UniProtKB/SwissProt variant VAR

Variant information

Variant position:

856

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

Type of variant:

LP/P [Disclaimer]

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 Arginine (R) to Cysteine (C) at position 856 (R856C, p.Arg856Cys).

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 (C)

The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:

-3

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

Variant description:

In AIS.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs886041132 [ dbSNP | Ensembl ]

Sequence information

Variant position:

856

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:

IKELDRIIACKRKNPTSCSR R FYQLTKLLDSVQPIARELHQ

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                         IKELDRIIACKRKNPTSCSRRFYQLTKLLDSVQPIARELHQ

                              IKELDRIIACKRKNPTSCSRRFYQLTKLLDSVQPIARELHQ

Rhesus macaque                IKELDRIIACKRKNPTSCSRRFYQLTKLLDSVQPIARELHQ

Chimpanzee                    IKELDRIIACKRKNPTSCSRRFYQLTKLLDSVQPIARELHQ

Mouse                         IKELDRIIACKRKNPTSCSRRFYQLTKLLDSVQPIARELHQ

Rat                           IKELDRIIACKRKNPTSCSRRFYQLTKLLDSVQPIARELHQ

Pig                           IKELDRIIACKRKNPTSCSRRFYQLTKLLDSVQPIARELHQ

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
Cross	846 – 846	Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
Cross	848 – 848	Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
Alternative sequence	645 – 920	Missing. In isoform 3.
Alternative sequence	649 – 920	Missing. In isoform 4.
Mutagenesis	846 – 846	K -> R. Prevents ubiquitination by RNF6. Prevents AR transcriptional activation by RNF14 in absence of hormone.
Mutagenesis	848 – 848	K -> R. Partially prevents ubiquitination by RNF6.
Helix	853 – 883

Literature citations

Single base mutations in the human androgen receptor gene causing complete androgen insensitivity: rapid detection by a modified denaturing gradient gel electrophoresis technique.
De Bellis A.; Quigley C.A.; Cariello N.F.; el-Awady M.K.; Sar M.; Lane M.V.; Wilson E.M.; French F.S.;
Mol. Endocrinol. 6:1909-1920(1992)
Cited for: VARIANTS AIS SER-706; VAL-750; PHE-760; HIS-775; CYS-856 AND GLY-865;

Androgen receptor (AR) gene mutations in 6 families with androgen insensitivity syndrome (Abstract #114).
Lobaccaro J.-M.; Lumbroso S.; Belon C.; Chaussain J.L.; Toublanc J.E.; Leheup B.; Sultan C.;
Cited for: VARIANTS AIS PHE-582; VAL-744; VAL-755; GLU-768 AND CYS-856;

Human androgen insensitivity due to point mutations encoding amino acid substitutions in the androgen receptor steroid-binding domain.
Murono K.; Mendonca B.B.; Arnhold I.J.P.; Rigon A.C.M.M.; Migeon C.J.; Brown T.R.;
Hum. Mutat. 6:152-162(1995)
Cited for: VARIANT PAIS CYS-764; VARIANTS AIS TRP-780; VAL-808 AND CYS-856;

Rapid detection of a mutation hot-spot in the human androgen receptor.
Malmgren H.; Gustavsson J.; Tuvemo T.; Dahl N.;
Clin. Genet. 50:202-205(1996)
Cited for: VARIANT AIS CYS-856;

DNA analysis of the androgen receptor gene in two cases with complete androgen insensitivity syndrome.
Komori S.; Sakata K.; Tanaka H.; Shima H.; Koyama K.;
J. Obstet. Gynaecol. Res. 23:277-281(1997)
Cited for: VARIANTS AIS ARG-196 AND CYS-856;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P10275: Variant p.Arg856Cys