INPP5E

Chr 9

inositol polyphosphate-5-phosphatase E

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

NCBI Gene: 56623ENSG00000148384UniProt: Q9NRR6

The protein encoded by this gene is an inositol 1,4,5-trisphosphate (InsP3) 5-phosphatase. InsP3 5-phosphatases hydrolyze Ins(1,4,5)P3, which mobilizes intracellular calcium and acts as a second messenger mediating cell responses to various stimulation. Studies of the mouse counterpart suggest that this protein may hydrolyze phosphatidylinositol 3,4,5-trisphosphate and phosphatidylinositol 3,5-bisphosphate on the cytoplasmic Golgi membrane and thereby regulate Golgi-vesicular trafficking. Mutations in this gene cause Joubert syndrome; a clinically and genetically heterogenous group of disorders characterized by midbrain-hindbrain malformation and various associated ciliopathies that include retinal dystrophy, nephronophthisis, liver fibrosis and polydactyly. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2016]

GeneReviewsResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtJoubert syndrome 1
UniProtImpaired intellectual development, truncal obesity, retinal dystrophy, and micropenis

Clinical highlights

Gene-disease validity (ClinGen)
Joubert syndrome 1 · ARDefinitivesufficient evidence for diagnostic panels2 gene-disease associations curated in total
Interpreting a novel variant
Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.
1
Active trials
20
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.68
LOEUF
LOF
Mechanism· G2P
📖
GeneReview available — INPP5E
Authoritative clinical overview · Recommended first read
Open GeneReview ↗
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?
0.68LOEUF
pLI 0.003
Z-score 2.68
OE 0.37 (0.22–0.68)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
0.51Z-score
OE missense 0.93 (0.85–1.01)
355 obs / 382.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.37 (0.22–0.68)
0≤0.351.4
Missense OE?0.93 (0.85–1.01)
0≤0.61.4
Synonymous OE?1.09
0≤1.21.6
LoF obs/exp: 8 / 21.4Missense obs/exp: 355 / 382.9Syn Z: -0.99

ClinVar Variant Classifications

0 submitted variants in ClinVar

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.

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