INPP5K

Chr 17AR

inositol polyphosphate-5-phosphatase K

Also known as: MDCCAID, PPS, SKIP

NCBI Gene: 51763ENSG00000132376UniProt: Q9BT40

This gene encodes a protein with 5-phosphatase activity toward polyphosphate inositol. The protein localizes to the cytosol in regions lacking actin stress fibers. It is thought that this protein may negatively regulate the actin cytoskeleton. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Oct 2008]

Primary Disease Associations & Inheritance

Muscular dystrophy, congenital, with cataracts and intellectual disabilityMIM #617404
AR
271
ClinVar variants
117
Pathogenic / LP
0.00
pLI score
1
Active trials
Clinical Summary— INPP5K
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
117 Pathogenic / Likely Pathogenic· 97 VUS of 271 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

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.
0.79LOEUF
pLI 0.000
Z-score 2.34
OE 0.48 (0.30–0.79)
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.
0.60Z-score
OE missense 0.90 (0.81–1.00)
248 obs / 276.1 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.0.48 (0.30–0.79)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.90 (0.81–1.00)
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.0.95
0≤1.21.6
LoF obs/exp: 11 / 23.1Missense obs/exp: 248 / 276.1Syn Z: 0.47

ClinVar Variant Classifications

271 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic95
Likely Pathogenic22
VUS97
Likely Benign36
Benign16
Conflicting5
95
Pathogenic
22
Likely Pathogenic
97
VUS
36
Likely Benign
16
Benign
5
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
5
88
0
95
Likely Pathogenic
1
2
19
0
22
VUS
0
75
20
2
97
Likely Benign
0
9
6
21
36
Benign
0
5
3
8
16
Conflicting
—5
Total39613631271

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

View in ClinVar →

Protein Context — Lollipop Plot

INPP5K · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

INPP5K-related muscular dystrophy, congenital, with cataracts, and intellectual disability

strong
ARUndeterminedAltered Gene Product Structure
Dev. DisordersEye
G2P ↗
missense variantinframe deletioninframe insertion

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Muscular dystrophy, congenital, with cataracts and intellectual disability

MIM #617404

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
INPP5K and SIL1 associated pathologies with overlapping clinical phenotypes converge through dysregulation of PHGDH.
Hathazi D et al.·Brain
2021
The Prediction and Prognostic Significance of INPP5K Expression in Patients with Liver Cancer.
Wang R et al.·Biomed Res Int
2020Cohort
The inositol 5-phosphatase INPP5K participates in the fine control of ER organization.
Dong R et al.·J Cell Biol
2018
INPP5K variant causes autosomal recessive congenital cataract in a Pakistani family.
Yousaf S et al.·Clin Genet
2018Case report
Mutations in INPP5K Cause a Form of Congenital Muscular Dystrophy Overlapping Marinesco-Sjögren Syndrome and Dystroglycanopathy.
Osborn DPS et al.·Am J Hum Genet
2017Case report
Pearls & Oy-sters: Use of Muscle Ultrasound as a Clinical Tool in INPP5K-Related Muscular Dystrophy: A Case Report.
Deng S et al.·Neurology
2024Case report
Genetic Disorders in Prenatal Onset Syndromic Short Stature Identified by Exome Sequencing.
Homma TK et al.·J Pediatr
2019
Genome-wide variant by serum urate interaction in Parkinson's disease.
Nazeri A et al.·Ann Neurol
2015
A novel five-gene metabolism-related risk signature for predicting prognosis and immune infiltration in endometrial cancer: A TCGA data mining.
Huang H et al.·Comput Biol Med
2023
Parkinson's Disease Risk Variant rs1109303 Regulates the Expression of INPP5K and CRK in Human Brain.
Liu G et al.·Neurosci Bull
2019
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
Muscular Dystrophy

Clinical Trial Readiness for the Dystroglycanopathies

RECRUITING
NCT00313677Katherine MathewsStarted 2006-04

External Resources

Links to major genomics databases and tools