INPP5E

Chr 9AR

inositol polyphosphate-5-phosphatase E

Also known as: CORS1, CPD4, JBTS1, MORMS, PPI5PIV, pharbin

The encoded phosphatidylinositol phosphatase hydrolyzes specific phosphoinositides and plays an essential role in primary cilium function by controlling ciliary growth and PI3K signaling. Mutations cause Joubert syndrome with characteristic midbrain-hindbrain malformation and associated ciliopathies including retinal dystrophy, nephronophthisis, liver fibrosis, and polydactyly, as well as a syndrome involving intellectual disability, truncal obesity, retinal dystrophy, and micropenis. Inheritance is autosomal recessive.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.682 OMIM phenotypes
Clinical SummaryINPP5E
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Gene-Disease Validity (ClinGen)
Joubert syndrome 1 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

2 total gene-disease associations curated

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.68LOEUF
pLI 0.003
Z-score 2.68
OE 0.37 (0.220.68)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.51Z-score
OE missense 0.93 (0.851.01)
355 obs / 382.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.37 (0.220.68)
00.351.4
Missense OE0.93 (0.851.01)
00.61.4
Synonymous OE1.09
01.21.6
LoF obs/exp: 8 / 21.4Missense obs/exp: 355 / 382.9Syn Z: -0.99
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveINPP5E-related intellectual development disorder, truncal obesity, retinal dystrophy, and micropenisLOFAR
definitiveINPP5E-related Joubert syndromeLOFAR

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

DN
0.6356th %ile
GOF
0.6442th %ile
LOF
0.3941th %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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

INPP5E · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC