Mutagenetix > Incidental Mutation

Incidental Mutation 'R1509:Aldh18a1'

168191

Institutional Source

Beutler Lab

Gene Symbol

Aldh18a1

Ensembl Gene

ENSMUSG00000025007

Gene Name

aldehyde dehydrogenase 18 family, member A1

Synonyms

2810433K04Rik, Pycs

MMRRC Submission

039556-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R1509 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

40538701-40576907 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 40545927 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Isoleucine to Threonine at position 620 (I620T)

Ref Sequence

ENSEMBL: ENSMUSP00000025979 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000025979] [ENSMUST00000175967] [ENSMUST00000176939]

AlphaFold

Q9Z110

Predicted Effect

probably damaging
Transcript: ENSMUST00000025979
AA Change: I620T

PolyPhen 2 Score 0.980 (Sensitivity: 0.75; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000025979
Gene: ENSMUSG00000025007
AA Change: I620T

Domain	Start	End	E-Value	Type
Pfam:AA_kinase	71	329	1e-41	PFAM
Pfam:Aldedh	350	659	3.9e-10	PFAM

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000120920

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000134749

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000155613

Predicted Effect

probably benign
Transcript: ENSMUST00000175967

SMART Domains

Protein: ENSMUSP00000135419
Gene: ENSMUSG00000025007

Domain	Start	End	E-Value	Type
PDB:2H5G\|B	1	83	9e-52	PDB
SCOP:d1a4sa_	11	95	1e-14	SMART

Predicted Effect

probably damaging
Transcript: ENSMUST00000176939
AA Change: I618T

PolyPhen 2 Score 0.975 (Sensitivity: 0.76; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000135426
Gene: ENSMUSG00000025007
AA Change: I618T

Domain	Start	End	E-Value	Type
Pfam:AA_kinase	71	327	1.9e-39	PFAM
Pfam:Aldedh	351	665	3.4e-11	PFAM

Meta Mutation Damage Score

0.8957

Coding Region Coverage

1x: 99.1%
3x: 98.3%
10x: 96.4%
20x: 93.1%

Validation Efficiency

99% (89/90)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene is a member of the aldehyde dehydrogenase family and encodes a bifunctional ATP- and NADPH-dependent mitochondrial enzyme with both gamma-glutamyl kinase and gamma-glutamyl phosphate reductase activities. The encoded protein catalyzes the reduction of glutamate to delta1-pyrroline-5-carboxylate, a critical step in the de novo biosynthesis of proline, ornithine and arginine. Mutations in this gene lead to hyperammonemia, hypoornithinemia, hypocitrullinemia, hypoargininemia and hypoprolinemia and may be associated with neurodegeneration, cataracts and connective tissue diseases. Alternatively spliced transcript variants, encoding different isoforms, have been described for this gene. [provided by RefSeq, Jul 2008]

Allele List at MGI

Other mutations in this stock

Total: 86 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
2210408I21Rik	T	C	13: 77,340,766 (GRCm39)	S132P	probably benign	Het
AC153895.1	T	C	6: 50,020,451 (GRCm39)	R54G	unknown	Het
Acot12	G	A	13: 91,919,994 (GRCm39)		probably null	Het
Adhfe1	T	A	1: 9,623,671 (GRCm39)	D98E	probably benign	Het
Ago2	A	G	15: 72,988,213 (GRCm39)	F594S	probably damaging	Het
Aspscr1	C	A	11: 120,592,342 (GRCm39)	A294D	probably damaging	Het
Bod1l	C	G	5: 41,976,883 (GRCm39)	R1477T	probably damaging	Het
Ccdc18	C	A	5: 108,336,844 (GRCm39)	A741D	possibly damaging	Het
Ces4a	G	A	8: 105,864,729 (GRCm39)	G69S	probably damaging	Het
Cfap52	C	T	11: 67,829,819 (GRCm39)	V317I	probably benign	Het
Cgn	A	T	3: 94,681,568 (GRCm39)	L509Q	probably benign	Het
Crb2	A	G	2: 37,676,631 (GRCm39)	H204R	probably benign	Het
Cspg4b	A	G	13: 113,504,790 (GRCm39)	N431S	probably damaging	Het
Ddx39a	G	A	8: 84,446,527 (GRCm39)	V99M	probably damaging	Het
Dis3l2	T	A	1: 86,948,808 (GRCm39)	C582S	possibly damaging	Het
Dmbt1	G	A	7: 130,676,061 (GRCm39)		probably benign	Het
Dnah6	T	C	6: 73,004,425 (GRCm39)	E3846G	probably damaging	Het
Dstyk	A	G	1: 132,384,084 (GRCm39)	E655G	probably damaging	Het
Epha4	T	C	1: 77,357,523 (GRCm39)	Y825C	probably damaging	Het
Esp36	T	A	17: 38,728,173 (GRCm39)	N36I	probably damaging	Het
Fabp3	C	T	4: 130,206,180 (GRCm39)	T57I	probably benign	Het
Fem1c	A	G	18: 46,657,280 (GRCm39)	S145P	probably benign	Het
Galnt13	T	C	2: 54,623,094 (GRCm39)	I80T	probably damaging	Het
Gm5698	T	C	1: 31,016,728 (GRCm39)	T108A	probably benign	Het
Hipk3	A	G	2: 104,271,607 (GRCm39)	S442P	probably benign	Het
Hmcn2	T	A	2: 31,204,491 (GRCm39)	V22D	possibly damaging	Het
Hspg2	C	T	4: 137,238,552 (GRCm39)		probably benign	Het
Ide	A	G	19: 37,262,603 (GRCm39)		probably null	Het
Ifnar1	C	A	16: 91,300,384 (GRCm39)	P462Q	probably damaging	Het
Itgb2l	T	A	16: 96,228,049 (GRCm39)	I485F	probably benign	Het
Jakmip3	C	T	7: 138,629,505 (GRCm39)	R549W	possibly damaging	Het
Lrrc36	A	G	8: 106,187,761 (GRCm39)	Q680R	probably damaging	Het
Lysmd3	T	G	13: 81,817,390 (GRCm39)	H122Q	probably benign	Het
Macf1	C	A	4: 123,577,802 (GRCm39)	V61L	possibly damaging	Het
Map1b	T	C	13: 99,568,036 (GRCm39)	T1562A	unknown	Het
Map3k20	A	T	2: 72,194,968 (GRCm39)		probably benign	Het
Mroh8	A	G	2: 157,075,125 (GRCm39)	V457A	probably benign	Het
Mrpl40	T	A	16: 18,694,159 (GRCm39)		probably null	Het
Ms4a10	C	T	19: 10,941,472 (GRCm39)	V166I	probably benign	Het
Mycl	A	G	4: 122,894,100 (GRCm39)	D300G	probably damaging	Het
Naca	T	A	10: 127,879,266 (GRCm39)		probably benign	Het
Ncoa4	T	C	14: 31,895,391 (GRCm39)	S172P	probably damaging	Het
Nfatc3	T	C	8: 106,810,486 (GRCm39)	F421L	possibly damaging	Het
Nucb1	C	A	7: 45,144,649 (GRCm39)	K301N	probably benign	Het
Or1af1	A	G	2: 37,109,966 (GRCm39)	H155R	probably damaging	Het
Or52ae9	A	T	7: 103,390,243 (GRCm39)	M68K	probably benign	Het
Or5b99	T	A	19: 12,976,815 (GRCm39)	I155N	possibly damaging	Het
Panx1	A	T	9: 14,921,341 (GRCm39)	V178E	possibly damaging	Het
Pkd1l3	G	A	8: 110,367,402 (GRCm39)	V1210I	probably damaging	Het
Polr2a	A	T	11: 69,638,039 (GRCm39)	H143Q	possibly damaging	Het
Potefam1	A	T	2: 111,048,972 (GRCm39)	M269K	probably benign	Het
Prdm12	G	A	2: 31,544,186 (GRCm39)	R263H	probably damaging	Het
Prkdc	A	C	16: 15,549,430 (GRCm39)	K1998T	probably damaging	Het
Rab11fip1	A	T	8: 27,643,051 (GRCm39)	S583T	probably damaging	Het
Rnf157	T	A	11: 116,237,921 (GRCm39)	T567S	probably benign	Het
Rp1	T	C	1: 4,417,917 (GRCm39)	K1065R	probably damaging	Het
Rp1	A	G	1: 4,418,760 (GRCm39)	I784T	probably benign	Het
Rps10	A	C	17: 27,850,182 (GRCm39)	F150V	probably benign	Het
Rrp12	A	T	19: 41,870,639 (GRCm39)	F499I	probably damaging	Het
Sez6l2	G	A	7: 126,562,535 (GRCm39)	R604H	probably damaging	Het
Slc25a21	G	T	12: 56,904,864 (GRCm39)	Q57K	probably benign	Het
Slc27a2	A	G	2: 126,395,234 (GRCm39)	T54A	possibly damaging	Het
Slc9a9	T	A	9: 95,111,011 (GRCm39)	S610T	probably benign	Het
Smc1b	A	T	15: 84,970,335 (GRCm39)	S973T	probably benign	Het
Smc6	G	A	12: 11,329,734 (GRCm39)	S164N	possibly damaging	Het
Sp1	A	G	15: 102,316,314 (GRCm39)	T32A	possibly damaging	Het
Spen	T	C	4: 141,202,946 (GRCm39)	I1894V	probably benign	Het
Spen	T	C	4: 141,203,011 (GRCm39)	K1872R	possibly damaging	Het
Stab1	C	A	14: 30,873,541 (GRCm39)		probably benign	Het
Taar7d	T	G	10: 23,904,102 (GRCm39)	F328C	probably damaging	Het
Ticam1	A	T	17: 56,578,113 (GRCm39)	S327R	probably benign	Het
Tmem248	C	T	5: 130,258,295 (GRCm39)		probably benign	Het
Tom1	T	C	8: 75,781,259 (GRCm39)	S83P	probably damaging	Het
Txk	T	A	5: 72,856,453 (GRCm39)	Y446F	probably damaging	Het
Ubap1l	T	A	9: 65,279,237 (GRCm39)	C179S	probably benign	Het
Utrn	T	C	10: 12,331,185 (GRCm39)	E474G	possibly damaging	Het
Vmn2r14	T	C	5: 109,363,862 (GRCm39)	M685V	probably benign	Het
Vmn2r7	A	T	3: 64,623,881 (GRCm39)	Y146*	probably null	Het
Wdr1	G	A	5: 38,697,905 (GRCm39)	T220M	probably damaging	Het
Xpo7	T	C	14: 70,915,582 (GRCm39)	D726G	probably damaging	Het
Zbtb14	C	G	17: 69,694,759 (GRCm39)	I152M	probably benign	Het
Zbtb3	A	G	19: 8,780,771 (GRCm39)	D128G	probably damaging	Het
Zeb1os1	A	G	18: 5,583,794 (GRCm39)		noncoding transcript	Het
Zfp462	T	A	4: 55,007,667 (GRCm39)	D35E	probably damaging	Het
Zfp467	A	G	6: 48,415,621 (GRCm39)	S344P	possibly damaging	Het
Zfpm1	A	T	8: 123,034,285 (GRCm39)	D73V	possibly damaging	Het

Other mutations in Aldh18a1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL01020:Aldh18a1	APN	19	40,557,625 (GRCm39)	splice site	probably benign
IGL02353:Aldh18a1	APN	19	40,566,364 (GRCm39)	missense	probably damaging	0.98
IGL02360:Aldh18a1	APN	19	40,566,364 (GRCm39)	missense	probably damaging	0.98
IGL02974:Aldh18a1	APN	19	40,557,528 (GRCm39)	missense	probably damaging	0.96
IGL03295:Aldh18a1	APN	19	40,551,386 (GRCm39)	missense	probably damaging	1.00
PIT4498001:Aldh18a1	UTSW	19	40,562,800 (GRCm39)	missense	probably benign
R0267:Aldh18a1	UTSW	19	40,562,233 (GRCm39)	missense	probably benign	0.25
R0498:Aldh18a1	UTSW	19	40,562,716 (GRCm39)	missense	probably benign	0.29
R1140:Aldh18a1	UTSW	19	40,562,729 (GRCm39)	missense	probably benign	0.01
R1142:Aldh18a1	UTSW	19	40,539,657 (GRCm39)	missense	probably damaging	0.97
R1640:Aldh18a1	UTSW	19	40,573,943 (GRCm39)	missense	probably benign
R1721:Aldh18a1	UTSW	19	40,553,282 (GRCm39)	missense	probably damaging	1.00
R3012:Aldh18a1	UTSW	19	40,546,135 (GRCm39)	nonsense	probably null
R3085:Aldh18a1	UTSW	19	40,562,813 (GRCm39)	missense	probably benign
R3815:Aldh18a1	UTSW	19	40,558,944 (GRCm39)	missense	probably damaging	1.00
R3863:Aldh18a1	UTSW	19	40,539,758 (GRCm39)	missense	probably damaging	1.00
R4156:Aldh18a1	UTSW	19	40,539,725 (GRCm39)	missense	probably damaging	1.00
R5116:Aldh18a1	UTSW	19	40,541,949 (GRCm39)	missense	probably benign
R5135:Aldh18a1	UTSW	19	40,543,261 (GRCm39)	intron	probably benign
R5393:Aldh18a1	UTSW	19	40,574,011 (GRCm39)	missense	probably benign	0.00
R5492:Aldh18a1	UTSW	19	40,539,734 (GRCm39)	missense	probably damaging	1.00
R5493:Aldh18a1	UTSW	19	40,539,734 (GRCm39)	missense	probably damaging	1.00
R5494:Aldh18a1	UTSW	19	40,539,734 (GRCm39)	missense	probably damaging	1.00
R5957:Aldh18a1	UTSW	19	40,558,981 (GRCm39)	nonsense	probably null
R6255:Aldh18a1	UTSW	19	40,568,487 (GRCm39)	missense	possibly damaging	0.93
R6320:Aldh18a1	UTSW	19	40,559,005 (GRCm39)	missense	probably benign	0.44
R6358:Aldh18a1	UTSW	19	40,566,122 (GRCm39)	missense	possibly damaging	0.83
R6379:Aldh18a1	UTSW	19	40,566,214 (GRCm39)	critical splice donor site	probably null
R6785:Aldh18a1	UTSW	19	40,556,788 (GRCm39)	missense	probably damaging	1.00
R7334:Aldh18a1	UTSW	19	40,539,696 (GRCm39)	missense	probably damaging	1.00
R7549:Aldh18a1	UTSW	19	40,553,291 (GRCm39)	missense	probably damaging	1.00
R7935:Aldh18a1	UTSW	19	40,562,226 (GRCm39)	nonsense	probably null
R7960:Aldh18a1	UTSW	19	40,546,264 (GRCm39)	missense	probably benign	0.03
R8152:Aldh18a1	UTSW	19	40,553,456 (GRCm39)	missense	probably benign	0.01
R8179:Aldh18a1	UTSW	19	40,545,952 (GRCm39)	missense	probably damaging	1.00
R8181:Aldh18a1	UTSW	19	40,545,881 (GRCm39)	missense	probably benign	0.27
R8222:Aldh18a1	UTSW	19	40,562,296 (GRCm39)	missense	probably benign	0.00
R8787:Aldh18a1	UTSW	19	40,546,230 (GRCm39)	missense	possibly damaging	0.50

Predicted Primers

PCR Primer
(F):5'- TGGAACACACATAGAAACGGGCATC -3'
(R):5'- GGTCAGAGACATCCAGAAAGCTGC -3'

Sequencing Primer
(F):5'- CATAGAAACGGGCATCTGTGTATC -3'
(R):5'- TACGTGGATTCCGAAGCCAG -3'

Posted On

2014-04-13