INTU

Chr 4AR

inturned planar cell polarity protein

Also known as: CPLANE4, INT, OFD17, PDZD6, PDZK6, SRTD20

NCBI Gene: 27152ENSG00000164066UniProt: Q9ULD6

Predicted to enable phosphatidylinositol binding activity. Involved in embryonic digit morphogenesis; roof of mouth development; and tongue morphogenesis. Located in several cellular components, including ciliary basal body; cytosol; and motile cilium. Implicated in asphyxiating thoracic dystrophy and orofaciodigital syndrome XVII. [provided by Alliance of Genome Resources, Apr 2025]

Primary Disease Associations & Inheritance

?Orofaciodigital syndrome XVIIMIM #617926
AR
?Short-rib thoracic dysplasia 20 with polydactylyMIM #617925
AR
490
ClinVar variants
33
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— INTU
🧬
Gene-Disease Validity (ClinGen)
INTU-related skeletal ciliopathy · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
33 Pathogenic / Likely Pathogenic· 288 VUS of 490 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.74LOEUF
pLI 0.000
Z-score 2.91
OE 0.52 (0.37–0.74)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.38Z-score
OE missense 0.95 (0.88–1.03)
463 obs / 486.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.52 (0.37–0.74)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.95 (0.88–1.03)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.89
0≤1.21.6
LoF obs/exp: 22 / 42.5Missense obs/exp: 463 / 486.8Syn Z: 1.17

ClinVar Variant Classifications

490 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic28
Likely Pathogenic5
VUS288
Likely Benign119
Benign43
Conflicting7
28
Pathogenic
5
Likely Pathogenic
288
VUS
119
Likely Benign
43
Benign
7
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
0
26
0
28
Likely Pathogenic
1
1
3
0
5
VUS
12
248
26
2
288
Likely Benign
0
9
41
69
119
Benign
0
8
30
5
43
Conflicting
—7
Total1526612676490

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

View in ClinVar →

Protein Context — Lollipop Plot

INTU · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

?Orofaciodigital syndrome XVII

MIM #617926

Molecular basis of disorder known

Autosomal recessive

?Short-rib thoracic dysplasia 20 with polydactyly

MIM #617925

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
INTU-related oral-facial-digital syndrome type VI: A confirmatory report.
Bruel AL et al.·Clin Genet
2018Case report
INTU-related oral-facial-digital syndrome XVII: Clinical spectrum of a rare disorder.
Yakar O et al.·Am J Med Genet A
2022Case report
Clinical and Hemodynamic Outcomes of Rapid-Deployment Aortic Bioprostheses.
D'Onofrio A et al.·Semin Thorac Cardiovasc Surg
2022
Molecular investigation in individuals with orofacial clefts and microphthalmia-anophthalmia-coloboma spectrum.
Atique Tacla M et al.·Eur J Hum Genet
2024
Bi-allelic INTU variants define a ciliopathy disorder characterized by orofacial, digital, and cardiac anomalies.
Rushforth R et al.·HGG Adv
2026Case report
Early and Mid-Term Results of Rapid Deployment Valves: The Intuity Italian Registry (INTU-ITA).
D'Onofrio A et al.·Ann Thorac Surg
2018
Gene and pathway based burden analyses in familial lymphoid cancer cases: Rare variants in immune pathway genes.
Ralli S et al.·PLoS One
2023Cohort
Fifteen years of research on oral-facial-digital syndromes: from 1 to 16 causal genes.
Bruel AL et al.·J Med Genet
2017Review
Minimally Invasive vs Conventional Aortic Valve Replacement With Rapid-Deployment Bioprostheses.
D'Onofrio A et al.·Ann Thorac Surg
2021
The CPLANE protein Fuzzy regulates ciliogenesis by suppressing actin polymerization at the base of the primary cilium via p190A RhoGAP.
Sharma R et al.·Development
2024
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools