UniProtKB/Swiss-Prot P52952 : Variant p.Arg25Cys
Homeobox protein Nkx-2.5
Gene: NKX2-5
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Variant information
Variant position:
25
The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:
US
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 Cysteine (C) at position 25 (R25C, p.Arg25Cys).
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 medium size and polar (C)
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 ASD7, TOF, CHNG5, HLHS2 and CTHM; uncertain significance; exhibits significant functional impairment with reduction of transactivation properties and dominant-negative effect; the mutant protein activity on the DIO2, TG and TPO promoters is significantly impaired.
Any additional useful information about the variant.
Other resources:
Links to websites of interest for the variant.
Sequence information
Variant position:
25
The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:
324
The length of the canonical sequence.
Location on the sequence:
PALTPTPFSVKDILNLEQQQ
R SLAAAGELSARLEATLAPSS
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 PALTPTPFSVKDILNLEQQQR SLAAAGELSARLEATLAPSS
Mouse PALTPTPFSVKDILNLE-QQQ RSLASGDLSARLEATLAPAS
Rat PALTHTPFSVKDILNLE-QQQ RSLAAGDLSARLEATLAPAS
Chicken P-VTTTPFSVKDILNLEQQQQ GGLAPMELSS--------PS
Xenopus laevis P-VTSTPFSVKDILNLE-QHQ SGLSPMDITSRLEN----SS
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
1 – 324
Homeobox protein Nkx-2.5
Literature citations
Mutations in the cardiac transcription factor NKX2.5 affect diverse cardiac developmental pathways.
Benson D.W.; Silberbach G.M.; Kavanaugh-McHugh A.; Cottrill C.; Zhang Y.; Riggs S.; Smalls O.; Johnson M.C.; Watson M.S.; Seidman J.G.; Seidman C.E.; Plowden J.; Kugler J.D.;
J. Clin. Invest. 104:1567-1573(1999)
Cited for: VARIANT TOF CYS-25; VARIANTS ASD7 LYS-188; GLY-189 AND CYS-191;
NKX2.5 mutations in patients with tetralogy of fallot.
Goldmuntz E.; Geiger E.; Benson D.W.;
Circulation 104:2565-2568(2001)
Cited for: VARIANTS TOF GLN-21; CYS-25; CYS-216 AND VAL-219;
NKX2.5 mutations in patients with congenital heart disease.
McElhinney D.B.; Geiger E.; Blinder J.; Benson D.W.; Goldmuntz E.;
J. Am. Coll. Cardiol. 42:1650-1655(2003)
Cited for: VARIANTS ASD7 ILE-15; VAL-63; GLU-127 AND THR-275; VARIANTS TOF GLN-21; PRO-22; CYS-25; CYS-216; VAL-219 AND THR-323; VARIANT CTMH ASN-291 DEL; VARIANT HLHS2 CYS-25; INVOLVEMENT IN CONGENITAL HEART MALFORMATIONS;
Somatic NKX2-5 mutations as a novel mechanism of disease in complex congenital heart disease.
Reamon-Buettner S.M.; Borlak J.;
J. Med. Genet. 41:684-690(2004)
Cited for: VARIANTS ASD7 PRO-7; SER-19; CYS-25; PRO-45; LEU-51; PRO-69; LEU-77; SER-114; ARG-114; ARG-118; ARG-124; VAL-126; SER-133; THR-135; PRO-144; MET-178; GLU-183; THR-192; ARG-192; ARG-194; GLU-205; VAL-219; ASN-226; HIS-248; PRO-279; PHE-279; VAL-281; VAL-286; HIS-294; GLY-299; GLY-305; SER-320 AND GLN-322;
Phenotypes with GATA4 or NKX2.5 mutations in familial atrial septal defect.
Hirayama-Yamada K.; Kamisago M.; Akimoto K.; Aotsuka H.; Nakamura Y.; Tomita H.; Furutani M.; Imamura S.; Takao A.; Nakazawa M.; Matsuoka R.;
Am. J. Med. Genet. A 135:47-52(2005)
Cited for: VARIANTS ASD7 ILE-15; GLN-21; PRO-22; CYS-25; VAL-63; GLU-127; CYS-142; MET-178; HIS-187; LYS-188; GLY-189; CYS-190; CYS-191; CYS-216; VAL-219; THR-275 AND THR-323; VARIANT HLHS2 CYS-25;
Missense mutation in the transcription factor NKX2-5: a novel molecular event in the pathogenesis of thyroid dysgenesis.
Dentice M.; Cordeddu V.; Rosica A.; Ferrara A.M.; Santarpia L.; Salvatore D.; Chiovato L.; Perri A.; Moschini L.; Fazzini C.; Olivieri A.; Costa P.; Stoppioni V.; Baserga M.; De Felice M.; Sorcini M.; Fenzi G.; Di Lauro R.; Tartaglia M.; Macchia P.E.;
J. Clin. Endocrinol. Metab. 91:1428-1433(2006)
Cited for: VARIANTS CHNG5 CYS-25; SER-119 AND PRO-161; CHARACTERIZATION OF VARIANTS CHNG5 CYS-25; SER-119 AND PRO-161;
The effect of p.Arg25Cys alteration in NKX2-5 on conotruncal heart anomalies: mutation or polymorphism?
Akcaboy M.I.; Cengiz F.B.; Inceoglu B.; Ucar T.; Atalay S.; Tutar E.; Tekin M.;
Pediatr. Cardiol. 29:126-129(2008)
Cited for: VARIANT CTHM CYS-25;
Comprehensive genotype-phenotype analysis in 230 patients with tetralogy of Fallot.
Rauch R.; Hofbeck M.; Zweier C.; Koch A.; Zink S.; Trautmann U.; Hoyer J.; Kaulitz R.; Singer H.; Rauch A.;
J. Med. Genet. 47:321-331(2010)
Cited for: VARIANT TOF CYS-25;
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.