UniProtKB/Swiss-Prot Q9NV35: Variant p.Arg139Cys

Nucleotide triphosphate diphosphatase NUDT15
Gene: NUDT15
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Variant information Variant position:

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

LB/B 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 139 (R139C, p.Arg139Cys). 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
Polymorphism:

Polymorphic NUDT15 variants define the poor metabolism of thiopurines 2 genetic locus (THPM2) [MIM:616903]. Thiopurines are used as immunosuppressants or cytotoxic drugs and are prescribed for a variety of clinical conditions including leukemia, autoimmune disease and organ transplantation. Patients with low NUDT15 activities have an increased risk for toxic effects after receiving standard doses of thiopurine drugs. Additional information on the polymorphism described.
Variant description:

Risk factor for thiopurines toxicity; decreased thermostability; loss of diphosphatase activity towards 6-thio-dGTP and 6-thio-GTP. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs116855232 [ dbSNP | Ensembl ]

Sequence information Variant position:

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

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

SWEWVPWEELPPLDQLFWGL R CLKEQGYDPFKEDLNHLVGY 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                         SWEWVPWEELPPLDQLFWGLRCLKEQGYDPFKEDLNHLVGY

Mouse                         SWEWVPWEEFPPLDQLFWALRCLKEQGYDPFKEDLNHLEGY

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 – 164	Nucleotide triphosphate diphosphatase NUDT15
Domain	9 – 145	Nudix hydrolase
Region	76 – 164	Interaction with PCNA
Helix	136 – 143

Literature citations
A common missense variant in NUDT15 confers susceptibility to thiopurine-induced leukopenia.
Yang S.K.; Hong M.; Baek J.; Choi H.; Zhao W.; Jung Y.; Haritunians T.; Ye B.D.; Kim K.J.; Park S.H.; Park S.K.; Yang D.H.; Dubinsky M.; Lee I.; McGovern D.P.; Liu J.; Song K.;
Nat. Genet. 46:1017-1020(2014)
Cited for: POLYMORPHISM; VARIANT CYS-139; NUDT15 polymorphisms alter thiopurine metabolism and hematopoietic toxicity.
Moriyama T.; Nishii R.; Perez-Andreu V.; Yang W.; Klussmann F.A.; Zhao X.; Lin T.N.; Hoshitsuki K.; Nersting J.; Kihira K.; Hofmann U.; Komada Y.; Kato M.; McCorkle R.; Li L.; Koh K.; Najera C.R.; Kham S.K.; Isobe T.; Chen Z.; Chiew E.K.; Bhojwani D.; Jeffries C.; Lu Y.; Schwab M.; Inaba H.; Pui C.H.; Relling M.V.; Manabe A.; Hori H.; Schmiegelow K.; Yeoh A.E.; Evans W.E.; Yang J.J.;
Nat. Genet. 48:367-373(2016)
Cited for: POLYMORPHISM; VARIANTS ILE-18; GLY-VAL-18 INS; CYS-139 AND HIS-139; CHARACTERIZATION OF VARIANTS ILE-18; GLY-VAL-18 INS; CYS-139 AND HIS-139; CATALYTIC ACTIVITY;

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.