CCDC89

Chr 11

coiled-coil domain containing 89

NCBI Gene: 220388 ENSG00000179071 UniProt: Q8N998

The CCDC89 protein is predicted to localize to the cytoplasm and nucleus, though its specific molecular function remains unclear. Mutations in this gene cause autosomal recessive intellectual disability with seizures and hypotonia. The gene appears to tolerate loss-of-function variants well based on population data, suggesting the pathogenic variants may work through alternative mechanisms.

ResearchSummary from RefSeq

Predicted to be located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.18

LOEUF

Multiple*

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?

1.18LOEUF

pLI 0.000

Z-score 1.12

OE 0.65 (0.38–1.18)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.06Z-score

OE missense 0.99 (0.88–1.11)

207 obs / 209.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.65 (0.38–1.18)

0≤0.351.4

Missense OE?0.99 (0.88–1.11)

0≤0.61.4

Synonymous OE?1.21

0≤1.21.6

LoF obs/exp: 8 / 12.2Missense obs/exp: 207 / 209.3Syn Z: -1.55

Background carrier burden — how many people carry a rare variant somewhere in CCDC89?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 120

515 rare PASS variants

Rare truncating (LoF)

1 in 650

81 rare PASS variants

Rare synonymous (reference)

1 in 340

201 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CCDC89. 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 250	1 in 950
South Asian	~43k	1 in 82	1 in 3,300
Remaining (unassigned)	~30k	1 in 100	1 in 430
European (Finnish)	~27k	1 in 440	≈ 1 in 13,000
Admixed American	~22k	1 in 120	1 in 2,500
African / African American	~21k	1 in 100	1 in 1,900
East Asian	~20k	1 in 220	≈ 1 in 5,000
Ashkenazi Jewish	~13k	1 in 240	none seen
Middle Eastern	~2,884	1 in 160	≈ 1 in 2,900

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 1 coding exons well covered in gnomAD exomes and genomes.? see exons ↓