UniProtKB/SwissProt variant VAR

Protein SCO2 homolog, mitochondrial
Gene: SCO2
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Variant information Variant position:

140 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 Glutamate (E) to Lysine (K) at position 140 (E140K, p.Glu140Lys). 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 medium size and acidic (E) to large size and basic (K) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

1 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 MC4DN2 and MYP6; reduced cytochrome c oxidase subunit II synthesis and reduced ability to regulate cellular copper homeostasis. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs74315511 [ dbSNP | Ensembl ]

Sequence information Variant position:

140 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

266 The length of the canonical sequence.
Location on the sequence:

RGQWVLMYFGFTHCPDICPD E LEKLVQVVRQLEAEPGLPPV 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                         RGQWVLMYFGFTHCPDICPDELEKLVQVVRQLEAEPGLPPV

Mouse                         RGQWVLMYFGFTHCPDICPDELEKLVQVVRKLEAEPDLPLV

Bovine                        RGQWVLLYFGFTHCPDICPDELEKLVQVVRQLEAEPGLPPV

Zebrafish                     LGHWVLLYFGFTHCPDICPDELEKLTSVVHILDKDPSLPSV

Baker's yeast                 KGKFSILYFGFSHCPDICPEELDRLTYWISELDDKDHIK-I

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	42 – 266	Protein SCO2 homolog, mitochondrial
Topological domain	79 – 266	Mitochondrial intermembrane
Domain	85 – 259	Thioredoxin
Binding site	133 – 133
Binding site	137 – 137
Helix	137 – 153

Literature citations
Fatal infantile cardioencephalomyopathy with COX deficiency and mutations in SCO2, a COX assembly gene.
Papadopoulou L.C.; Sue C.M.; Davidson M.M.; Tanji K.; Nishino I.; Sadlock J.E.; Krishna S.; Walker W.; Selby J.; Glerum D.M.; Van Coster R.; Lyon G.; Scalais E.; Lebel R.; Kaplan P.; Shanske S.; De Vivo D.C.; Bonilla E.; Hirano M.; DiMauro S.; Schon E.A.;
Nat. Genet. 23:333-337(1999)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]; VARIANTS MC4DN2 LYS-140 AND PHE-225; The human cytochrome c oxidase assembly factors SCO1 and SCO2 have regulatory roles in the maintenance of cellular copper homeostasis.
Leary S.C.; Cobine P.A.; Kaufman B.A.; Guercin G.H.; Mattman A.; Palaty J.; Lockitch G.; Winge D.R.; Rustin P.; Horvath R.; Shoubridge E.A.;
Cell Metab. 5:9-20(2007)
Cited for: FUNCTION; CHARACTERIZATION OF VARIANT MC4DN2 LYS-140; Human SCO2 is required for the synthesis of CO II and as a thiol-disulphide oxidoreductase for SCO1.
Leary S.C.; Sasarman F.; Nishimura T.; Shoubridge E.A.;
Hum. Mol. Genet. 18:2230-2240(2009)
Cited for: FUNCTION; CHARACTERIZATION OF VARIANT MC4DN2 LYS-140; Mutations in SCO2 are associated with a distinct form of hypertrophic cardiomyopathy and cytochrome c oxidase deficiency.
Jaksch M.; Ogilvie I.; Yao J.; Kortenhaus G.; Bresser H.G.; Gerbitz K.D.; Shoubridge E.A.;
Hum. Mol. Genet. 9:795-801(2000)
Cited for: VARIANTS MC4DN2 LYS-140 AND TRP-171; Homozygosity (E140K) in SCO2 causes delayed infantile onset of cardiomyopathy and neuropathy.
Jaksch M.; Horvath R.; Horn N.; Auer D.P.; Macmillan C.; Peters J.; Gerbitz K.D.; Kraegeloh-Mann I.; Muntau A.; Karcagi V.; Kalmanchey R.; Lochmuller H.; Shoubridge E.A.; Freisinger P.;
Neurology 57:1440-1446(2001)
Cited for: VARIANT MC4DN2 LYS-140; Novel SCO2 mutation (G1521A) presenting as a spinal muscular atrophy type I phenotype.
Tarnopolsky M.A.; Bourgeois J.M.; Fu M.H.; Kataeva G.; Shah J.; Simon D.K.; Mahoney D.; Johns D.; MacKay N.; Robinson B.H.;
Am. J. Med. Genet. A 125A:310-314(2004)
Cited for: VARIANTS MC4DN2 TYR-133 AND LYS-140; Mutations in SCO2 are associated with autosomal-dominant high-grade myopia.
Tran-Viet K.N.; Powell C.; Barathi V.A.; Klemm T.; Maurer-Stroh S.; Limviphuvadh V.; Soler V.; Ho C.; Yanovitch T.; Schneider G.; Li Y.J.; Nading E.; Metlapally R.; Saw S.M.; Goh L.; Rozen S.; Young T.L.;
Am. J. Hum. Genet. 92:820-826(2013)
Cited for: VARIANTS MYP6 HIS-114; LYS-140 AND VAL-259;

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.

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot O43819: Variant p.Glu140Lys