Mutagenetix > Incidental Mutation

Incidental Mutation 'R6358:Aldh18a1'

513373

Institutional Source

Beutler Lab

Gene Symbol

Aldh18a1

Ensembl Gene

ENSMUSG00000025007

Gene Name

aldehyde dehydrogenase 18 family, member A1

Synonyms

2810433K04Rik, Pycs

MMRRC Submission

044508-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R6358 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

40550257-40588463 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

A to T at 40577678 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Isoleucine to Asparagine at position 42 (I42N)

Ref Sequence

ENSEMBL: ENSMUSP00000135417 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000025979] [ENSMUST00000149476] [ENSMUST00000175932] [ENSMUST00000176939] [ENSMUST00000176955]

AlphaFold

Q9Z110

Predicted Effect

probably benign
Transcript: ENSMUST00000025979
AA Change: I153N

PolyPhen 2 Score 0.014 (Sensitivity: 0.96; Specificity: 0.79)

SMART Domains

Protein: ENSMUSP00000025979
Gene: ENSMUSG00000025007
AA Change: I153N

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: ENSMUST00000134749

Predicted Effect

possibly damaging
Transcript: ENSMUST00000149476
AA Change: I153N

PolyPhen 2 Score 0.806 (Sensitivity: 0.84; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000115429
Gene: ENSMUSG00000025007
AA Change: I153N

Domain	Start	End	E-Value	Type
Pfam:AA_kinase	71	173	3.3e-13	PFAM

Predicted Effect

possibly damaging
Transcript: ENSMUST00000175932
AA Change: I42N

PolyPhen 2 Score 0.830 (Sensitivity: 0.84; Specificity: 0.93)

Predicted Effect

probably benign
Transcript: ENSMUST00000176939
AA Change: I153N

PolyPhen 2 Score 0.014 (Sensitivity: 0.96; Specificity: 0.79)

SMART Domains

Protein: ENSMUSP00000135426
Gene: ENSMUSG00000025007
AA Change: I153N

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

Predicted Effect

probably benign
Transcript: ENSMUST00000176955
AA Change: I42N

PolyPhen 2 Score 0.179 (Sensitivity: 0.92; Specificity: 0.87)

SMART Domains

Protein: ENSMUSP00000135759
Gene: ENSMUSG00000025007
AA Change: I42N

Domain	Start	End	E-Value	Type
PDB:4Q1T\|D	1	83	1e-5	PDB

Coding Region Coverage

1x: 99.9%
3x: 99.6%
10x: 98.2%
20x: 94.8%

Validation Efficiency

100% (61/61)

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: 61 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Adam39	T	C	8: 40,826,681	V703A	probably benign	Het
Adgrv1	T	A	13: 81,414,583	Q5389L	probably damaging	Het
Ankrd28	A	C	14: 31,710,864	C575W	probably damaging	Het
Car14	T	A	3: 95,898,175	T329S	possibly damaging	Het
Cdhr2	T	C	13: 54,736,546	F1298S	probably damaging	Het
Crhr2	A	G	6: 55,093,043	I341T	probably benign	Het
D5Ertd579e	T	A	5: 36,616,236		probably null	Het
Emilin1	A	G	5: 30,918,218	E601G	probably damaging	Het
Erbin	T	A	13: 103,845,565	Q456L	probably damaging	Het
Glp1r	T	C	17: 30,932,644	V405A	probably benign	Het
Gm10220	C	G	5: 26,120,305		probably null	Het
Gm2016	A	G	12: 87,877,000	E139G	unknown	Het
Gm527	A	T	12: 64,923,548	H219L	possibly damaging	Het
Gorasp2	T	A	2: 70,672,760	M1K	probably null	Het
H2-DMa	T	A	17: 34,137,984	L152H	probably damaging	Het
Hsd3b7	T	A	7: 127,801,537	H54Q	probably damaging	Het
Hspa12b	T	C	2: 131,137,066		probably benign	Het
Iars	C	A	13: 49,727,143	T1006K	possibly damaging	Het
Jmjd1c	T	C	10: 67,225,939	V1357A	probably benign	Het
Magi3	T	C	3: 104,050,952	M606V	probably damaging	Het
Mia	T	C	7: 27,180,978	D24G	probably benign	Het
Mon2	A	T	10: 123,013,504	L1297Q	probably damaging	Het
Musk	T	A	4: 58,373,171	S691T	possibly damaging	Het
Myo5c	A	T	9: 75,296,012	E1463D	possibly damaging	Het
Ndufs6	C	T	13: 73,320,319	G87D	probably damaging	Het
Npnt	C	T	3: 132,904,718	V415I	probably benign	Het
Ntsr2	A	G	12: 16,656,768	I266V	probably benign	Het
Olfr259	T	C	2: 87,108,434		probably benign	Het
Olfr736	A	T	14: 50,393,388	I211F	possibly damaging	Het
Pkmyt1	T	A	17: 23,733,656		probably null	Het
Polr1e	T	C	4: 45,026,813	L166P	probably damaging	Het
Ppib	T	G	9: 66,061,474	F48C	probably damaging	Het
Ppl	C	A	16: 5,087,929	E1501*	probably null	Het
Prpf8	T	C	11: 75,491,495	V384A	probably benign	Het
Ptch1	T	G	13: 63,513,689	S1212R	probably damaging	Het
Ralb	C	A	1: 119,476,005	D131Y	probably damaging	Het
Rfx4	T	A	10: 84,844,235	M141K	probably damaging	Het
Rgl2	T	A	17: 33,937,131		probably null	Het
Rpl27	A	G	11: 101,443,956		probably benign	Het
Sdc1	A	C	12: 8,791,297	T213P	probably damaging	Het
Setx	T	A	2: 29,171,348	N2256K	possibly damaging	Het
Shank2	A	G	7: 144,031,297	M12V	probably benign	Het
Slc22a28	T	A	19: 8,071,888	K332M	probably damaging	Het
Slf2	A	T	19: 44,935,425	H226L	probably benign	Het
Tbc1d10b	T	C	7: 127,203,412	S362G	probably benign	Het
Tbxas1	G	A	6: 38,952,112		probably benign	Het
Tctn1	A	G	5: 122,261,512	V83A	probably damaging	Het
Tgm4	A	G	9: 123,056,518	E375G	probably damaging	Het
Tmeff2	T	A	1: 51,133,114	Y247*	probably null	Het
Tmem167b	C	T	3: 108,558,895	R79H	possibly damaging	Het
Tmprss7	T	G	16: 45,669,573	M429L	probably benign	Het
Tnfsf18	T	A	1: 161,503,579	D99E	probably benign	Het
Tnrc18	A	T	5: 142,727,981	S2534T	probably damaging	Het
Tnxb	A	G	17: 34,678,994	E872G	probably damaging	Het
Tomm40l	C	T	1: 171,219,637	V237I	possibly damaging	Het
Trbv2	A	G	6: 41,047,902	Q84R	probably benign	Het
Tspan18	T	C	2: 93,209,874	R179G	probably benign	Het
Tspan8	G	T	10: 115,833,227	V56L	probably benign	Het
Zbtb22	T	C	17: 33,918,737	S619P	probably damaging	Het
Zfp2	A	T	11: 50,900,601	I205N	probably damaging	Het
Zfpm1	A	G	8: 122,337,111		probably benign	Het

Other mutations in Aldh18a1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL01020:Aldh18a1	APN	19	40569181	splice site	probably benign
IGL02353:Aldh18a1	APN	19	40577920	missense	probably damaging	0.98
IGL02360:Aldh18a1	APN	19	40577920	missense	probably damaging	0.98
IGL02974:Aldh18a1	APN	19	40569084	missense	probably damaging	0.96
IGL03295:Aldh18a1	APN	19	40562942	missense	probably damaging	1.00
PIT4498001:Aldh18a1	UTSW	19	40574356	missense	probably benign
R0267:Aldh18a1	UTSW	19	40573789	missense	probably benign	0.25
R0498:Aldh18a1	UTSW	19	40574272	missense	probably benign	0.29
R1140:Aldh18a1	UTSW	19	40574285	missense	probably benign	0.01
R1142:Aldh18a1	UTSW	19	40551213	missense	probably damaging	0.97
R1509:Aldh18a1	UTSW	19	40557483	missense	probably damaging	0.98
R1640:Aldh18a1	UTSW	19	40585499	missense	probably benign
R1721:Aldh18a1	UTSW	19	40564838	missense	probably damaging	1.00
R3012:Aldh18a1	UTSW	19	40557691	nonsense	probably null
R3085:Aldh18a1	UTSW	19	40574369	missense	probably benign
R3815:Aldh18a1	UTSW	19	40570500	missense	probably damaging	1.00
R3863:Aldh18a1	UTSW	19	40551314	missense	probably damaging	1.00
R4156:Aldh18a1	UTSW	19	40551281	missense	probably damaging	1.00
R5116:Aldh18a1	UTSW	19	40553505	missense	probably benign
R5135:Aldh18a1	UTSW	19	40554817	intron	probably benign
R5393:Aldh18a1	UTSW	19	40585567	missense	probably benign	0.00
R5492:Aldh18a1	UTSW	19	40551290	missense	probably damaging	1.00
R5493:Aldh18a1	UTSW	19	40551290	missense	probably damaging	1.00
R5494:Aldh18a1	UTSW	19	40551290	missense	probably damaging	1.00
R5957:Aldh18a1	UTSW	19	40570537	nonsense	probably null
R6255:Aldh18a1	UTSW	19	40580043	missense	possibly damaging	0.93
R6320:Aldh18a1	UTSW	19	40570561	missense	probably benign	0.44
R6379:Aldh18a1	UTSW	19	40577770	critical splice donor site	probably null
R6785:Aldh18a1	UTSW	19	40568344	missense	probably damaging	1.00
R7334:Aldh18a1	UTSW	19	40551252	missense	probably damaging	1.00
R7549:Aldh18a1	UTSW	19	40564847	missense	probably damaging	1.00
R7935:Aldh18a1	UTSW	19	40573782	nonsense	probably null
R7960:Aldh18a1	UTSW	19	40557820	missense	probably benign	0.03
R8152:Aldh18a1	UTSW	19	40565012	missense	probably benign	0.01
R8179:Aldh18a1	UTSW	19	40557508	missense	probably damaging	1.00
R8181:Aldh18a1	UTSW	19	40557437	missense	probably benign	0.27
R8222:Aldh18a1	UTSW	19	40573852	missense	probably benign	0.00
R8787:Aldh18a1	UTSW	19	40557786	missense	possibly damaging	0.50

Predicted Primers

PCR Primer
(F):5'- ACTGCAGTAGTAACTCTTGGG -3'
(R):5'- TGCGCCATGAGATCCTTCTG -3'

Sequencing Primer
(F):5'- AACCCTCTGATGTAGGCACTGATG -3'
(R):5'- ATGAGATCCTTCTGTCTCAGAGCG -3'

Posted On

2018-04-27