PRKCI

Chr 3

protein kinase C iota

Also known as: DXS1179E, PKCI, PKCiota, PKClambda, nPKC-iota

NCBI Gene: 5584 ENSG00000163558 UniProt: P41743

This gene encodes a member of the protein kinase C (PKC) family of serine/threonine protein kinases. The PKC family comprises at least eight members, which are differentially expressed and are involved in a wide variety of cellular processes. This protein kinase is calcium-independent and phospholipid-dependent. It is not activated by phorbolesters or diacylglycerol. This kinase can be recruited to vesicle tubular clusters (VTCs) by direct interaction with the small GTPase RAB2, where this kinase phosphorylates glyceraldehyde-3-phosphate dehydrogenase (GAPD/GAPDH) and plays a role in microtubule dynamics in the early secretory pathway. This kinase is found to be necessary for BCL-ABL-mediated resistance to drug-induced apoptosis and therefore protects leukemia cells against drug-induced apoptosis. There is a single exon pseudogene mapped on chromosome X. [provided by RefSeq, Jul 2008]

Research

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

0.44

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

Moderate LoF intolerance

LoF Constraint?

0.44LOEUF

pLI 0.068

Z-score 4.27

OE 0.26 (0.16–0.44)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.79Z-score

OE missense 0.57 (0.51–0.64)

190 obs / 333.4 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.26 (0.16–0.44)

0≤0.351.4

Missense OE?0.57 (0.51–0.64)

0≤0.61.4

Synonymous OE?1.09

0≤1.21.6

LoF obs/exp: 10 / 38.6Missense obs/exp: 190 / 333.4Syn Z: -0.72

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

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 180

500 rare PASS variants

Rare truncating (LoF)

1 in 2,600

74 rare PASS variants

Rare synonymous (reference)

1 in 210

238 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PRKCI. 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 240	1 in 2,300
South Asian	~43k	1 in 130	1 in 4,800
Remaining (unassigned)	~30k	1 in 140	1 in 890
European (Finnish)	~27k	1 in 860	1 in 3,800
Admixed American	~22k	1 in 140	1 in 4,400
African / African American	~21k	1 in 190	1 in 3,200
East Asian	~20k	1 in 140	≈ 1 in 4,900
Ashkenazi Jewish	~13k	1 in 440	≈ 1 in 6,400
Middle Eastern	~2,884	1 in 120	≈ 1 in 2,600

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): 16 of 18 coding exons well covered in gnomAD exomes; exons 15, 18 marginal. Genomes: 17 of 18 (exon 8 below).? see exons ↓