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UniProtKB/Swiss-Prot P11511: Variant p.Cys437Tyr

Aromatase
Gene: CYP19A1
Chromosomal location: 15q21.1
Variant information

Variant position:  437
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 Cysteine (C) to Tyrosine (Y) at position 437 (C437Y, p.Cys437Tyr).
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 polar (C) to large size and aromatic (Y)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -2
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:  Aromatase deficiency (AROD) [MIM:613546]: A rare disease in which fetal androgens are not converted into estrogens due to placental aromatase deficiency. Thus, pregnant women exhibit a hirsutism, which spontaneously resolves after post-partum. At birth, female babies present with pseudohermaphroditism due to virilization of extern genital organs. In adult females, manifestations include delay of puberty, breast hypoplasia and primary amenorrhoea with multicystic ovaries. {ECO:0000269|PubMed:24705274, ECO:0000269|PubMed:8265607, ECO:0000269|PubMed:8530621, ECO:0000269|PubMed:9211678}. 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 AROD; complete loss of activity.
Any additional useful information about the variant.

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



Sequence information

Variant position:  437
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  503
The length of the canonical sequence.

Location on the sequence:   NFAKNVPYRYFQPFGFGPRG  C AGKYIAMVMMKAILVTLLRR
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                         NFAKNVPYRYFQPFGFGPRGCAGKYIAMVMMKAILVTLLRR

                              NFAKNVPYRYFQPFGFGPRSCAGKYIAMVMMKVVLVTLLRR

Mouse                         NFEKNVPYRYFQPFGFGPRGCAGKYIAMVMMKVVLVTLLRR

Rat                           NFEKNVPYRYFQPFGFGPRSCAGKYIAMVMMKVVLVTLLKR

Bovine                        NFAKNVPYRYFQPFGFGPRACAGKYITMVMMKVVLVTLLRR

Rabbit                        NFAKNVPYRYFQPFGFGPRGCAGKYIAMVMMKVILVTLLRR

Goat                          NFAKNVPYRYFQPFGFGPRACAGKYIAMVMMKVILVTLLRR

Sheep                         NFAKNVPYRYFQPFGFGPRACAGKYIAMVMMKVILVTLLRR

Horse                         NFEKNVPYRYFQPFGFGPRSCAGKFIAMVMMKVMLVSLLRR

Chicken                       NFEKNVPSRYFQPFGFGPRGCVGKFIAMVMMKAILVTLLRR

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 – 503 Aromatase
Metal binding 437 – 437 Iron (heme axial ligand)
Alternative sequence 219 – 503 Missing. In isoform 2.


Literature citations

Molecular basis of aromatase deficiency in an adult female with sexual infantilism and polycystic ovaries.
Ito Y.; Fisher C.R.; Conte F.A.; Grumbach M.M.; Simpson E.R.;
Proc. Natl. Acad. Sci. U.S.A. 90:11673-11677(1993)
Cited for: VARIANTS AROD CYS-435 AND TYR-437;

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.