Mutagenetix > Incidental Mutation

Incidental Mutation 'N/A - 535:Ogdh'

214

Institutional Source

Beutler Lab

Gene Symbol

Ogdh

Ensembl Gene

ENSMUSG00000020456

Gene Name

oxoglutarate (alpha-ketoglutarate) dehydrogenase (lipoamide)

Synonyms

alpha-ketoglutarate dehydrogenase, 2210403E04Rik, 2210412K19Rik, d1401

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

N/A - 535 of strain bumble

Quality Score

Status

Validated

Chromosome

Chromosomal Location

6241633-6306642 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 6274911 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Leucine to Proline at position 180 (L180P)

Ref Sequence

ENSEMBL: ENSMUSP00000091041 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000003461] [ENSMUST00000081894] [ENSMUST00000093350] [ENSMUST00000101554]

AlphaFold

Q60597

PDB Structure

Structure of the m67 high-affinity mutant of the 2C TCR in complex with Ld/QL9 [X-RAY DIFFRACTION]
42F3 QL9/H2-Ld complex [X-RAY DIFFRACTION]

Predicted Effect

probably benign
Transcript: ENSMUST00000003461

SMART Domains

Protein: ENSMUSP00000003461
Gene: ENSMUSG00000020456

Domain	Start	End	E-Value	Type
Blast:Transket_pyr	131	199	8e-13	BLAST
Pfam:E1_dh	256	582	1.4e-95	PFAM
Transket_pyr	651	865	3.44e-50	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000081894

SMART Domains

Protein: ENSMUSP00000080569
Gene: ENSMUSG00000020456

Domain	Start	End	E-Value	Type
Pfam:E1_dh	252	578	1e-96	PFAM
Transket_pyr	647	861	3.44e-50	SMART

Predicted Effect

possibly damaging
Transcript: ENSMUST00000093350
AA Change: L180P

PolyPhen 2 Score 0.600 (Sensitivity: 0.87; Specificity: 0.91)

SMART Domains

Protein: ENSMUSP00000091041
Gene: ENSMUSG00000020456
AA Change: L180P

Domain	Start	End	E-Value	Type
Pfam:2-oxogl_dehyd_N	47	87	6.6e-21	PFAM
Pfam:E1_dh	267	593	1.1e-101	PFAM
Transket_pyr	662	876	3.44e-50	SMART
Pfam:OxoGdeHyase_C	880	1025	8.7e-58	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000101554

SMART Domains

Protein: ENSMUSP00000099090
Gene: ENSMUSG00000020456

Domain	Start	End	E-Value	Type
Blast:Transket_pyr	131	199	8e-13	BLAST
Pfam:E1_dh	256	582	1.4e-95	PFAM
Transket_pyr	651	865	3.44e-50	SMART

Meta Mutation Damage Score

0.1616

Coding Region Coverage

1x: 83.1%
3x: 57.4%

Validation Efficiency

88% (80/91)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes one subunit of the 2-oxoglutarate dehydrogenase complex. This complex catalyzes the overall conversion of 2-oxoglutarate (alpha-ketoglutarate) to succinyl-CoA and CO(2) during the Krebs cycle. The protein is located in the mitochondrial matrix and uses thiamine pyrophosphate as a cofactor. A congenital deficiency in 2-oxoglutarate dehydrogenase activity is believed to lead to hypotonia, metabolic acidosis, and hyperlactatemia. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, Sep 2009]

Allele List at MGI

All alleles(34) : Gene trapped(34)

Other mutations in this stock

Total: 11 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Cacna1e	A	T	1: 154,341,510 (GRCm39)	L1166Q	probably damaging	Het
Cd44	T	C	2: 102,644,534 (GRCm39)	M481V	possibly damaging	Het
Eif4g3	T	A	4: 137,847,739 (GRCm39)	V220D	probably damaging	Het
Gm12778	T	A	7: 33,875,347 (GRCm39)		noncoding transcript	Homo
Klhl29	C	T	12: 5,134,019 (GRCm39)	A773T	probably damaging	Homo
Lifr	A	T	15: 7,216,434 (GRCm39)	H803L	possibly damaging	Het
Macf1	T	C	4: 123,367,601 (GRCm39)	T822A	possibly damaging	Het
Obscn	A	T	11: 58,891,134 (GRCm39)	C1653S	possibly damaging	Het
Rnf5	T	C	17: 34,822,330 (GRCm39)	S40G	possibly damaging	Het
Sbf2	T	C	7: 109,911,959 (GRCm39)	T1696A	probably benign	Het
Ska2	C	T	11: 87,008,680 (GRCm39)		probably benign	Het

Other mutations in Ogdh

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL01109:Ogdh	APN	11	6,298,790 (GRCm39)	missense	probably damaging	1.00
IGL01503:Ogdh	APN	11	6,305,069 (GRCm39)	missense	probably damaging	1.00
IGL01684:Ogdh	APN	11	6,292,546 (GRCm39)	missense	probably damaging	1.00
IGL02141:Ogdh	APN	11	6,305,015 (GRCm39)	missense	probably damaging	1.00
IGL02313:Ogdh	APN	11	6,305,400 (GRCm39)	missense	probably damaging	0.98
IGL02818:Ogdh	APN	11	6,298,270 (GRCm39)	missense	probably benign
PIT4498001:Ogdh	UTSW	11	6,290,504 (GRCm39)	missense	probably benign	0.09
R0328:Ogdh	UTSW	11	6,297,216 (GRCm39)	missense	probably benign	0.01
R0505:Ogdh	UTSW	11	6,289,936 (GRCm39)	splice site	probably benign
R0627:Ogdh	UTSW	11	6,297,216 (GRCm39)	missense	possibly damaging	0.78
R1119:Ogdh	UTSW	11	6,290,544 (GRCm39)	missense	probably damaging	1.00
R1480:Ogdh	UTSW	11	6,297,827 (GRCm39)	critical splice acceptor site	probably null
R1591:Ogdh	UTSW	11	6,299,384 (GRCm39)	missense	probably damaging	1.00
R1804:Ogdh	UTSW	11	6,288,565 (GRCm39)	missense	probably damaging	1.00
R1873:Ogdh	UTSW	11	6,290,438 (GRCm39)	splice site	probably benign
R1959:Ogdh	UTSW	11	6,296,638 (GRCm39)	missense	possibly damaging	0.49
R2004:Ogdh	UTSW	11	6,284,626 (GRCm39)	missense	possibly damaging	0.90
R2080:Ogdh	UTSW	11	6,299,393 (GRCm39)	missense	probably benign	0.00
R2384:Ogdh	UTSW	11	6,292,526 (GRCm39)	missense	probably damaging	1.00
R2656:Ogdh	UTSW	11	6,298,678 (GRCm39)	missense	probably benign
R2883:Ogdh	UTSW	11	6,284,545 (GRCm39)	missense	probably damaging	1.00
R3405:Ogdh	UTSW	11	6,299,462 (GRCm39)	missense	probably damaging	1.00
R3838:Ogdh	UTSW	11	6,288,627 (GRCm39)	nonsense	probably null
R3933:Ogdh	UTSW	11	6,292,601 (GRCm39)	missense	possibly damaging	0.72
R3939:Ogdh	UTSW	11	6,300,655 (GRCm39)	nonsense	probably null
R4296:Ogdh	UTSW	11	6,299,374 (GRCm39)	missense	probably damaging	0.97
R4393:Ogdh	UTSW	11	6,266,772 (GRCm39)	missense	probably damaging	1.00
R4427:Ogdh	UTSW	11	6,305,421 (GRCm39)	missense	probably benign	0.01
R4667:Ogdh	UTSW	11	6,290,600 (GRCm39)	missense	probably benign	0.20
R4669:Ogdh	UTSW	11	6,290,600 (GRCm39)	missense	probably benign	0.20
R4728:Ogdh	UTSW	11	6,292,549 (GRCm39)	missense	probably damaging	1.00
R4737:Ogdh	UTSW	11	6,247,044 (GRCm39)	missense	probably benign
R4785:Ogdh	UTSW	11	6,299,875 (GRCm39)	missense	probably damaging	1.00
R4796:Ogdh	UTSW	11	6,290,570 (GRCm39)	missense	probably benign	0.01
R5333:Ogdh	UTSW	11	6,302,126 (GRCm39)	missense	probably damaging	1.00
R5592:Ogdh	UTSW	11	6,266,763 (GRCm39)	splice site	probably null
R6318:Ogdh	UTSW	11	6,299,390 (GRCm39)	missense	probably damaging	0.99
R6875:Ogdh	UTSW	11	6,290,477 (GRCm39)	missense	probably benign	0.12
R6988:Ogdh	UTSW	11	6,263,806 (GRCm39)	nonsense	probably null
R7406:Ogdh	UTSW	11	6,298,351 (GRCm39)	missense	probably benign	0.00
R7724:Ogdh	UTSW	11	6,274,887 (GRCm39)	missense	probably benign
R7763:Ogdh	UTSW	11	6,288,558 (GRCm39)	missense	probably benign
R7909:Ogdh	UTSW	11	6,263,965 (GRCm39)	missense	possibly damaging	0.55
R8207:Ogdh	UTSW	11	6,299,329 (GRCm39)	missense	probably benign	0.38
R8348:Ogdh	UTSW	11	6,292,619 (GRCm39)	missense	probably damaging	0.98
R8401:Ogdh	UTSW	11	6,247,174 (GRCm39)	nonsense	probably null
R8448:Ogdh	UTSW	11	6,292,619 (GRCm39)	missense	probably damaging	0.98
R8770:Ogdh	UTSW	11	6,305,336 (GRCm39)	missense	probably damaging	1.00
R8796:Ogdh	UTSW	11	6,297,129 (GRCm39)	missense	possibly damaging	0.75
R9132:Ogdh	UTSW	11	6,290,488 (GRCm39)	missense	probably benign	0.01
R9328:Ogdh	UTSW	11	6,297,838 (GRCm39)	missense	probably benign	0.30
R9479:Ogdh	UTSW	11	6,297,854 (GRCm39)	missense	possibly damaging	0.89
R9696:Ogdh	UTSW	11	6,289,209 (GRCm39)	missense	probably damaging	1.00
Z1088:Ogdh	UTSW	11	6,305,427 (GRCm39)	missense	probably benign
Z1177:Ogdh	UTSW	11	6,266,982 (GRCm39)	missense	probably benign	0.07
Z1177:Ogdh	UTSW	11	6,247,051 (GRCm39)	missense	probably benign

Nature of Mutation

DNA sequencing using the SOLiD technique identified a T to C transition at position 591 of the Ogdh transcript using Ensembl record ENSMUST00000093350 in exon 5 of 24 total exons. Multiple transcripts of the Ogdh gene are displayed on Ensembl. The mutated nucleotide causes a leucine to proline substitution at amino acid 180 of the encoded protein. The mutation has been confirmed by DNA sequencing using the Sanger method (Figure 1).

Protein Function and Prediction

If using the Ensembl record ENSMUSP00000091041, the Ogdh gene encodes the 1034 amino 2-oxoglutarate dehydrogenase, which is a subunit of a complex that catalyzes the overall conversion of 2-oxoglutarate to succinyl-CoA and CO₂ in the mitochondria (Uniprot Q9JLC8).

The L180P change is predicted to be benign by the PolyPhen program.

Posted On

2010-05-04