CLUAP1

Chr 16

intraflagellar transport 38

Also known as: CFAP22, CLUAP1, FAP22

NCBI Gene: 23059 ENSG00000103351 UniProt: Q96AJ1 OMIM: 616787

The protein is required for cilia biogenesis and functions within the intraflagellar transport complex B (IFT-B) as a key regulator of hedgehog signaling. Mutations cause autosomal recessive ciliopathies including Joubert syndrome and nephronophthisis, which are multisystem disorders affecting the brain, kidneys, and other organs. The gene shows low constraint to loss-of-function variants (pLI = 0.0004), consistent with its recessive inheritance pattern.

OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene contains a single coiled-coil region. Alternative splicing results in multiple transcript variants and protein isoforms. [provided by RefSeq, Jul 2012]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.68

Clinical Summary— CLUAP1

⚡

Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

📋

ClinVar Variants

1 unique Pathogenic / Likely Pathogenic· 285 VUS of 469 total submissions

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?

0.68LOEUF

pLI 0.000

Z-score 2.76

OE 0.40 (0.25–0.68)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.04Z-score

OE missense 0.99 (0.89–1.11)

229 obs / 230.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.40 (0.25–0.68)

0≤0.351.4

Missense OE?0.99 (0.89–1.11)

0≤0.61.4

Synonymous OE?1.05

0≤1.21.6

LoF obs/exp: 10 / 24.8Missense obs/exp: 229 / 230.9Syn Z: -0.38

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

strongIFT38-related Leber congenital amaurosisOTHERAR

strongIFT38-related ciliopathy syndromeLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.83top 10%

GOF

0.5954th %ile

LOF

0.2581th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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

ClinVar Variant Classifications

469 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

VUS285

Likely Benign153

Benign18

Conflicting3

Pathogenic

285

VUS

153

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	1	0	0	1
Likely Pathogenic	0	0	0	0	0
VUS	22	237	23	3	285
Likely Benign	0	3	75	75	153
Benign	0	5	8	5	18
Conflicting	—				3
Total	22	246	106	83	460

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

View in ClinVar →

34 pathogenic / likely-pathogenic (of 52) ClinVar copy-number / structural variants overlap CLUAP1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →