CCDC32
protein-codingcoiled-coil domain containing 32
Gene summary
Involved in head development and regulation of clathrin-dependent endocytosis. Part of clathrin-coated pit. [provided by Alliance of Genome Resources, Jul 2025]
- C15orf57
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~36.4 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0030873
Submitter: G2P
Inheritance Pattern: AR
Disease ID:MONDO:0030873
Submitter: Illumina
Inheritance Pattern: AD
Disease ID:MONDO:0000508
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0030873
Submitter: ClinGen
The *CCDC32* gene is located on chromosome 15 at 15q15.1 and encodes coiled-coil domain-containing protein 32, which has a role in cephalic and left-right axis development, as well as cilia formation and maintenance. *CCDC32* was first reported in relation to autosomal recessive cardiofacioneurodevelopmental syndrome (CFNDS) in 2020 (Harel et al., PMID: 32307552). CFNDS is characterized by cardiac defects, craniofacial features including bilateral cleft lip and palate, and developmental delays. Evidence supporting this gene-disease relationship includes case-level data and experimental data. Three variants (including 2 frameshift variants and an intragenic deletion) that have been reported in three probands in two publications (PMIDs:32307552, 35451546) are included in this curation. An additional 21 kb deletion was reported in a fourth proband (PMID: 38818818) but was not included in this curation. The mechanism of pathogenicity appears to be loss of function. This gene-disease relationship is also supported by experimental evidence from zebrafish models (PMID: 32307552). Zebrafish with depleted *ccdc32* display cerebellar hypoplasia, microcephaly, altered facial skeletal morphology, disrupted cardiac looping, and impaired expression of a ket left/right patterning transcript (southpaw). In summary, there is moderate evidence to support this gene-disease relationship. While more evidence is needed to establish this relationship definitively, no convincing contradictory evidence has emerged. This classification was approved by the ClinGen Syndromic Disorders GCEP on the meeting date October 18th, 2024 (SOP Version 11).
Clinical Genomic Database (CGD)
Manifestation: Cardiovascular; Craniofacial; Musculoskeletal; Neurologic
Intervention: Cardiovascular
Rationale: Individuals have been described with congenital heart anomalies, including valvulvar defects, and awareness may allow early diagnosis and management of these issues
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to CCDC32 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001080792.4. 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 | 1 | 4 | 5 | |||
| missense | 4 | 4 | ||||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 2 | 2 | ||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 2 | 0 | 6 | 4 | 0 | 12 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001074261.1 | 3 | MANE Select | |
| Ensembl | ENSP00000397515.2 | 3 | MANE Select | |
| RefSeq | NP_001074260.2 | 3 | Standard | |
| RefSeq | NP_001276061.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Molecular Function
- protein binding
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000558750
- Coding exons
- 4
- Length
- 36375
- Individuals with no LoFs
- 125733
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 13
- Defined
- 125746
- p
- 0.0000517
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.769 | 80 | 102 | 0.786 | 0.00000486 | 1267 |
| Missense (PolyPhen) | 24 | 38.394 | 0.62509 | 502 | ||
| Synonymous | 1.58 | 26 | 38.5 | 0.676 | 0.00000201 | 368 |
| Loss of Function | 2.20 | 2 | 9.19 | 0.218 | 4.56e-7 | 106 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000088 | 0.000088 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
Intolerance Scores
- RVIS EVS
- 0.04
- RVIS percentile EVS
- 56.64
Essentials
- Essential (gene trap)
- N