CFAP74

Chr 1AR

cilia and flagella associated protein 74

Also known as: C1orf222, CILD49, KIAA1751

The protein is involved in axoneme assembly and cilium movement as part of the central apparatus, playing an important role in sperm architecture and function. Mutations cause primary ciliary dyskinesia without situs inversus, presenting with respiratory symptoms, infertility, and ciliary dysfunction. This condition follows autosomal recessive inheritance.

Summary from RefSeq, OMIM, UniProt
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Primary Disease Associations & Inheritance

Ciliary dyskinesia, primary, 49, without situs inversusMIM #620197
AR
0
Active trials
4
Pubs (1 yr)
0
P/LP submissions
P/LP missense
0.79
LOEUF
DN
Mechanism· predicted
Clinical SummaryCFAP74
🧬
Gene-Disease Validity (ClinGen)
ciliary dyskinesia, primary, 49, without situs inversus · ARModerate

Moderate evidence — consider for supplementary testing

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
0.79LOEUF
pLI 0.000
Z-score 2.61
OE 0.56 (0.400.79)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.16Z-score
OE missense 0.86 (0.790.93)
436 obs / 509.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.56 (0.400.79)
00.351.4
Missense OE0.86 (0.790.93)
00.61.4
Synonymous OE0.88
01.21.6
LoF obs/exp: 23 / 41.1Missense obs/exp: 436 / 509.4Syn Z: 1.41
DN
0.6260th %ile
GOF
0.5857th %ile
LOF
0.3648th %ile

The highest-scoring mechanism for this gene is dominant-negative.

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

CFAP74 · 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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Clinical Literature
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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC