UniProtKB/Swiss-Prot P08100: Variant p.Pro23His

Rhodopsin
Gene: RHO
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Variant information Variant position:

23 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 Proline (P) to Histidine (H) at position 23 (P23H, p.Pro23His). 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 medium size and hydrophobic (P) to medium size and polar (H) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

-2 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 RP4; pathogenic; severely decreased light-activated signaling when expressed in a heterologous system; impairs protein folding; decreased localization to the cell surface due to retention in the ER; leads to interaction with EDEM1 followed by degradation by the ERAD system; the orthologous bovine mutation results in decreased 11-cis retinal binding. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs104893768 [ dbSNP | Ensembl ]

Sequence information Variant position:

23 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

348 The length of the canonical sequence.
Location on the sequence:

GTEGPNFYVPFSNATGVVRS P FEYPQYYLAEPWQFSMLAAY 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                         GTEGPNFYVPFSNATGVVRSPFEYPQYYLAEPWQFSMLAAY

                              GTEGPNFYVPFSNKTGVVRSPFEYPQYYLAEPWQFSMLAAY

Mouse                         GTEGPNFYVPFSNVTGVVRSPFEQPQYYLAEPWQFSMLAAY

Rat                           GTEGPNFYVPFSNITGVVRSPFEQPQYYLAEPWQFSMLAAY

Pig                           GTEGPNFYVPFSNKTGVVRSPFEYPQYYLAEPWQFSMLAAY

Bovine                        GTEGPNFYVPFSNKTGVVRSPFEAPQYYLAEPWQFSMLAAY

Rabbit                        GTEGPDFYIPMSNQTGVVRSPFEYPQYYLAEPWQFSMLAAY

Sheep                         GTEGPNFYVPFSNKTGVVRSPFEAPQYYLAEPWQFSMLAAY

Cat                           GTEGPNFYVPFSNKTGVVRSPFEYPQYYLAEPWQFSMLAAY

Chicken                       GTEGQDFYVPMSNKTGVVRSPFEYPQYYLAEPWKFSALAAY

Xenopus laevis                GTEGPNFYVPMSNKTGVVRSPFDYPQYYLAEPWQYSALAAY

Zebrafish                     GTEGPAFYVPMSNATGVVRSPYEYPQYYLVAPWAYGLLAAY

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 – 348	Rhodopsin
Topological domain	1 – 36	Extracellular
Glycosylation	15 – 15	N-linked (GlcNAc...) asparagine
Turn	23 – 25

Literature citations
A point mutation of the rhodopsin gene in one form of retinitis pigmentosa.
Dryja T.P.; McGee T.L.; Reichei E.; Hahn L.B.; Cowley G.S.; Yandell D.W.; Sandberg M.A.; Berson E.L.;
Nature 343:364-366(1990)
Cited for: VARIANT RP4 HIS-23;
Mutations within the rhodopsin gene in patients with autosomal dominant retinitis pigmentosa.
Dryja T.P.; McGee T.L.; Hahn L.B.; Cowley G.S.; Olsson J.E.; Reichel E.; Sandberg M.A.; Berson E.L.;
N. Engl. J. Med. 323:1302-1307(1990)
Cited for: VARIANTS RP4 HIS-23; ARG-58; LEU-347 AND SER-347; FUNCTION;
Identification of novel rhodopsin mutations associated with retinitis pigmentosa by GC-clamped denaturing gradient gel electrophoresis.
Sheffield V.C.; Fishman G.A.; Beck J.S.; Kimura A.E.; Stone E.M.;
Am. J. Hum. Genet. 49:699-706(1991)
Cited for: VARIANTS RP4 MET-17; HIS-23; ARG-58; SER-182 AND LEU-267;
Rhodopsin mutations in autosomal dominant retinitis pigmentosa.
Sung C.H.; Davenport C.M.; Hennessey J.C.; Maumenee I.H.; Jacobson S.G.; Heckenlively J.R.; Nowakowski R.; Fishman G.; Gouras P.; Nathans J.;
Proc. Natl. Acad. Sci. U.S.A. 88:6481-6485(1991)
Cited for: VARIANTS RP4 MET-17; HIS-23; LEU-45; ARG-58; ASP-87; ASP-89; TRP-106; LEU-135; TRP-135; CYS-178; GLY-190 AND LEU-347;
Mutation spectrum of the rhodopsin gene among patients with autosomal dominant retinitis pigmentosa.
Dryja T.P.; Hahn L.B.; Cowley G.S.; McGee T.L.; Berson E.L.;
Proc. Natl. Acad. Sci. U.S.A. 88:9370-9374(1991)
Cited for: VARIANTS RP4 MET-17; LEU-23; HIS-23; VAL-51; ARG-58; ASP-89; ARG-125; ARG-167; LEU-171; LYS-181; PRO-186; ARG-188; ASN-190; GLY-190; MET-345; SER-347 AND LEU-347;
Structure and function in rhodopsin. 7. Point mutations associated with autosomal dominant retinitis pigmentosa.
Kaushal S.; Khorana H.G.;
Biochemistry 33:6121-6128(1994)
Cited for: CHARACTERIZATION OF VARIANTS LYS-4; MET-17; HIS-23; LEU-23; HIS-28; LEU-45; VAL-51; ARG-51; ARG-53; ARG-58; 68-LEU--PRO-71 DEL; ASP-87; ASP-89; ASP-90; ARG-106; TRP-106; TYR-110; ARG-125; ARG-167; LEU-171; CYS-178; LYS-181; PRO-186; ARG-188; GLY-190; ASN-190; TYR-190; PRO-211; ARG-222; ILE-256 DEL; GLU-296; MET-345; LEU-347 AND SER-347;
Prevalence of mutations causing retinitis pigmentosa and other inherited retinopathies.
Sohocki M.M.; Daiger S.P.; Bowne S.J.; Rodriquez J.A.; Northrup H.; Heckenlively J.R.; Birch D.G.; Mintz-Hittner H.; Ruiz R.S.; Lewis R.A.; Saperstein D.A.; Sullivan L.S.;
Hum. Mutat. 17:42-51(2001)
Cited for: VARIANTS RP4 MET-17; HIS-23; ARG-46; TRP-106; ARG-106; PHE-110; TRP-135; LEU-135; VAL-164; ARG-170; SER-171; GLN-171; ALA-180; LYS-181; ARG-185; ASN-190; ARG-207; ARG-211; ARG-270; ASN-296; ALA-347; LEU-347 AND THR-347;
Pharmacological chaperone-mediated in vivo folding and stabilization of the P23H-opsin mutant associated with autosomal dominant retinitis pigmentosa.
Noorwez S.M.; Kuksa V.; Imanishi Y.; Zhu L.; Filipek S.; Palczewski K.; Kaushal S.;
J. Biol. Chem. 278:14442-14450(2003)
Cited for: CHARACTERIZATION OF VARIANT RP4 HIS-23; FUNCTION; SUBCELLULAR LOCATION;
A dual role for EDEM1 in the processing of rod opsin.
Kosmaoglou M.; Kanuga N.; Aguila M.; Garriga P.; Cheetham M.E.;
J. Cell Sci. 122:4465-4472(2009)
Cited for: CHARACTERIZATION OF VARIANT RP4 HIS-23; SUBCELLULAR LOCATION;
Clinically Focused Molecular Investigation of 1000 Consecutive Families with Inherited Retinal Disease.
Stone E.M.; Andorf J.L.; Whitmore S.S.; DeLuca A.P.; Giacalone J.C.; Streb L.M.; Braun T.A.; Mullins R.F.; Scheetz T.E.; Sheffield V.C.; Tucker B.A.;
Ophthalmology 124:1314-1331(2017)
Cited for: VARIANTS RP4 ASP-3; MET-17; HIS-23; HIS-59; ASP-87; ARG-106; ASP-114; ARG-125; LEU-135; TRP-135; ASP-166; ARG-171; LEU-171; GLU-188; GLU-296; 312-GLN--ALA-348 DEL; PRO-346; LEU-347 AND ALA-347;
Coupling of human rhodopsin to a yeast signaling pathway enables characterization of mutations associated with retinal disease.
Scott B.M.; Chen S.K.; Bhattacharyya N.; Moalim A.Y.; Plotnikov S.V.; Heon E.; Peisajovich S.G.; Chang B.S.W.;
Genetics 211:597-615(2019)
Cited for: CHARACTERIZATION OF VARIANTS LYS-4; SER-15; MET-17; GLY-20; HIS-23; HIS-28; ARG-39; THR-44; LEU-45; ALA-51; ASP-89; TRP-106; TYR-110; ASP-114; ARG-125; GLY-135; LEU-171; MET-209 AND MET-345; MUTAGENESIS OF ASN-55 AND PHE-220;
Sector retinitis pigmentosa: Report of ten cases and a review of the literature.
Coussa R.G.; Basali D.; Maeda A.; DeBenedictis M.; Traboulsi E.I.;
Mol. Vis. 25:869-889(2019)
Cited for: VARIANTS RP4 SER-15; HIS-23; ARG-109; PRO-226 AND ARG-270;
Variants identified by next-generation sequencing cause endoplasmic reticulum stress in Rhodopsin-associated retinitis pigmentosa.
Wang Y.; Chen X.; Gao X.; Zhao A.; Zhao C.; Chen X.;
BMC Ophthalmol. 21:371-371(2021)
Cited for: VARIANT RP4 PRO-95; CHARACTERIZATION OF VARIANTS RP4 HIS-23; ARG-53 AND PRO-95;

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.