Incidental Mutation 'P0014:Ddah1'
ID7627
Institutional Source Beutler Lab
Gene Symbol Ddah1
Ensembl Gene ENSMUSG00000028194
Gene Namedimethylarginine dimethylaminohydrolase 1
Synonyms2410006N07Rik, 2510015N06Rik
MMRRC Submission 038267-MU
Accession Numbers

NCBI RefSeq: NM_026993.3; MGI: 1916469

Is this an essential gene? Possibly non essential (E-score: 0.326) question?
Stock #P0014 (G1)
Quality Score
Status Validated
Chromosome3
Chromosomal Location145758675-145894277 bp(+) (GRCm38)
Type of Mutationmissense
DNA Base Change (assembly) A to G at 145853158 bp
ZygosityHeterozygous
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]
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

DomainStartEndE-ValueType
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

DomainStartEndE-ValueType
Pfam:Amidinotransf 1 178 2.2e-24 PFAM
Predicted Effect noncoding transcript
Transcript: ENSMUST00000127193
Meta Mutation Damage Score 0.3656 question?
Coding Region Coverage
  • 1x: 85.4%
  • 3x: 80.7%
  • 10x: 66.7%
  • 20x: 50.4%
Validation Efficiency 95% (100/105)
MGI Phenotype Strain: 3711768; 5424370
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
GeneRefVarChr/LocMutationPredicted EffectZygosity
3632451O06Rik C T 14: 49,751,659 E618K probably damaging Het
Abcb4 A G 5: 8,950,083 Y1017C probably benign Het
Acly T C 11: 100,484,604 I787V probably benign Het
Aldob T C 4: 49,538,153 Q325R probably benign Het
Capns2 A G 8: 92,902,214 T244A probably damaging Het
Clec16a C T 16: 10,560,156 probably benign Het
Creb3 A G 4: 43,563,265 T121A possibly damaging Het
Dhx57 A T 17: 80,275,191 H328Q probably benign Het
Dmxl2 A C 9: 54,401,764 L1901R probably damaging Het
Dnah5 T A 15: 28,403,473 L3448Q probably damaging Het
Gcdh A G 8: 84,888,525 probably null Het
Lrrc8c T C 5: 105,607,244 V295A probably benign Het
Nek1 A T 8: 61,071,747 probably benign Het
Pkp2 C T 16: 16,240,522 P356L probably benign Het
Sipa1l3 T C 7: 29,383,215 T752A probably damaging Het
Slc38a2 C A 15: 96,690,161 W494L probably damaging Het
Ttn T C 2: 76,798,470 D12734G probably damaging Het
Uggt2 A G 14: 119,044,538 S742P probably damaging Het
Vwa3b C T 1: 37,173,914 probably benign Het
Other mutations in Ddah1
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL02947:Ddah1 APN 3 145759087 missense probably benign 0.44
R1386:Ddah1 UTSW 3 145889211 missense probably benign 0.00
R1455:Ddah1 UTSW 3 145889109 missense probably benign 0.29
R1464:Ddah1 UTSW 3 145853274 nonsense probably null
R1464:Ddah1 UTSW 3 145853274 nonsense probably null
R1557:Ddah1 UTSW 3 145891472 missense probably benign 0.00
R1724:Ddah1 UTSW 3 145891506 missense probably damaging 0.99
R1853:Ddah1 UTSW 3 145891549 missense probably benign
R3700:Ddah1 UTSW 3 145891495 missense probably benign
R6170:Ddah1 UTSW 3 145891506 missense probably benign 0.06
R7603:Ddah1 UTSW 3 145759019 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

Ddah1tm1.1Yjch/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).

 

Ddah1tm1Pval/tm1Pval; MGI:3711768

involves: 129X1/SvJ

Homozygous animals exhibit lethality around E2 (2).

 

Ddah1tm1Pval/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
Posted On2012-10-05
Science WriterAnne Murray