UniProtKB/Swiss-Prot P40763: Variant p.Arg152Trp

Signal transducer and activator of transcription 3
Gene: STAT3
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Variant information Variant position:

152 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

LP/P [Disclaimer] The variants are classified into three categories: LP/P, LB/B and US.

LP/P: likely pathogenic or pathogenic.
LB/B: likely benign or benign.
US: uncertain significance

Residue change:

From Arginine (R) to Tryptophan (W) at position 152 (R152W, p.Arg152Trp). Indicates the amino acid change of the variant. The one-letter and three-letter codes for amino acids used in UniProtKB/Swiss-Prot are those adopted by the commission on Biochemical Nomenclature of the IUPAC-IUB.
Physico-chemical properties:

Change from large size and basic (R) to large size and aromatic (W) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

-3 The score within a Blosum matrix for the corresponding wild-type to variant amino acid change. The log-odds score measures the logarithm for the ratio of the likelihood of two amino acids appearing by chance. The Blosum62 substitution matrix is used. This substitution matrix contains scores for all possible exchanges of one amino acid with another:

Lowest score: -4 (low probability of substitution).
Highest score: 11 (high probability of substitution).

More information can be found on the following page
Variant description:

In ADMIO1; likely pathogenic; results in increased transcriptional activation. Any additional useful information about the variant.

Sequence information Variant position:

152 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

770 The length of the canonical sequence.
Location on the sequence:

PTAAVVTEKQQMLEQHLQDV R KRVQDLEQKMKVVENLQDDF The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.
Residue conservation:

The multiple alignment of the region surrounding the variant against various orthologous sequences.

Human                         PTAAVVTEKQQMLEQHLQDVRKRVQDLEQKMKVVENLQDDF

Mouse                         PTAAVVTEKQQMLEQHLQDVRKRVQDLEQKMKVVENLQDDF

Rat                           PTAAVVTEKQQMLEQHLQDVRKRVQDLEQKMKVVENLQDDF

Pig                           PTAAVVTEKQQMLEQHLQDVRKRVQDLEQKMKVVENLQDDF

Bovine                        PTAAVVTEKQQMLEQHLQDVRKRVQDLEQKMKVVENLLDDF

Chicken                       PTAAVVTEKQQMLEQHLQDVRKRVQDLEQKMKVVENLQDDF

Sequence annotation in neighborhood:

The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:

Type: the type of sequence feature.
Positions: endpoints of the sequence feature.
Description: contains additional information about the feature.

Type	Positions	Description
Chain	2 – 770	Signal transducer and activator of transcription 3
Motif	150 – 162	Essential for nuclear import
Modified residue	140 – 140	N6-methyllysine
Helix	139 – 177

Literature citations
Early-onset lymphoproliferation and autoimmunity caused by germline STAT3 gain-of-function mutations.
Milner J.D.; Vogel T.P.; Forbes L.; Ma C.A.; Stray-Pedersen A.; Niemela J.E.; Lyons J.J.; Engelhardt K.R.; Zhang Y.; Topcagic N.; Roberson E.D.; Matthews H.; Verbsky J.W.; Dasu T.; Vargas-Hernandez A.; Varghese N.; McClain K.L.; Karam L.B.; Nahmod K.; Makedonas G.; Mace E.M.; Sorte H.S.; Perminow G.; Rao V.K.; O'Connell M.P.; Price S.; Su H.C.; Butrick M.; McElwee J.; Hughes J.D.; Willet J.; Swan D.; Xu Y.; Santibanez-Koref M.; Slowik V.; Dinwiddie D.L.; Ciaccio C.E.; Saunders C.J.; Septer S.; Kingsmore S.F.; White A.J.; Cant A.J.; Hambleton S.; Cooper M.A.;
Blood 125:591-599(2015)
Cited for: VARIANTS ADMIO1 TRP-152; HIS-344; PHE-353; LYS-415; LYS-420; ARG-421; ILE-663; THR-703 AND MET-716; CHARACTERIZATION OF VARIANTS ADMIO1 TRP-152; HIS-344; PHE-353; LYS-415; LYS-420; ARG-421; THR-703 AND MET-716; INVOLVEMENT IN ADMIO1;
Monogenic early-onset lymphoproliferation and autoimmunity: Natural history of STAT3 gain-of-function syndrome.
Leiding J.W.; Vogel T.P.; Santarlas V.G.J.; Mhaskar R.; Smith M.R.; Carisey A.; Vargas-Hernandez A.; Silva-Carmona M.; Heeg M.; Rensing-Ehl A.; Neven B.; Hadjadj J.; Hambleton S.; Ronan Leahy T.; Meesilpavikai K.; Cunningham-Rundles C.; Dutmer C.M.; Sharapova S.O.; Taskinen M.; Chua I.; Hague R.; Klemann C.; Kostyuchenko L.; Morio T.; Thatayatikom A.; Ozen A.; Scherbina A.; Bauer C.S.; Flanagan S.E.; Gambineri E.; Giovannini-Chami L.; Heimall J.; Sullivan K.E.; Allenspach E.; Romberg N.; Deane S.G.; Prince B.T.; Rose M.J.; Bohnsack J.; Mousallem T.; Jesudas R.; Santos Vilela M.M.D.; O'Sullivan M.; Pachlopnik Schmid J.; Pruhova S.; Klocperk A.; Rees M.; Su H.; Bahna S.; Baris S.; Bartnikas L.M.; Chang Berger A.; Briggs T.A.; Brothers S.; Bundy V.; Chan A.Y.; Chandrakasan S.; Christiansen M.; Cole T.; Cook M.C.; Desai M.M.; Fischer U.; Fulcher D.A.; Gallo S.; Gauthier A.; Gennery A.R.; Goncalo Marques J.; Gottrand F.; Grimbacher B.; Grunebaum E.; Haapaniemi E.; Haemaelaeinen S.; Heiskanen K.; Heiskanen-Kosma T.; Hoffman H.M.; Gonzalez-Granado L.I.; Guerrerio A.L.; Kainulainen L.; Kumar A.; Lawrence M.G.; Levin C.; Martelius T.; Neth O.; Olbrich P.; Palma A.; Patel N.C.; Pozos T.; Preece K.; Lugo Reyes S.O.; Russell M.A.; Schejter Y.; Seroogy C.; Sinclair J.; Skevofilax E.; Suan D.; Suez D.; Szabolcs P.; Velasco H.; Warnatz K.; Walkovich K.; Worth A.; Seppaenen M.R.J.; Torgerson T.R.; Sogkas G.; Ehl S.; Tangye S.G.; Cooper M.A.; Milner J.D.; Forbes Satter L.R.;
J. Allergy Clin. Immunol. 151:1081-1095(2023)
Cited for: VARIANTS ADMIO1 HIS-70; TRP-103; TRP-107; TRP-152; ARG-162; ASP-166; LYS-166; SER-174; ALA-218; PRO-260; CYS-278; HIS-278; GLN-302; TRP-325; ARG-331; HIS-344; PHE-353; ARG-361; ARG-387; ALA-389; ARG-389; SER-389; THR-394; LEU-408; GLN-415; LYS-415; GLY-415; ARG-419; LYS-420; ARG-421; ARG-422; ILE-443; ASP-447; GLU-448; LYS-506; ARG-546; PHE-640; ARG-643; LYS-646; ARG-658; ILE-663; TYR-664; LEU-715 AND MET-716;

Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.