SIK1

Chr 21AD

salt inducible kinase 1

Also known as: DEE30, MSK, SIK, SIK-1, SIK1B, SNF1LK

The protein is a serine/threonine kinase containing a ubiquitin-associated domain and functions as a member of the AMPK subfamily involved in cellular signal transduction pathways. Mutations cause developmental and epileptic encephalopathy 30, which follows an autosomal dominant inheritance pattern. The high pLI score (0.94) and low LOEUF score (0.34) indicate the gene is highly intolerant to loss-of-function variants, suggesting haploinsufficiency as the likely mechanism of pathogenicity.

OMIMResearchSummary from RefSeq, OMIM, UniProt
GOFmechanismADLOEUF 0.341 OMIM phenotype
Clinical SummarySIK1
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Gene-Disease Validity (ClinGen)
genetic developmental and epileptic encephalopathy · ADLimited

Limited evidence — not for standalone diagnostic reporting

Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.94). One damaged copy is likely sufficient to cause disease.
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ClinVar Variants
19 unique Pathogenic / Likely Pathogenic· 215 VUS of 400 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.34LOEUF
pLI 0.937
Z-score 4.31
OE 0.16 (0.080.34)
Highly constrained

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

Missense Constraint
1.49Z-score
OE missense 0.80 (0.740.88)
365 obs / 454.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.16 (0.080.34)
00.351.4
Missense OE0.80 (0.740.88)
00.61.4
Synonymous OE0.99
01.21.6
LoF obs/exp: 5 / 30.8Missense obs/exp: 365 / 454.3Syn Z: 0.08

ClinVar Variant Classifications

400 submitted variants in ClinVar

Classification Summary

Pathogenic16
Likely Pathogenic3
VUS215
Likely Benign142
Benign10
Conflicting6
16
Pathogenic
3
Likely Pathogenic
215
VUS
142
Likely Benign
10
Benign
6
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
16
0
16
Likely Pathogenic
2
0
1
0
3
VUS
10
182
21
2
215
Likely Benign
0
2
56
84
142
Benign
0
0
10
0
10
Conflicting
6
Total1218410486392

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

SIK1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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