INTU

Chr 4AR

inturned planar cell polarity protein

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

NCBI Gene: 27152 ENSG00000164066 UniProt: Q9ULD6 OMIM: 610621

The INTU protein regulates cilia formation by controlling basal body positioning and apical actin cytoskeleton organization, functioning as a core component of the CPLANE complex essential for normal ciliogenesis. Biallelic mutations cause orofaciodigital syndrome XVII and short-rib thoracic dysplasia with polydactyly, both congenital ciliopathies affecting craniofacial structures, digits, and the thoracic cage with autosomal recessive inheritance. This gene shows extremely low tolerance to loss-of-function variants (pLI near 1), indicating strong evolutionary constraint.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

ARLOEUF 0.742 OMIM phenotypes

Clinical Summary— INTU

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Gene-Disease Validity (ClinGen)

INTU-related skeletal ciliopathy · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

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

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ClinVar Variants

6 unique Pathogenic / Likely Pathogenic· 284 VUS of 475 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.74LOEUF

pLI 0.000

Z-score 2.91

OE 0.52 (0.37–0.74)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.38Z-score

OE missense 0.95 (0.88–1.03)

463 obs / 486.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.52 (0.37–0.74)

0≤0.351.4

Missense OE?0.95 (0.88–1.03)

0≤0.61.4

Synonymous OE?0.89

0≤1.21.6

LoF obs/exp: 22 / 42.5Missense obs/exp: 463 / 486.8Syn Z: 1.17

ClinVar Variant Classifications

475 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic2

Likely Pathogenic4

VUS284

Likely Benign119

Benign43

Conflicting8

Pathogenic

Likely Pathogenic

284

VUS

119

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	2	0	0	0	2
Likely Pathogenic	3	1	0	0	4
VUS	19	253	10	2	284
Likely Benign	0	9	41	69	119
Benign	0	8	30	5	43
Conflicting	—				8
Total	24	271	81	76	460

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

View in ClinVar →

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