PIK3CB

Chr 3

phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta

Also known as: P110BETA, PI3K, PI3KBETA, PIK3C1

NCBI Gene: 5291 ENSG00000051382 UniProt: P42338 OMIM: 602925

This gene encodes an isoform of the catalytic subunit of phosphoinositide 3-kinase (PI3K). These kinases are important in signaling pathways involving receptors on the outer membrane of eukaryotic cells and are named for their catalytic subunit. The encoded protein is the catalytic subunit for PI3Kbeta (PI3KB). PI3KB has been shown to be part of the activation pathway in neutrophils which have bound immune complexes at sites of injury or infection. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2011]

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

104

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.25

LOEUF· LoF intol.

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.25LOEUF

pLI 1.000

Z-score 6.27

OE 0.14 (0.09–0.25)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

3.09Z-score

OE missense 0.63 (0.58–0.69)

357 obs / 563.6 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.14 (0.09–0.25)

0≤0.351.4

Missense OE?0.63 (0.58–0.69)

0≤0.61.4

Synonymous OE?0.94

0≤1.21.6

LoF obs/exp: 9 / 62.4Missense obs/exp: 357 / 563.6Syn Z: 0.62

Background carrier burden — how many people carry a rare variant somewhere in PIK3CB?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 120

931 rare PASS variants

Rare truncating (LoF)

1 in 3,600

76 rare PASS variants

Rare synonymous (reference)

1 in 110

451 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PIK3CB. 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 110	1 in 3,700
South Asian	~43k	1 in 62	≈ 1 in 11,000
Remaining (unassigned)	~30k	1 in 110	1 in 3,200
European (Finnish)	~27k	1 in 280	1 in 4,400
Admixed American	~22k	1 in 120	≈ 1 in 7,300
African / African American	~21k	1 in 110	1 in 3,600
East Asian	~20k	1 in 110	1 in 1,500
Ashkenazi Jewish	~13k	1 in 520	≈ 1 in 6,500
Middle Eastern	~2,884	1 in 110	none seen

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): 13 of 22 coding exons well covered in gnomAD exomes; exons 4, 5, 6, 8, 10 and 4 more marginal. Genomes: all 22.? see exons ↓