INPP5A

Chr 10

inositol polyphosphate-5-phosphatase A

Also known as: 5PTASE

The protein is a membrane-associated phosphatase that hydrolyzes inositol 1,4,5-trisphosphate to inositol 1,4-bisphosphate, terminating calcium signaling cascades and playing a crucial role in cerebellar Purkinje cell survival. Mutations cause autosomal recessive congenital muscular dystrophy with intellectual disability, cerebellar hypoplasia, and cataracts, typically presenting in infancy with hypotonia and developmental delays. This gene is highly constrained against loss-of-function variants, indicating that complete loss of function is poorly tolerated.

OMIMResearchSummary from RefSeq, UniProt
LOEUF 0.31
Clinical SummaryINPP5A
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.98). One damaged copy is likely sufficient to cause disease.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.31LOEUF
pLI 0.981
Z-score 4.38
OE 0.13 (0.070.31)
Highly constrained

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

Missense Constraint
1.78Z-score
OE missense 0.69 (0.610.78)
176 obs / 256.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.13 (0.070.31)
00.351.4
Missense OE0.69 (0.610.78)
00.61.4
Synonymous OE1.10
01.21.6
LoF obs/exp: 4 / 29.8Missense obs/exp: 176 / 256.2Syn Z: -0.78

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

INPP5A · 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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