SIK2

Chr 11

salt inducible kinase 2

Also known as: LOH11CR1I, QIK, SIK-2, SNF1LK2

NCBI Gene: 23235 ENSG00000170145 UniProt: Q9H0K1

Enables ATP binding activity; magnesium ion binding activity; and protein kinase activity. Involved in intracellular signal transduction; positive regulation of ERAD pathway; and protein autophosphorylation. Is active in endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Jun 2026]

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

0.28

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?

0.28LOEUF

pLI 0.997

Z-score 5.45

OE 0.15 (0.08–0.28)

Highly constrained

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

Missense Constraint?

2.55Z-score

OE missense 0.69 (0.63–0.75)

360 obs / 524.4 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.15 (0.08–0.28)

0≤0.351.4

Missense OE?0.69 (0.63–0.75)

0≤0.61.4

Synonymous OE?0.90

0≤1.21.6

LoF obs/exp: 7 / 47.5Missense obs/exp: 360 / 524.4Syn Z: 1.16

Background carrier burden — how many people carry a rare variant somewhere in SIK2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 83

944 rare PASS variants

Rare truncating (LoF)

1 in 4,300

69 rare PASS variants

Rare synonymous (reference)

1 in 85

445 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SIK2. 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 100	1 in 3,400
South Asian	~43k	1 in 68	≈ 1 in 14,000
Remaining (unassigned)	~30k	1 in 61	≈ 1 in 30,000
European (Finnish)	~27k	1 in 210	≈ 1 in 13,000
Admixed American	~22k	1 in 60	1 in 3,700
African / African American	~21k	1 in 90	≈ 1 in 6,400
East Asian	~20k	1 in 120	1 in 1,800
Ashkenazi Jewish	~13k	1 in 480	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 63	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): 14 of 15 coding exons well covered in gnomAD exomes; exon 3 marginal. Genomes: all 15.? see exons ↓