INPP5K

Chr 17AR

inositol polyphosphate-5-phosphatase K

Also known as: MDCCAID, PPS, SKIP

NCBI Gene: 51763 ENSG00000132376 UniProt: Q9BT40 OMIM: 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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

ARLOEUF 0.791 OMIM phenotype

Clinical Summary— INPP5K

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

11 unique Pathogenic / Likely Pathogenic· 84 VUS of 174 total submissions

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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 OE?0.48 (0.30–0.79)

0≤0.351.4

Missense OE?0.90 (0.81–1.00)

0≤0.61.4

Synonymous OE?0.95

0≤1.21.6

LoF obs/exp: 11 / 23.1Missense obs/exp: 248 / 276.1Syn Z: 0.47

ClinVar Variant Classifications

174 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic7

Likely Pathogenic4

VUS84

Likely Benign36

Benign16

Conflicting5

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	2	5	0	0	7
Likely Pathogenic	2	2	0	0	4
VUS	1	78	3	2	84
Likely Benign	0	9	6	21	36
Benign	0	5	3	8	16
Conflicting	—				5
Total	5	99	12	31	152

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

View in ClinVar →

107 pathogenic / likely-pathogenic (of 124) ClinVar copy-number / structural variants overlap INPP5K — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →