INPP5B

Chr 1

inositol polyphosphate-5-phosphatase B

Also known as: 5PTase

NCBI Gene: 3633ENSG00000204084UniProt: P32019

This gene encodes a member of a family of inositol polyphosphate-5-phosphatases. These enzymes function in the regulation of calcium signaling by inactivating inositol phosphates. The encoded protein is localized to the cytosol and mitochondria, and associates with membranes through an isoprenyl modification near the C-terminus. Alternatively spliced transcript variants of this gene have been described. [provided by RefSeq, Jul 2014]

195
ClinVar variants
6
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— INPP5B
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
6 Pathogenic / Likely Pathogenic· 127 VUS of 195 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.83LOEUF
pLI 0.000
Z-score 2.54
OE 0.62 (0.47–0.83)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.11Z-score
OE missense 0.86 (0.80–0.93)
436 obs / 506.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.62 (0.47–0.83)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.86 (0.80–0.93)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.89
0≤1.21.6
LoF obs/exp: 33 / 52.9Missense obs/exp: 436 / 506.6Syn Z: 1.22

ClinVar Variant Classifications

195 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic4
Likely Pathogenic2
VUS127
Likely Benign12
Benign50
4
Pathogenic
2
Likely Pathogenic
127
VUS
12
Likely Benign
50
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
4
0
4
Likely Pathogenic
0
1
1
0
2
VUS
0
124
3
0
127
Likely Benign
0
5
2
5
12
Benign
0
7
40
3
50
Total0137508195

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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
📖
GeneReview available — INPP5B
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Species-specific difference in expression and splice-site choice in Inpp5b, an inositol polyphosphate 5-phosphatase paralogous to the enzyme deficient in Lowe Syndrome.
Bothwell SP et al.·Mamm Genome
2010
Multi-ancestry meta-analysis of genome-wide association studies discovers 67 new loci associated with chronic back pain.
Stanaway IB et al.·Nat Commun
2025Meta-analysis
Functional overlap between murine Inpp5b and Ocrl1 may explain why deficiency of the murine ortholog for OCRL1 does not cause Lowe syndrome in mice.
Jänne PA et al.·J Clin Invest
1998Functional
Identification of inhibitors of inositol 5-phosphatases through multiple screening strategies.
Pirruccello M et al.·ACS Chem Biol
2014
Coronary artery disease-associated variants regulate vascular smooth muscle cell gene expression.
Barbera N et al.·Nat Cardiovasc Res
2025
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
Evolutionary analysis of endogenous intronic retroviruses in primates reveals an enrichment in transcription binding sites associated with key regulatory processes.
Calero-Layana M et al.·PeerJ
2022
Lowe syndrome patient fibroblasts display Ocrl1-specific cell migration defects that cannot be rescued by the homologous Inpp5b phosphatase.
Coon BG et al.·Hum Mol Genet
2009
Identifying the Prognostic Risk Factors of Synaptojanin 2 and Its Underlying Perturbations Pathways in Hepatocellular Carcinoma.
Zhang R et al.·Bioengineered
2021
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools