Aliases for SIK3 Gene

Aliases for SIK3 Gene

  • SIK Family Kinase 3 2 3 5
  • QSK 2 3 4
  • Serine/Threonine-Protein Kinase SIK3 3 4
  • Serine/Threonine-Protein Kinase QSK 3 4
  • Salt-Inducible Kinase 3 3 4
  • EC 4 50
  • KIAA0999 2 4
  • SIK-3 3 4
  • L19 2 3
  • EC 2.7.11 50
  • FLJ12240 2
  • SEMDK 3
  • SIK3 5

External Ids for SIK3 Gene

Previous GeneCards Identifiers for SIK3 Gene

  • GC11M116222
  • GC11M116714
  • GC11M112646

Summaries for SIK3 Gene

GeneCards Summary for SIK3 Gene

SIK3 (SIK Family Kinase 3) is a Protein Coding gene. Diseases associated with SIK3 include Spondyloepimetaphyseal Dysplasia, Krakow Type and Mesomelia. Among its related pathways are LKB1 signaling events. Gene Ontology (GO) annotations related to this gene include transferase activity, transferring phosphorus-containing groups and protein tyrosine kinase activity. An important paralog of this gene is SIK2.

UniProtKB/Swiss-Prot Summary for SIK3 Gene

  • Positive regulator of mTOR signaling that functions by triggering the degradation of DEPTOR, an mTOR inhibitor. Involved in the dynamic regulation of mTOR signaling in chondrocyte differentiation during skeletogenesis (PubMed:30232230). Negatively regulates cAMP signaling pathway possibly by acting on CRTC2/TORC2 and CRTC3/TORC3 (Probable). Prevents HDAC4 translocation to the nucleus (By similarity).

Gene Wiki entry for SIK3 Gene

No data available for Entrez Gene Summary , CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for SIK3 Gene

Genomics for SIK3 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for SIK3 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around SIK3 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for SIK3

Genomic Locations for SIK3 Gene

Latest Assembly
255,052 bases
Minus strand

Previous Assembly
(GRCh37/hg19 by Entrez Gene)
255,027 bases
Minus strand

(GRCh37/hg19 by Ensembl)
255,036 bases
Minus strand

Genomic View for SIK3 Gene

Genes around SIK3 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
SIK3 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for SIK3 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for SIK3 Gene

Proteins for SIK3 Gene

  • Protein details for SIK3 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Recommended name:
    Serine/threonine-protein kinase SIK3
    Protein Accession:
    Secondary Accessions:
    • A1A5A8
    • H0Y494
    • J3KPC8
    • Q59FY2
    • Q5M9N1
    • Q6P3R6
    • Q8IYM8
    • Q9HA50

    Protein attributes for SIK3 Gene

    1321 amino acids
    Molecular mass:
    144851 Da
    Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
    Quaternary structure:
    • Binds to and is activated by YWHAZ when phosphorylated on Thr-221 (PubMed:16306228). Interacts with 14-3-3 proteins (PubMed:29211348). Interacts with HDAC4; this interaction leads to HDAC4 retention in the cytoplasm (By similarity). Interacts with DEPTOR, MLST8/GbetaL, RICTOR and RPTOR (PubMed:30232230).
    • Sequence=AAH63887.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=AAI28511.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=BAA76843.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; Sequence=BAB14006.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};

    Alternative splice isoforms for SIK3 Gene


neXtProt entry for SIK3 Gene

Selected DME Specific Peptides for SIK3 Gene


Post-translational modifications for SIK3 Gene

  • Phosphorylated at Thr-221 by STK11/LKB1 in complex with STE20-related adapter-alpha (STRADA) pseudo kinase and CAB39 (PubMed:14976552). Phosphorylation at Thr-221 is inhibited in response to PTHLH/PTHrP (PubMed:30232230). Phosphorylated at Thr-469 and Ser-551 in response to cAMP signaling (Probable).
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Domains & Families for SIK3 Gene

Gene Families for SIK3 Gene

Human Protein Atlas (HPA):
  • Predicted intracellular proteins
  • Predicted membrane proteins

Protein Domains for SIK3 Gene

  • Ubiquitin-associated domain

Suggested Antigen Peptide Sequences for SIK3 Gene

GenScript: Design optimal peptide antigens:
  • KIAA0999 protein (Q0IJ40_HUMAN)
  • Serine/threonine-protein kinase QSK (SIK3_HUMAN)

Graphical View of Domain Structure for InterPro Entry



  • Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. SNF1 subfamily.
  • Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. SNF1 subfamily.
genes like me logo Genes that share domains with SIK3: view

Function for SIK3 Gene

Molecular function for SIK3 Gene

UniProtKB/Swiss-Prot Function:
Positive regulator of mTOR signaling that functions by triggering the degradation of DEPTOR, an mTOR inhibitor. Involved in the dynamic regulation of mTOR signaling in chondrocyte differentiation during skeletogenesis (PubMed:30232230). Negatively regulates cAMP signaling pathway possibly by acting on CRTC2/TORC2 and CRTC3/TORC3 (Probable). Prevents HDAC4 translocation to the nucleus (By similarity).
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-[protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=; Evidence={ECO:0000269|PubMed:30232230};.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; EC=; Evidence={ECO:0000269|PubMed:30232230};.
UniProtKB/Swiss-Prot EnzymeRegulation:
Activated by phosphorylation on Thr-221.

Enzyme Numbers (IUBMB) for SIK3 Gene

Phenotypes From GWAS Catalog for SIK3 Gene

Gene Ontology (GO) - Molecular Function for SIK3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000166 nucleotide binding IEA --
GO:0000287 magnesium ion binding IDA 14976552
GO:0004672 protein kinase activity IEA --
GO:0004674 protein serine/threonine kinase activity IBA,IDA 14976552
GO:0005515 protein binding IPI 16306228
genes like me logo Genes that share ontologies with SIK3: view
genes like me logo Genes that share phenotypes with SIK3: view

Human Phenotype Ontology for SIK3 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for SIK3 Gene

MGI Knock Outs for SIK3:
  • Sik3 Sik3<tm1a(EUCOMM)Hmgu>
  • Sik3 Sik3<tm1Htake>

Animal Models for research

  • Taconic Biosciences Mouse Models for SIK3

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for SIK3

No data available for Transcription Factor Targets and HOMER Transcription for SIK3 Gene

Localization for SIK3 Gene

Subcellular locations from UniProtKB/Swiss-Prot for SIK3 Gene

Cytoplasm. Note=Locates to punctate structures within the cytoplasm on binding to YWHAZ. {ECO:0000269 PubMed:16306228}.

Subcellular locations from

Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for SIK3 gene
Compartment Confidence
nucleus 4
cytosol 3
mitochondrion 2
plasma membrane 1
extracellular 1
cytoskeleton 1
peroxisome 1
endoplasmic reticulum 0

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for SIK3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005654 nucleoplasm IDA --
GO:0005737 cytoplasm IBA 21873635
genes like me logo Genes that share ontologies with SIK3: view

Pathways & Interactions for SIK3 Gene

PathCards logo

SuperPathways for SIK3 Gene

SuperPathway Contained pathways
1 LKB1 signaling events
genes like me logo Genes that share pathways with SIK3: view

Pathways by source for SIK3 Gene

1 BioSystems pathway for SIK3 Gene

SIGNOR curated interactions for SIK3 Gene

Is activated by:

Gene Ontology (GO) - Biological Process for SIK3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000226 microtubule cytoskeleton organization IBA 21873635
GO:0006468 protein phosphorylation IEA,IDA 14976552
GO:0016310 phosphorylation IEA --
GO:0035556 intracellular signal transduction IBA 21873635
GO:1904263 positive regulation of TORC1 signaling IMP 30232230
genes like me logo Genes that share ontologies with SIK3: view

Drugs & Compounds for SIK3 Gene

(3) Drugs for SIK3 Gene - From: DrugBank, ApexBio, and HMDB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
fostamatinib Approved, Investigational Pharma Target, inhibitor Kinase Inhibitors 0
Magnesium Approved, Experimental, Investigational Pharma 0
HG-9-91-01 Pharma Pan-SIK (salt-inducible kinases) inhibitor 0

(1) ApexBio Compounds for SIK3 Gene

Compound Action Cas Number
HG-9-91-01 Pan-SIK (salt-inducible kinases) inhibitor 1456858-58-4
genes like me logo Genes that share compounds with SIK3: view

Drug products for research

Transcripts for SIK3 Gene

mRNA/cDNA for SIK3 Gene

22 NCBI additional mRNA sequence :
13 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for SIK3

Alternative Splicing Database (ASD) splice patterns (SP) for SIK3 Gene

No ASD Table

Relevant External Links for SIK3 Gene

GeneLoc Exon Structure for

Expression for SIK3 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for SIK3 Gene

Protein differential expression in normal tissues from HIPED for SIK3 Gene

This gene is overexpressed in Lung (13.4), Peripheral blood mononuclear cells (9.0), Frontal cortex (7.1), and Testis (6.8).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for SIK3 Gene

Protein tissue co-expression partners for SIK3 Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for SIK3

SOURCE GeneReport for Unigene cluster for SIK3 Gene:


mRNA Expression by UniProt/SwissProt for SIK3 Gene:

Tissue specificity: Expressed in chondrocytes.

Evidence on tissue expression from TISSUES for SIK3 Gene

  • Nervous system(4.7)
  • Liver(4.5)
  • Lung(2.5)
genes like me logo Genes that share expression patterns with SIK3: view

Primer products for research

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues and Phenotype-based relationships between genes and organs from Gene ORGANizer for SIK3 Gene

Orthologs for SIK3 Gene

This gene was present in the common ancestor of animals.

Orthologs for SIK3 Gene

Organism Taxonomy Gene Similarity Type Details
(Pan troglodytes)
Mammalia SIK3 29 30
  • 99.68 (n)
(Canis familiaris)
Mammalia SIK3 29 30
  • 90.32 (n)
(Bos Taurus)
Mammalia SIK3 29 30
  • 89.82 (n)
(Mus musculus)
Mammalia Sik3 29 16 30
  • 88.25 (n)
(Rattus norvegicus)
Mammalia Sik3 29
  • 88.11 (n)
(Monodelphis domestica)
Mammalia SIK3 30
  • 79 (a)
(Ornithorhynchus anatinus)
Mammalia SIK3 30
  • 78 (a)
(Gallus gallus)
Aves -- 30
  • 79 (a)
LOC777317 29
  • 78.73 (n)
-- 30
  • 78 (a)
-- 30
  • 77 (a)
-- 30
  • 76 (a)
-- 30
  • 76 (a)
-- 30
  • 76 (a)
(Anolis carolinensis)
Reptilia SIK3 30
  • 71 (a)
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia sik3 29
  • 71.49 (n)
(Danio rerio)
Actinopterygii SIK3 30
  • 76 (a)
zgc:66101 29
  • 65.45 (n)
zgc66101 29
Fruit Fly
(Drosophila melanogaster)
Insecta Sik2 30
  • 29 (a)
(Caenorhabditis elegans)
Secernentea kin-29 30
  • 27 (a)
Sea Squirt
(Ciona savignyi)
Ascidiacea -- 30
  • 52 (a)
Species where no ortholog for SIK3 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)

Evolution for SIK3 Gene

Gene Tree for SIK3 (if available)
Gene Tree for SIK3 (if available)
Evolutionary constrained regions (ECRs) for SIK3: view image
Alliance of Genome Resources:
Additional Orthologs for SIK3

Paralogs for SIK3 Gene

genes like me logo Genes that share paralogs with SIK3: view

Variants for SIK3 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for SIK3 Gene

SNP ID Clinical significance and condition Chr 11 pos Variation AA Info Type
1030912 Uncertain Significance: Spondyloepimetaphyseal dysplasia, Krakow type 116,873,519(-) G/A
NM_025164.6(SIK3):c.1699C>T (p.Arg567Cys)
rs146679016 Benign: not provided 116,849,225(-) C/T
NM_025164.6(SIK3):c.3570G>A (p.Pro1190=)
rs156546085 Spondyloepimetaphyseal dysplasia, Krakow type (SEMDK) [MIM:618162] p.Arg187Cys
rs1565460853 Pathogenic: Spondyloepimetaphyseal dysplasia, Krakow type 116,927,276(-) G/A
NM_025164.6(SIK3):c.559C>T (p.Arg187Cys)
rs376144593 A breast cancer sample p.His389Leu

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for SIK3 Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for SIK3 Gene

Variant ID Type Subtype PubMed ID
dgv2185n54 CNV loss 21841781
dgv245e199 CNV deletion 23128226
dgv245n67 CNV loss 20364138
dgv729n106 CNV tandem duplication 24896259
esv1183056 CNV insertion 17803354
esv24446 CNV loss 19812545
esv2678480 CNV deletion 23128226
esv3303435 CNV mobile element insertion 20981092
esv3323959 CNV insertion 20981092
esv3379224 CNV insertion 20981092
esv3548401 CNV deletion 23714750
esv3627836 CNV loss 21293372
esv3627837 CNV loss 21293372
esv3627841 CNV loss 21293372
esv3627843 CNV loss 21293372
nsv1050142 CNV loss 25217958
nsv1136139 CNV deletion 24896259
nsv1144595 CNV deletion 24896259
nsv507620 OTHER sequence alteration 20534489
nsv556451 CNV loss 21841781
nsv556454 CNV loss 21841781
nsv556455 CNV loss 21841781
nsv7223 OTHER inversion 18451855
nsv832280 CNV gain+loss 17160897
nsv952739 CNV duplication 24416366
nsv983064 CNV duplication 23825009

Variation tolerance for SIK3 Gene

Residual Variation Intolerance Score: 10.5% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for SIK3 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
Leiden Open Variation Database (LOVD)

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for SIK3 Gene

Disorders for SIK3 Gene

MalaCards: The human disease database

(6) MalaCards diseases for SIK3 Gene - From: OMI, CVR, SWI, COP, and GCD

- elite association - COSMIC cancer census association via MalaCards
Search SIK3 in MalaCards View complete list of genes associated with diseases


  • Spondyloepimetaphyseal dysplasia, Krakow type (SEMDK) [MIM:618162]: An autosomal recessive skeletal disorder characterized by severe spondyloepimetaphyseal dysplasia, rhizomelia, mesomelia with significant anterior bowing of all limbs, severe immunodeficiency, and developmental delay. {ECO:0000269 PubMed:30232230}. Note=The disease is caused by variants affecting the gene represented in this entry.

Additional Disease Information for SIK3

Human Genome Epidemiology Navigator
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with SIK3: view

No data available for Genatlas for SIK3 Gene

Publications for SIK3 Gene

  1. The PTH/PTHrP-SIK3 pathway affects skeletogenesis through altered mTOR signaling. (PMID: 30232230) Csukasi F … Krakow D (Science translational medicine 2018) 3 4 72
  2. Prediction of the coding sequences of unidentified human genes. XIII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro. (PMID: 10231032) Nagase T … Ohara O (DNA research : an international journal for rapid publication of reports on genes and genomes 1999) 2 3 4
  3. 14-3-3 proteins mediate inhibitory effects of cAMP on salt-inducible kinases (SIKs). (PMID: 29211348) Sonntag T … Montminy M (The FEBS journal 2018) 3 4
  4. Common variants near MBNL1 and NKX2-5 are associated with infantile hypertrophic pyloric stenosis. (PMID: 22306654) Feenstra B … Melbye M (Nature genetics 2012) 3 40
  5. Novel association to the proprotein convertase PCSK7 gene locus revealed by analysing soluble transferrin receptor (sTfR) levels. (PMID: 21149283) Oexle K … Meitinger T (Human molecular genetics 2011) 3 40

Products for SIK3 Gene

Sources for SIK3 Gene