To improve security and privacy, we are moving our web pages and services from HTTP to HTTPS.
To give users of web services time to transition to HTTPS, we will support separate HTTP and HTTPS services until the end of 2017.
From January 2018 most HTTP traffic will be automatically redirected to HTTPS. [more...]
View this page in https

UniProtKB/Swiss-Prot P16435: Variant p.Ala284Pro

NADPH--cytochrome P450 reductase
Gene: POR
Chromosomal location: 7q11.2
Variant information

Variant position:  284
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 Alanine (A) to Proline (P) at position 284 (A284P, p.Ala284Pro).
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 hydrophobic (P)
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:  Disordered steroidogenesis due to cytochrome P450 oxidoreductase deficiency (DISPORD) [MIM:613571]: A disorder resulting in a rare variant of congenital adrenal hyperplasia, with apparent combined P450C17 and P450C21 deficiency and accumulation of steroid metabolites. Affected girls are born with ambiguous genitalia, but their circulating androgens are low and virilization does not progress. Conversely, affected boys are sometimes born undermasculinized. Boys and girls can present with bone malformations, in some cases resembling the pattern seen in patients with Antley-Bixler syndrome. {ECO:0000269|PubMed:14758361, ECO:0000269|PubMed:15220035}. 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.

Involvement in disease:  Antley-Bixler syndrome, with genital anomalies and disordered steroidogenesis (ABS1) [MIM:201750]: A disease characterized by the association of Antley-Bixler syndrome with steroidogenesis defects and abnormal genitalia. Antley-Bixler syndrome is characterized by craniosynostosis, radiohumeral synostosis present from the perinatal period, midface hypoplasia, choanal stenosis or atresia, femoral bowing and multiple joint contractures. {ECO:0000269|PubMed:14758361, ECO:0000269|PubMed:15264278, ECO:0000269|PubMed:15483095}. 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 ABS1 and DISPORD; significant reduction of activity.
Any additional useful information about the variant.



Sequence information

Variant position:  284
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  677
The length of the canonical sequence.

Location on the sequence:   GRLKSYENQKPPFDAKNPFL  A AVTTNRKLNQGTERHLMHLE
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                         GR--LKSYENQKP-------PFDAKNPFLAAVTTNRKLNQG-TERHLMHLE

Mouse                         GR--LKSYENQKP-------PFDAKNPFLAAVTTNRKLNQG

Rat                           GR--LKSYENQKP-------PFDAKNPFLAAVTANRKLNQG

Pig                           GR--LKSYENQKP-------PFDAKNPFLAVVTTNRKLNQG

Bovine                        GR--LKSYENQKP-------PFDAKNPFLAVVTTNRKLNQG

Rabbit                        GR--LKSYENQKP-------PFDAKNPFLATVTTNRKLNQG

Drosophila                    AR--LHSIQNQRP-------PFDAKNPFLAPIKVNRELHKG

Slime mold                    STPLKPKLSTDNKV------IYDMKNPYYAEVLENRELHSN

Baker's yeast                 SAHYLPSHQLNRNADGIQLGPFDLSQPYIAPIVKSRELFSS

Fission yeast                 SRQQLKGNVASKA-------PRSQANPFFSSPVRSLELFKS

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 2 – 677 NADPH--cytochrome P450 reductase
Topological domain 43 – 677 Cytoplasmic
Domain 279 – 521 FAD-binding FR-type
Binding site 298 – 298 NADP
Beta strand 282 – 291


Literature citations

Congenital adrenal hyperplasia caused by mutant P450 oxidoreductase and human androgen synthesis: analytical study.
Arlt W.; Walker E.A.; Draper N.; Ivison H.E.; Ride J.P.; Hammer F.; Chalder S.M.; Borucka-Mankiewicz M.; Hauffa B.P.; Malunowicz E.M.; Stewart P.M.; Shackleton C.H.L.;
Lancet 363:2128-2135(2004)
Cited for: VARIANTS DISPORD ASP-178; PRO-284; HIS-454 AND TYR-566; CHARACTERIZATION OF VARIANTS DISPORD ASP-178; PRO-284; HIS-454 AND TYR-566;

Mutant P450 oxidoreductase causes disordered steroidogenesis with and without Antley-Bixler syndrome.
Flueck C.E.; Tajima T.; Pandey A.V.; Arlt W.; Okuhara K.; Verge C.F.; Jabs E.W.; Mendonca B.B.; Fujieda K.; Miller W.L.;
Nat. Genet. 36:228-230(2004)
Cited for: VARIANTS ABS1 PRO-284; HIS-454 AND GLU-489; VARIANTS DISPORD TYR-566 AND PHE-605; CHARACTERIZATION OF VARIANTS ABS1 PRO-284; HIS-454 AND GLU-489; CHARACTERIZATION OF VARIANTS DISPORD TYR-566 AND PHE-605;

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.