INPP5K

Chr 17AR

inositol polyphosphate-5-phosphatase K

Also known as: MDCCAID, PPS, SKIP

NCBI Gene: 51763ENSG00000132376UniProt: Q9BT40OMIM: 607875

INPP5K encodes an inositol 5-phosphatase that regulates phosphoinositide signaling and negatively controls actin cytoskeleton assembly, with particular importance for insulin signaling in skeletal muscle. Biallelic mutations cause autosomal recessive congenital muscular dystrophy with cataracts and intellectual disability. This multisystem disorder affects muscle, ocular, and cognitive development from birth.

OMIMResearchSummary from RefSeq, OMIM, UniProt
ARLOEUF 0.791 OMIM phenotype
Clinical Summary— INPP5K
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
117 unique Pathogenic / Likely Pathogenic· 98 VUS of 295 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.79LOEUF
pLI 0.000
Z-score 2.34
OE 0.48 (0.30–0.79)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.60Z-score
OE missense 0.90 (0.81–1.00)
248 obs / 276.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.48 (0.30–0.79)
0≤0.351.4
Missense OE0.90 (0.81–1.00)
0≤0.61.4
Synonymous OE0.95
0≤1.21.6
LoF obs/exp: 11 / 23.1Missense obs/exp: 248 / 276.1Syn Z: 0.47

ClinVar Variant Classifications

295 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic95
Likely Pathogenic22
VUS98
Likely Benign36
Benign16
Conflicting5
95
Pathogenic
22
Likely Pathogenic
98
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
2
2
18
0
22
VUS
1
76
19
2
98
Likely Benign
0
9
6
21
36
Benign
0
5
3
8
16
Conflicting
—5
Total59713431272

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.

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
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