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UniProtKB/Swiss-Prot P10275: Variant p.Arg841His

Androgen receptor
Gene: AR
Variant information

Variant position:  841
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 Arginine (R) to Histidine (H) at position 841 (R841H, p.Arg841His).
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

Involvement in disease:  Androgen insensitivity syndrome (AIS) [MIM:300068]: An X-linked recessive form of pseudohermaphroditism due end-organ resistance to androgen. Affected males have female external genitalia, female breast development, blind vagina, absent uterus and female adnexa, and abdominal or inguinal testes, despite a normal 46,XY karyotype. {ECO:0000269|PubMed:10022458, ECO:0000269|PubMed:10221692, ECO:0000269|PubMed:10221770, ECO:0000269|PubMed:10404311, ECO:0000269|PubMed:10458483, ECO:0000269|PubMed:10571951, ECO:0000269|PubMed:10590024, ECO:0000269|PubMed:10690872, ECO:0000269|PubMed:11587068, ECO:0000269|PubMed:11744994, ECO:0000269|PubMed:1307250, ECO:0000269|PubMed:1316540, ECO:0000269|PubMed:1426313, ECO:0000269|PubMed:1430233, ECO:0000269|PubMed:1464650, ECO:0000269|PubMed:14756668, ECO:0000269|PubMed:1480178, ECO:0000269|PubMed:1487249, ECO:0000269|PubMed:1569163, ECO:0000269|PubMed:1609793, ECO:0000269|PubMed:16129672, ECO:0000269|PubMed:16595706, ECO:0000269|PubMed:1775137, ECO:0000269|PubMed:1999491, ECO:0000269|PubMed:2082179, ECO:0000269|PubMed:2594783, ECO:0000269|PubMed:7537149, ECO:0000269|PubMed:7581399, ECO:0000269|PubMed:7633398, ECO:0000269|PubMed:7641413, ECO:0000269|PubMed:7671849, ECO:0000269|PubMed:7929841, ECO:0000269|PubMed:7962294, ECO:0000269|PubMed:7970939, ECO:0000269|PubMed:7981687, ECO:0000269|PubMed:7981689, ECO:0000269|PubMed:7993455, ECO:0000269|PubMed:8040309, ECO:0000269|PubMed:8096390, ECO:0000269|PubMed:8103398, ECO:0000269|PubMed:8162033, ECO:0000269|PubMed:8224266, ECO:0000269|PubMed:8281140, ECO:0000269|PubMed:8325950, ECO:0000269|PubMed:8339746, ECO:0000269|PubMed:8413310, ECO:0000269|PubMed:8446106, ECO:0000269|PubMed:8626869, ECO:0000269|PubMed:8647313, ECO:0000269|PubMed:8683794, ECO:0000269|PubMed:8723113, ECO:0000269|PubMed:8768864, ECO:0000269|PubMed:8809734, ECO:0000269|PubMed:8830623, ECO:0000269|PubMed:8918984, ECO:0000269|PubMed:8990010, ECO:0000269|PubMed:9001799, ECO:0000269|PubMed:9007482, ECO:0000269|PubMed:9039340, ECO:0000269|PubMed:9106550, ECO:0000269|PubMed:9160185, ECO:0000269|PubMed:9252933, ECO:0000269|PubMed:9255042, ECO:0000269|PubMed:9302173, ECO:0000269|PubMed:9328206, ECO:0000269|PubMed:9544375, ECO:0000269|PubMed:9554754, ECO:0000269|PubMed:9610419, ECO:0000269|PubMed:9627582, ECO:0000269|PubMed:9698822, ECO:0000269|PubMed:9851768, ECO:0000269|PubMed:9856504, ECO:0000269|Ref.113, ECO:0000269|Ref.179}. 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 AIS.
Any additional useful information about the variant.

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



Sequence information

Variant position:  841
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:   GLKNQKFFDELRMNYIKELD  R IIACKRKNPTSCSRRFYQLT
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                         GLKNQKFFDELRMNYIKELDRIIACKRKNPTSCSRRFYQLT

                              GLKNQKFFDELRMNYIKELDRIIACKRKNPTSCSRRFYQLT

Rhesus macaque                GLKNQKFFDELRMNYIKELDRIIACKRKNPTSCSRRFYQLT

Chimpanzee                    GLKNQKFFDELRMNYIKELDRIIACKRKNPTSCSRRFYQLT

Mouse                         GLKNQKFFDELRMNYIKELDRIIACKRKNPTSCSRRFYQLT

Rat                           GLKNQKFFDELRMNYIKELDRIIACKRKNPTSCSRRFYQLT

Pig                           GLKNQKFFDELRMNYIKELDRIIACKRKNPTSCSRRFYQLT

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 – 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 825 – 843


Literature citations

Single strand conformation polymorphism analysis of androgen receptor gene mutations in patients with androgen insensitivity syndromes: application for diagnosis, genetic counseling, and therapy.
Hiort O.; Huang Q.; Sinnecker G.H.; Sadeghi-Nejad A.; Kruse K.; Wolfe H.J.; Yandell D.W.;
J. Clin. Endocrinol. Metab. 77:262-266(1993)
Cited for: VARIANTS AIS LYS-682 AND THR-843; VARIANTS PAIS HIS-841 AND LEU-867;

Molecular prenatal exclusion of familial partial androgen insensitivity (Reifenstein syndrome).
Lumbroso S.; Lobaccaro J.-M.; Belon C.; Amram S.; Bachelard B.; Garandeau P.; Sultan C.;
Eur. J. Endocrinol. 130:327-332(1994)
Cited for: VARIANT PAIS HIS-841;

Single amino acid substitution (840Arg-->His) in the hormone-binding domain of the androgen receptor leads to incomplete androgen insensitivity syndrome associated with a thermolabile androgen receptor.
Imasaki K.; Hasegawa T.; Okabe T.; Sakai Y.; Haji M.; Takayanagi R.; Nawata H.;
Eur. J. Endocrinol. 130:569-574(1994)
Cited for: VARIANT PAIS HIS-841;

Characterization of mutant androgen receptors causing partial androgen insensitivity syndrome.
De Bellis A.; Quigley C.A.; Marschke K.B.; el-Awady M.K.; Lane M.V.; Smith E.P.; Sar M.; Wilson E.M.; French F.S.;
J. Clin. Endocrinol. Metab. 78:513-522(1994)
Cited for: VARIANTS PAIS ARG-617; HIS-841 AND MET-890;

Substitution of arginine-839 by cysteine or histidine in the androgen receptor causes different receptor phenotypes in cultured cells and coordinate degrees of clinical androgen resistance.
Beitel L.K.; Kazemi-Esfarjani P.; Kaufman M.; Lumbroso R.; DiGeorge A.M.; Killinger D.W.; Trifiro M.A.; Pinsky L.;
J. Clin. Invest. 94:546-554(1994)
Cited for: VARIANTS AIS CYS-841 AND HIS-841;

A frame-shift mutation of the androgen receptor gene in a patient with receptor-negative complete testicular feminization: comparison with a single base substitution in a receptor-reduced incomplete form.
Imai A.; Ohno T.; Iida K.; Ohsuye K.; Okano Y.; Tamaya T.;
Ann. Clin. Biochem. 32:482-486(1995)
Cited for: VARIANT AIS HIS-841;

Clinical and biochemical investigations and molecular analysis of subjects with mutations in the androgen receptor gene.
Weidemann W.; Linck B.; Haupt H.; Mentrup B.; Romalo G.; Stockklauser K.; Brinkmann A.O.; Schweikert H.-U.; Spindler K.D.;
Clin. Endocrinol. (Oxf.) 45:733-739(1996)
Cited for: VARIANTS PAIS GLN-608; THR-611; LEU-755; HIS-841; THR-843 AND HIS-856; VARIANT AIS MET-867;

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.