CFAP74

Chr 1AR

cilia and flagella associated protein 74

Also known as: C1orf222, CILD49, KIAA1751

NCBI Gene: 85452 ENSG00000142609 UniProt: Q9C0B2 OMIM: 620187

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.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

Predicted to be involved in axoneme assembly. Located in cytoplasm; nucleus; and sperm flagellum. Implicated in primary ciliary dyskinesia. [provided by Alliance of Genome Resources, Jul 2025]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Ciliary dyskinesia, primary, 49, without situs inversusMIM #620197

Clinical highlights

Gene–disease validity (ClinGen)

Moderate · ciliary dyskinesia, primary, 49, without situs inversus · AR · ClinGen 2025

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.79

LOEUF

Mechanism· predicted

📖

GeneReview available — CFAP74

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.79LOEUF

pLI 0.000

Z-score 2.61

OE 0.56 (0.40–0.79)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.16Z-score

OE missense 0.86 (0.79–0.93)

436 obs / 509.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.56 (0.40–0.79)

0≤0.351.4

Missense OE?0.86 (0.79–0.93)

0≤0.61.4

Synonymous OE?0.88

0≤1.21.6

LoF obs/exp: 23 / 41.1Missense obs/exp: 436 / 509.4Syn Z: 1.41

Background carrier burden — how many people carry a rare variant somewhere in CFAP74?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 18

2,343 rare PASS variants

Rare truncating (LoF)

1 in 290

354 rare PASS variants

Rare synonymous (reference)

1 in 35

1,022 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CFAP74. 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 24	1 in 390
South Asian	~43k	1 in 15	1 in 140
Remaining (unassigned)	~30k	1 in 14	1 in 240
European (Finnish)	~27k	1 in 59	1 in 910
Admixed American	~22k	1 in 19	1 in 170
African / African American	~21k	1 in 19	1 in 230
East Asian	~20k	1 in 16	1 in 260
Ashkenazi Jewish	~13k	1 in 60	1 in 960
Middle Eastern	~2,884	1 in 18	1 in 260

Each group is summed over the variants that are rare in that group. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 36 of 38 coding exons well covered in gnomAD exomes; exons 3, 16 marginal. Genomes: 36 of 38 (exons 3, 34 below).? see exons ↓