INPP4A

Chr 2

inositol polyphosphate-4-phosphatase type I A

Also known as: INPP4, NEDGQS, TVAS1

NCBI Gene: 3631 ENSG00000040933 UniProt: Q96PE3

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.

ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes an Mg++ independent enzyme that hydrolyzes the 4-position phosphate from the inositol ring of phosphatidylinositol 3,4-bisphosphate, inositol 1,3,4-trisphosphate, and inositol 3,4-bisphosphate. Multiple transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Aug 2008]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtNeurodevelopmental disorder with growth impairment, quadriparesis, and poor or absent speech

Clinical highlights

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.25

LOEUF· LoF intol.

LOF

Mechanism· G2P

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429