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UniProtKB/Swiss-Prot P82279: Variant p.Gly1103Arg

Protein crumbs homolog 1
Gene: CRB1
Variant information

Variant position:  1103
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 Glycine (G) to Arginine (R) at position 1103 (G1103R, p.Gly1103Arg).
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 glycine (G) to large size and basic (R)
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

Involvement in disease:  Retinitis pigmentosa 12 (RP12) [MIM:600105]: A retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. RP12 is an autosomal recessive, severe form often manifesting in early childhood. Patients experiment progressive visual field loss with severe visual impairment before the age of twenty. Some patients have a preserved paraarteriolar retinal pigment epithelium (PPRPE) and hypermetropia. {ECO:0000269|PubMed:10508521, ECO:0000269|PubMed:11389483, ECO:0000269|PubMed:11559858, ECO:0000269|PubMed:12573663, ECO:0000269|PubMed:12843338, ECO:0000269|PubMed:15459956, ECO:0000269|PubMed:19140180, ECO:0000269|PubMed:19956407, ECO:0000269|PubMed:20591486, ECO:0000269|PubMed:20956273, ECO:0000269|PubMed:21987686, ECO:0000269|PubMed:22065545, ECO:0000269|PubMed:22128245, ECO:0000269|PubMed:22334370, ECO:0000269|PubMed:28819299}. 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:  Leber congenital amaurosis 8 (LCA8) [MIM:613835]: A severe dystrophy of the retina, typically becoming evident in the first years of life. Visual function is usually poor and often accompanied by nystagmus, sluggish or near-absent pupillary responses, photophobia, high hyperopia and keratoconus. {ECO:0000269|PubMed:11231775, ECO:0000269|PubMed:11389483, ECO:0000269|PubMed:12567265, ECO:0000269|PubMed:12573663, ECO:0000269|PubMed:12700176, ECO:0000269|PubMed:12843338, ECO:0000269|PubMed:15024725, ECO:0000269|PubMed:15459956, ECO:0000269|PubMed:15691574, ECO:0000269|PubMed:16205573, ECO:0000269|PubMed:16936081, ECO:0000269|PubMed:17128490, ECO:0000269|PubMed:17438615, ECO:0000269|PubMed:17724218, ECO:0000269|PubMed:18055821, ECO:0000269|PubMed:18682808, ECO:0000269|PubMed:20108431, ECO:0000269|PubMed:20956273, ECO:0000269|PubMed:21602930, ECO:0000269|PubMed:28819299}. 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 LCA8 and RP12.
Any additional useful information about the variant.

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



Sequence information

Variant position:  1103
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  1406
The length of the canonical sequence.

Location on the sequence:   GDRAIDNIKGLQGCLSTIEI  G GIYLSYFENVHGFINKPQEE
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                         GDRAIDNIKGLQGCLSTIEIGGIYLSYFENVHGFINKPQEE

Mouse                         GDQSVDNPKGLQGCLSTIEIGGIYLSYFENLHGFPGKPQEE

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 26 – 1406 Protein crumbs homolog 1
Topological domain 26 – 1347 Extracellular
Domain 950 – 1137 Laminin G-like 3
Disulfide bond 1096 – 1137
Alternative sequence 710 – 1245 Missing. In isoform 5.


Literature citations

Leber congenital amaurosis: comprehensive survey of the genetic heterogeneity, refinement of the clinical definition, and genotype-phenotype correlations as a strategy for molecular diagnosis.
Hanein S.; Perrault I.; Gerber S.; Tanguy G.; Barbet F.; Ducroq D.; Calvas P.; Dollfus H.; Hamel C.; Lopponen T.; Munier F.; Santos L.; Shalev S.; Zafeiriou D.; Dufier J.-L.; Munnich A.; Rozet J.-M.; Kaplan J.;
Hum. Mutat. 23:306-317(2004)
Cited for: VARIANTS LCA8 TYR-584; GLN-710; THR-741; MET-745; CYS-764; THR-852; TYR-948; ILE-1025; ARG-1103; ARG-1107; PRO-1107 AND SER-1321;

Clinical and molecular genetics of Leber's congenital amaurosis: a multicenter study of Italian patients.
Simonelli F.; Ziviello C.; Testa F.; Rossi S.; Fazzi E.; Bianchi P.E.; Fossarello M.; Signorini S.; Bertone C.; Galantuomo S.; Brancati F.; Valente E.M.; Ciccodicola A.; Rinaldi E.; Auricchio A.; Banfi S.;
Invest. Ophthalmol. Vis. Sci. 48:4284-4290(2007)
Cited for: VARIANTS LCA8 TYR-438; MET-745; THR-852 AND ARG-1103; VARIANT MET-289;

Genetic heterogeneity in two consanguineous families segregating early onset retinal degeneration: the pitfalls of homozygosity mapping.
Benayoun L.; Spiegel R.; Auslender N.; Abbasi A.H.; Rizel L.; Hujeirat Y.; Salama I.; Garzozi H.J.; Allon-Shalev S.; Ben-Yosef T.;
Am. J. Med. Genet. A 149:650-656(2009)
Cited for: VARIANT RP12 ARG-1103;

Phenotypic variability in patients with retinal dystrophies due to mutations in CRB1.
Henderson R.H.; Mackay D.S.; Li Z.; Moradi P.; Sergouniotis P.; Russell-Eggitt I.; Thompson D.A.; Robson A.G.; Holder G.E.; Webster A.R.; Moore A.T.;
Br. J. Ophthalmol. 95:811-817(2011)
Cited for: VARIANTS RP12 SER-157; TRP-250; LYS-312; CYS-675; VAL-710; MET-745; CYS-764; THR-836; ARG-846; TYR-948; SER-1012; ASN-1025 AND GLY-1174; VARIANTS LCA8 THR-205; SER-850; THR-1003; ARG-1103; PRO-1107; GLY-1174 AND LEU-1381; VARIANTS EARLY-ONSET RETINAL DYSTROPHY THR-741 AND ASP-1365;

CRB1 mutations in inherited retinal dystrophies.
Bujakowska K.; Audo I.; Mohand-Said S.; Lancelot M.E.; Antonio A.; Germain A.; Leveillard T.; Letexier M.; Saraiva J.P.; Lonjou C.; Carpentier W.; Sahel J.A.; Bhattacharya S.S.; Zeitz C.;
Hum. Mutat. 33:306-315(2012)
Cited for: INVOLVEMENT IN RETINAL DYSTROPHIES; VARIANTS RP12 TYR-584; PHE-740; THR-741; THR-836; TYR-948 AND ARG-1103; VARIANTS EARLY-ONSET RETINAL DYSTROPHY ASN-789 DEL; CYS-1198 AND SER-1223;

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.