INPP4A

Chr 2AR

inositol polyphosphate-4-phosphatase type I A

Also known as: INPP4, NEDGQS, TVAS1

The protein is an inositol phosphatase that hydrolyzes phosphatidylinositol 3,4-bisphosphate and inositol phosphates, regulating PI3K-AKT signaling and protecting neurons from excitotoxic death. Biallelic mutations cause autosomal recessive neurodevelopmental disorder with growth impairment, quadriparesis, and poor or absent speech. The gene is highly constrained against loss-of-function variants (pLI 1.0, LOEUF 0.25), indicating intolerance to functional disruption.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.251 OMIM phenotype
Clinical SummaryINPP4A
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint
0.25LOEUF
pLI 1.000
Z-score 5.84
OE 0.13 (0.070.25)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
3.35Z-score
OE missense 0.61 (0.560.67)
357 obs / 584.7 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.13 (0.070.25)
00.351.4
Missense OE0.61 (0.560.67)
00.61.4
Synonymous OE0.94
01.21.6
LoF obs/exp: 7 / 52.8Missense obs/exp: 357 / 584.7Syn Z: 0.69
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
moderateINPP4A-related neurodevelopmental disorder with spasticity, epilepsy and cerebellar hypoplasiaLOFAR

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

DN
0.4190th %ile
GOF
0.4579th %ile
LOF
0.70top 10%

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. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

INPP4A · 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.

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Clinical Literature
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