UniProtKB/Swiss-Prot O43819: Variant p.Glu140Lys

Protein SCO2 homolog, mitochondrial
Gene: SCO2
Chromosomal location: 22q13.33
Variant information

Variant position:  140
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 have been found in patients and disease-association is reported in literature. However, this classification is not a definitive assessment of variant pathogenicity.
  • Polymorphism: No disease-association has been reported.
  • Unclassified: Variants have been found in patients but disease-association remains unclear.

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

Involvement in disease:  Myopia 6 (MYP6) [MIM:608908]: A refractive error of the eye, in which parallel rays from a distant object come to focus in front of the retina, vision being better for near objects than for far. {ECO:0000269|PubMed:23643385, ECO:0000269|PubMed:25525168}. 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:  Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 1 (CEMCOX1) [MIM:604377]: A disorder characterized by hypotonia, developmental delay, hypertrophic cardiomyopathy, lactic acidosis, gliosis, neuronal loss in basal ganglia, brainstem and spinal cord, and cytochrome c oxidase deficiency. {ECO:0000269|PubMed:10545952, ECO:0000269|PubMed:10749987, ECO:0000269|PubMed:11673586, ECO:0000269|PubMed:14994243}. 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 CEMCOX1 and MYP6.
Any additional useful information about the variant.



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.

TypePositionsDescription
Chain 42 – 266 Protein SCO2 homolog, mitochondrial
Domain 85 – 259 Thioredoxin
Metal binding 133 – 133 Copper
Metal binding 137 – 137 Copper
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 CEMCOX1 LYS-140 AND PHE-225;

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 CEMCOX1 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 CEMCOX1 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 CEMCOX1 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.