Mutagenetix > Incidental Mutation

Incidental Mutation 'P0014:Ddah1'

7627

Institutional Source

Beutler Lab

Gene Symbol

Ddah1

Ensembl Gene

ENSMUSG00000028194

Gene Name

dimethylarginine dimethylaminohydrolase 1

Synonyms

2410006N07Rik, 2510015N06Rik

MMRRC Submission

038267-MU

Accession Numbers

Essential gene?

Possibly non essential (E-score: 0.323) question?

Stock #

P0014 (G1)

Quality Score

Status

Validated

Chromosome

Chromosomal Location

145464447-145600032 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 145558913 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Aspartic acid to Glycine at position 160 (D160G)

Ref Sequence

ENSEMBL: ENSMUSP00000029845 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000029845] [ENSMUST00000120310]

AlphaFold

Q9CWS0

Predicted Effect

probably benign
Transcript: ENSMUST00000029845
AA Change: D160G

PolyPhen 2 Score 0.364 (Sensitivity: 0.90; Specificity: 0.89)

SMART Domains

Protein: ENSMUSP00000029845
Gene: ENSMUSG00000028194
AA Change: D160G

Domain	Start	End	E-Value	Type
Pfam:Amidinotransf	12	279	9.4e-16	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000120310
AA Change: D57G

PolyPhen 2 Score 0.314 (Sensitivity: 0.90; Specificity: 0.89)

SMART Domains

Protein: ENSMUSP00000112747
Gene: ENSMUSG00000028194
AA Change: D57G

Domain	Start	End	E-Value	Type
Pfam:Amidinotransf	1	178	2.2e-24	PFAM

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000127193

Meta Mutation Damage Score

0.3656

Coding Region Coverage

1x: 85.4%
3x: 80.7%
10x: 66.7%
20x: 50.4%

Validation Efficiency

95% (100/105)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene belongs to the dimethylarginine dimethylaminohydrolase (DDAH) gene family. The encoded enzyme plays a role in nitric oxide generation by regulating cellular concentrations of methylarginines, which in turn inhibit nitric oxide synthase activity. [provided by RefSeq, Jul 2008]
PHENOTYPE: Both heterozygous and homozygous inactivation of this gene leads to increased plasma asymmetrical dimethylarginine (ADMA) levels, reduced cardiovascular nitric oxide production, and increased blood pressure. [provided by MGI curators]

Allele List at MGI

All alleles(7) : Targeted(4) Gene trapped(3)

Other mutations in this stock

Total: 19 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abcb4	A	G	5: 9,000,083 (GRCm39)	Y1017C	probably benign	Het
Acly	T	C	11: 100,375,430 (GRCm39)	I787V	probably benign	Het
Aldob	T	C	4: 49,538,153 (GRCm39)	Q325R	probably benign	Het
Armh4	C	T	14: 49,989,116 (GRCm39)	E618K	probably damaging	Het
Capns2	A	G	8: 93,628,842 (GRCm39)	T244A	probably damaging	Het
Clec16a	C	T	16: 10,378,020 (GRCm39)		probably benign	Het
Creb3	A	G	4: 43,563,265 (GRCm39)	T121A	possibly damaging	Het
Dhx57	A	T	17: 80,582,620 (GRCm39)	H328Q	probably benign	Het
Dmxl2	A	C	9: 54,309,048 (GRCm39)	L1901R	probably damaging	Het
Dnah5	T	A	15: 28,403,619 (GRCm39)	L3448Q	probably damaging	Het
Gcdh	A	G	8: 85,615,154 (GRCm39)		probably null	Het
Lrrc8c	T	C	5: 105,755,110 (GRCm39)	V295A	probably benign	Het
Nek1	A	T	8: 61,524,781 (GRCm39)		probably benign	Het
Pkp2	C	T	16: 16,058,386 (GRCm39)	P356L	probably benign	Het
Sipa1l3	T	C	7: 29,082,640 (GRCm39)	T752A	probably damaging	Het
Slc38a2	C	A	15: 96,588,042 (GRCm39)	W494L	probably damaging	Het
Ttn	T	C	2: 76,628,814 (GRCm39)	D12734G	probably damaging	Het
Uggt2	A	G	14: 119,281,950 (GRCm39)	S742P	probably damaging	Het
Vwa3b	C	T	1: 37,212,995 (GRCm39)		probably benign	Het

Other mutations in Ddah1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL02947:Ddah1	APN	3	145,464,842 (GRCm39)	missense	probably benign	0.44
R1386:Ddah1	UTSW	3	145,594,966 (GRCm39)	missense	probably benign	0.00
R1455:Ddah1	UTSW	3	145,594,864 (GRCm39)	missense	probably benign	0.29
R1464:Ddah1	UTSW	3	145,559,029 (GRCm39)	nonsense	probably null
R1464:Ddah1	UTSW	3	145,559,029 (GRCm39)	nonsense	probably null
R1557:Ddah1	UTSW	3	145,597,227 (GRCm39)	missense	probably benign	0.00
R1724:Ddah1	UTSW	3	145,597,261 (GRCm39)	missense	probably damaging	0.99
R1853:Ddah1	UTSW	3	145,597,304 (GRCm39)	missense	probably benign
R3700:Ddah1	UTSW	3	145,597,250 (GRCm39)	missense	probably benign
R6170:Ddah1	UTSW	3	145,597,261 (GRCm39)	missense	probably benign	0.06
R7603:Ddah1	UTSW	3	145,464,774 (GRCm39)	missense	probably benign	0.17

Protein Function and Prediction

Dimethylarginine dimethylaminohydrolase (Ddah1) functions to regulate cellular methylarginine concentration, which will subsequently inhibit nitric oxide synthase activity [OMIM *604743].

Expression/Localization

Northern blot analysis of human tissues found that DDAH1 expression is highest in brain, kidney, pancreas, and liver (4;5). In the brain, DDAH1 is primarily expressed in the forebrain (5).

Background

Ddah1^{tm1.1Yjch/tm1.1Yjch}; MGI:5424370

Not specified

Homozygous animals of this conditional knockout model have slightly elevated blood pressure, increased levels of ADMA and L-NMMA in the plasma and tissues, and both urinary and plamsa NOx content are decreased (3).

Ddah1^{tm1Pval/tm1Pval}; MGI:3711768

involves: 129X1/SvJ

Homozygous animals exhibit lethality around E2 (2).

Ddah1^{tm1Pval/tm1Pval}; MGI:3711768

involves: 129X1/SvJ * C57BL/6

Similar to the genetic background above, in this genetic background, these homozygous animals exhibit complete prenatal lethality (1).

References

1. Leiper, J., Nandi, M., Torondel, B., Murray-Rust, J., Malaki, M., O'Hara, B., Rossiter, S., Anthony, S., Madhani, M., Selwood, D., Smith, C., Wojciak-Stothard, B., Rudiger, A., Stidwill, R., McDonald, N. Q., and Vallance, P. (2007) Disruption of Methylarginine Metabolism Impairs Vascular Homeostasis. Nat Med. 13, 198-203.

2. Breckenridge, R. A., Kelly, P., Nandi, M., Vallance, P. J., Ohun, T. J., and Leiper, J. (2010) A Role for Dimethylarginine Dimethylaminohydrolase 1 (DDAH1) in Mammalian Development. Int J Dev Biol. 54, 215-220.

3. Hu, X., Atzler, D., Xu, X., Zhang, P., Guo, H., Lu, Z., Fassett, J., Schwedhelm, E., Boger, R. H., Bache, R. J., and Chen, Y. (2011) Dimethylarginine Dimethylaminohydrolase-1 is the Critical Enzyme for Degrading the Cardiovascular Risk Factor Asymmetrical Dimethylarginine. Arterioscler Thromb Vasc Biol. 31, 1540-1546.

4. Leiper, J. M., Santa Maria, J., Chubb, A., MacAllister, R. J., Charles, I. G., Whitley, G. S., and Vallance, P. (1999) Identification of Two Human Dimethylarginine Dimethylaminohydrolases with Distinct Tissue Distributions and Homology with Microbial Arginine Deiminases. Biochem J. 343 Pt 1, 209-214.

5. Tran, C. T., Fox, M. F., Vallance, P., and Leiper, J. M. (2000) Chromosomal Localization, Gene Structure, and Expression Pattern of DDAH1: Comparison with DDAH2 and Implications for Evolutionary Origins. Genomics. 68, 101-105.

Posted On

2012-10-05

Science Writer

Anne Murray