INPP5A

Chr 10

inositol polyphosphate-5-phosphatase A

Also known as: 5PTASE

NCBI Gene: 3632 ENSG00000068383 UniProt: Q14642 OMIM: 600106

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.

OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene is a membrane-associated type I 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. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

LOEUF 0.31

Clinical Summary— INPP5A

⚡

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.

📋

ClinVar Variants

51 VUS of 78 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.31LOEUF

pLI 0.981

Z-score 4.38

OE 0.13 (0.07–0.31)

Highly constrained

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

Missense Constraint?

1.78Z-score

OE missense 0.69 (0.61–0.78)

176 obs / 256.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.13 (0.07–0.31)

0≤0.351.4

Missense OE?0.69 (0.61–0.78)

0≤0.61.4

Synonymous OE?1.10

0≤1.21.6

LoF obs/exp: 4 / 29.8Missense obs/exp: 176 / 256.2Syn Z: -0.78

ClinVar Variant Classifications

78 submitted variants in ClinVar

ClinVar

Classification Summary

VUS51

Likely Benign2

Benign2

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	51	0	51
Likely Benign	0	2	2
Benign	0	2	2
Total	51	4	55

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

98 pathogenic / likely-pathogenic (of 118) ClinVar copy-number / structural variants overlap INPP5A — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →