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UniProtKB/Swiss-Prot Q63HN8: Variant p.Ala4399Thr

E3 ubiquitin-protein ligase RNF213
Gene: RNF213
Chromosomal location: 17q25.3
Variant information

Variant position:  4399
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 Alanine (A) to Threonine (T) at position 4399 (A4399T, p.Ala4399Thr).
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 small size and hydrophobic (A) to medium size and polar (T)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  0
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:  Moyamoya disease 2 (MYMY2) [MIM:607151]: A progressive cerebral angiopathy characterized by bilateral intracranial carotid artery stenosis and telangiectatic vessels in the region of the basal ganglia. The abnormal vessels resemble a 'puff of smoke' (moyamoya) on cerebral angiogram. Affected individuals can develop transient ischemic attacks and/or cerebral infarction, and rupture of the collateral vessels can cause intracranial hemorrhage. Hemiplegia of sudden onset and epileptic seizures constitute the prevailing presentation in childhood, while subarachnoid bleeding occurs more frequently in adults. {ECO:0000269|PubMed:21048783, ECO:0000269|PubMed:21799892, ECO:0000269|PubMed:23110205, ECO:0000269|PubMed:23994138, ECO:0000269|PubMed:25278557, ECO:0000269|PubMed:25956231, ECO:0000269|PubMed:26126547, ECO:0000269|PubMed:26198278, ECO:0000269|PubMed:27736983}. Note=Disease susceptibility is associated with variations 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 MYMY2.
Any additional useful information about the variant.

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



Sequence information

Variant position:  4399
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  5207
The length of the canonical sequence.

Location on the sequence:   VAILYRSHNASLHPTPEQCE  A VSKFIGECKILSPPDISRFA
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                         VAILYRSHNASLHPTPEQCEAVSKFIGECKILSPPDISRFA

Mouse                         VAALYRSPNGSLHPEAKQLEAVNKFIKESKILSDPNIRCFA

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 – 5207 E3 ubiquitin-protein ligase RNF213
Alternative sequence 1 – 4650 Missing. In isoform 4.
Alternative sequence 1064 – 5207 Missing. In isoform 3.


Literature citations

A genome-wide association study identifies RNF213 as the first Moyamoya disease gene.
Kamada F.; Aoki Y.; Narisawa A.; Abe Y.; Komatsuzaki S.; Kikuchi A.; Kanno J.; Niihori T.; Ono M.; Ishii N.; Owada Y.; Fujimura M.; Mashimo Y.; Suzuki Y.; Hata A.; Tsuchiya S.; Tominaga T.; Matsubara Y.; Kure S.;
J. Hum. Genet. 56:34-40(2011)
Cited for: VARIANTS GLU-2554; VAL-3891; GLY-3915; MET-4567 AND MET-4765; VARIANTS MYMY2 THR-4399 AND LYS-4810;

Molecular analysis of RNF213 gene for moyamoya disease in the Chinese Han population.
Wu Z.; Jiang H.; Zhang L.; Xu X.; Zhang X.; Kang Z.; Song D.; Zhang J.; Guan M.; Gu Y.;
PLoS ONE 7:E48179-E48179(2012)
Cited for: VARIANTS MYMY2 THR-4399 AND LYS-4810; VARIANTS ARG-4007; LEU-4367; PRO-4586; VAL-4631; ASP-4950; VAL-5021 AND ILE-5136;

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.