.46026 | 1233 | ||
| Synonymous | -1.48 | 211 | 185 | 1.14 | 0.00000942 | 1928 |
| Loss of Function | 3.29 | 27 | 52.8 | 0.511 | 0.00000275 | 660 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00081 | 0.00080 | rare |
| Latino/Admixed American | 0.00030 | 0.00029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00045 | 0.00044 | rare |
| Finnish | 0.00014 | 0.00014 | rare |
| European (Non-Finnish) | 0.00028 | 0.00026 | rare |
| South Asian | 0.00026 | 0.00026 | rare |
| Other | 0.00049 | 0.00049 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Required for insulin-stimulated glucose transport and glucose transporter SLC2A4/GLUT4 translocation from intracellular glucose storage vesicle (GSV) to the plasma membrane (PM) in adipocytes. Binds phospholipid membranes in a calcium-dependent manner and is necessary for the optimal membrane fusion between SLC2A4/GLUT4 GSV and the PM. {ECO:0000269|PubMed:21907143}.;
Recessive Scores
- pRec
- 0.103
Intolerance Scores
- RVIS EVS
- -0.73
- RVIS percentile EVS
- 14.02
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |