UniProtKB/Swiss-Prot P40763: Variant p.Thr716Met

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

716 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 Threonine (T) to Methionine (M) at position 716 (T716M, p.Thr716Met). 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 medium size and polar (T) to medium size and hydrophobic (M) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

-1 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; pathogenic; results in increased transcriptional activation. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs869312892 [ dbSNP | Ensembl ]

Sequence information Variant position:

716 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:

EADPGSAAPYLKTKFICVTP T TCSNTIDLPMSPRTLDSLMQ 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                         EA-DPGSAAPYLKTKFICVTPTTCSNTIDLPMSPRTLDSLMQ

Mouse                         EA-DPGSAAPYLKTKFICVTPTTCSNTIDLPMSPRTLDSLM

Rat                           EA-DPGSAAPYLKTKFICVTPTTCSNTIDLPMSPRTLDSLM

Pig                           EA-DPGSAAPYLKTKFICVTPTTCSNTIDLPMSPRTLDSLM

Bovine                        EA-DPGSAAPYLKTKFICVTPTTCSNTIDLPMSPRTLDSLM

Chicken                       EATDSGSAAPYLKTKFICVTPTSFSNTIDLPMSPRTLDSLM

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
Modified residue	705 – 705	Phosphotyrosine; by FER and PTK6
Modified residue	707 – 707	N6-acetyllysine
Modified residue	714 – 714	Phosphothreonine
Modified residue	727 – 727	Phosphoserine; by DYRK2, NLK, NEK6, IRAK1, RPS6KA5, ZIPK/DAPK3 and PKC/PRKCE
Alternative sequence	701 – 701	Missing. In isoform Del-701.
Alternative sequence	716 – 722	TTCSNTI -> FIDAVWK. In isoform 3.
Mutagenesis	705 – 705	Y -> F. Inhibits leptin-mediated transactivation of CCND1 promoter. Abolished phosphorylation by isoform M2 of PKM (PKM2).

Literature citations
Activating germline mutations in STAT3 cause early-onset multi-organ autoimmune disease.
Flanagan S.E.; Haapaniemi E.; Russell M.A.; Caswell R.; Lango Allen H.; De Franco E.; McDonald T.J.; Rajala H.; Ramelius A.; Barton J.; Heiskanen K.; Heiskanen-Kosma T.; Kajosaari M.; Murphy N.P.; Milenkovic T.; Seppaenen M.; Lernmark A.; Mustjoki S.; Otonkoski T.; Kere J.; Morgan N.G.; Ellard S.; Hattersley A.T.;
Nat. Genet. 46:812-814(2014)
Cited for: VARIANTS ADMIO1 ARG-392; LYS-646; ASN-658 AND MET-716; INVOLVEMENT IN ADMIO1; 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.