PPIP5K1

Chr 15

diphosphoinositol pentakisphosphate kinase 1

Also known as: HISPPD2A, IP6K, IPS1, VIP1, hsVIP1

NCBI Gene: 9677 ENSG00000168781 UniProt: Q6PFW1

This gene encodes a dual functional inositol kinase. The encoded enzyme converts inositol hexakisphosphate to diphosphoinositol pentakisphosphate and diphosphoinositol pentakisphosphate to bis-diphosphoinositol tetrakisphosphate. This protein may be important for intracellular signaling pathways. Alternate splicing results in multiple transcript variants. A pseudogene of this gene is found on chromosome 15.[provided by RefSeq, Jun 2010]

Research

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.69

LOEUF

Multiple*

Mechanism· predicted

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?

0.69LOEUF

pLI 0.003

Z-score 2.63

OE 0.38 (0.22–0.69)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.57Z-score

OE missense 0.72 (0.64–0.82)

182 obs / 252.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.38 (0.22–0.69)

0≤0.351.4

Missense OE?0.72 (0.64–0.82)

0≤0.61.4

Synonymous OE?0.84

0≤1.21.6

LoF obs/exp: 8 / 21.0Missense obs/exp: 182 / 252.1Syn Z: 1.21

Background carrier burden — how many people carry a rare variant somewhere in PPIP5K1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 97

463 rare PASS variants

Rare truncating (LoF)

1 in 2,500

48 rare PASS variants

Rare synonymous (reference)

1 in 240

176 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PPIP5K1. 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 150	1 in 2,200
South Asian	~43k	1 in 150	1 in 5,100
Remaining (unassigned)	~30k	1 in 91	≈ 1 in 8,700
European (Finnish)	~27k	1 in 680	≈ 1 in 8,500
Admixed American	~22k	1 in 100	≈ 1 in 22,000
African / African American	~21k	1 in 70	1 in 2,700
East Asian	~20k	1 in 120	≈ 1 in 6,600
Ashkenazi Jewish	~13k	1 in 290	none seen
Middle Eastern	~2,884	1 in 100	≈ 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.

Exome coverage (gnomAD): 4 of 30 coding exons well covered in gnomAD exomes; exons 3, 4, 5, 6, 7 and 19 more poorly covered; exons 10, 29 marginal. Genomes: 3 of 30 (exons 3, 4, 5, 6, 7 and 22 more below).? see exons ↓