SIK3

SIK family kinase 3, the group of SIK family kinases

Basic information

Region (hg38): 11:116843402-117098437

Links

ENSG00000160584 ∙ NCBI:23387 ∙ OMIM:614776 ∙ HGNC:29165 ∙ Uniprot:Q9Y2K2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• spondyloepimetaphyseal dysplasia, Krakow type (Limited), mode of inheritance: Unknown
• autism (Limited), mode of inheritance: AD
• hearing loss disorder (Limited), mode of inheritance: AD
• spondyloepimetaphyseal dysplasia, Krakow type (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spondyloepimetaphyseal dysplasia, Krakow type	AR	Allergy/Immunology/Infectious	The condition can include immunodeficiency, and awareness may allow antiinfectious prophylaxis and early and aggressive treatment of infection	Allergy/Immunology/Infectious; Endocrine; Musculoskeletal; Neurologic	30232230

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SIK3 gene.

• not_specified (120 variants)
• not_provided (17 variants)
• SIK3-related_disorder (17 variants)
• Spondyloepimetaphyseal_dysplasia,_Krakow_type (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SIK3 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001366686.3. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				14	2	16
missense	1	1	116	10	2	130
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	1	1	116	24	4

Highest pathogenic variant AF is 6.84149e-7

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SIK3	protein_coding	protein_coding	ENST00000292055	23	255036

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	3.76e-8	125733	0	15	125748	0.0000596

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.83	524	741	0.707	0.0000420	8338
Missense in Polyphen		145	289.33	0.50117		3448
Synonymous	-0.440	298	288	1.03	0.0000169	2450
Loss of Function	6.85	3	60.5	0.0496	0.00000275	688

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00107	0.000580
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000354	0.0000352
Middle Eastern	0.0000544	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Pathway: LKB1 signaling events (Consensus)

Intolerance Scores

• loftool: 0.312
• rvis_EVS: -0.99
• rvis_percentile_EVS: 8.6

Haploinsufficiency Scores

• hipred: Y
• hipred_score: 0.728
• ghis: 0.609

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.781

Mouse Genome Informatics

• Gene name: Sik3
• Phenotype: skeleton phenotype; renal/urinary system phenotype; limbs/digits/tail phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); homeostasis/metabolism phenotype; cellular phenotype; craniofacial phenotype; endocrine/exocrine gland phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan)

Gene ontology

• Biological process: microtubule cytoskeleton organization;protein phosphorylation;intracellular signal transduction
• Cellular component: cytoplasm
• Molecular function: magnesium ion binding;protein serine/threonine kinase activity;protein binding;ATP binding;tau-protein kinase activity