CCDC32

Chr 15

coiled-coil domain containing 32

Also known as: C15orf57, CFNDS

NCBI Gene: 90416 ENSG00000128891 UniProt: Q9BV29

CCDC32 encodes a protein that regulates clathrin-mediated endocytosis of cellular cargos like transferrin and is required for proper head development and left-right body axis formation. Mutations cause autosomal recessive developmental anomalies affecting craniofacial structures and organ positioning. The gene shows moderate constraint against loss-of-function variants, consistent with its essential developmental roles.

ResearchSummary from RefSeq, UniProt

Involved in head development and regulation of clathrin-dependent endocytosis. Part of clathrin-coated pit. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtCardiofacioneurodevelopmental syndrome

Clinical highlights

Gene–disease validity (ClinGen)

Moderate · cardiofacioneurodevelopmental syndrome · AR · ClinGen 2024

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.69

LOEUF

LOF

Mechanism· G2P

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.69LOEUF

pLI 0.388

Z-score 2.20

OE 0.22 (0.09–0.69)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.77Z-score

OE missense 0.79 (0.66–0.95)

80 obs / 101.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.22 (0.09–0.69)

0≤0.351.4

Missense OE?0.79 (0.66–0.95)

0≤0.61.4

Synonymous OE?0.68

0≤1.21.6

LoF obs/exp: 2 / 9.2Missense obs/exp: 80 / 101.8Syn Z: 1.58

Background carrier burden — how many people carry a rare variant somewhere in CCDC32?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 380

317 rare PASS variants

Rare truncating (LoF)

1 in 1,100

60 rare PASS variants

Rare synonymous (reference)

1 in 560

102 rare PASS variants

Rare missense and truncating variants are carried at similar rates in CCDC32; this gene does not show strong loss-of-function constraint by this measure. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 350	1 in 1,200
South Asian	~43k	1 in 360	1 in 1,000
Remaining (unassigned)	~30k	1 in 250	1 in 1,500
European (Finnish)	~27k	1 in 520	≈ 1 in 10,000
Admixed American	~22k	1 in 360	1 in 690
African / African American	~21k	1 in 220	1 in 1,300
East Asian	~20k	1 in 200	1 in 1,500
Ashkenazi Jewish	~13k	1 in 960	1 in 1,700
Middle Eastern	~2,884	1 in 240	≈ 1 in 2,800

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 3 coding exons well covered in gnomAD exomes and genomes.? see exons ↓