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UniProtKB/Swiss-Prot Q13488: Variant p.Gly405Arg

V-type proton ATPase 116 kDa subunit a3
Gene: TCIRG1
Variant information

Variant position:  405
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 405 (G405R, p.Gly405Arg).
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:  Osteopetrosis, autosomal recessive 1 (OPTB1) [MIM:259700]: A rare genetic disease characterized by abnormally dense bone, due to defective resorption of immature bone. Osteopetrosis occurs in two forms: a severe autosomal recessive form occurring in utero, infancy, or childhood, and a benign autosomal dominant form occurring in adolescence or adulthood. Recessive osteopetrosis commonly manifests in early infancy with macrocephaly, feeding difficulties, evolving blindness and deafness, bone marrow failure, severe anemia, and hepatosplenomegaly. Deafness and blindness are generally thought to represent effects of pressure on nerves. {ECO:0000269|PubMed:11532986, ECO:0000269|PubMed:12552563, ECO:0000269|PubMed:15300850}. 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 OPTB1.
Any additional useful information about the variant.

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



Sequence information

Variant position:  405
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  830
The length of the canonical sequence.

Location on the sequence:   EVNPAPYTIITFPFLFAVMF  G DVGHGLLMFLFALAMVLAEN
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.

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 – 830 V-type proton ATPase 116 kDa subunit a3
Topological domain 405 – 406 Vacuolar


Literature citations

The mutational spectrum of human malignant autosomal recessive osteopetrosis.
Sobacchi C.; Frattini A.; Orchard P.; Porras O.; Tezcan I.; Andolina M.; Babul-Hirji R.; Baric I.; Canham N.; Chitayat D.; Dupuis-Girod S.; Ellis I.; Etzioni A.; Fasth A.; Fisher A.; Gerritsen B.; Gulino V.; Horwitz E.; Klamroth V.; Lanino E.; Mirolo M.; Musio A.; Matthijs G.; Nonomaya S.; Notarangelo L.D.; Ochs H.D.; Superti-Furga A.; Valiaho J.; van Hove J.L.K.; Vihinen M.; Vujic D.; Vezzoni P.; Villa A.;
Hum. Mol. Genet. 10:1767-1773(2001)
Cited for: VARIANTS OPTB1 ARG-405 AND LEU-444;

Novel mutations in the TCIRG1 gene encoding the a3 subunit of the vacuolar proton pump in patients affected by infantile malignant osteopetrosis.
Scimeca J.-C.; Quincey D.; Parrinello H.; Romatet D.; Grosgeorge J.; Gaudray P.; Philip N.; Fischer A.; Carle G.F.;
Hum. Mutat. 21:151-157(2003)
Cited for: VARIANT OPTB1 ARG-405;

TCIRG1-dependent recessive osteopetrosis: mutation analysis, functional identification of the splicing defects, and in vitro rescue by U1 snRNA.
Susani L.; Pangrazio A.; Sobacchi C.; Taranta A.; Mortier G.; Savarirayan R.; Villa A.; Orchard P.; Vezzoni P.; Albertini A.; Frattini A.; Pagani F.;
Hum. Mutat. 24:225-235(2004)
Cited for: VARIANTS OPTB1 PRO-141; ARG-405; ASN-462 DEL; ASN-517 AND ARG-775;

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.