TYK2
Basic information
Region (hg38): 19:10350528-10380608
Links
Phenotypes
GenCC
Source:
- immunodeficiency 35 (Strong), mode of inheritance: AR
- immunodeficiency 35 (Supportive), mode of inheritance: AR
Clinical Genomic Database
Source:
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
- Immunodeficiency 35 (10 variants)
- not provided (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 | 11 | 175 | 191 | |||
missense | 370 | 12 | 389 | |||
nonsense | 7 | |||||
start loss | 0 | |||||
frameshift | 5 | |||||
inframe indel | 6 | |||||
splice donor/acceptor (+/-2bp) | 10 | 10 | ||||
splice region | 18 | 30 | 8 | 56 | ||
non coding | 26 | 120 | 51 | 197 | ||
Total | 10 | 12 | 412 | 308 | 63 |
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 |
---|---|---|---|---|
19-10350532-G-A | Immunodeficiency 35 | Uncertain significance (Jan 12, 2018) | ||
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) |
GnomAD
Source:
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:
- 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