PIK3R4

Chr 3

phosphoinositide-3-kinase regulatory subunit 4

Also known as: VPS15, p150

NCBI Gene: 30849 ENSG00000196455 UniProt: Q99570 OMIM: 602610

Predicted to enable protein serine/threonine kinase activity. Involved in several processes, including autophagosome maturation; early endosome to late endosome transport; and phosphatidylinositol 3-kinase/protein kinase B signal transduction. Located in late endosome. [provided by Alliance of Genome Resources, Jun 2026]

OMIM Research

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.39

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.39LOEUF

pLI 0.025

Z-score 5.43

OE 0.26 (0.17–0.39)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.48Z-score

OE missense 0.74 (0.69–0.80)

548 obs / 737.4 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.26 (0.17–0.39)

0≤0.351.4

Missense OE?0.74 (0.69–0.80)

0≤0.61.4

Synonymous OE?0.99

0≤1.21.6

LoF obs/exp: 16 / 62.3Missense obs/exp: 548 / 737.4Syn Z: 0.17

Background carrier burden — how many people carry a rare variant somewhere in PIK3R4?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 51

1,425 rare PASS variants

Rare truncating (LoF)

1 in 610

132 rare PASS variants

Rare synonymous (reference)

1 in 120

596 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PIK3R4. 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 79	1 in 820
South Asian	~43k	1 in 47	1 in 810
Remaining (unassigned)	~30k	1 in 44	1 in 340
European (Finnish)	~27k	1 in 140	1 in 450
Admixed American	~22k	1 in 59	1 in 480
African / African American	~21k	1 in 45	1 in 590
East Asian	~20k	1 in 40	1 in 670
Ashkenazi Jewish	~13k	1 in 210	1 in 790
Middle Eastern	~2,884	1 in 47	≈ 1 in 760

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): 15 of 19 coding exons well covered in gnomAD exomes; exons 5, 17, 18, 19 marginal. Genomes: all 19.? see exons ↓