CFAP95

Chr 9

cilia and flagella associated protein 95

Also known as: C9orf135

The CFAP95 protein is a microtubule inner protein component of dynein-decorated doublet microtubules in cilia axoneme that is required for motile cilia beating. Mutations cause primary ciliary dyskinesia, a disorder affecting the respiratory system, fertility, and organ positioning due to defective cilia motility. Primary ciliary dyskinesia follows autosomal recessive inheritance and typically presents in infancy or childhood with chronic respiratory symptoms.

ResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 1.46
Clinical SummaryCFAP95
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.46LOEUF
pLI 0.000
Z-score 0.32
OE 0.90 (0.581.46)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.30Z-score
OE missense 1.07 (0.931.24)
137 obs / 127.5 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.90 (0.581.46)
00.351.4
Missense OE1.07 (0.931.24)
00.61.4
Synonymous OE0.99
01.21.6
LoF obs/exp: 12 / 13.3Missense obs/exp: 137 / 127.5Syn Z: 0.03
DN
0.6649th %ile
GOF
0.7125th %ile
LOF
0.3549th %ile

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

GOFprediction above median
DNprediction 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

CFAP95 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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