TYK2

tyrosine kinase 2, the group of FERM domain containing|Jak family tyrosine kinases

Basic information

Region (hg38): 19:10350532-10380608

Links

ENSG00000105397 ∙ NCBI:7297 ∙ OMIM:176941 ∙ HGNC:12440 ∙ Uniprot:P29597 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• immunodeficiency 35 (Strong), mode of inheritance: AR
• immunodeficiency 35 (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Immunodeficiency 35	AR	Allergy/Immunology/Infectious	Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial	Allergy/Immunology/Infectious	17088085; 17521577; 18270328; 26304966

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TYK2 gene.

• Immunodeficiency 35 (738 variants)
• not provided (123 variants)
• not specified (47 variants)
• Inborn genetic diseases (38 variants)
• TYK2-related condition (3 variants)
• Virus-induced diabetes (3 variants)
• Recurrent skin infections;Immunodeficiency (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TYK2 gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			13	148	5	166
missense			363	13	7	383
nonsense	4	1				5
start loss						0
frameshift	4	1				5
inframe indel			5	1		6
splice donor/acceptor (+/-2bp)		7				7
splice region			18	23	8	49
non coding			26	106	51	183
Total	8	9	407	268	63

Highest pathogenic variant AF is 0.0000131

Variants in TYK2

This is a list of pathogenic ClinVar variants found in the TYK2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
19-10350543-A-G		Immunodeficiency 35	Uncertain significance (Jan 13, 2018)
19-10350573-G-T		Immunodeficiency 35	Uncertain significance (Jan 13, 2018)
19-10350574-G-A		Immunodeficiency 35	Uncertain significance (Jan 13, 2018)
19-10350635-T-C		Immunodeficiency 35	Likely benign (Jun 01, 2021)
19-10350660-C-T		Immunodeficiency 35	Uncertain significance (Jan 13, 2018)
19-10350661-G-A		Immunodeficiency 35	Uncertain significance (Jan 12, 2018)
19-10350688-A-T		Immunodeficiency 35	Benign (Jan 13, 2018)
19-10350700-T-C		Immunodeficiency 35	Benign (Jan 16, 2019)
19-10350714-G-A		Immunodeficiency 35	Uncertain significance (Jan 13, 2018)
19-10350771-C-T		Immunodeficiency 35	Uncertain significance (Jan 13, 2018)
19-10350815-G-A		Immunodeficiency 35	Benign (Jan 13, 2018)
19-10350835-C-T		Immunodeficiency 35	Likely benign (Jan 28, 2024)
19-10350838-C-T		Immunodeficiency 35	Uncertain significance (Jan 22, 2024)
19-10350840-C-A		Immunodeficiency 35	Likely benign (Jan 25, 2024)
19-10350842-C-T		Immunodeficiency 35	Uncertain significance (Aug 27, 2021)
19-10350843-G-A		Immunodeficiency 35	Conflicting classifications of pathogenicity (Oct 27, 2023)
19-10350854-A-G		Immunodeficiency 35	Uncertain significance (Jul 17, 2021)
19-10350855-A-C		Immunodeficiency 35	Likely benign (Nov 26, 2022)
19-10350856-G-A		Immunodeficiency 35	Uncertain significance (Jul 30, 2020)
19-10350859-G-A		Immunodeficiency 35	Uncertain significance (Jun 15, 2022)
19-10350866-C-T		Immunodeficiency 35	Uncertain significance (Jan 22, 2019)
19-10350873-C-T		Immunodeficiency 35	Uncertain significance (Jan 13, 2018)
19-10350878-C-T		Immunodeficiency 35	Uncertain significance (Aug 16, 2021)
19-10350891-C-T		Immunodeficiency 35	Likely benign (Feb 03, 2022)
19-10350909-C-T		Immunodeficiency 35	Likely benign (Jun 08, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TYK2	protein_coding	protein_coding	ENST00000525621	23	30144

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.50e-8	1.00	125700	0	48	125748	0.000191

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.59	620	742	0.836	0.0000506	7674
Missense in Polyphen		156	247.92	0.62924		2810
Synonymous	0.818	297	315	0.941	0.0000221	2412
Loss of Function	4.24	23	57.7	0.398	0.00000309	618

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000359	0.000358
Ashkenazi Jewish	0.00	0.00
East Asian	0.00120	0.00120
Finnish	0.00	0.00
European (Non-Finnish)	0.000127	0.000123
Middle Eastern	0.00120	0.00120
South Asian	0.0000987	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Probably involved in intracellular signal transduction by being involved in the initiation of type I IFN signaling. Phosphorylates the interferon-alpha/beta receptor alpha chain. {ECO:0000269|PubMed:7526154}.
• Disease: DISEASE: Immunodeficiency 35 (IMD35) [MIM:611521]: A primary immunodeficiency characterized by recurrent skin abscesses, pneumonia, and highly elevated serum IgE. {ECO:0000269|PubMed:17088085}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Kaposi,s sarcoma-associated herpesvirus infection - Homo sapiens (human);Jak-STAT signaling pathway - Homo sapiens (human);Influenza A - Homo sapiens (human);Necroptosis - Homo sapiens (human);NOD-like receptor signaling pathway - Homo sapiens (human);Th17 cell differentiation - Homo sapiens (human);Th1 and Th2 cell differentiation - Homo sapiens (human);Toxoplasmosis - Homo sapiens (human);Hepatitis C - Homo sapiens (human);Measles - Homo sapiens (human);Osteoclast differentiation - Homo sapiens (human);Epstein-Barr virus infection - Homo sapiens (human);Human papillomavirus infection - Homo sapiens (human);Herpes simplex infection - Homo sapiens (human);JAK-STAT-Core;Type III interferon signaling;Interleukin-11 Signaling Pathway;Oncostatin M Signaling Pathway;IL-6 signaling pathway;IL-4 Signaling Pathway;The human immune response to tuberculosis;no2-dependent il-12 pathway in nk cells;Interferon type I signaling pathways;Interleukin-4 and 13 signaling;Interleukin-12 family signaling;Signal Transduction;Other interleukin signaling;Signaling by Interleukins;il12 and stat4 dependent signaling pathway in th1 development;IL-6-type cytokine receptor ligand interactions;stat3 signaling pathway;il22 soluble receptor signaling pathway;ifn alpha signaling pathway;Prolactin;Cytokine Signaling in Immune system;JAK STAT MolecularVariation 1;IL-12 signaling;Interleukin-20 family signaling;Immune System;IFN alpha signaling;IL-10 signaling;IL-23 signaling;MAPK1 (ERK2) activation;RAF-independent MAPK1/3 activation;IL-7 signaling;Interleukin-23 signaling;EGFR1;Interleukin-10 signaling;JAK STAT MolecularVariation 2;MAPK1/MAPK3 signaling;MAPK family signaling cascades;JAK STAT pathway and regulation;EPO signaling;IL4;Interleukin-27 signaling;IL6;Regulation of IFNA signaling;Interferon alpha/beta signaling;Interleukin-12 signaling;MAPK3 (ERK1) activation;VEGF;IL9;IL23-mediated signaling events;IL27-mediated signaling events;Interferon Signaling;Signaling events mediated by PTP1B;Interleukin-6 signaling;Interleukin-6 family signaling;IL6-mediated signaling events;IL12-mediated signaling events;IL-13 signaling (Consensus)

Recessive Scores

• pRec: 0.671

Intolerance Scores

• loftool: 0.209
• rvis_EVS: -0.5
• rvis_percentile_EVS: 21.86

Haploinsufficiency Scores

• pHI: 0.351
• hipred: Y
• hipred_score: 0.637
• ghis: 0.566

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.999

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Tyk2
• 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; homeostasis/metabolism phenotype; cellular phenotype; hematopoietic system phenotype; 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); skeleton phenotype; immune system phenotype

Gene ontology

• Biological process: protein phosphorylation;peptidyl-tyrosine phosphorylation;cytokine-mediated signaling pathway;intracellular signal transduction;interleukin-12-mediated signaling pathway;interleukin-23-mediated signaling pathway;type I interferon signaling pathway;interleukin-27-mediated signaling pathway
• Cellular component: nucleus;cytoplasm;cytosol;cytoskeleton;membrane;extracellular exosome
• Molecular function: protein tyrosine kinase activity;non-membrane spanning protein tyrosine kinase activity;growth hormone receptor binding;protein binding;ATP binding;type 1 angiotensin receptor binding