SIK3

Chr 11

SIK family kinase 3

Also known as: L19, QSK, SEMDK, SIK-3

NCBI Gene: 23387 ENSG00000160584 UniProt: Q9Y2K2

Enables ATP binding activity; magnesium ion binding activity; and protein serine/threonine kinase activity. Involved in positive regulation of TORC1 signaling; positive regulation of TORC2 signaling; and protein phosphorylation. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Jul 2025]

Research

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtSpondyloepimetaphyseal dysplasia, Krakow type

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

0.13

LOEUF· LoF intol.

LOF

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

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.13LOEUF

pLI 1.000

Z-score 6.85

OE 0.05 (0.02–0.13)

Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?

2.83Z-score

OE missense 0.71 (0.66–0.76)

524 obs / 740.8 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.05 (0.02–0.13)

0≤0.351.4

Missense OE?0.71 (0.66–0.76)

0≤0.61.4

Synonymous OE?1.03

0≤1.21.6

LoF obs/exp: 3 / 60.5Missense obs/exp: 524 / 740.8Syn Z: -0.44

Background carrier burden — how many people carry a rare variant somewhere in SIK3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 45

1,412 rare PASS variants

Rare truncating (LoF)

1 in 3,500

82 rare PASS variants

Rare synonymous (reference)

1 in 86

740 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SIK3. 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 49	1 in 4,800
South Asian	~43k	1 in 38	1 in 7,100
Remaining (unassigned)	~30k	1 in 41	1 in 660
European (Finnish)	~27k	1 in 160	1 in 2,900
Admixed American	~22k	1 in 44	1 in 2,600
African / African American	~21k	1 in 45	1 in 470
East Asian	~20k	1 in 35	1 in 1,500
Ashkenazi Jewish	~13k	1 in 210	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 53	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): 23 of 24 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: 23 of 24 (exon 1 below).? see exons ↓