CLK3

Chr 15

CDC like kinase 3

Also known as: PHCLK3, PHCLK3/152

NCBI Gene: 1198 ENSG00000179335 UniProt: P49761 OMIM: 602990

This gene encodes a protein belonging to the serine/threonine type protein kinase family. This protein is a nuclear dual-specificity kinase that regulates the intranuclear distribution of the serine/arginine-rich (SR) family of splicing factors. Two transcript variants encoding different isoforms have been found for this gene. Related pseudogenes are located on chromosomes 1 and 9. [provided by RefSeq, Jul 2008]

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

0.43

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.43LOEUF

pLI 0.230

Z-score 4.09

OE 0.24 (0.14–0.43)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.03Z-score

OE missense 0.69 (0.61–0.77)

228 obs / 332.3 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.24 (0.14–0.43)

0≤0.351.4

Missense OE?0.69 (0.61–0.77)

0≤0.61.4

Synonymous OE?0.99

0≤1.21.6

LoF obs/exp: 8 / 33.6Missense obs/exp: 228 / 332.3Syn Z: 0.13

Background carrier burden — how many people carry a rare variant somewhere in CLK3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 140

672 rare PASS variants

Rare truncating (LoF)

1 in 440

83 rare PASS variants

Rare synonymous (reference)

1 in 120

283 rare PASS variants

Rare missense and truncating variants are carried at similar rates in CLK3; this gene does not show strong loss-of-function constraint by this measure. 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 160	1 in 1,800
South Asian	~43k	1 in 97	1 in 560
Remaining (unassigned)	~30k	1 in 120	1 in 790
European (Finnish)	~27k	1 in 250	≈ 1 in 8,800
Admixed American	~22k	1 in 130	1 in 1,600
African / African American	~21k	1 in 120	1 in 1,300
East Asian	~20k	1 in 140	1 in 3,900
Ashkenazi Jewish	~13k	1 in 300	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 150	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): 11 of 12 coding exons well covered in gnomAD exomes; exon 10 marginal. Genomes: all 12.? see exons ↓