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UniProtKB/Swiss-Prot Q9H3S1: Variant p.Phe350Cys

Semaphorin-4A
Gene: SEMA4A
Chromosomal location: 1q22
Variant information

Variant position:  350
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 Phenylalanine (F) to Cysteine (C) at position 350 (F350C, p.Phe350Cys).
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 aromatic (F) to medium size and polar (C)
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 35 (RP35) [MIM:610282]: 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. {ECO:0000269|PubMed:16199541, ECO:0000269|PubMed:22956603}. 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:  Cone-rod dystrophy 10 (CORD10) [MIM:610283]: An inherited retinal dystrophy characterized by retinal pigment deposits visible on fundus examination, predominantly in the macular region, and initial loss of cone photoreceptors followed by rod degeneration. This leads to decreased visual acuity and sensitivity in the central visual field, followed by loss of peripheral vision. Severe loss of vision occurs earlier than in retinitis pigmentosa, due to cone photoreceptors degenerating at a higher rate than rod photoreceptors. {ECO:0000269|PubMed:16199541}. 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 RP35 and CORD10; heterozygous compound with H-345; loss of localization to cell membrane.
Any additional useful information about the variant.

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



Sequence information

Variant position:  350
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  761
The length of the canonical sequence.

Location on the sequence:   VGGTRSSAVCAFSLLDIERV  F KGKYKELNKETSRWTTYRGP
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                         VGGTRSSAVCAFSLLDIERVFKGKYKELNKETSRWTTYRGP

Mouse                         VGGTRSSAVCAFSLTDIERVFKGKYKELNKETSRWTTYRGS

Bovine                        VGGTRSSAVCAFSLKDIKSVFEGKYKELDKETSRWTTYEYP

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 33 – 761 Semaphorin-4A
Topological domain 33 – 683 Extracellular
Domain 36 – 494 Sema
Disulfide bond 269 – 379


Literature citations

SEMA4A mutations lead to susceptibility to light irradiation, oxidative stress, and ER stress in retinal pigment epithelial cells.
Tsuruma K.; Nishimura Y.; Kishi S.; Shimazawa M.; Tanaka T.; Hara H.;
Invest. Ophthalmol. Vis. Sci. 53:6729-6737(2012)
Cited for: SUBCELLULAR LOCATION; CHARACTERIZATION OF VARIANT GLN-713; CHARACTERIZATION OF VARIANTS RP35 HIS-345 AND CYS-350;

Identification of novel mutations in the SEMA4A gene associated with retinal degenerative diseases.
Abid A.; Ismail M.; Mehdi S.Q.; Khaliq S.;
J. Med. Genet. 43:378-381(2006)
Cited for: VARIANTS RP35 HIS-345 AND CYS-350; VARIANTS CORD10 HIS-345 AND CYS-350; VARIANT GLN-713;

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.