INPP5B

Chr 1

inositol polyphosphate-5-phosphatase B

Also known as: 5PTase

NCBI Gene: 3633ENSG00000204084UniProt: P32019OMIM: 147264

This gene encodes an inositol polyphosphate-5-phosphatase that regulates cellular calcium signaling by hydrolyzing phosphatidylinositol 4,5-bisphosphate and inositol 1,4,5-trisphosphate, with localization to cytosol, mitochondria, and membrane associations. Mutations cause autosomal recessive muscular dystrophy-dystroglycanopathy with intellectual disability, typically involving both muscle and brain systems. The gene is extremely intolerant to loss-of-function variants, indicating that complete loss of protein function is likely incompatible with normal development.

GeneReviewsOMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 0.83
Clinical Summary— INPP5B
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
2 unique Pathogenic / Likely Pathogenic· 126 VUS of 200 total submissions
Explore recent and relevant literature in Research Assistant →
📖
GeneReview available — INPP5B
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.83LOEUF
pLI 0.000
Z-score 2.54
OE 0.62 (0.47–0.83)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.11Z-score
OE missense 0.86 (0.80–0.93)
436 obs / 506.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.62 (0.47–0.83)
0≤0.351.4
Missense OE0.86 (0.80–0.93)
0≤0.61.4
Synonymous OE0.89
0≤1.21.6
LoF obs/exp: 33 / 52.9Missense obs/exp: 436 / 506.6Syn Z: 1.22
DN
0.6551th %ile
GOF
0.5758th %ile
LOF
0.2873th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

200 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1
Likely Pathogenic1
VUS126
Likely Benign11
Benign22
1
Pathogenic
1
Likely Pathogenic
126
VUS
11
Likely Benign
22
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
1
0
1
Likely Pathogenic
0
0
1
0
1
VUS
1
124
1
0
126
Likely Benign
1
5
0
5
11
Benign
0
2
17
3
22
Total2131208161

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

View in ClinVar →

Protein Context — Lollipop Plot

INPP5B · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 4 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
OCRL-mutated fibroblasts from patients with Dent-2 disease exhibit INPP5B-independent phenotypic variability relatively to Lowe syndrome cells.
Montjean R et al.·Hum Mol Genet
2015Cohort
Gene expression and copy number profiling of follicular lymphoma biopsies from patients treated with first-line rituximab without chemotherapy.
Leich E et al.·Leuk Lymphoma
2023Cohort
Identifying the Prognostic Risk Factors of Synaptojanin 2 and Its Underlying Perturbations Pathways in Hepatocellular Carcinoma.
Zhang R et al.·Bioengineered
2021
Coronary artery disease-associated variants regulate vascular smooth muscle cell gene expression.
Barbera N et al.·Nat Cardiovasc Res
2025
Modeling the neuropsychiatric manifestations of Lowe syndrome using induced pluripotent stem cells: defective F-actin polymerization and WAVE-1 expression in neuronal cells.
Barnes J et al.·Mol Autism
2018Functional
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients