C2CD2L
protein-codingC2CD2 like
Gene summary
Enables phosphatidylinositol binding activity and phosphatidylinositol transfer activity. Involved in positive regulation of insulin secretion involved in cellular response to glucose stimulus. Located in cortical endoplasmic reticulum; cytoplasmic side of apical plasma membrane; and endoplasmic reticulum-plasma membrane contact site. [provided by Alliance of Genome Resources, Jul 2025]
- TMEM24
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~16.3 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 C2CD2L variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001290474.2. 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 | 4 | 1 | 5 | |||
| missense | 106 | 3 | 109 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 110 | 7 | 1 | 118 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001277403.1 | 14 | MANE Select | |
| Ensembl | ENSP00000497391.1 | 14 | MANE Select | |
| RefSeq | NP_001369540.1 | 13 | Standard | |
| RefSeq | NP_001369541.1 | 14 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- phospholipid transport
- positive regulation of insulin secretion involved in cellular response to glucose stimulus
Molecular Function
- phospholipid transporter activity
- phosphatidylinositol transporter activity
- phosphatidylinositol binding
- insulin binding
Cellular Component
- endoplasmic reticulum membrane
- integral component of membrane
- cortical endoplasmic reticulum
- cytoplasmic side of apical plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000336702
- Coding exons
- 14
- Length
- 16345
- Individuals with no LoFs
- 125740
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 8
- Defined
- 125748
- p
- 0.0000318
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.78 | 320 | 423 | 0.757 | 0.0000255 | 4478 |
| Missense (PolyPhen) | 114 | 166.74 | 0.68368 | 1759 | ||
| Synonymous | 1.24 | 154 | 175 | 0.880 | 0.0000106 | 1565 |
| Loss of Function | 4.48 | 4 | 30.8 | 0.130 | 0.00000157 | 337 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000044 | 0.000035 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Lipid-binding protein that transports phosphatidylinositol, the precursor of phosphatidylinositol 4,5- bisphosphate (PI(4,5)P2), from its site of synthesis in the endoplasmic reticulum to the cell membrane (PubMed:28209843). It thereby maintains the pool of cell membrane phosphoinositides, which are degraded during phospholipase C (PLC) signaling (PubMed:28209843). Plays a key role in the coordination of Ca(2+) and phosphoinositide signaling: localizes to sites of contact between the endoplasmic reticulum and the cell membrane, where it tethers the two bilayers (PubMed:28209843). In response to elevation of cytosolic Ca(2+), it is phosphorylated at its C- terminus and dissociates from the cell membrane, abolishing phosphatidylinositol transport to the cell membrane (PubMed:28209843). Positively regulates insulin secretion in response to glucose: phosphatidylinositol transfer to the cell membrane allows replenishment of PI(4,5)P2 pools and calcium channel opening, priming a new population of insulin granules (PubMed:28209843). {ECO:0000269|PubMed:28209843}.;
Recessive Scores
- pRec
- 0.126
Intolerance Scores
- LoFtool
- 0.133
- RVIS EVS
- -0.31
- RVIS percentile EVS
- 32.15
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.373
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |