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This gene encodes a membrane protein that is a member of a class of protein-tyrosine kinases (PTK) characterized by the presence of a second phosphotransferase-related domain immediately N-terminal to the PTK domain. The encoded kinase phosphorylates STAT proteins (signal transducers and activators of transcription) and plays a key role in interferon-alpha/beta, interferon-gamma, and cytokine signal transduction. This gene plays a crucial role in effecting the expression of genes that mediate inflammation, epithelial remodeling, and metastatic cancer progression. This gene is a key component of the interleukin-6 (IL-6)/JAK1/STAT3 immune and inflammation response and is a therapeutic target for alleviating cytokine storms. The kinase activity of this gene is directly inhibited by the suppressor of cytokine signalling 1 (SOCS1) protein. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2020]
JAK1 (Janus Kinase 1) is a Protein Coding gene. Diseases associated with JAK1 include Autoinflammation, Immune Dysregulation, And Eosinophilia and Autosomal Recessive Mendelian Susceptibility To Mycobacterial Diseases Due To Partial Jak1 Deficiency. Among its related pathways are Regulation of lipid metabolism Insulin signaling-generic cascades and Signaling by GPCR. 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 TYK2.
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000166 | nucleotide binding | IEA | -- |
GO:0004672 | protein kinase activity | IEA | -- |
GO:0004713 | protein tyrosine kinase activity | IEA,TAS | -- |
GO:0004715 | non-membrane spanning protein tyrosine kinase activity | IEA,TAS | -- |
GO:0005131 | growth hormone receptor binding | ISS | 10502458 |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0005634 | nucleus | IDA | 10502458 |
GO:0005737 | cytoplasm | IDA | 10502458 |
GO:0005768 | endosome | TAS | -- |
GO:0005829 | cytosol | TAS | -- |
GO:0005856 | cytoskeleton | IEA | -- |
SuperPathway | Contained pathways | ||
---|---|---|---|
1 | RET signaling |
.92
|
.92
|
2 | Common Cytokine Receptor Gamma-Chain Family Signaling Pathways |
Immune response IL-9 signaling pathway
.42
IL-9 Pathway
.36
|
|
3 | Th17 cell differentiation |
Immune response IL-22 signaling pathway
.36
IL-22 Pathway
.01
|
|
4 | ErbB signaling pathway | ||
5 | Measles |
.35
|
.33
|
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000165 | MAPK cascade | TAS | -- |
GO:0006468 | protein phosphorylation | IEA,TAS | 1848670 |
GO:0016310 | phosphorylation | IEA | -- |
GO:0018108 | peptidyl-tyrosine phosphorylation | IEA | -- |
GO:0019221 | cytokine-mediated signaling pathway | TAS | -- |
Name | Status | Disease Links | Group | Role | Mechanism of Action | Clinical Trials |
---|---|---|---|---|---|---|
Baricitinib | Approved, Investigational | Pharma | Target, inhibitor | 0 | ||
Fedratinib | Approved, Investigational | Pharma | Target, inhibitor | 0 | ||
ruxolitinib | Approved | Pharma | Target, inhibitor | Kinase Inhibitors | 0 | |
Filgotinib | Approved, Investigational | Pharma | Target, inhibitor | 0 | ||
fostamatinib | Approved, Investigational | Pharma | Target, inhibitor | Kinase Inhibitors | 0 |
Name | Synonyms | Role | CAS Number | PubChem IDs | PubMed IDs | |
---|---|---|---|---|---|---|
ADP |
|
58-64-0 |
|
Compound | Action | Cas Number |
---|---|---|
AZ 960 | JAKs inhibitor | 905586-69-8 |
Bardoxolone methyl | IKK inhibitor, potent antioxidant inflammation modulator | 218600-53-4 |
Baricitinib (LY3009104, INCB028050) | JAK1/JAK2 inhibitor,selective orally bioavailable | 1187594-09-7 |
Baricitinib phosphate | JAK1/JAK2 inhibitor | 1187595-84-1 |
Cerdulatinib | Syk/JAK inhibitor | 1198300-79-6 |
CYT387 | JAK-1/-2 inhibitor,ATP competitive | 1056634-68-4 |
CYT387 sulfate salt | JAK1/JAK2 inhibitor | 1056636-06-6 |
GLPG0634 | JAK1 inhibitor | 1206161-97-8 |
NVP-BSK805 | ATP-competitive JAK2 inhibitor | 1092499-93-8 |
Peficitinb (ASP015K, JNJ-54781532) | JAK inhibitor | 944118-01-8 |
Pyridone 6 | Pan-JAK inhibitor | 457081-03-7 |
Ruxolitinib (INCB018424) | JAK inhibitor | 941678-49-5 |
Ruxolitinib phosphate | JAK1/JAK2 inhibitor | 1092939-17-7 |
S-Ruxolitinib (INCB018424) | JAK1/2 inhibitor,potent and selective | 941685-37-6 |
Tofacitinib (CP-690550) Citrate | Potent JAK inhibitor | 540737-29-9 |
Tofacitinib (CP-690550,Tasocitinib) | Janus kinase inhibitor | 477600-75-2 |
WHI-P154 | JAK3 inhibitor | 211555-04-3 |
ZM 39923 HCl | JAK3 inhibitor,potent and selective | 1021868-92-7 |
ExUns: | 1 | ^ | 2a | · | 2b | ^ | 3 | ^ | 4 | ^ | 5 | ^ | 6 | ^ | 7 | ^ | 8 | ^ | 9 | ^ | 10a | · | 10b | ^ | 11 | ^ | 12a | · | 12b | · | 12c | ^ | 13 | ^ | 14 | ^ | 15a | · | 15b | ^ | 16 | ^ | 17 | ^ | 18 | ^ | 19a | · | 19b | · | 19c | ^ |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
SP1: | - | - | - | - | ||||||||||||||||||||||||||||||||||||||||||||||||
SP2: | ||||||||||||||||||||||||||||||||||||||||||||||||||||
SP3: | - | - | - | |||||||||||||||||||||||||||||||||||||||||||||||||
SP4: | - | |||||||||||||||||||||||||||||||||||||||||||||||||||
SP5: | - | |||||||||||||||||||||||||||||||||||||||||||||||||||
SP6: | - | - | ||||||||||||||||||||||||||||||||||||||||||||||||||
SP7: | ||||||||||||||||||||||||||||||||||||||||||||||||||||
SP8: |
ExUns: | 20a | · | 20b | ^ | 21 | ^ | 22 | ^ | 23 | ^ | 24 | ^ | 25 | ^ | 26 | ^ | 27a | · | 27b |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
SP1: | |||||||||||||||||||
SP2: | |||||||||||||||||||
SP3: | |||||||||||||||||||
SP4: | |||||||||||||||||||
SP5: | |||||||||||||||||||
SP6: | |||||||||||||||||||
SP7: | |||||||||||||||||||
SP8: |
This gene was present in the common ancestor of animals.
Organism | Taxonomy | Gene | Similarity | Type | Details |
---|---|---|---|---|---|
Chimpanzee (Pan troglodytes) |
Mammalia | JAK1 30 31 |
|
OneToOne | |
Dog (Canis familiaris) |
Mammalia | JAK1 30 31 |
|
OneToOne | |
Cow (Bos Taurus) |
Mammalia | JAK1 30 31 |
|
OneToOne | |
Mouse (Mus musculus) |
Mammalia | Jak1 30 17 31 |
|
OneToOne | |
Rat (Rattus norvegicus) |
Mammalia | Jak1 30 |
|
||
Oppossum (Monodelphis domestica) |
Mammalia | -- 31 |
|
OneToMany | |
-- 31 |
|
OneToMany | |||
-- 31 |
|
OneToMany | |||
Platypus (Ornithorhynchus anatinus) |
Mammalia | JAK1 31 |
|
OneToOne | |
Chicken (Gallus gallus) |
Aves | JAK1 30 31 |
|
OneToOne | |
Lizard (Anolis carolinensis) |
Reptilia | -- 31 |
|
OneToMany | |
-- 31 |
|
OneToMany | |||
Tropical Clawed Frog (Silurana tropicalis) |
Amphibia | jak1 30 |
|
||
Str.19081 30 |
|
||||
Zebrafish (Danio rerio) |
Actinopterygii | jak1 30 31 |
|
OneToOne | |
Rainbow Trout (Oncorhynchus mykiss) |
Actinopterygii | Omy.9095 30 |
|
||
Worm (Caenorhabditis elegans) |
Secernentea | T14E8.1a 32 |
|
|
|
T14E8.1b 32 |
|
|
|||
Sea Squirt (Ciona savignyi) |
Ascidiacea | -- 31 |
|
OneToMany |
SNP ID | Clinical significance and condition | Chr 01 pos | Variation | AA Info | Type |
---|---|---|---|---|---|
977461 | Pathogenic: Autoinflammation, immune dysregulation, and eosinophilia | 64,845,520(-) |
C/A NM_002227.4(JAK1):c.2108G>T (p.Ser703Ile) |
MISSENSE | |
rs1057519753 | Likely Pathogenic: Acute myeloid leukemia; Lymphoblastic leukemia, acute, with lymphomatous features; Polycythemia vera; Leukemia, acute, ?X-linked | 64,846,664(-) |
C/A NM_002227.4(JAK1):c.1972G>T (p.Val658Phe) |
MISSENSE | |
rs1129739 | Benign: not provided | 64,834,649(-) |
T/C NM_002227.4(JAK1):c.3378A>G (p.Gln1126=) |
SYNONYMOUS | |
rs145378558 | Benign: not provided | 64,869,304(-) |
G/A NM_002227.4(JAK1):c.647+7C>T |
INTRON | |
rs149968614 | Not Provided: not specified | 64,846,685(-) |
C/T NM_002227.4(JAK1):c.1951G>A (p.Val651Met) |
MISSENSE |
Variant ID | Type | Subtype | PubMed ID |
---|---|---|---|
dgv172n100 | CNV | gain | 25217958 |
esv2421783 | CNV | deletion | 20811451 |
esv2671749 | CNV | deletion | 23128226 |
esv275588 | CNV | loss | 21479260 |
esv2763311 | CNV | gain | 21179565 |
esv3577904 | CNV | loss | 25503493 |
esv3578582 | CNV | gain | 25503493 |
esv3586273 | CNV | loss | 21293372 |
nsv1005169 | CNV | gain | 25217958 |
nsv1006347 | CNV | gain+loss | 25217958 |
nsv1126199 | CNV | deletion | 24896259 |
nsv525227 | CNV | loss | 19592680 |
nsv823098 | CNV | loss | 20364138 |
nsv830059 | CNV | loss | 17160897 |
nsv945979 | CNV | duplication | 23825009 |
Disorder | Aliases | PubMed IDs |
---|---|---|
autoinflammation, immune dysregulation, and eosinophilia |
|
|
autosomal recessive mendelian susceptibility to mycobacterial diseases due to partial jak1 deficiency |
|
|
leukemia, acute, x-linked |
|
|
polycythemia vera |
|
|
lymphoblastic leukemia, acute, with lymphomatous features |
|
|