SIK2
protein-codingsalt inducible kinase 2, the group of SIK family kinases
Gene summary
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]
- SNF1LK2
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~128.4 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to SIK2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_015191.3. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | 1 | 3 | ||
| missense | 91 | 3 | 94 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 94 | 4 | 1 | 99 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_056006.1 | 15 | MANE Select | |
| Ensembl | ENSP00000305976.3 | 15 | MANE Select | |
| Ensembl | ENSP00000546628.1 | 14 | Standard | |
| Ensembl | ENSP00000546628.1 | 14 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Glucagon signaling pathway - Homo sapiens (human)
- LKB1 signaling events
Biological Process
- protein phosphorylation
- negative regulation of TOR signaling
- intracellular signal transduction
- cellular response to glucose starvation
- regulation of insulin receptor signaling pathway
Molecular Function
- magnesium ion binding
- protein serine/threonine kinase activity
- protein binding
- ATP binding
Cellular Component
- nucleus
- cytoplasm
- nucleotide-activated protein kinase complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000304987
- Coding exons
- 15
- Length
- 128463
- Individuals with no LoFs
- 125733
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 15
- Defined
- 125748
- p
- 0.0000596
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.55 | 360 | 524 | 0.686 | 0.0000295 | 6046 |
| Missense (PolyPhen) | 93 | 215.78 | 0.43099 | 2432 | ||
| Synonymous | 1.16 | 183 | 204 | 0.897 | 0.0000120 | 1853 |
| Loss of Function | 5.45 | 7 | 47.5 | 0.147 | 0.00000272 | 491 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.000087 | 0.000087 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00016 | 0.00016 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.000064 | 0.000062 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Phosphorylates 'Ser-794' of IRS1 in insulin-stimulated adipocytes, potentially modulating the efficiency of insulin signal transduction. Inhibits CREB activity by phosphorylating and repressing TORCs, the CREB-specific coactivators. {ECO:0000269|PubMed:15454081}.;
Recessive Scores
- pRec
- 0.172
Intolerance Scores
- RVIS EVS
- -0.42
- RVIS percentile EVS
- 25.79
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.522
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |