UniProtKB/SwissProt variant VAR

Variant information

Variant position:

775

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 Histidine (H) at position 775 (R775H, p.Arg775His).

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 (H)

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

Variant description:

In AIS and PAIS; almost complete loss of androgen binding.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs137852572 [ dbSNP | Ensembl ]

Sequence information

Variant position:

775

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:

FTNVNSRMLYFAPDLVFNEY R MHKSRMYSQCVRMRHLSQEF

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                         FTNVNSRMLYFAPDLVFNEYRMHKSRMYSQCVRMRHLSQEF

                              FTNVNSRMLYFAPDLVFNEYRMHKSRMYSQCVRMRHLSQEF

Rhesus macaque                FTNVNSRMLYFAPDLVFNEYRMHKSRMYSQCVRMRHLSQEF

Chimpanzee                    FTNVNSRMLYFAPDLVFNEYRMHKSRMYSQCVRMRHLSQEF

Mouse                         FTNVNSRMLYFAPDLVFNEYRMHKSRMYSQCVRMRHLSQEF

Rat                           FTNVNSRMLYFAPDLVFNEYRMHKSRMYSQCVRMRHLSQEF

Pig                           FTNVNSRMLYFAPDLVFNEYRMHKSRMYSQCVRMRHLSQEF

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
Alternative sequence	645 – 920	Missing. In isoform 3.
Alternative sequence	649 – 920	Missing. In isoform 4.
Helix	773 – 778

Literature citations

Replacement of arginine 773 by cysteine or histidine in the human androgen receptor causes complete androgen insensitivity with different receptor phenotypes.
Prior L.; Bordet S.; Trifiro M.A.; Mhatre A.; Kaufman M.; Pinsky L.; Wrogemann K.; Belsham D.D.; Pereira F.; Greenberg C.R.; Trapman J.; Brinkmann A.O.; Chang C.; Liao S.;
Am. J. Hum. Genet. 51:143-155(1992)
Cited for: VARIANTS AIS CYS-775 AND HIS-775;

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 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;

Human androgen receptor gene ligand-binding-domain mutations leading to disrupted interaction between the N- and C-terminal domains.
Jaeaeskelaeinen J.; Deeb A.; Schwabe J.W.; Mongan N.P.; Martin H.; Hughes I.A.;
J. Mol. Endocrinol. 36:361-368(2006)
Cited for: CHARACTERIZATION OF VARIANTS AIS ASN-696; CYS-764; HIS-775; GLU-799; HIS-856 AND PHE-908;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P10275: Variant p.Arg775His