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UniProtKB/Swiss-Prot P31213: Variant p.Arg227Gln

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

Variant position:  227
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Disease [Disclaimer]
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants implicated in disease according to literature reports.
  • Polymorphism: Variants not reported to be implicated in disease.
  • Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:  From Arginine (R) to Glutamine (Q) at position 227 (R227Q, p.Arg227Gln).
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 (Q)
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

Involvement in disease:  Pseudovaginal perineoscrotal hypospadias (PPSH) [MIM:264600]: A form of male pseudohermaphroditism in which 46,XY males show ambiguous genitalia at birth, including perineal hypospadias and a blind perineal pouch, and develop masculinization at puberty. The name of the disorder stems from the finding of a blind-ending perineal opening resembling a vagina and a severely hypospadiac penis with the urethra opening onto the perineum. {ECO:0000269|PubMed:10718838, ECO:0000269|PubMed:10898110, ECO:0000269|PubMed:10999800, ECO:0000269|PubMed:12843198, ECO:0000269|PubMed:15064320, ECO:0000269|PubMed:1522235, ECO:0000269|PubMed:15528927, ECO:0000269|PubMed:15770495, ECO:0000269|PubMed:16098368, ECO:0000269|PubMed:16181229, ECO:0000269|PubMed:7554313, ECO:0000269|PubMed:8626825, ECO:0000269|PubMed:8768837, ECO:0000269|PubMed:9208814, ECO:0000269|PubMed:9745434, ECO:0000269|PubMed:9843052}. Note=The disease is caused by mutations affecting the gene represented in this entry.
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:  In PPSH; also in individuals with micropenis; increased affinity for testosterone; increased affinity for NADPH; decreased Vmax.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  227
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:   ATWSLPALAFAFFSLCFLGL  R AFHHHRFYLKMFEDYPKSRK
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                         ATWSLPALAFAFFSLCFLGLRAFHHHRFYLKMFEDYPKSRK

Mouse                         ATWSVPAFAFAFFTLCFLGMQAFYHHRFYLKMFKDYPKSRK

Rat                           ATWSVPAFAFAFFTLCFLGMQAFYHHRFYLKMFKDYPKSRK

Pig                           ATWSLPALAFAFFSLCFLGLRAFHHHRFYVKMFEDYPKSRK

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.

TypePositionsDescription
Chain 1 – 254 3-oxo-5-alpha-steroid 4-dehydrogenase 2


Literature citations

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; LEU-89; MET-187; LEU-194 AND LEU-234; VARIANT PPSH GLN-227; FUNCTION; CATALYTIC ACTIVITY; BIOPHYSICOCHEMICAL PROPERTIES;

Micropenis and the 5alpha-reductase-2 (SRD5A2) gene: mutation and V89L polymorphism analysis in 81 Japanese patients.
Sasaki G.; Ogata T.; Ishii T.; Kosaki K.; Sato S.; Homma K.; Takahashi T.; Hasegawa T.; Matsuo N.;
J. Clin. Endocrinol. Metab. 88:3431-3436(2003)
Cited for: VARIANT PPSH GLN-227; VARIANT LEU-89;

Compound heterozygous mutations in the SRD5A2 gene exon 4 in a male pseudohermaphrodite patient of Chinese origin.
Fernandez-Cancio M.; Nistal M.; Gracia R.; Molina M.A.; Tovar J.A.; Esteban C.; Carrascosa A.; Audi L.;
J. Androl. 25:412-416(2004)
Cited for: VARIANT PPSH GLN-227;

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.