INPP5K

Chr 17

inositol polyphosphate-5-phosphatase K

Also known as: MDCCAID, PPS, SKIP

NCBI Gene: 51763 ENSG00000132376 UniProt: Q9BT40

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.

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]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtMuscular dystrophy, congenital, with cataracts and impaired intellectual development

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.79

LOEUF

—

Mechanism

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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

Background carrier burden — how many people carry a rare variant somewhere in INPP5K?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 74

591 rare PASS variants

Rare truncating (LoF)

1 in 1,700

100 rare PASS variants

Rare synonymous (reference)

1 in 110

266 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for INPP5K. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 100	1 in 1,500
South Asian	~43k	1 in 150	1 in 4,200
Remaining (unassigned)	~30k	1 in 77	1 in 2,300
European (Finnish)	~27k	1 in 260	1 in 2,700
Admixed American	~22k	1 in 74	1 in 1,200
African / African American	~21k	1 in 79	1 in 1,700
East Asian	~20k	1 in 85	≈ 1 in 5,000
Ashkenazi Jewish	~13k	1 in 330	none seen
Middle Eastern	~2,884	1 in 80	≈ 1 in 2,900

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.