Mutagenetix > Incidental Mutations

Incidental Mutation 'R5215:Alas1'

403426

Institutional Source

Beutler Lab

Gene Symbol

Alas1

Ensembl Gene

ENSMUSG00000032786

Gene Name

aminolevulinic acid synthase 1

Synonyms

succinyl-CoA: glycine C-succinyl transferase, Alas-1, ALAS-N, 5-aminolevulinate synthase

MMRRC Submission

042788-MU

Accession Numbers

Is this an essential gene?

Essential (E-score: 1.000) question?

Stock #

R5215 (G1)

Quality Score

141

Status

Validated

Chromosome

Chromosomal Location

106233455-106248654 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

C to A at 106243375 bp

Zygosity

Heterozygous

Amino Acid Change

Alanine to Serine at position 73 (A73S)

Ref Sequence

ENSEMBL: ENSMUSP00000122117 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000074082] [ENSMUST00000112524] [ENSMUST00000133617] [ENSMUST00000141118] [ENSMUST00000143125] [ENSMUST00000214989] [ENSMUST00000215222] [ENSMUST00000219129]

Predicted Effect

probably benign
Transcript: ENSMUST00000074082
AA Change: A74S

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)

SMART Domains

Protein: ENSMUSP00000073725
Gene: ENSMUSG00000032786
AA Change: A74S

Domain	Start	End	E-Value	Type
Pfam:Preseq_ALAS	1	81	1.1e-21	PFAM
Pfam:Preseq_ALAS	73	141	2.8e-12	PFAM
Pfam:Aminotran_1_2	245	591	2.1e-77	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000112524
AA Change: A74S

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)

SMART Domains

Protein: ENSMUSP00000108143
Gene: ENSMUSG00000032786
AA Change: A74S

Domain	Start	End	E-Value	Type
Pfam:Preseq_ALAS	2	140	1.3e-49	PFAM
Pfam:Aminotran_1_2	245	592	5.3e-80	PFAM
Pfam:Cys_Met_Meta_PP	283	423	1.5e-6	PFAM

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000123601

Predicted Effect

probably benign
Transcript: ENSMUST00000133617
AA Change: A73S

PolyPhen 2 Score 0.047 (Sensitivity: 0.94; Specificity: 0.83)

SMART Domains

Protein: ENSMUSP00000122117
Gene: ENSMUSG00000032786
AA Change: A73S

Domain	Start	End	E-Value	Type
Pfam:Preseq_ALAS	1	79	3.1e-22	PFAM
Pfam:Preseq_ALAS	73	141	8.7e-13	PFAM

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000134053

Predicted Effect

probably benign
Transcript: ENSMUST00000141118
AA Change: A74S

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)

SMART Domains

Protein: ENSMUSP00000117014
Gene: ENSMUSG00000032786
AA Change: A74S

Domain	Start	End	E-Value	Type
Pfam:Preseq_ALAS	1	81	1.7e-20	PFAM
Pfam:Preseq_ALAS	73	141	4.2e-11	PFAM
Pfam:Aminotran_1_2	245	592	5.3e-80	PFAM
Pfam:Aminotran_5	257	422	3.4e-6	PFAM
Pfam:Cys_Met_Meta_PP	285	423	1.8e-6	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000143125

SMART Domains

Protein: ENSMUSP00000119968
Gene: ENSMUSG00000032786

Domain	Start	End	E-Value	Type
Pfam:Aminotran_5	1	61	7.7e-7	PFAM
Pfam:Aminotran_1_2	1	93	2.2e-17	PFAM

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000180701

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000214249

Predicted Effect

probably benign
Transcript: ENSMUST00000214989

Predicted Effect

probably benign
Transcript: ENSMUST00000215222
AA Change: A74S

PolyPhen 2 Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)

Predicted Effect

probably benign
Transcript: ENSMUST00000219129
AA Change: A74S

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000219340

Meta Mutation Damage Score

0.0898

Coding Region Coverage

1x: 99.3%
3x: 98.7%
10x: 97.5%
20x: 95.8%

Validation Efficiency

100% (79/79)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes the mitochondrial enzyme which is catalyzes the rate-limiting step in heme (iron-protoporphyrin) biosynthesis. The enzyme encoded by this gene is the housekeeping enzyme; a separate gene encodes a form of the enzyme that is specific for erythroid tissue. The level of the mature encoded protein is regulated by heme: high levels of heme down-regulate the mature enzyme in mitochondria while low heme levels up-regulate. A pseudogene of this gene is located on chromosome 12. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2015]
PHENOTYPE: Mice homozygous for a reporter allele exhibit embryonic lethality. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 68 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Aldoart2	G	A	12: 55,565,419	R43Q	probably benign	Het
Ano4	T	C	10: 89,317,303	H49R	possibly damaging	Het
Atic	T	C	1: 71,564,507	S161P	probably damaging	Het
Atp6v1c2	T	C	12: 17,291,658	E244G	probably benign	Het
Cd164l2	C	A	4: 133,221,478	L42I	unknown	Het
Cdc42ep2	T	C	19: 5,918,210	R156G	probably benign	Het
Cdc45	C	T	16: 18,795,897	R205H	probably damaging	Het
Cdk5	T	A	5: 24,419,461	N265I	probably benign	Het
Cfap69	G	T	5: 5,589,133	N262K	possibly damaging	Het
Chd6	C	T	2: 160,949,953	V2495M	probably damaging	Het
Cps1	T	A	1: 67,166,380	F521I	possibly damaging	Het
Crb2	A	G	2: 37,793,753	E1089G	probably benign	Het
Decr1	T	C	4: 15,929,795	D166G	probably damaging	Het
Dhodh	G	A	8: 109,606,343		probably benign	Het
Dnaaf5	G	A	5: 139,161,877	V399I	probably benign	Het
Dnah11	T	C	12: 118,157,361	T526A	probably benign	Het
Drosha	T	C	15: 12,885,133		probably benign	Het
Elfn2	T	A	15: 78,674,201	I49F	probably damaging	Het
Gabra1	T	C	11: 42,154,828	T152A	probably damaging	Het
Gigyf2	C	A	1: 87,365,266	T85K	probably damaging	Het
Gimap8	A	T	6: 48,651,083	Y258F	possibly damaging	Het
Glmn	A	G	5: 107,561,886	C351R	probably benign	Het
Gm10032	T	C	14: 66,792,549		noncoding transcript	Het
Gm340	T	C	19: 41,585,932	I1042T	probably damaging	Het
Gorasp2	G	A	2: 70,689,254	A328T	probably benign	Het
Grin1	A	T	2: 25,303,907	H392Q	probably benign	Het
Gzmn	A	G	14: 56,167,862	V55A	probably damaging	Het
Herc4	T	A	10: 63,289,097	S497T	probably benign	Het
Hrc	A	T	7: 45,336,091	D222V	probably damaging	Het
Iars2	T	C	1: 185,294,769	H761R	probably damaging	Het
Jmjd1c	T	A	10: 67,240,701	D2101E	possibly damaging	Het
Kcng1	C	T	2: 168,263,133	M264I	probably benign	Het
Klra14-ps	C	A	6: 130,157,683		noncoding transcript	Het
Krtap5-3	T	A	7: 142,202,237	C270*	probably null	Het
Lama3	A	G	18: 12,577,900	H3164R	probably damaging	Het
Mdn1	T	C	4: 32,741,418	M3840T	possibly damaging	Het
Mtor	A	T	4: 148,453,983	H166L	probably benign	Het
Mx1	T	C	16: 97,448,360	N556D	possibly damaging	Het
Oca2	A	T	7: 56,295,498	R285*	probably null	Het
Olfr103	T	A	17: 37,336,813	I140F	probably benign	Het
Olfr1285	T	C	2: 111,409,286		noncoding transcript	Het
Olfr521	A	G	7: 99,767,510	E116G	probably damaging	Het
Olfr681	G	A	7: 105,126,564	H246Y	probably damaging	Het
Olfr952	A	T	9: 39,426,623	Y149*	probably null	Het
Pan3	A	G	5: 147,455,105		probably null	Het
Pard3	G	A	8: 127,378,264	V496M	probably damaging	Het
Pdcd2l	A	T	7: 34,192,889	V185D	possibly damaging	Het
Pgghg	T	C	7: 140,946,564	V623A	possibly damaging	Het
Pigu	C	A	2: 155,335,329		probably benign	Het
Pkmyt1	G	A	17: 23,732,592	R40Q	probably benign	Het
Prag1	G	A	8: 36,099,889	A65T	probably benign	Het
Prkdc	C	A	16: 15,772,121	T2616N	possibly damaging	Het
Prpf8	G	A	11: 75,500,204	E1360K	probably benign	Het
Ptprt	C	T	2: 162,278,164	V128M	probably damaging	Het
Rp1l1	C	T	14: 64,030,013	S1016L	probably benign	Het
Rprd1a	G	T	18: 24,488,200	D307E	probably damaging	Het
Slc11a1	A	T	1: 74,383,777		probably benign	Het
Slc22a16	T	A	10: 40,581,390	M209K	probably damaging	Het
Slf2	T	G	19: 44,948,037	L707R	probably damaging	Het
Son	T	A	16: 91,656,675	M770K	probably damaging	Het
Taf6l	T	C	19: 8,778,053		probably benign	Het
Tbc1d2	C	A	4: 46,614,006	V692L	probably benign	Het
Tnpo3	C	T	6: 29,582,153		probably benign	Het
Txndc16	A	T	14: 45,211,140		probably benign	Het
Ubr1	T	C	2: 120,904,044	K1125R	probably benign	Het
Vmn2r9	A	G	5: 108,846,485	S433P	probably benign	Het
Zc3h12a	A	G	4: 125,126,913	S46P	probably benign	Het
Zwilch	T	G	9: 64,146,874	I490L	probably benign	Het

Other mutations in Alas1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00911:Alas1	APN	9	106236472	missense	probably benign	0.17
IGL02165:Alas1	APN	9	106238783	missense	probably damaging	1.00
IGL02355:Alas1	APN	9	106236639	missense	probably damaging	1.00
IGL02362:Alas1	APN	9	106236639	missense	probably damaging	1.00
IGL02499:Alas1	APN	9	106241321	missense	probably damaging	1.00
IGL02606:Alas1	APN	9	106241110	unclassified	probably benign
IGL03121:Alas1	APN	9	106246914	missense	probably damaging	0.99
R0115:Alas1	UTSW	9	106238252	splice site	probably null
R0294:Alas1	UTSW	9	106241256	missense	probably damaging	1.00
R0333:Alas1	UTSW	9	106241281	missense	probably benign	0.08
R0346:Alas1	UTSW	9	106243351	missense	possibly damaging	0.78
R1700:Alas1	UTSW	9	106239646	missense	possibly damaging	0.46
R1982:Alas1	UTSW	9	106238185	missense	probably damaging	1.00
R2056:Alas1	UTSW	9	106241290	missense	probably damaging	1.00
R2058:Alas1	UTSW	9	106241290	missense	probably damaging	1.00
R2059:Alas1	UTSW	9	106241290	missense	probably damaging	1.00
R2355:Alas1	UTSW	9	106236474	missense	probably damaging	0.96
R2516:Alas1	UTSW	9	106238660	missense	probably damaging	1.00
R3896:Alas1	UTSW	9	106241801	splice site	probably null
R4091:Alas1	UTSW	9	106241801	splice site	probably null
R4093:Alas1	UTSW	9	106241801	splice site	probably null
R4095:Alas1	UTSW	9	106241801	splice site	probably null
R4673:Alas1	UTSW	9	106236477	missense	probably damaging	1.00
R4948:Alas1	UTSW	9	106246878	nonsense	probably null
R5165:Alas1	UTSW	9	106241255	missense	probably damaging	1.00
R5420:Alas1	UTSW	9	106234159	missense	probably benign	0.13
R5993:Alas1	UTSW	9	106234129	missense	probably benign	0.11
R6033:Alas1	UTSW	9	106241204	missense	probably damaging	1.00
R6033:Alas1	UTSW	9	106241204	missense	probably damaging	1.00
R7489:Alas1	UTSW	9	106241634	critical splice donor site	probably null
R7726:Alas1	UTSW	9	106246951	missense	probably benign	0.00
R8012:Alas1	UTSW	9	106246763	missense	probably benign
R8036:Alas1	UTSW	9	106235522	missense	probably benign	0.19
R8353:Alas1	UTSW	9	106236522	missense	possibly damaging	0.83
R8453:Alas1	UTSW	9	106236522	missense	possibly damaging	0.83
Z1176:Alas1	UTSW	9	106238769	missense	probably benign	0.42
Z1176:Alas1	UTSW	9	106243367	missense	probably benign	0.00

Predicted Primers

PCR Primer
(F):5'- CTCACAGCATGCATTTCCTG -3'
(R):5'- AAAGCCACTGTCAGGTGAGG -3'

Sequencing Primer
(F):5'- ACGTCCTCCTGGAGCTC -3'
(R):5'- CACTGTCAGGTGAGGCAGGTG -3'

Posted On

2016-07-22