JAK1

Janus kinase 1, the group of FERM domain containing|Jak family tyrosine kinases

Basic information

Region (hg38): 1:64833222-65067754

Previous symbols: [ "JAK1B" ]

Links

ENSG00000162434 ∙ NCBI:3716 ∙ OMIM:147795 ∙ HGNC:6190 ∙ Uniprot:P23458 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autoinflammation, immune dysregulation, and eosinophilia (Moderate), mode of inheritance: AD
• autoinflammation, immune dysregulation, and eosinophilia (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Autoinflammation, immune dysregulation, and eosinophilia	AD	Allergy/Immunology/Infectious	Individuals have been described as being affected by manifestations such as atopic dermatitis and chronic gastrointestinal inflammation, and medical management (with JAK inhibitors such as ruxolitinib and tofacitinib) has been described as clinically beneficial	Allergy/Immunology/Infectious	28111307; 32750333

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the JAK1 gene.

• not provided (410 variants)
• not specified (27 variants)
• Inborn genetic diseases (17 variants)
• Autoinflammation, immune dysregulation, and eosinophilia (10 variants)
• JAK1-related condition (5 variants)
• - (2 variants)
• Acute megakaryoblastic leukemia in down syndrome (1 variants)
• Lymphoblastic leukemia, acute, with lymphomatous features (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the JAK1 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			2	126	16	144
missense		2	157	7	1	167
nonsense				1		1
start loss			1			1
frameshift			2			2
inframe indel			3			3
splice donor/acceptor (+/-2bp)			3			3
splice region			11	26	4	41
non coding			2	59	16	77
Total	0	2	170	193	33

Variants in JAK1

This is a list of pathogenic ClinVar variants found in the JAK1 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-64834559-T-G		JAK1-related disorder	Uncertain significance (Apr 11, 2023)
1-64834564-A-G		not specified	Likely benign (Dec 02, 2023)
1-64834565-T-A			Uncertain significance (Aug 16, 2023)
1-64834614-T-C			Uncertain significance (Sep 08, 2023)
1-64834622-T-C			Likely benign (Jan 11, 2022)
1-64834625-G-C		Inborn genetic diseases	Uncertain significance (Jan 16, 2024)
1-64834629-T-C			Uncertain significance (Aug 23, 2022)
1-64834649-T-C		JAK1-related disorder	Benign/Likely benign (Dec 26, 2023)
1-64834655-A-C			Likely benign (Jun 22, 2022)
1-64834671-G-A			Likely benign (Jan 31, 2022)
1-64834672-A-G			Likely benign (Sep 20, 2023)
1-64835380-C-T			Likely benign (Nov 29, 2023)
1-64835381-G-A			Likely benign (Jul 06, 2022)
1-64835383-G-A			Likely benign (Dec 07, 2023)
1-64835392-A-C			Uncertain significance (Mar 18, 2022)
1-64835392-A-G			Uncertain significance (Sep 06, 2023)
1-64835404-G-A			Uncertain significance (Oct 03, 2022)
1-64835404-G-C			Uncertain significance (Nov 24, 2022)
1-64835410-T-C			Uncertain significance (Oct 22, 2023)
1-64835417-G-A			Likely benign (Jan 06, 2023)
1-64835418-C-T			Uncertain significance (Dec 26, 2023)
1-64835420-C-A			Likely benign (Apr 28, 2022)
1-64835420-C-T			Likely benign (Dec 14, 2020)
1-64835421-G-A		Inborn genetic diseases	Uncertain significance (Dec 19, 2023)
1-64835422-G-A			Uncertain significance (Jul 01, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
JAK1	protein_coding	protein_coding	ENST00000342505	24	133276

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.0000194	124680	5	109	124794	0.000457

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	4.61	332	667	0.498	0.0000380	7712
Missense in Polyphen		92	276.47	0.33276		3318
Synonymous	0.470	243	253	0.962	0.0000154	2077
Loss of Function	6.44	7	61.4	0.114	0.00000311	739

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000152	0.000151
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000464	0.0000464
European (Non-Finnish)	0.0000623	0.0000618
Middle Eastern	0.00	0.00
South Asian	0.00334	0.00314
Other	0.000990	0.000990

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Tyrosine kinase of the non-receptor type, involved in the IFN-alpha/beta/gamma signal pathway (PubMed:7615558). Kinase partner for the interleukin (IL)-2 receptor (PubMed:11909529). {ECO:0000269|PubMed:11909529, ECO:0000269|PubMed:7615558}.
• Pathway: PI3K-Akt signaling pathway - Homo sapiens (human);Kaposi,s sarcoma-associated herpesvirus infection - Homo sapiens (human);Jak-STAT signaling pathway - Homo sapiens (human);Influenza A - Homo sapiens (human);HTLV-I infection - Homo sapiens (human);Signaling pathways regulating pluripotency of stem cells - Homo sapiens (human);Necroptosis - Homo sapiens (human);NOD-like receptor signaling pathway - Homo sapiens (human);Tuberculosis - Homo sapiens (human);Th17 cell differentiation - Homo sapiens (human);Th1 and Th2 cell differentiation - Homo sapiens (human);Leishmaniasis - Homo sapiens (human);Toxoplasmosis - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Viral carcinogenesis - Homo sapiens (human);Hepatitis C - Homo sapiens (human);Hepatitis B - Homo sapiens (human);Measles - Homo sapiens (human);Osteoclast differentiation - Homo sapiens (human);Epstein-Barr virus infection - Homo sapiens (human);Pancreatic cancer - Homo sapiens (human);EGFR Inhibitor Pathway, Pharmacodynamics;Human papillomavirus infection - Homo sapiens (human);Herpes simplex infection - Homo sapiens (human);EGF-Core;JAK-STAT-Core;IL-5 Signaling Pathway;Leptin signaling pathway;Human Thyroid Stimulating Hormone (TSH) signaling pathway;Prolactin Signaling Pathway;IL-7 Signaling Pathway;IL17 signaling pathway;Type III interferon signaling;IL-9 Signaling Pathway;Thymic Stromal LymphoPoietin (TSLP) Signaling Pathway;Interleukin-11 Signaling Pathway;Oncostatin M Signaling Pathway;JAK-STAT;IL-3 Signaling Pathway;TCA Cycle Nutrient Utilization and Invasiveness of Ovarian Cancer;IL-6 signaling pathway;Hepatitis C and Hepatocellular Carcinoma;IL-4 Signaling Pathway;ESC Pluripotency Pathways;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;PDGFR-beta pathway;PI3K-Akt Signaling Pathway;The human immune response to tuberculosis;EGF-EGFR Signaling Pathway;IL-2 Signaling Pathway;TGF-beta Receptor Signaling;Interferon type I signaling pathways;Type II interferon signaling (IFNG);Signaling by GPCR;Interleukin-4 and 13 signaling;Interleukin-7 signaling;Interleukin-12 family signaling;IL-3 signaling;Signal Transduction;Other interleukin signaling;Signaling by Interleukins;IL-6-type cytokine receptor ligand interactions;egf signaling pathway;il 2 signaling pathway;stat3 signaling pathway;ifn gamma signaling pathway;il-7 signal transduction;il-2 receptor beta chain in t cell activation;il22 soluble receptor signaling pathway;il-10 anti-inflammatory signaling pathway;il 4 signaling pathway;il 6 signaling pathway;ifn alpha signaling pathway;role of erbb2 in signal transduction and oncology;Prolactin;Cytokine Signaling in Immune system;JAK STAT MolecularVariation 1;Regulation of IFNG signaling;Interleukin-20 family signaling;Oncostatin_M;Interleukin-9 signaling;Immune System;Interleukin-15 signaling;Interleukin receptor SHC signaling;Interleukin-2 family signaling;IFN alpha signaling;IFN gamma signaling;p73 transcription factor network;IL-10 signaling;IL-2 signaling;pdgf signaling pathway;MAPK1 (ERK2) activation;IL-5 signaling;IL-6 signaling;RAF-independent MAPK1/3 activation;IL-7 signaling;IL-4 signaling;EGFR1;Interleukin-10 signaling;SHP2 signaling;JAK STAT MolecularVariation 2;RAF/MAP kinase cascade;MAPK1/MAPK3 signaling;MAPK family signaling cascades;Signaling events mediated by TCPTP;JAK STAT pathway and regulation;IL2;LIF signaling;IL11;EPO signaling;IL2-mediated signaling events;Interferon gamma signaling;IFN-gamma pathway;Interleukin-2 signaling;IL4;IL5;Leptin;Interleukin-27 signaling;IL6;IL-7;Regulation of IFNA signaling;Interferon alpha/beta signaling;Interleukin-12 signaling;MAPK3 (ERK1) activation;VEGF;G beta:gamma signalling through PI3Kgamma;G-protein beta:gamma signalling;GPCR downstream signalling;IL9;IL2 signaling events mediated by STAT5;IL27-mediated signaling events;ISG15 antiviral mechanism;Antiviral mechanism by IFN-stimulated genes;Interferon Signaling;IL2 signaling events mediated by PI3K;IL4-mediated signaling events;Interleukin-6 signaling;Interleukin-6 family signaling;IL6-mediated signaling events;PDGFR-alpha signaling pathway;IL-13 signaling;TSLP;Interleukin-3, 5 and GM-CSF signaling (Consensus)

Recessive Scores

• pRec: 0.174

Intolerance Scores

• loftool: 0.168
• rvis_EVS: -1.33
• rvis_percentile_EVS: 4.69

Haploinsufficiency Scores

• pHI: 0.951
• hipred: Y
• hipred_score: 0.790
• ghis: 0.642

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.975

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Jak1
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; liver/biliary 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); normal phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; hearing/vestibular/ear phenotype; limbs/digits/tail phenotype; immune system phenotype; renal/urinary system phenotype; skeleton 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); growth/size/body region phenotype; endocrine/exocrine gland phenotype; craniofacial phenotype; homeostasis/metabolism phenotype

Zebrafish Information Network

• Gene name: jak1
• Affected structure: pro-T cell
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: MAPK cascade;protein phosphorylation;peptidyl-tyrosine phosphorylation;cytokine-mediated signaling pathway;intracellular signal transduction;interleukin-12-mediated signaling pathway;interleukin-15-mediated signaling pathway;interleukin-2-mediated signaling pathway;interleukin-7-mediated signaling pathway;interleukin-9-mediated signaling pathway;interleukin-21-mediated signaling pathway;response to antibiotic;interferon-gamma-mediated signaling pathway;regulation of interferon-gamma-mediated signaling pathway;type I interferon signaling pathway;interleukin-6-mediated signaling pathway;interleukin-27-mediated signaling pathway;interleukin-35-mediated signaling pathway;positive regulation of sprouting angiogenesis
• Cellular component: nucleus;cytoplasm;endosome;cytosol;cytoskeleton;focal adhesion;membrane
• Molecular function: protein tyrosine kinase activity;non-membrane spanning protein tyrosine kinase activity;Ras guanyl-nucleotide exchange factor activity;growth hormone receptor binding;protein binding;ATP binding;protein phosphatase binding;ubiquitin protein ligase binding;CCR5 chemokine receptor binding;metal ion binding