INPPL1

Chr 11AR

inositol polyphosphate phosphatase like 1

Also known as: OPSMD, SHIP2

The protein is a phosphatidylinositol phosphatase that hydrolyzes PtdIns(3,4,5)P3 to negatively regulate PI3K signaling pathways and plays essential roles in actin cytoskeleton remodeling, cell adhesion, mitotic spindle orientation, and endochondral ossification. Biallelic mutations cause opsismodysplasia, a severe skeletal dysplasia with autosomal recessive inheritance. The gene is highly constrained against loss-of-function variation (LOEUF 0.423), indicating strong selective pressure for normal gene function.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
GOFmechanismARLOEUF 0.421 OMIM phenotype
Clinical SummaryINPPL1
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.28) despite low pLI — interpret in context.
📖
GeneReview available — INPPL1
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.42LOEUF
pLI 0.002
Z-score 5.17
OE 0.28 (0.190.42)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.60Z-score
OE missense 0.83 (0.780.89)
620 obs / 742.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.28 (0.190.42)
00.351.4
Missense OE0.83 (0.780.89)
00.61.4
Synonymous OE1.05
01.21.6
LoF obs/exp: 17 / 60.3Missense obs/exp: 620 / 742.9Syn Z: -0.65
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveINPPL1-related opsismodysplasiaOTHERAR

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

DN
0.5674th %ile
GOF
0.6541th %ile
LOF
0.3841th %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

INPPL1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC