UniProtKB/Swiss-Prot P31213: Variant p.Ala49Thr

3-oxo-5-alpha-steroid 4-dehydrogenase 2
Gene: SRD5A2
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Variant information Variant position:

49 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 Alanine (A) to Threonine (T) at position 49 (A49T, p.Ala49Thr). 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 small size and hydrophobic (A) to medium size and polar (T) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

0 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:

Individuals with Thr-49 have an increased risk of prostate cancer (PubMed:10501358). The enzyme with Thr-49 has a higher in vitro V(max) than the Ala-49 enzyme (PubMed:10501358). Additional information on the polymorphism described.
Variant description:

Increased affinity for testosterone; no effect on affinity for NADPH; increased Vmax. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs9282858 [ dbSNP | Ensembl ]

Sequence information Variant position:

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

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

KPSGYGKHTESLKPAATRLP A RAAWFLQELPSFAVPAGILA 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                         KPSGYGKHTESLKPAATRLPARAAWFLQELPSFAVPAGILA

Mouse                         KPASYGKHSESVSSGVPLLPARIAWFLQELPSFVVSVGMLA

Rat                           KPASYGKHTESVSSGVPFLPARIAWFLQELPSFVVSVGMLA

Pig                           EPSGYGKYTESLTPAAIRLPARAAWFLQELPSFVVPAGILA

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 – 254	3-oxo-5-alpha-steroid 4-dehydrogenase 2
Helix	49 – 57

Literature citations
Submission
NIEHS SNPs program;
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]; VARIANTS THR-49; VAL-89 AND VAL-113; Association of mis-sense substitution in SRD5A2 gene with prostate cancer in African-American and Hispanic men in Los Angeles, USA.
Makridakis N.M.; Ross R.K.; Pike M.C.; Crocitto L.E.; Kolonel L.N.; Pearce C.L.; Henderson B.E.; Reichardt J.K.V.;
Lancet 354:975-978(1999)
Cited for: VARIANT THR-49; POLYMORPHISM; Biochemical and pharmacogenetic dissection of human steroid 5 alpha-reductase type II.
Makridakis N.M.; di Salle E.; Reichardt J.K.;
Pharmacogenetics 10:407-413(2000)
Cited for: VARIANTS ARG-5; LEU-30; ARG-48; THR-49; THR-51; VAL-89; MET-187; LEU-194 AND LEU-234; VARIANT PPSH GLN-227; FUNCTION; CATALYTIC ACTIVITY; BIOPHYSICOCHEMICAL PROPERTIES; CHARACTERIZATION OF VARIANTS THR-49; VAL-89; MET-187 AND LEU-234; Comprehensive evaluation of the association between prostate cancer and genotypes/haplotypes in CYP17A1, CYP3A4, and SRD5A2.
Loukola A.; Chadha M.; Penn S.G.; Rank D.; Conti D.V.; Thompson D.; Cicek M.; Love B.; Bivolarevic V.; Yang Q.; Jiang Y.; Hanzel D.K.; Dains K.; Paris P.L.; Casey G.; Witte J.S.;
Eur. J. Hum. Genet. 12:321-332(2004)
Cited for: VARIANT THR-49; LACK OF ASSOCIATION WITH PROSTATE CANCER; SRD5A2 gene analysis in an Italian population of under-masculinized 46,XY subjects.
Nicoletti A.; Baldazzi L.; Balsamo A.; Barp L.; Pirazzoli P.; Gennari M.; Radetti G.; Cacciari E.; Cicognani A.;
Clin. Endocrinol. (Oxf.) 63:375-380(2005)
Cited for: VARIANTS PPSH TRP-145; LEU-181; SER-196; PHE-235 AND GLN-246; VARIANTS THR-49 AND VAL-89; New mutations, hotspots, and founder effects in Brazilian patients with steroid 5alpha-reductase deficiency type 2.
Hackel C.; Oliveira L.E.; Ferraz L.F.; Tonini M.M.; Silva D.N.; Toralles M.B.; Stuchi-Perez E.G.; Guerra-Junior G.;
J. Mol. Med. 83:569-576(2005)
Cited for: VARIANTS PPSH ARG-126; ARG-158; SER-183; SER-196; ASP-207 AND TRP-246; VARIANTS THR-49 AND VAL-89;

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.