Mutagenetix > Incidental Mutation

Incidental Mutation 'R9475:Alas1'

715720

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

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R9475 (G1)

Quality Score

225.009

Status

Not validated

Chromosome

Chromosomal Location

106233455-106248654 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

C to T at 106234062 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Serine to Asparagine at position 635 (S635N)

Ref Sequence

ENSEMBL: ENSMUSP00000108143 (fasta)

Gene Model

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

AlphaFold

Q8VC19

Predicted Effect

probably benign
Transcript: ENSMUST00000074082
AA Change: S634N

PolyPhen 2 Score 0.076 (Sensitivity: 0.93; Specificity: 0.85)

SMART Domains

Protein: ENSMUSP00000073725
Gene: ENSMUSG00000032786
AA Change: S634N

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: S635N

PolyPhen 2 Score 0.076 (Sensitivity: 0.93; Specificity: 0.85)

SMART Domains

Protein: ENSMUSP00000108143
Gene: ENSMUSG00000032786
AA Change: S635N

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

probably benign
Transcript: ENSMUST00000133617

SMART Domains

Protein: ENSMUSP00000122117
Gene: ENSMUSG00000032786

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

probably benign
Transcript: ENSMUST00000141118
AA Change: S635N

PolyPhen 2 Score 0.076 (Sensitivity: 0.93; Specificity: 0.85)

SMART Domains

Protein: ENSMUSP00000117014
Gene: ENSMUSG00000032786
AA Change: S635N

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

probably benign
Transcript: ENSMUST00000214989

Coding Region Coverage

1x: 100.0%
3x: 99.9%
10x: 99.6%
20x: 98.5%

Validation Efficiency

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: 64 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abcc6	A	T	7: 46,016,468	W243R	probably damaging	Het
Ablim1	T	G	19: 57,239,180	K18Q	probably benign	Het
Adamts18	T	A	8: 113,777,938	N174Y	possibly damaging	Het
Agbl2	A	G	2: 90,784,093	H23R	probably benign	Het
Akap6	T	G	12: 53,010,552	Y934D	probably damaging	Het
Ankrd24	A	G	10: 81,642,299		probably null	Het
Atp6v0a4	A	G	6: 38,060,982	L560P	probably damaging	Het
Cacng1	C	T	11: 107,716,292	V34M	possibly damaging	Het
Clcn3	C	T	8: 60,934,517	A233T	probably damaging	Het
Cntnap3	A	G	13: 64,799,135	F160S	probably damaging	Het
Ctnnd2	A	G	15: 30,881,130	S719G	probably damaging	Het
Exosc2	G	A	2: 31,674,743	V107I	probably benign	Het
Fam83b	C	A	9: 76,491,803	V673F	probably benign	Het
Fras1	T	C	5: 96,780,070	F3781L	probably damaging	Het
Gal3st1	T	A	11: 3,998,660	L289H	probably damaging	Het
Garem1	T	C	18: 21,148,313	I329V	probably benign	Het
Gli3	G	A	13: 15,725,711	G1228S	possibly damaging	Het
Gpbp1l1	T	C	4: 116,574,361	F72S	possibly damaging	Het
Hao1	T	A	2: 134,548,261	M53L	probably benign	Het
Hjurp	CTCTGGGAGGGCTTGCTCCGGGGGCAGTGTGTCCTGTTCTTGTGCAGCCCCT	C	1: 88,266,277		probably benign	Het
Iqcm	A	G	8: 75,753,455	E347G	probably damaging	Het
Itpr3	G	A	17: 27,118,677		probably benign	Het
Kcnrg	A	G	14: 61,607,657	I49V	possibly damaging	Het
Lrrc8e	G	A	8: 4,235,346	G524S	probably benign	Het
Lrrn1	A	T	6: 107,568,300	Y353F	probably damaging	Het
Mdn1	A	G	4: 32,739,849	D3701G	possibly damaging	Het
Mtmr2	A	G	9: 13,805,471	T623A	probably benign	Het
Ndst4	C	A	3: 125,714,647	S287*	probably null	Het
Ntrk3	A	C	7: 78,302,732	M579R	probably benign	Het
Oas1a	G	A	5: 120,899,254	L237F	probably damaging	Het
Olfr1350	A	T	7: 6,570,819	Y276F	probably damaging	Het
Olfr169	T	C	16: 19,566,520	D121G	probably benign	Het
Olfr857	T	C	9: 19,713,643	M272T	probably benign	Het
Paqr5	T	A	9: 61,956,225	I272F	probably damaging	Het
Pcdha11	T	A	18: 37,007,538	V740E	probably damaging	Het
Pdgfra	A	C	5: 75,167,927	N240T	possibly damaging	Het
Plbd2	G	A	5: 120,494,380	Q186*	probably null	Het
Plce1	G	A	19: 38,777,893	E2121K	possibly damaging	Het
Ppargc1a	C	A	5: 51,495,738	G161C	probably damaging	Het
Ptprk	T	C	10: 28,334,480	I166T	possibly damaging	Het
Rhox8	GCTTCTTCTTCTTCTTCTTCTTCTTCTTCTTCTTCTTCTTCTTCTTCTTCTTCTTCTTCTTCTTCTTCTTCTTCTTCT	GCTTCTTCTTCTTCTTCTTCTTCTTCTTCTTCTTCTTCTTCTTCTTCTTCTTCTTCTTCTTCTTCTTCTTCTTCTTCTTCT	X: 37,878,114		probably benign	Het
Rpap2	T	A	5: 107,620,589	L431Q	probably damaging	Het
Rslcan18	T	A	13: 67,102,064	K160*	probably null	Het
Sema7a	T	C	9: 57,954,905	F180L	probably benign	Het
Sh2d3c	C	T	2: 32,753,027	L741F	probably damaging	Het
Shank1	G	A	7: 44,312,918	S71N	unknown	Het
Skint6	C	T	4: 112,806,840		probably null	Het
Skiv2l	A	T	17: 34,841,102	D897E	probably benign	Het
Slc35f3	T	C	8: 126,382,254	S181P	probably damaging	Het
Slc4a9	A	T	18: 36,529,216	E127V	probably null	Het
Spata5	T	C	3: 37,431,909	V260A	probably benign	Het
Speg	C	T	1: 75,388,091	T372I	probably damaging	Het
Syce1l	A	G	8: 113,655,103	T204A	probably benign	Het
Tas2r138	T	A	6: 40,612,458	M285L	probably benign	Het
Tbc1d10a	G	C	11: 4,213,604	K285N	probably damaging	Het
Trim9	T	A	12: 70,346,454	M239L	probably benign	Het
Trp53bp1	A	G	2: 121,209,280	S1293P	probably benign	Het
Uaca	C	T	9: 60,872,216	T1295M	possibly damaging	Het
Ubald1	G	T	16: 4,875,569	Q161K	possibly damaging	Het
Ugt1a10	C	T	1: 88,216,260	R201C	probably damaging	Het
Vps45	T	G	3: 96,042,925	T231P	probably damaging	Het
Wdr17	A	T	8: 54,635,477	D1186E	probably benign	Het
Zfp534	G	A	4: 147,682,274	T8I	probably benign	Het
Zfp68	T	C	5: 138,607,255	N269D	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
R5215:Alas1	UTSW	9	106243375	missense	probably benign	0.05
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
R8928:Alas1	UTSW	9	106241314	missense	probably benign
R9015:Alas1	UTSW	9	106236471	missense	probably benign	0.17
R9259:Alas1	UTSW	9	106241636	missense	probably benign	0.01
R9516:Alas1	UTSW	9	106238641	critical splice donor site	probably null
R9797:Alas1	UTSW	9	106236643	missense	probably damaging	1.00
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'- GTGGTCAACAGCAGAAACAC -3'
(R):5'- TCACCCTCCTGAATGCTAGC -3'

Sequencing Primer
(F):5'- GTGGTCAACAGCAGAAACACCTAAC -3'
(R):5'- ATGCAACTTCTGCAGGAG -3'

Posted On

2022-06-15