UniProtKB/Swiss-Prot Q9Y5X4: Variant p.Arg311Gln

Photoreceptor-specific nuclear receptor
Gene: NR2E3
Chromosomal location: 15q23
Variant information

Variant position:  311
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 have been found in patients and disease-association is reported in literature. However, this classification is not a definitive assessment of variant pathogenicity.
  • Polymorphism: No disease-association has been reported.
  • Unclassified: Variants have been found in patients but disease-association remains unclear.

Residue change:  From Arginine (R) to Glutamine (Q) at position 311 (R311Q, p.Arg311Gln).
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 (Q)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  1
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 ESCS; impairs protein folding and stability and hinders the ability to form stable dimers.
Any additional useful information about the variant.

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



Sequence information

Variant position:  311
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  410
The length of the canonical sequence.

Location on the sequence:   GRLTLASMETRVLQETISRF  R ALAVDPTEFACMKALVLFKP
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                         GRLTLASMETRVLQETISRFRALAVDPTEFACMKALVLFKP

Mouse                         GRLALASAETRFLQETISRFRALAVDPTEFACLKALVLFKP

Bovine                        GRLVLASAETRILQETISRFRALAVDPTEFACMKALVLFKP

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 – 410 Photoreceptor-specific nuclear receptor
Cross 330 – 330 Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)


Literature citations

The crystal structure of the orphan nuclear receptor NR2E3/PNR ligand binding domain reveals a dimeric auto-repressed conformation.
Tan M.H.; Zhou X.E.; Soon F.F.; Li X.; Li J.; Yong E.L.; Melcher K.; Xu H.E.;
PLoS ONE 8:E74359-E74359(2013)
Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 217-410; SUBUNIT; MUTAGENESIS OF LEU-372 AND LEU-375; FUNCTION; CHARACTERIZATION OF VARIANT ASSOCIATED WITH ESCS GLY-334; CHARACTERIZATION OF VARIANTS ESCS PRO-263; GLY-309; GLN-311; PRO-336; VAL-353 AND LYS-407;

The photoreceptor cell-specific nuclear receptor gene (PNR) accounts for retinitis pigmentosa in the Crypto-Jews from Portugal (Marranos), survivors from the Spanish Inquisition.
Gerber S.; Rozet J.-M.; Takezawa S.; dos Santos L.C.; Lopes L.; Gribouval O.; Penet C.; Perrault I.; Ducroq D.; Souied E.; Jeanpierre M.; Romana S.; Frezal J.; Ferraz F.; Yu-Umesono R.; Munnich A.; Kaplan J.;
Hum. Genet. 107:276-284(2000)
Cited for: VARIANT ESCS GLN-311; CHARACTERIZATION OF VARIANT ESCS GLN-311;

Mutation of a nuclear receptor gene, NR2E3, causes enhanced S cone syndrome, a disorder of retinal cell fate.
Haider N.B.; Jacobson S.G.; Cideciyan A.V.; Swiderski R.; Streb L.M.; Searby C.; Beck G.; Hockey R.; Hanna D.B.; Gorman S.; Duhl D.; Carmi R.; Bennett J.; Weleber R.G.; Fishman G.A.; Wright A.F.; Stone E.M.; Sheffield V.C.;
Nat. Genet. 24:127-131(2000)
Cited for: VARIANTS ESCS 67-CYS--GLY-69 DEL; GLN-76; TRP-76; HIS-97; TRP-104; LYS-121; SER-234; GLY-309; GLN-311; PRO-385 AND LYS-407; VARIANTS GLY-140; THR-163; ILE-232 AND ILE-302;

Shared mutations in NR2E3 in enhanced S-cone syndrome, Goldmann-Favre syndrome, and many cases of clumped pigmentary retinal degeneration.
Sharon D.; Sandberg M.A.; Caruso R.C.; Berson E.L.; Dryja T.P.;
Arch. Ophthalmol. 121:1316-1323(2003)
Cited for: VARIANTS ESCS 67-CYS--GLY-69 DEL; HIS-97; GLU-256 AND GLN-311;

Mutation analysis of NR2E3 and NRL genes in enhanced S cone syndrome.
Wright A.F.; Reddick A.C.; Schwartz S.B.; Ferguson J.S.; Aleman T.S.; Kellner U.; Jurklies B.; Schuster A.; Zrenner E.; Wissinger B.; Lennon A.; Shu X.; Cideciyan A.V.; Stone E.M.; Jacobson S.G.; Swaroop A.;
Hum. Mutat. 24:439-439(2004)
Cited for: VARIANTS ESCS 67-CYS--GLY-69 DEL; VAL-88; HIS-97; TRP-104; SER-234; GLU-256; PRO-263; GLY-309; GLN-311; PRO-336; VAL-353 AND LYS-407;

Analysis of the involvement of the NR2E3 gene in autosomal recessive retinal dystrophies.
Bernal S.; Solans T.; Gamundi M.J.; Hernan I.; de Jorge L.; Carballo M.; Navarro R.; Tizzano E.; Ayuso C.; Baiget M.;
Clin. Genet. 73:360-366(2008)
Cited for: VARIANT ESCS GLN-311; VARIANTS LEU-44; GLY-140; THR-163; SER-287 AND ARG-324;

Mutations in NR2E3 can cause dominant or recessive retinal degenerations in the same family.
Escher P.; Gouras P.; Roduit R.; Tiab L.; Bolay S.; Delarive T.; Chen S.; Tsai C.C.; Hayashi M.; Zernant J.; Merriam J.E.; Mermod N.; Allikmets R.; Munier F.L.; Schorderet D.F.;
Hum. Mutat. 30:342-351(2009)
Cited for: VARIANT RP37 ARG-56; VARIANT ESCS GLN-311;

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.