JAK2
Janus kinase 2
Summary
This gene encodes a non-receptor tyrosine kinase that plays a central role in cytokine and growth factor signalling. The primary isoform of this protein has an N-terminal FERM domain that is required for erythropoietin receptor association, an SH2 domain that binds STAT transcription factors, a pseudokinase domain and a C-terminal tyrosine kinase domain. Cytokine binding induces autophosphorylation and activation of this kinase. This kinase then recruits and phosphorylates signal transducer and activator of transcription (STAT) proteins. Growth factors like TGF-beta 1 also induce phosphorylation and activation of this kinase and translocation of downstream STAT proteins to the nucleus where they influence gene transcription. Mutations in this gene are associated with numerous inflammatory diseases and malignancies. This gene is a downstream target of the pleiotropic cytokine IL6 that is produced by B cells, T cells, dendritic cells and macrophages to produce an immune response or inflammation. Disregulation of the IL6/JAK2/STAT3 signalling pathways produces increased cellular proliferation and myeloproliferative neoplasms of hematopoietic stem cells. A nonsynonymous mutation in the pseudokinase domain of this gene disrupts the domains inhibitory effect and results in constitutive tyrosine phosphorylation activity and hypersensitivity to cytokine signalling. This gene and the IL6/JAK2/STAT3 signalling pathway is a therapeutic target for the treatment of excessive inflammatory responses to viral infections. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2020]
Known Variants355 total
| rsid | Position (GRCh37) | Alleles | Class | ClinVar |
|---|---|---|---|---|
| rs1887428 | 9:4,984,530 | G/C | regulatory region variant | — |
| rs4495487 | 9:4,985,087 | G/A | intron variant | benign |
| rs1057515590 | 9:4,985,601 | C/T | — | uncertain significance |
| rs2274471 | 9:4,985,879 | A/G | regulatory region variant | — |
| rs3780374 | 9:4,985,955 | C/T | intron variant | — |
| rs7849191 | 9:4,988,761 | C/G | — | — |
| rs1327494 | 9:4,999,303 | A/G | intron variant | — |
| rs4587378 | 9:5,002,011 | C/T | intron variant | — |
| rs10815144 | 9:5,010,192 | G/A | intron variant | — |
| rs10974919 | 9:5,021,738 | G/A | — | benign |
| rs759031245 | 9:5,022,025 | G/T | — | likely benign |
| rs150159583 | 9:5,022,042 | A/G | — | conflicting classifications of pathogenicity |
| rs1321992857 | 9:5,022,073 | C/T | — | uncertain significance |
| rs778174935 | 9:5,022,081 | A/G | — | uncertain significance |
| rs761588246 | 9:5,022,091 | T/C | — | uncertain significance |
| rs138655335 | 9:5,022,124 | C/A | — | conflicting classifications of pathogenicity |
| rs149333413 | 9:5,022,128 | T/G | — | likely benign |
| rs143227399 | 9:5,022,130 | G/A | — | conflicting classifications of pathogenicity |
| rs754086152 | 9:5,022,163 | C/G | — | uncertain significance |
| rs1439413818 | 9:5,022,168 | G/A | — | uncertain significance |
| rs1211921813 | 9:5,022,175 | T/C | — | uncertain significance |
| rs1237113183 | 9:5,022,213 | G/T | — | uncertain significance |
| rs2488857097 | 9:5,022,214 | G/T | — | likely pathogenic |
| rs745497028 | 9:5,022,218 | G/A | — | uncertain significance |
| rs2488878759 | 9:5,029,779 | C/G | — | likely benign |
| rs2488878770 | 9:5,029,785 | A/G | — | uncertain significance |
| rs2488878863 | 9:5,029,804 | A/C | — | uncertain significance |
| rs1823027113 | 9:5,029,845 | C/G | — | uncertain significance |
| rs760406225 | 9:5,029,858 | T/C | — | uncertain significance |
| rs751548297 | 9:5,029,878 | A/G | — | uncertain significance |
| rs969443461 | 9:5,029,884 | C/T | — | uncertain significance |
| rs143103233 | 9:5,029,893 | C/G | — | conflicting classifications of pathogenicity |
| rs753508497 | 9:5,029,912 | T/C | — | uncertain significance |
| rs374591930 | 9:5,029,914 | C/G | — | likely benign |
| rs74715056 | 9:5,030,080 | T/C | — | benign |
| rs59668095 | 9:5,043,688 | C/A | — | — |
| rs1183813595 | 9:5,044,383 | A/G | — | likely benign |
| rs761744348 | 9:5,044,388 | T/C | — | likely benign |
| rs114448906 | 9:5,044,397 | T/C | — | likely benign |
| rs370926996 | 9:5,044,399 | G/A | — | likely benign |
| rs147483622 | 9:5,044,416 | C/T | — | uncertain significance |
| rs757898652 | 9:5,044,417 | G/A | — | likely benign |
| rs56118985 | 9:5,044,432 | G/A | missense variant | likely benign |
| rs371826393 | 9:5,044,449 | C/T | — | uncertain significance |
| rs140052813 | 9:5,044,458 | A/T | — | likely benign |
| rs1299892808 | 9:5,044,488 | G/A | — | conflicting classifications of pathogenicity |
| rs1423362345 | 9:5,044,529 | A/G | — | likely benign |
| rs2488935937 | 9:5,044,533 | T/G | — | likely benign |
| rs1816856850 | 9:5,044,536 | C/G | — | likely benign |
| rs201672634 | 9:5,044,540 | C/T | — | benign |
| rs62541556 | 9:5,049,092 | G/T | intron variant | — |
| rs1028912 | 9:5,050,369 | G/C | — | benign |
| rs1817353412 | 9:5,050,670 | A/C | — | likely benign |
| rs2488957279 | 9:5,050,685 | G/C | — | uncertain significance |
| rs2230722 | 9:5,050,706 | C/T | synonymous variant | benign |
| rs1168347611 | 9:5,050,707 | G/A | — | uncertain significance |
| rs907414891 | 9:5,050,713 | A/G | — | uncertain significance |
| rs1489246318 | 9:5,050,763 | A/C | — | likely benign |
| rs1445295304 | 9:5,050,791 | G/A | — | uncertain significance |
| rs41302214 | 9:5,050,796 | C/T | — | likely benign |
| rs559371331 | 9:5,050,809 | C/T | — | benign |
| rs2488958012 | 9:5,050,811 | G/A | — | likely benign |
| rs1429131183 | 9:5,050,813 | C/T | — | uncertain significance |
| rs375180351 | 9:5,050,827 | A/G | — | uncertain significance |
| rs752012407 | 9:5,050,836 | T/G | — | uncertain significance |
| rs1163257946 | 9:5,050,837 | T/A | — | uncertain significance |
| rs753837462 | 9:5,050,840 | C/G | — | benign |
| rs2488958229 | 9:5,050,850 | T/C | — | likely benign |
| rs7872649 | 9:5,050,910 | C/T | — | benign |
| rs1276845749 | 9:5,054,590 | T/C | — | likely benign |
| rs772744665 | 9:5,054,630 | C/T | — | uncertain significance |
| rs765286468 | 9:5,054,648 | C/T | — | uncertain significance |
| rs373174105 | 9:5,054,649 | G/A | — | uncertain significance |
| rs62637625 | 9:5,054,679 | A/G | — | likely benign |
| rs920001853 | 9:5,054,691 | G/C | — | uncertain significance |
| rs200778413 | 9:5,054,706 | A/G | — | uncertain significance |
| rs755432226 | 9:5,054,707 | G/A | — | likely benign |
| rs759144937 | 9:5,054,775 | G/C | — | uncertain significance |
| rs1269895569 | 9:5,054,779 | T/G | — | uncertain significance |
| rs765196728 | 9:5,054,784 | C/T | — | uncertain significance |
| rs775577651 | 9:5,054,786 | T/C | — | uncertain significance |
| rs2130412360 | 9:5,054,848 | A/T | — | uncertain significance |
| rs1447845301 | 9:5,054,862 | A/C | — | uncertain significance |
| rs1245776198 | 9:5,054,879 | G/A | — | uncertain significance |
| rs528112691 | 9:5,054,897 | G/A | — | benign |
| rs1536799 | 9:5,055,015 | T/C | — | benign |
| rs1536800 | 9:5,055,434 | T/C | — | benign |
| rs12343867 | 9:5,055,522 | T/C | intron variant | — |
| rs373315248 | 9:5,055,653 | A/G | — | likely benign |
| rs1287074277 | 9:5,055,665 | A/G | — | likely benign |
| rs2488977229 | 9:5,055,668 | G/C | — | uncertain significance |
| rs2488977542 | 9:5,055,711 | A/C | — | uncertain significance |
| rs769401778 | 9:5,055,712 | G/T | — | uncertain significance |
| rs1817717168 | 9:5,055,727 | A/G | — | uncertain significance |
| rs1817717386 | 9:5,055,732 | G/A | — | uncertain significance |
| rs748854741 | 9:5,055,736 | G/A | — | uncertain significance |
| rs149683525 | 9:5,055,741 | A/G | — | benign |
| rs761540696 | 9:5,055,746 | A/G | — | likely benign |
| rs776830350 | 9:5,055,751 | G/A | — | uncertain significance |
| rs2488977949 | 9:5,055,766 | A/G | — | uncertain significance |
Showing 100 of 355 variants. Use the SNP search for the full list.
Gene information from NCBI Gene. Variant classifications from ClinVar.