UniProtKB/Swiss-Prot P11245: Variant p.Ile114Thr

Arylamine N-acetyltransferase 2
Gene: NAT2
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Variant information Variant position:

114 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 Isoleucine (I) to Threonine (T) at position 114 (I114T, p.Ile114Thr). 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 hydrophobic (I) to medium size and polar (T) 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
Polymorphism:

Genetic variations in NAT2 determine the rate of acetylation of various arylamine and heterocyclic amine substrates that include therapeutic and carcinogenic agents. They influence drug therapy response and susceptibility to chemical toxicity [MIM:243400]. Different alleles are known, whose combination defines the rapid, intermediate and slow acetylator phenotypes. Allele NAT2*4 sequence is historically considered as the reference in most publications. The sequence shown in this entry corresponds to the translation of allele NAT2*12A, which is the one represented in the human reference genome (GRCh38/hg38 assembly) and has an arginine at position 268 (Ref.7). The enzyme encoded by allele NAT2*4 differs by the variant p.Arg268Lys (PubMed:2734109). The two alloenzymes have comparable arylamine N-acetyltransferase activity (PubMed:11337936). Additional information on the polymorphism described.
Variant description:

In allele NAT2*5A, allele NAT2*5B, allele NAT2*5C, allele NAT2*5D, allele NAT2*5E, allele NAT2*5F, allele NAT2*5G, allele NAT2*5I, allele NAT2*5K, allele NAT2*5L, allele NAT2*5M, allele NAT2*14C and allele NAT2*14F; 7 to 12-fold lower Vmax; decreased arylamine N-acetyltransferase activity when associated in cis with K-268; loss of arylamine N-acetyltransferase activity when associated in cis with F-137. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs1801280 [ dbSNP | Ensembl ]

Sequence information Variant position:

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

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

YIPPVNKYSTGMVHLLLQVT I DGRNYIVDAGSGSSSQMWQP 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                         YIPP-VNKYSTGMVHLLLQVTIDGRNYIVDAGSGSSSQMWQP

Rhesus macaque                YIPA-ANKYSTGMIHLLLQVTIDGRNYIADAGFGSSSQMWQ

Mouse                         FNTP-ANKYSSGMIHLLVQVTISGKDYIVDAGFGRSYQMWE

Rat                           FNTP-ANKYSSGMIHLLVQVTLSGKDYIVDAGFGRSYQMWE

Rabbit                        YGSN-NDKYSTGMIHLIVQVTINGRNYIVDAGFGRSYQMWQ

Chicken                       YIPE-HDAYADDIDHLLLKVVLHDKSYIVDGGFGMAYQLWQ

Slime mold                    ENQETHDCWQINGAHIINIIEYENKKYLADVAFGCNLS-YE

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 – 290	Arylamine N-acetyltransferase 2
Active site	107 – 107
Active site	122 – 122
Binding site	103 – 103
Binding site	104 – 104
Beta strand	107 – 114

Literature citations
Cloning, expression, and functional characterization of two mutant (NAT2(191) and NAT2(341/803)) and wild-type human polymorphic N-acetyltransferase (NAT2) alleles.
Ferguson R.J.; Doll M.A.; Rustan T.D.; Gray K.; Hein D.W.;
Drug Metab. Dispos. 22:371-376(1994)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ALLELES NAT2*5C AND NAT2*14A); VARIANTS GLN-64; THR-114 AND LYS-268; FUNCTION; CATALYTIC ACTIVITY; BIOPHYSICOCHEMICAL PROPERTIES; CHARACTERIZATION OF VARIANTS GLN-64; THR-114 AND LYS-268; Deciphering the ancient and complex evolutionary history of human arylamine N-acetyltransferase genes.
Patin E.; Barreiro L.B.; Sabeti P.C.; Austerlitz F.; Luca F.; Sajantila A.; Behar D.M.; Semino O.; Sakuntabhai A.; Guiso N.; Gicquel B.; McElreavey K.; Harding R.M.; Heyer E.; Quintana-Murci L.;
Am. J. Hum. Genet. 78:423-436(2006)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]; VARIANTS ILE-24; GLN-64; THR-114; MET-193; GLN-197; HIS-208; LYS-268 AND GLU-286; Submission
Leff M.A.; Doll M.A.; Feng Y.; Fretland A.J.; Hein D.W.;
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ALLELES NAT2*5D; NAT2*6D; NAT2*14G); VARIANTS GLN-64; THR-114; GLN-197 AND LYS-268; A novel linkage of two NAT2 mutations.
Banerjee M.; Anitha A.;
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]; VARIANTS THR-114 AND LYS-268; A novel allele showing linkage with 282, 341, 481, 803 point mutations in the NAT2 gene.
Pillai A.A.; Banerjee M.;
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]; VARIANT THR-114; A novel NAT2 allele with point mutations 341, 481, 803, 859 in the ethnic populations of Kerala.
Pillai A.A.; Banerjee M.;
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]; VARIANT THR-114; Submission
Doll M.A.; Zang Y.; Yeager M.; Welch R.; Chanock S.; Hein D.W.;
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ALLELES NAT2*5I AND NAT2*12D); VARIANTS THR-114; ASN-122 AND PHE-137; Submission
NIEHS SNPs program;
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]; VARIANTS ILE-24; GLN-64; THR-114; GLN-197; LEU-228; LYS-268 AND GLU-286; Functional characterization of human N-acetyltransferase 2 (NAT2) single nucleotide polymorphisms.
Fretland A.J.; Leff M.A.; Doll M.A.; Hein D.W.;
Pharmacogenetics 11:207-215(2001)
Cited for: CHARACTERIZATION OF VARIANTS GLN-64; THR-114; PRO-145; GLN-197; LYS-268; THR-282 AND GLU-286; Functional characterization of the A411T (L137F) and G364A (D122N) genetic polymorphisms in human N-acetyltransferase 2.
Zang Y.; Zhao S.; Doll M.A.; States J.C.; Hein D.W.;
Pharmacogenet. Genomics 17:37-45(2007)
Cited for: CHARACTERIZATION OF VARIANTS THR-114; ASN-122; PHE-137 AND LYS-268; Worldwide distribution of NAT2 diversity: implications for NAT2 evolutionary history.
Sabbagh A.; Langaney A.; Darlu P.; Gerard N.; Krishnamoorthy R.; Poloni E.S.;
BMC Genet. 9:21-21(2008)
Cited for: VARIANTS GLN-64; THR-114; VAL-135; GLN-197; ASP-203; LEU-213; LYS-268; MET-280 AND GLU-286;

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.