CFAP46

Chr 10

cilia and flagella associated protein 46

Also known as: C10orf123, C10orf124, C10orf92, C10orf93, TTC40, bA288G11.4, bA288G11.5, bB137A17.2

NCBI Gene: 54777ENSG00000171811UniProt: Q8IYW2

The CFAP46 protein is part of the central apparatus of the cilium axoneme and plays a role in cilium movement. Mutations cause primary ciliary dyskinesia with autosomal recessive inheritance. This gene shows moderate constraint against loss-of-function variants, affecting the respiratory system and ciliary function.

Summary from RefSeq, UniProt
Research Assistant →
1
Active trials
2
Pubs (1 yr)
98
P/LP submissions
0%
P/LP missense
0.69
LOEUF
—
Mechanism
Clinical Summary— CFAP46
🧬
Gene-Disease Validity (ClinGen)
primary ciliary dyskinesia · ARLimited

Limited evidence — not for standalone diagnostic reporting

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
98 unique Pathogenic / Likely Pathogenic· 187 VUS of 362 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.69LOEUF
pLI 0.000
Z-score 4.62
OE 0.57 (0.47–0.69)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.91Z-score
OE missense 0.86 (0.82–0.90)
1333 obs / 1544.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.57 (0.47–0.69)
0≤0.351.4
Missense OE0.86 (0.82–0.90)
0≤0.61.4
Synonymous OE0.98
0≤1.21.6
LoF obs/exp: 76 / 133.7Missense obs/exp: 1333 / 1544.5Syn Z: 0.51

ClinVar Variant Classifications

362 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic92
Likely Pathogenic6
VUS187
Likely Benign46
Benign3
Conflicting1
92
Pathogenic
6
Likely Pathogenic
187
VUS
46
Likely Benign
3
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
92
0
92
Likely Pathogenic
0
0
6
0
6
VUS
1
170
16
0
187
Likely Benign
0
26
5
15
46
Benign
0
0
3
0
3
Conflicting
—1
Total119612215335

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

CFAP46 · protein map & ClinVar variants

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

Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients