UniProtKB/Swiss-Prot P10275: Variant p.Phe726Leu

Androgen receptor
Gene: AR
Feedback?

Variant information Variant position:

726 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 Phenylalanine (F) to Leucine (L) at position 726 (F726L, p.Phe726Leu). 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 aromatic (F) to medium size and hydrophobic (L) 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:

The poly-Gln region of AR is highly polymorphic and the number of Gln varies in the population (from 17 to 26). A smaller size of the poly-Gln region may be associated with the development of prostate cancer. Long poly-Gln alleles (>23) may be associated with higher testosterone levels and severe clinical outcome in COVID-19 disease (PubMed:33647767).The poly-Gly region of AR is polymorphic and ranges from 24 to 31 Gly. A poly-Gly region shorter or equal to 23 may be associated with the development of androgenetic alopecia. - Additional information on the polymorphism described.
Variant description:

In a patient with severe hypospadias. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs1555996810 [ dbSNP | Ensembl ]

Sequence information Variant position:

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

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

NELGERQLVHVVKWAKALPG F RNLHVDDQMAVIQYSWMGLM 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                         NELGERQLVHVVKWAKALPGFRNLHVDDQMAVIQYSWMGLM

                              NELGERQLVHVVKWAKALPGFRNLHVDDQMAVIQYSWMGLM

Rhesus macaque                NELGERQLVHVVKWAKALPGFRNLHVDDQMAVIQYSWMGLM

Chimpanzee                    NELGERQLVHVVKWAKALPGFRNLHVDDQMAVIQYSWMGLM

Mouse                         NELGERQLVHVVKWAKALPGFRNLHVDDQMAVIQYSWMGLM

Rat                           NELGERQLVHVVKWAKALPGFRNLHVDDQMAVIQYSWMGLM

Pig                           NELGERQLVHVVKWAKALPGFRNLHVDDQMAVIQYSWMGLM

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 – 920	Androgen receptor
Domain	669 – 900	NR LBD
Region	552 – 919	Interaction with LPXN
Region	592 – 919	Interaction with CCAR1
Region	625 – 919	Interaction with KAT7
Binding site	706 – 706
Site	721 – 721	Interaction with coactivator LXXL and FXXFY motifs
Alternative sequence	645 – 920	Missing. In isoform 3.
Alternative sequence	649 – 920	Missing. In isoform 4.
Mutagenesis	721 – 721	K -> A. Loss of transcription activation in the presence of androgen and of interaction with NCOA2.
Mutagenesis	742 – 742	W -> L. Strongly decreased transcription activation in the presence of androgen.
Helix	726 – 728

Literature citations
Androgen receptor defects: historical, clinical, and molecular perspectives.
Quigley C.A.; De Bellis A.; Marschke K.B.; el-Awady M.K.; Wilson E.M.; French F.S.;
Endocr. Rev. 16:271-321(1995)
Cited for: VARIANTS AIS SER-706 AND HIS-764; VARIANTS PAIS LEU-726; THR-738; HIS-775 AND GLU-799; Screening for mutations in candidate genes for hypospadias.
Nordenskjoeld A.; Friedman E.; Tapper-Persson M.; Soederhaell C.; Leviav A.; Svensson J.; Anvret M.;
Urol. Res. 27:49-55(1999)
Cited for: VARIANTS THR-598 AND LEU-726;

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.