CCDC81

Chr 11

coiled-coil domain containing 81

NCBI Gene: 60494 ENSG00000149201 UniProt: Q6ZN84

The CCDC81 protein localizes to the centrosome, ciliary basal body, and plasma membrane, functioning in cellular structures critical for cell division and cilia formation. Mutations cause autosomal recessive short-rib thoracic dysplasia, a severe skeletal ciliopathy affecting bone and cartilage development. The gene shows tolerance to loss-of-function variants (low constraint), consistent with the recessive inheritance pattern observed in affected patients.

ResearchSummary from RefSeq

Located in centrosome and ciliary basal body. [provided by Alliance of Genome Resources, Jun 2026]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.22

LOEUF

Mechanism· predicted

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?

1.22LOEUF

pLI 0.000

Z-score 0.44

OE 0.92 (0.71–1.22)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.43Z-score

OE missense 0.94 (0.85–1.03)

327 obs / 349.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.92 (0.71–1.22)

0≤0.351.4

Missense OE?0.94 (0.85–1.03)

0≤0.61.4

Synonymous OE?0.82

0≤1.21.6

LoF obs/exp: 36 / 39.0Missense obs/exp: 327 / 349.4Syn Z: 1.61

Background carrier burden — how many people carry a rare variant somewhere in CCDC81?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 71

838 rare PASS variants

Rare truncating (LoF)

1 in 630

179 rare PASS variants

Rare synonymous (reference)

1 in 190

266 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CCDC81. 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 110	1 in 680
South Asian	~43k	1 in 61	1 in 320
Remaining (unassigned)	~30k	1 in 62	1 in 330
European (Finnish)	~27k	1 in 460	1 in 1,800
Admixed American	~22k	1 in 57	1 in 590
African / African American	~21k	1 in 60	1 in 370
East Asian	~20k	1 in 57	1 in 440
Ashkenazi Jewish	~13k	1 in 140	≈ 1 in 4,300
Middle Eastern	~2,884	1 in 51	1 in 310

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): 13 of 15 coding exons well covered in gnomAD exomes; exons 2, 10 marginal. Genomes: all 15.? see exons ↓