Mutagenetix > Incidental Mutation

Incidental Mutation 'R0529:Aasdh'

49040

Institutional Source

Beutler Lab

Gene Symbol

Aasdh

Ensembl Gene

ENSMUSG00000055923

Gene Name

aminoadipate-semialdehyde dehydrogenase

Synonyms

A230062G08Rik

MMRRC Submission

038721-MU

Accession Numbers

Genbank: NM_173765.3; Ensembl: ENSMUST00000120963

Essential gene?

Probably non essential (E-score: 0.218) question?

Stock #

R0529 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

76873659-76905514 bp(-) (GRCm38)

Type of Mutation

nonsense

DNA Base Change (assembly)

A to C at 76876267 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Tyrosine to Stop codon at position 179 (Y179*)

Ref Sequence

ENSEMBL: ENSMUSP00000117489 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000069709] [ENSMUST00000120639] [ENSMUST00000120963] [ENSMUST00000121160] [ENSMUST00000123682] [ENSMUST00000126741] [ENSMUST00000149602] [ENSMUST00000163347]

AlphaFold

Q80WC9

Predicted Effect

probably null
Transcript: ENSMUST00000069709
AA Change: Y1020*

SMART Domains

Protein: ENSMUSP00000069279
Gene: ENSMUSG00000055923
AA Change: Y1020*

Domain	Start	End	E-Value	Type
Pfam:AMP-binding	7	449	1.3e-50	PFAM
Pfam:AMP-binding_C	458	526	7.4e-6	PFAM
Pfam:PP-binding	556	628	1.2e-6	PFAM
PQQ	775	808	5.29e-1	SMART
PQQ	818	850	4.37e-2	SMART
PQQ	860	892	2.3e1	SMART
PQQ	901	934	2.83e1	SMART
Blast:PQQ	943	973	2e-9	BLAST
PQQ	982	1014	2.61e2	SMART
PQQ	1029	1061	8.53e0	SMART
Blast:PQQ	1070	1100	2e-12	BLAST

Predicted Effect

probably benign
Transcript: ENSMUST00000120639

SMART Domains

Protein: ENSMUSP00000113796
Gene: ENSMUSG00000036377

Domain	Start	End	E-Value	Type
Pfam:DUF4592	44	173	1.7e-45	PFAM
low complexity region	210	220	N/A	INTRINSIC
coiled coil region	224	291	N/A	INTRINSIC
coiled coil region	328	482	N/A	INTRINSIC
low complexity region	533	547	N/A	INTRINSIC
low complexity region	580	593	N/A	INTRINSIC
low complexity region	875	888	N/A	INTRINSIC
internal_repeat_1	947	1025	1.47e-5	PROSPERO
low complexity region	1034	1047	N/A	INTRINSIC
internal_repeat_1	1065	1122	1.47e-5	PROSPERO
low complexity region	1268	1280	N/A	INTRINSIC

Predicted Effect

probably null
Transcript: ENSMUST00000120963
AA Change: Y1020*

SMART Domains

Protein: ENSMUSP00000113792
Gene: ENSMUSG00000055923
AA Change: Y1020*

Domain	Start	End	E-Value	Type
Pfam:AMP-binding	7	449	1.3e-50	PFAM
Pfam:AMP-binding_C	458	526	7.4e-6	PFAM
Pfam:PP-binding	556	628	1.2e-6	PFAM
PQQ	775	808	5.29e-1	SMART
PQQ	818	850	4.37e-2	SMART
PQQ	860	892	2.3e1	SMART
PQQ	901	934	2.83e1	SMART
Blast:PQQ	943	973	2e-9	BLAST
PQQ	982	1014	2.61e2	SMART
PQQ	1029	1061	8.53e0	SMART
Blast:PQQ	1070	1100	2e-12	BLAST

Predicted Effect

probably benign
Transcript: ENSMUST00000121160

SMART Domains

Protein: ENSMUSP00000113947
Gene: ENSMUSG00000036377

Domain	Start	End	E-Value	Type
Pfam:DUF4592	45	172	1.8e-41	PFAM
low complexity region	210	220	N/A	INTRINSIC
coiled coil region	224	291	N/A	INTRINSIC
coiled coil region	328	482	N/A	INTRINSIC
low complexity region	533	547	N/A	INTRINSIC
low complexity region	580	593	N/A	INTRINSIC
low complexity region	875	888	N/A	INTRINSIC
low complexity region	1034	1047	N/A	INTRINSIC
low complexity region	1271	1283	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000123682

SMART Domains

Protein: ENSMUSP00000121050
Gene: ENSMUSG00000055923

Domain	Start	End	E-Value	Type
Pfam:AMP-binding	7	231	1.7e-23	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000126741

SMART Domains

Protein: ENSMUSP00000118854
Gene: ENSMUSG00000055923

Domain	Start	End	E-Value	Type
Pfam:AMP-binding	7	403	7.5e-51	PFAM

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000135697

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000145022

Predicted Effect

probably null
Transcript: ENSMUST00000149602
AA Change: Y179*

SMART Domains

Protein: ENSMUSP00000117489
Gene: ENSMUSG00000055923
AA Change: Y179*

Domain	Start	End	E-Value	Type
PQQ	21	53	4.37e-2	SMART
PQQ	63	95	2.3e1	SMART
Blast:PQQ	104	130	2e-6	BLAST
PQQ	141	173	2.61e2	SMART
low complexity region	191	200	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000163347

SMART Domains

Protein: ENSMUSP00000127212
Gene: ENSMUSG00000036377

Domain	Start	End	E-Value	Type
Pfam:DUF4592	44	173	1.7e-45	PFAM
low complexity region	210	220	N/A	INTRINSIC
coiled coil region	224	291	N/A	INTRINSIC
coiled coil region	328	482	N/A	INTRINSIC
low complexity region	533	547	N/A	INTRINSIC
low complexity region	580	593	N/A	INTRINSIC
low complexity region	875	888	N/A	INTRINSIC
internal_repeat_1	947	1025	1.47e-5	PROSPERO
low complexity region	1034	1047	N/A	INTRINSIC
internal_repeat_1	1065	1122	1.47e-5	PROSPERO
low complexity region	1268	1280	N/A	INTRINSIC

Meta Mutation Damage Score

0.9755

Coding Region Coverage

1x: 99.2%
3x: 98.4%
10x: 96.5%
20x: 93.3%

Validation Efficiency

97% (58/60)

MGI Phenotype

FUNCTION: The gene product is a cytosolic enzyme involved in the production of alpha-aminoadipic acid from alpha-aminoadipic semialdehyde. It is postulated that this enzyme plays a role in lysine metabolism. There is currently debate regarding this enzyme's putative requirement of pyrroloquinoline quinine as an essential cofactor. A related pseudogene has been identified on chromosome 2. [provided by RefSeq, Jan 2010]

Allele List at MGI

All alleles(14) : Gene trapped(14)

Other mutations in this stock

Total: 57 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
1700010I14Rik	G	A	17: 8,992,396	V126I	probably benign	Het
Afp	A	G	5: 90,504,395	Y415C	probably damaging	Het
Aldh5a1	G	T	13: 24,913,873	T393K	probably benign	Het
Arhgef26	T	C	3: 62,339,725	S77P	probably benign	Het
Axl	A	G	7: 25,787,287		probably benign	Het
Card10	A	G	15: 78,780,475		probably null	Het
Ccdc71l	G	A	12: 32,379,252	S90N	probably damaging	Het
Cebpa	A	T	7: 35,120,199	T261S	probably benign	Het
Cnmd	T	C	14: 79,642,041	E219G	probably benign	Het
Cntln	T	A	4: 85,067,825	L1010H	probably damaging	Het
Cul9	A	G	17: 46,520,468		probably benign	Het
Cyld	A	G	8: 88,729,759	E479G	probably benign	Het
Dmp1	A	G	5: 104,212,226	E256G	probably benign	Het
Dnmt1	T	C	9: 20,911,550	D1140G	probably damaging	Het
Drd2	A	C	9: 49,407,074	M439L	probably benign	Het
Drd3	G	A	16: 43,822,714	V438M	probably damaging	Het
Dyrk3	A	G	1: 131,130,121	I70T	probably benign	Het
Fam46c	A	G	3: 100,472,370	Y357H	probably benign	Het
Fbxo38	T	C	18: 62,505,986	K1082E	probably damaging	Het
Fbxw10	A	C	11: 62,859,845	D428A	probably damaging	Het
Fmn1	T	A	2: 113,707,853		probably benign	Het
Fmnl2	A	T	2: 53,042,365	I119F	probably damaging	Het
Frmd4a	A	G	2: 4,606,023	T995A	probably damaging	Het
Gda	T	A	19: 21,425,537	I82F	probably damaging	Het
Gpatch4	T	A	3: 88,051,276	H22Q	probably damaging	Het
Gpr55	A	G	1: 85,941,503	F119L	probably benign	Het
Gtf2i	A	T	5: 134,261,869	L425*	probably null	Het
Knstrn	T	A	2: 118,830,980		probably benign	Het
Lipo2	T	A	19: 33,746,935	I144L	probably benign	Het
Lrp1	T	C	10: 127,541,594		probably null	Het
Mtmr14	T	C	6: 113,266,252		probably benign	Het
Nsmce4a	A	T	7: 130,533,806	S345R	probably benign	Het
Oacyl	T	A	18: 65,742,219	V385D	probably damaging	Het
Olfr421-ps1	G	A	1: 174,152,130	A205T	probably benign	Het
Olfr917	A	T	9: 38,665,512	C111S	probably benign	Het
Phlpp2	T	C	8: 109,876,971	S55P	probably benign	Het
Pkhd1l1	T	A	15: 44,526,754	V1422E	possibly damaging	Het
Plcd3	T	G	11: 103,080,187	H181P	probably benign	Het
Psmc5	G	A	11: 106,261,164		probably null	Het
Psmd11	T	C	11: 80,470,689		probably benign	Het
Rab39	T	C	9: 53,686,716	Y83C	probably damaging	Het
Ric8a	A	G	7: 140,860,893	E93G	probably damaging	Het
Rtp3	T	C	9: 110,987,084	E133G	possibly damaging	Het
Serpina1e	A	C	12: 103,949,104	L281R	probably damaging	Het
Slc35e1	T	C	8: 72,492,571		probably benign	Het
Tmem63a	A	T	1: 180,961,094	E332V	probably benign	Het
Tnk1	T	C	11: 69,855,164	T312A	probably damaging	Het
Traf3ip3	G	T	1: 193,194,811		probably benign	Het
Trappc11	A	G	8: 47,526,979	V174A	possibly damaging	Het
Vmn1r174	G	A	7: 23,754,197	R96H	probably benign	Het
Vmn1r7	T	A	6: 57,024,465	Y270F	possibly damaging	Het
Vmn2r12	A	G	5: 109,092,848	V133A	probably benign	Het
Vmn2r18	T	A	5: 151,562,523	E502V	probably damaging	Het
Wipf3	C	A	6: 54,485,363	P186Q	probably damaging	Het
Yipf5	A	T	18: 40,212,162	M55K	probably benign	Het
Zbtb7a	G	A	10: 81,143,986	V5M	probably damaging	Het
Zfy1	G	T	Y: 726,040	S575Y	probably damaging	Het

Other mutations in Aasdh

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00823:Aasdh	APN	5	76878534	unclassified	probably benign
IGL01013:Aasdh	APN	5	76886206	missense	possibly damaging	0.68
IGL01558:Aasdh	APN	5	76888617	missense	possibly damaging	0.89
IGL02544:Aasdh	APN	5	76902114	missense	probably benign	0.27
IGL02614:Aasdh	APN	5	76896368	splice site	probably benign
IGL02678:Aasdh	APN	5	76888020	splice site	probably benign
IGL02739:Aasdh	APN	5	76878517	missense	possibly damaging	0.64
IGL02947:Aasdh	APN	5	76902110	missense	probably benign	0.01
IGL03116:Aasdh	APN	5	76902089	splice site	probably null
IGL03398:Aasdh	APN	5	76891719	missense	probably benign	0.02
1mM(1):Aasdh	UTSW	5	76896617	missense	possibly damaging	0.91
R0183:Aasdh	UTSW	5	76886235	missense	probably benign	0.05
R0226:Aasdh	UTSW	5	76902002	missense	probably damaging	1.00
R0367:Aasdh	UTSW	5	76902114	missense	probably damaging	0.99
R0386:Aasdh	UTSW	5	76896461	missense	probably damaging	0.98
R0881:Aasdh	UTSW	5	76876283	missense	probably damaging	1.00
R0882:Aasdh	UTSW	5	76876283	missense	probably damaging	1.00
R1033:Aasdh	UTSW	5	76876283	missense	probably damaging	1.00
R1034:Aasdh	UTSW	5	76876283	missense	probably damaging	1.00
R1035:Aasdh	UTSW	5	76876283	missense	probably damaging	1.00
R1036:Aasdh	UTSW	5	76876283	missense	probably damaging	1.00
R1366:Aasdh	UTSW	5	76888804	missense	probably benign	0.10
R1446:Aasdh	UTSW	5	76886289	missense	probably benign	0.45
R1449:Aasdh	UTSW	5	76886289	missense	probably benign	0.45
R1469:Aasdh	UTSW	5	76891679	missense	probably damaging	0.97
R1469:Aasdh	UTSW	5	76891679	missense	probably damaging	0.97
R1583:Aasdh	UTSW	5	76882681	missense	probably benign	0.00
R1641:Aasdh	UTSW	5	76891779	missense	probably benign	0.36
R1876:Aasdh	UTSW	5	76877549	missense	probably damaging	1.00
R1895:Aasdh	UTSW	5	76891704	missense	probably damaging	1.00
R1946:Aasdh	UTSW	5	76891704	missense	probably damaging	1.00
R3615:Aasdh	UTSW	5	76888782	missense	probably benign	0.20
R3616:Aasdh	UTSW	5	76888782	missense	probably benign	0.20
R3746:Aasdh	UTSW	5	76888654	nonsense	probably null
R3747:Aasdh	UTSW	5	76888654	nonsense	probably null
R3748:Aasdh	UTSW	5	76888654	nonsense	probably null
R3750:Aasdh	UTSW	5	76888654	nonsense	probably null
R3836:Aasdh	UTSW	5	76878468	missense	probably benign	0.32
R4857:Aasdh	UTSW	5	76887284	missense	probably benign	0.01
R4928:Aasdh	UTSW	5	76896688	missense	possibly damaging	0.65
R4937:Aasdh	UTSW	5	76888654	nonsense	probably null
R5762:Aasdh	UTSW	5	76896598	missense	probably benign	0.00
R5866:Aasdh	UTSW	5	76876211	missense	probably damaging	1.00
R5940:Aasdh	UTSW	5	76882898	missense	probably benign	0.07
R6253:Aasdh	UTSW	5	76886258	missense	possibly damaging	0.81
R6542:Aasdh	UTSW	5	76883055	missense	probably damaging	1.00
R6825:Aasdh	UTSW	5	76888849	splice site	probably null
R6868:Aasdh	UTSW	5	76891680	missense	probably damaging	0.99
R6876:Aasdh	UTSW	5	76896441	missense	probably damaging	1.00
R6961:Aasdh	UTSW	5	76876301	missense	probably damaging	1.00
R6963:Aasdh	UTSW	5	76896456	missense	probably damaging	0.99
R7069:Aasdh	UTSW	5	76876356	missense	probably benign	0.03
R7220:Aasdh	UTSW	5	76901925	missense	probably benign	0.13
R7545:Aasdh	UTSW	5	76880014	missense	probably damaging	1.00
R7673:Aasdh	UTSW	5	76882708	missense	probably benign	0.03
R7703:Aasdh	UTSW	5	76888077	missense	probably damaging	0.99
R7890:Aasdh	UTSW	5	76884122	missense	probably benign	0.19
R7978:Aasdh	UTSW	5	76888668	missense	probably damaging	0.99
R8046:Aasdh	UTSW	5	76896478	missense	probably benign
R8152:Aasdh	UTSW	5	76896458	missense	probably damaging	1.00
R8425:Aasdh	UTSW	5	76886277	missense	possibly damaging	0.49
R8884:Aasdh	UTSW	5	76891794	missense	possibly damaging	0.94
R9028:Aasdh	UTSW	5	76876130	missense	probably damaging	1.00
R9361:Aasdh	UTSW	5	76882378	missense	probably benign	0.01
R9519:Aasdh	UTSW	5	76882725	missense	probably benign	0.00
Z1088:Aasdh	UTSW	5	76901157	splice site	probably null
Z1176:Aasdh	UTSW	5	76891796	critical splice acceptor site	probably null

Predicted Primers

PCR Primer
(F):5'- AAGCATTGATTCCCAGACCACAGG -3'
(R):5'- TGAAGAGACCCCGTTGGACTCAAG -3'

Sequencing Primer
(F):5'- TTCCCAGACCACAGGAGAGG -3'
(R):5'- CCGTTGGACTCAAGAGTTGC -3'

Nature of Mutation

Multiple transcripts of the Aasdh gene are displayed on Ensembl and Vega.

Protein Function and Prediction

The Aasdh gene encodes an 1100 amino acid acyl-CoA synthase that can catalyze the initial reaction in fatty acid metabolism, by forming a thioester with CoA. The enzyme is a putative 2-aminoadipic 6-semialdehyde dehydrogenase, which may be involved in lysine catabolism. The protein contains an acyl carrier domain at residues 554-628 (Uniprot Q80WC9).

The aminoadipate-semialdehyde dehydrogenase (AASDH) protein (alternatively, U26 or ACYL-CoA synthetase family member 4; ACSF4) contains an N-terminal adenylation domain, a thiolation domain, and seven C-terminal binding sites for pyrroloquinoline quinone (PQQ), a redox cofactor (1).

Expression/Localization

Aasdh is expressed in all mouse tissues examined; highest expression is in the heart, liver, and kidney (1).

Background

In lysine metabolism, lysine is degraded after use to 2-aminoapdipic 6-semaldehyde (AAS), which is subsequently oxidized to 2-aminoapidipic acid (AAA) by AASDH.

References

1. Kasahara, T., and Kato, T. (2003) Nutritional Biochemistry: A New Redox-Cofactor Vitamin for Mammals. Nature. 422, 832.

Posted On

2013-06-12

Science Writer

Nora G. Smart, Anne Murray