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. 2019 Nov 8;11(11):1757. doi: 10.3390/cancers11111757

Table 1.

Disease-associated mutations in the STAT3 SH2 domain.

Mutation Position Location Residue Relevance Nucleotide Substitution Cases Pathology Type Ref
K591E αA2 pY Sheinerman 1771A>G 1 AD-HIES Germline [30]
K591M αA2 pY Sheinerman 1772A>T 1 AD-HIES Germline [31]
R593P αA4 pY - 1778G>C 1 AD-HIES Germline [32]
R609G βB5 pY Sheinerman& Signature 1825A>G 1 AD-HIES Germline [33]
S611G βB7 pY Sheinerman 1831A>G 2 AD-HIES Germline [34,35]
S611N βB7 pY & Signature Sheinerman 1832G>A 2 AD-HIES Germline [36,37]
S611I βB7 pY Sheinerman & Signature 1832G>T 1 AD-HIES Germline [38]
S614G BC3 pY Sheinerman 18040A>G 1 AD-HIES Germline [34]
S614R BC3 pY Sheinerman 1842C>G 1 T-LGLL Somatic [39,40,41,42,43]
2 NK-LGLL
1 ALK-ALCL
1 HSTL
E616G BC5 pY BC loop 1847A>G 1 DLBCL, NOS Somatic [44]
E616K BC5 pY BC loop 1846G>A 1 NKTL Somatic [45]
G617E BC6 pY BC loop 1850G>A 1 AD-HIES Germline [46]
G617V BC6 pY BC loop 1850G>T 1 AD-HIES Germline [34]
G617R BC6 pY BC loop 1849G>A 1 DLBCL, NOS Somatic [44]
G618R BC6 pY BC loop 1852G>C 1 ALK-ALCL Somatic [47,48]
1 T-LGLL
G618D BC6 pY BC loop 1853G>A 2 AD-HIES Germline [35,37]
T620A βC2 pY - 1858A>G 2 AD-HIES Germline [34,49]
T620S βC2 pY - 1859C>G 1 AD-HIES Germline [33]
F621V βC3 pY+3 Hydro. Sys. 1861T>G 3 AD-HIES Germline [36,37,50]
F621L βC3 pY+3 Hydro. Sys. 1863C>G 2 AD-HIES Germline [51,52]
F621S βC3 pY+3 Hydro. Sys. 1862T>C 1 AD-HIES Germline [53]
T622I βC4 pY - 1865C>T 4 AD-HIES Germline [30,34,36]
D627E CD1 - 1881C>A 1 ATLL Somatic [54]
S636F βD4 pY Sheinerman 1907C>T, 1 AD-HIES Germline [49]
S636Y βD4 pY Sheinerman 1907C>A 1 AD-HIES Germline [30]
V637M βD5 pY+3 Sel. Filter 1909G>A 43 AD-HIES Germline [30,32,33,34,35,36,37,49,52,55,56]
V637L βD5 pY+3 Sel. Filter 1909G>T 1 AD-HIES Germline [36]
V637A βD5 pY+3 Sel. Filter 1910T>C 1 AD-HIES Germline [30]
E638G βD6 pY Sheinerman 1913A>G 4 AD-HIES Germline [49,51,57,58]
P639A βD7 pY+3 - 1915C>G 1 AD-HIES Germline [37]
P639S βD7 pY+3 - 1915C>T* 2 AD-HIES Germline [30,34]
P639T βD7 pY+3 - 1915C>A 1 AD-HIES Germline [35]
Y640F DB’1 pY+3 - 1919A>T 56 T-LGLL Somatic [43,44,47,48,57,59,60,61,62,63,64,65,66,67,68,69]
2 IHT
3 CLPD-NKs
2 NK-LGLL
1 DLBCL, NOS
1 ANKL
1 NKTL
1 Sezary
3 HSTL
K642E αB’1 - Dimer Inter 1924A>G 1 AD-HIES Germline [34]
Q643K αB’2 - Dimer Inter 1927C>A 1 T-LGLL Somatic [68]
Q644P αB’3 - Dimer Inter 1929A>C 3 AD-HIES Germline [52,70]
Q644del αB’3 - Dimer Inter 1930del CAG 2 AD-HIES Germline [35,36]
N646K αB’5 pY+3 Dimer Inter 1938C>G 2 EOAD Germline [71]
N647D αB’6 pY+3 Dimer Inter 1939A>G 8 AD-HIES Germline [36,72]
N647I αB’6 pY+3 Dimer Inter 1940A>T 3 CLPD-NK Somatic [43,57,65,67]
6 T-LGLL
1 HSTL
E652K αB3 pY+3 Dimer Inter 1954G>A 1 AD-HIES Germline [36]
G656D αB7 pY+3 Dimer Inter 1967G>A 1 T-LGLL Somatic [73]
G656_Y657insF αB7 pY+3 Hydro. Sys. 1968C>T; 1969_1970insTTT 1 IHCA Somatic [66]
Y657C BC1* pY+3 Hydro. Sys. 1970A>G 5 AD-HIES Germline [30,34,36,58]
Y657S BC1* pY+3 Hydro. Sys. 1970A>C 1 AD-HIES Germline [74]
Y657N BC1* pY+3 Hydro. Sys. 1969T>A 1 AD-HIES Germline [52]
Y657ins BC1* pY+3 Hydro. Sys. - 1 TCL Somatic [47]
Y657dup BC1* pY+3 Hydro. Sys. - 3 T-LGLL Somatic [48,65,72]
Y657_M660dup BC1* pY+3 Hydro. Sys. 1969T_1980G dup 1 IHCA Somatic [66]
K658M BC2* pY+3 Dimer Inter 1973A>T 2 T-LGLL Somatic [67,72]
K658N BC2* pY+3 Dimer Inter 1974G>T 1 T-LGLL
EOAD		 Somatic/Germline [65,71]
K658Y BC2* pY+3 Dimer Inter 1972A>T; 1974G>T 1 IHCA Somatic [66]
K658E BC2* pY+3 Dimer Inter 1972A>G 1 AD-HIES Germline [75]
I659N BC3* pY+3 Hydro. Sys. 1976A>T 1 AD-HIES Germline [58]
I659L BC3* pY+3 Hydro. Sys. 1975A>C 2 T-LGLL Somatic [57,72]
M660R BC4* pY+3 Dimer Inter 1979T>G 1 AD-HIES Germline [55]
M660T BC4* pY+3 Dimer Inter 1978T>A 1 AD-HIES Germline [76]
D661I BC5* - Dimer Inter 1981G>A; 1982A>T 1 CLPD-NK Somatic [67]
D661Y BC5* - Dimer Inter 1981G>T 1 NK-LGL Somatic [41,47,48,60,63,65,67,68,72,77]
56 T-LGL
1 HSTL
10 NKTL
D661ins BC5* - Dimer Inter - 1 T-LGLL Somatic [47]
D661V BC5* - Dimer Inter 1981A>T 10 T-LGLL Somatic [65,67]
D661H BC5* - Dimer Inter 1981G>C 1 T-LGLL Somatic [65]
A662V BC6* - Dimer Inter 1985C>T 1 ALK-ALCL Somatic [78]
T663I BC7* - Dimer Inter 1988, 1989>TT 2 DLBCL/B1 Germline [44,75]
I665N BC9* - Dimer Inter 1998T>A 2 AD-HIES Germline [34]
V667L BC11* - Dimer Inter 1999C>G 1 NKTL Somatic [45]
S668F BC12* - Dimer Inter 2003C>T 3 AD-HIES Germline [30,34,37]
S668Y BC12* - Dimer Inter 2003C>A 1 AD-HIES Germline [34]

The final search date for mutations from medical case reports and literature was 30 August, 2019. Abbreviations: AD-HIES, autosomal-dominant Hyper IgE syndrome; ALK-ALCL, anaplastic lymphoma kinase negative anaplastic large cell lymphoma; ANKL, aggressive natural killer cell leukemia; ATLL, adult T-cell leukemia lymphoma; EOAD, early onset autoimmune disease; CLPD-NKs, Chronic lymphoproliferative disorders of natural killer cells; DLBCL, NOS, Diffuse large B-cell lymphoma, not-otherwise-specified; NKTL, extranodal NK/T-cell lymphoma; HSTL, Hepatosplenic T-cell lymphoma; IHAC, inflammatory hepatocellular adenomas; IHT, inflammatory hepatocellular tumors; NK-LGLL, Natural killer cell large granular lymphocytic leukemia; T-LGLL, T-cell large granular lymphocytic leukemia; TCL, γδ-T-cell lymphoma.