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NC_012920.1(MT-CO1):m.6277G>A AND Familial colorectal cancer

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Mar 3, 2009
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV000010310.3

Allele description [Variation Report for NC_012920.1(MT-CO1):m.6277G>A]

NC_012920.1(MT-CO1):m.6277G>A

Gene:
MT-CO1:mitochondrially encoded cytochrome c oxidase I [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Genomic location:
Preferred name:
NC_012920.1(MT-CO1):m.6277G>A
Other names:
G125D
HGVS:
NC_012920.1:m.6277G>A
Protein change:
GLY125ASP
Links:
OMIM: 516030.0010; dbSNP: rs281865417
NCBI 1000 Genomes Browser:
rs281865417

Condition(s)

Name:
Familial colorectal cancer
Identifiers:
MONDO: MONDO:0023113; MedGen: CN280943

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000030535OMIM
no assertion criteria provided
Pathogenic
(Mar 3, 2009) 		germlineliterature only

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

Mitochondrial DNA mutations are established in human colonic stem cells, and mutated clones expand by crypt fission.

Greaves LC, Preston SL, Tadrous PJ, Taylor RW, Barron MJ, Oukrif D, Leedham SJ, Deheragoda M, Sasieni P, Novelli MR, Jankowski JA, Turnbull DM, Wright NA, McDonald SA.

Proc Natl Acad Sci U S A. 2006 Jan 17;103(3):714-9. Epub 2006 Jan 6.

PubMed [citation]
PMID:
16407113
PMCID:
PMC1325106

A mitochondrial DNA mutation linked to colon cancer results in proton leaks in cytochrome c oxidase.

Namslauer I, Brzezinski P.

Proc Natl Acad Sci U S A. 2009 Mar 3;106(9):3402-7. doi: 10.1073/pnas.0811450106. Epub 2009 Feb 13.

PubMed [citation]
PMID:
19218458
PMCID:
PMC2651238

Details of each submission

From OMIM, SCV000030535.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (2)

Description

In colonocytes from cytochrome c oxidase-deficient crypts from a patient with colon cancer (114500), Greaves et al. (2006) identified a 6277A-G transition in the MTCO1 gene, predicted to result in a gly125-to-asp (G125D) substitution at a well-conserved residue.

Namslauer and Brzezinski (2009) used site-directed mutagenesis to alter the residue corresponding to gly125 in the MTCO1 gene of the bacterium Rhodobacter sphaeroides (G171D), and demonstrated that G171D-mutant COX displayed steady-state catalytic activity linked to proton pumping that was approximately 34% of wildtype. In addition, an intrinsic proton leak was found in the enzyme, which would lead to decreased overall energy-conversion efficiency of the respiratory chain, perturbing transport processes such as protein, ion, and metabolite trafficking.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jun 9, 2024