UniProtKB/Swiss-Prot P10275: Variant p.Ala646Asp

Androgen receptor
Gene: AR
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Variant information Variant position:

646 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 Aspartate (D) at position 646 (A646D, p.Ala646Asp). 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 acidic (D) 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
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.
Other resources:

Links to websites of interest for the variant.

Variant rs1800053 [ dbSNP | Ensembl ]

Sequence information Variant position:

646 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:

TLGARKLKKLGNLKLQEEGE A SSTTSPTEETTQKLTVSHIE 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                         TLGARKLKKLGNLKLQEEGEASSTTSPTEETTQKLTVSHIE

                              TLGARKLKKLGNLKLQEEGEASNVTSPTEEPTQKLTVSHIE

Rhesus macaque                TLGARKLKKLGNLKLQEEGEASSTTSPTEETAQKLTVSHIE

Chimpanzee                    TLGARKLKKLGNLKLQEEGEASSTTSPTEETTQKLTVSHIE

Mouse                         TLGARKLKKLGNLKLQEEGENSNAGSPTEDPSQKMTVSHIE

Rat                           TLGARKLKKLGNLKLQEEGENSSAGSPTEDPSQKMTVSHIE

Pig                           TLGARKLKKLGNLKLQEEGEASSATSPTEEPAQKLTVSHIE

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
Region	552 – 919	Interaction with LPXN
Region	572 – 662	Interaction with HIPK3
Region	592 – 919	Interaction with CCAR1
Region	625 – 919	Interaction with KAT7
Modified residue	651 – 651	Phosphoserine; by STK4/MST1
Alternative sequence	630 – 648	RKLKKLGNLKLQEEGEASS -> AVVVSERILRVFGVSEWLP. In isoform 4.
Alternative sequence	645 – 920	Missing. In isoform 3.

Literature citations
An androgen receptor gene mutation (A645D) in a boy with a normal phenotype.
Nordenskjoeld A.; Soederhaell S.;
Hum. Mutat. 11:339-339(1998)
Cited for: VARIANT ASP-646;

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.