CCDC89

Chr 11

coiled-coil domain containing 89

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.

OMIMResearchSummary from RefSeq
MultiplemechanismLOEUF 1.18
Clinical SummaryCCDC89
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
Some data sources returned errors (1)

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.18LOEUF
pLI 0.000
Z-score 1.12
OE 0.65 (0.381.18)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.06Z-score
OE missense 0.99 (0.881.11)
207 obs / 209.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.65 (0.381.18)
00.351.4
Missense OE0.99 (0.881.11)
00.61.4
Synonymous OE1.21
01.21.6
LoF obs/exp: 8 / 12.2Missense obs/exp: 207 / 209.3Syn Z: -1.55

This gene — mechanism propensity

DN
0.77top 25%
GOF
0.72top 25%
LOF
0.2092th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

CCDC89 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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