UniProtKB/Swiss-Prot Q63HN8: Variant p.Arg4810Lys

E3 ubiquitin-protein ligase RNF213
Gene: RNF213
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Variant information Variant position:

4810 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 Arginine (R) to Lysine (K) at position 4810 (R4810K, p.Arg4810Lys). 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:

Similar physico-chemical property. Both residues are large size and basic. 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 MYMY2; very frequent in individuals affected by Moyamoya disease; strongly increases the risk of Moyamoya disease; induces genomic instability; shows decreased ATPase activity; does not affect ubiquitination of lipopolysaccharide. Any additional useful information about the variant.

Sequence information Variant position:

4810 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:

LQRDLVKQFQNVQQVEYSSI R GFLSKHSSDGLRQLLHNRIT 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                         LQRDLVKQFQNVQQVEYSSIRGFLSKHSSDGLRQLLHNRIT

Mouse                         LQRDLVKQFQNVSRVEYSSIRGFIHSHSSDGLRKLLHDRIT

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

Literature citations
Identification of RNF213 as a susceptibility gene for moyamoya disease and its possible role in vascular development.
Liu W.; Morito D.; Takashima S.; Mineharu Y.; Kobayashi H.; Hitomi T.; Hashikata H.; Matsuura N.; Yamazaki S.; Toyoda A.; Kikuta K.; Takagi Y.; Harada K.H.; Fujiyama A.; Herzig R.; Krischek B.; Zou L.; Kim J.E.; Kitakaze M.; Miyamoto S.; Nagata K.; Hashimoto N.; Koizumi A.;
PLoS ONE 6:E22542-E22542(2011)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1); FUNCTION; CATALYTIC ACTIVITY; AUTOUBIQUITINATION; SUBCELLULAR LOCATION; TISSUE SPECIFICITY; VARIANTS ASP-3962; GLN-4062; SER-4608; ASN-4863; ASP-4950; VAL-5021; GLU-5160 AND GLY-5176; VARIANTS MYMY2 ASN-4013 AND LYS-4810; Ubiquitylation of lipopolysaccharide by RNF213 during bacterial infection.
Otten E.G.; Werner E.; Crespillo-Casado A.; Boyle K.B.; Dharamdasani V.; Pathe C.; Santhanam B.; Randow F.;
Nature 594:111-116(2021)
Cited for: FUNCTION; SUBCELLULAR LOCATION; DOMAIN; CHARACTERIZATION OF VARIANTS ILE-4638; ASP-4950 AND VAL-5021; CHARACTERIZATION OF VARIANT MYMY2 LYS-4810; MUTAGENESIS OF LYS-2426; GLU-2488; LYS-2775; GLU-2845; HIS-4014; TRP-4024 AND HIS-4509; 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; Sibling cases of moyamoya disease having homozygous and heterozygous c.14576G>A variant in RNF213 showed varying clinical course and severity.
Miyatake S.; Touho H.; Miyake N.; Ohba C.; Doi H.; Saitsu H.; Taguri M.; Morita S.; Matsumoto N.;
J. Hum. Genet. 57:804-806(2012)
Cited for: VARIANT MYMY2 LYS-4810; Temporal profile of de novo development of moyamoya vasculopathy in an adult: case report.
Shimoda Y.; Fujimura M.; Inoue T.; Shimizu H.; Tominaga T.;
Neurol. Med. Chir. 52:339-342(2012)
Cited for: VARIANT MYMY2 LYS-4810; Homozygous c.14576G>A variant of RNF213 predicts early-onset and severe form of moyamoya disease.
Miyatake S.; Miyake N.; Touho H.; Nishimura-Tadaki A.; Kondo Y.; Okada I.; Tsurusaki Y.; Doi H.; Sakai H.; Saitsu H.; Shimojima K.; Yamamoto T.; Higurashi M.; Kawahara N.; Kawauchi H.; Nagasaka K.; Okamoto N.; Mori T.; Koyano S.; Kuroiwa Y.; Taguri M.; Morita S.; Matsubara Y.; Kure S.; Matsumoto N.;
Neurology 78:803-810(2012)
Cited for: VARIANT MYMY2 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; The moyamoya disease susceptibility variant RNF213 R4810K (rs112735431) induces genomic instability by mitotic abnormality.
Hitomi T.; Habu T.; Kobayashi H.; Okuda H.; Harada K.H.; Osafune K.; Taura D.; Sone M.; Asaka I.; Ameku T.; Watanabe A.; Kasahara T.; Sudo T.; Shiota F.; Hashikata H.; Takagi Y.; Morito D.; Miyamoto S.; Nakao K.; Koizumi A.;
Biochem. Biophys. Res. Commun. 439:419-426(2013)
Cited for: CHARACTERIZATION OF VARIANT MYMY2 LYS-4810; RNF213 rare variants in an ethnically diverse population with Moyamoya disease.
Cecchi A.C.; Guo D.; Ren Z.; Flynn K.; Santos-Cortez R.L.; Leal S.M.; Wang G.T.; Regalado E.S.; Steinberg G.K.; Shendure J.; Bamshad M.J.; Grotta J.C.; Nickerson D.A.; Pannu H.; Milewicz D.M.;
Stroke 45:3200-3207(2014)
Cited for: VARIANTS MYMY2 ASN-4013 AND LYS-4810; VARIANTS ALA-529 DEL; GLN-3922; TYR-3997; CYS-4019; VAL-4076; LYS-4115 DEL; GLU-4237; THR-4732 AND ILE-5163; Biochemical and functional characterization of RNF213 (Mysterin) R4810K, a susceptibility mutation of Moyamoya disease, in angiogenesis in vitro and in vivo.
Kobayashi H.; Matsuda Y.; Hitomi T.; Okuda H.; Shioi H.; Matsuda T.; Imai H.; Sone M.; Taura D.; Harada K.H.; Habu T.; Takagi Y.; Miyamoto S.; Koizumi A.;
J. Am. Heart Assoc. 4:0-0(2015)
Cited for: CHARACTERIZATION OF VARIANT MYMY2 LYS-4810; FUNCTION; CATALYTIC ACTIVITY; MUTAGENESIS OF GLU-2488; Mutation genotypes of RNF213 gene from moyamoya patients in Taiwan.
Lee M.J.; Chen Y.F.; Fan P.C.; Wang K.C.; Wang K.; Wang J.; Kuo M.F.;
J. Neurol. Sci. 353:161-165(2015)
Cited for: VARIANTS VAL-1622; MET-3933 AND CYS-4131; VARIANT MYMY2 LYS-4810;

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.