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UniProtKB/Swiss-Prot Q13285: Variant p.Arg92Trp

Steroidogenic factor 1
Gene: NR5A1
Chromosomal location: 9q33
Variant information

Variant position:  92
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 Tryptophan (W) at position 92 (R92W, p.Arg92Trp).
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 large size and aromatic (W)
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

Involvement in disease:  46,XY sex reversal 3 (SRXY3) [MIM:612965]: A condition characterized by male-to-female sex reversal in the presence of a normal 46,XY karyotype. {ECO:0000269|PubMed:10369247, ECO:0000269|PubMed:11932325, ECO:0000269|PubMed:17200175, ECO:0000269|PubMed:17694559, ECO:0000269|PubMed:24405868, ECO:0000269|PubMed:27378692, ECO:0000269|PubMed:27490115}. 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.

Involvement in disease:  46,XX sex reversal 4 (SRXX4) [MIM:617480]: A condition in which male gonads develop in a genetic female (female to male sex reversal). {ECO:0000269|PubMed:27378692, ECO:0000269|PubMed:27490115, ECO:0000269|PubMed:27610946, ECO:0000269|PubMed:27855412}. 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 SRXY3 and SRXX4; decreased transactivator activity; loss of DNA binding, at least to some known consensus target sequences; no effect on nuclear location.
Any additional useful information about the variant.



Sequence information

Variant position:  92
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  461
The length of the canonical sequence.

Location on the sequence:   KCLTVGMRLEAVRADRMRGG  R NKFGPMYKRDRALKQQKKAQ
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                         KCLTVGMRLEAVRADRMRGGRNKFGPMYKRDRALKQQKKAQ

Mouse                         KCLTVGMRLEAVRADRMRGGRNKFGPMYKRDRALKQQKKAQ

Rat                           KCLTVGMRLEAVRADRMRGGRNKFGPMYKRDRALKQQKKAQ

Pig                           KCLTVGMRLEAVRADRMRGGRNKFGPMYKRDRALKQQKKAQ

Bovine                        KCLTVGMRLEAVRADRMRGGRNKFGPMYKRDRALKQQKKAQ

Horse                         KCLTVGMRLEAVRADRMRGGRNKFGPMYKRDRALKQQKKAQ

Baker's yeast                 RCISRNTRL--------------------------------

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 – 461 Steroidogenic factor 1
Modified residue 72 – 72 N6-acetyllysine


Literature citations

NR5A1 is a novel disease gene for 46,XX testicular and ovotesticular disorders of sex development.
Baetens D.; Stoop H.; Peelman F.; Todeschini A.L.; Rosseel T.; Coppieters F.; Veitia R.A.; Looijenga L.H.; De Baere E.; Cools M.;
Genet. Med. 19:367-376(2017)
Cited for: VARIANT SRXX4 TRP-92; CHARACTERIZATION OF VARIANT SRXX4 TRP-92; INVOLVEMENT IN SRXX4; CHARACTERIZATIONOF VARIANT SRXY3 GLN-92; SUBCELLULAR LOCATION;

A recurrent p.Arg92Trp variant in steroidogenic factor-1 (NR5A1) can act as a molecular switch in human sex development.
Bashamboo A.; Donohoue P.A.; Vilain E.; Rojo S.; Calvel P.; Seneviratne S.N.; Buonocore F.; Barseghyan H.; Bingham N.; Rosenfeld J.A.; Mulukutla S.N.; Jain M.; Burrage L.; Dhar S.; Balasubramanyam A.; Lee B.; Dumargne M.C.; Eozenou C.; Suntharalingham J.P.; de Silva K.; Lin L.; Bignon-Topalovic J.; Poulat F.; Lagos C.F.; McElreavey K.; Achermann J.C.;
Hum. Mol. Genet. 25:3446-3453(2016)
Cited for: INVOLVEMENT IN SRXX4; INVOLVEMENT IN SRXY3; VARIANT SRXX4 TRP-92; VARIANT SRXY3 TRP-92; CHARACTERIZATION OF VARIANT SRXX4 TRP-92; FUNCTION;

Identical NR5A1 missense mutations in two unrelated 46,XX individuals with testicular tissues.
Igarashi M.; Takasawa K.; Hakoda A.; Kanno J.; Takada S.; Miyado M.; Baba T.; Morohashi K.I.; Tajima T.; Hata K.; Nakabayashi K.; Matsubara Y.; Sekido R.; Ogata T.; Kashimada K.; Fukami M.;
Hum. Mutat. 38:39-42(2017)
Cited for: VARIANT SRXX4 TRP-92; CHARACTERIZATION OF VARIANT SRXX4 TRP-92; INVOLVEMENT IN SRXX4;

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.