Mutagenetix > Incidental Mutation

Incidental Mutation 'R9015:Alas1'

685926

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

068845-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R9015 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

106110654-106125153 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to T at 106113670 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Isoleucine to Asparagine at position 525 (I525N)

Ref Sequence

ENSEMBL: ENSMUSP00000108143 (fasta)

Gene Model

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

AlphaFold

Q8VC19

Predicted Effect

probably benign
Transcript: ENSMUST00000074082
AA Change: I524N

PolyPhen 2 Score 0.173 (Sensitivity: 0.92; Specificity: 0.87)

SMART Domains

Protein: ENSMUSP00000073725
Gene: ENSMUSG00000032786
AA Change: I524N

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: I525N

PolyPhen 2 Score 0.173 (Sensitivity: 0.92; Specificity: 0.87)

SMART Domains

Protein: ENSMUSP00000108143
Gene: ENSMUSG00000032786
AA Change: I525N

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: I525N

PolyPhen 2 Score 0.173 (Sensitivity: 0.92; Specificity: 0.87)

SMART Domains

Protein: ENSMUSP00000117014
Gene: ENSMUSG00000032786
AA Change: I525N

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
AA Change: I119N

PolyPhen 2 Score 0.045 (Sensitivity: 0.94; Specificity: 0.83)

Predicted Effect

probably benign
Transcript: ENSMUST00000219129

Coding Region Coverage

1x: 100.0%
3x: 99.9%
10x: 99.7%
20x: 98.9%

Validation Efficiency

100% (93/93)

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: 93 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Adam22	T	C	5: 8,136,688 (GRCm39)		probably benign	Het
Adamtsl1	A	G	4: 86,150,847 (GRCm39)	D335G	probably damaging	Het
Adcy8	T	C	15: 64,597,206 (GRCm39)		probably benign	Het
Aoah	A	T	13: 21,184,197 (GRCm39)		silent	Het
Aox1	G	A	1: 58,382,851 (GRCm39)	V1044M	probably damaging	Het
Apcdd1	A	T	18: 63,083,157 (GRCm39)	Y329F	possibly damaging	Het
Arhgap10	A	C	8: 77,985,687 (GRCm39)	C727G	probably benign	Het
Arid4a	G	A	12: 71,122,168 (GRCm39)	D528N	possibly damaging	Het
Atp8a1	A	G	5: 67,887,250 (GRCm39)	V611A		Het
BC004004	T	C	17: 29,517,637 (GRCm39)	F284L	probably damaging	Het
Bean1	CT	C	8: 104,908,664 (GRCm39)		probably null	Het
Cep295	T	C	9: 15,244,264 (GRCm39)	I1397M	probably benign	Het
Cep63	A	G	9: 102,496,111 (GRCm39)	S99P	probably damaging	Het
Coq3	T	A	4: 21,899,107 (GRCm39)	S147T	probably benign	Het
Crym	A	T	7: 119,801,090 (GRCm39)	S20T	probably benign	Het
Ctr9	T	A	7: 110,643,108 (GRCm39)	N493K	probably benign	Het
Dchs2	A	G	3: 83,188,751 (GRCm39)	I1372V	possibly damaging	Het
Ddi2	G	A	4: 141,412,747 (GRCm39)	T55M	probably benign	Het
Dnah1	T	C	14: 30,986,316 (GRCm39)	M3724V	probably damaging	Het
Dst	A	G	1: 34,326,337 (GRCm39)	I4690V	probably benign	Het
Ect2l	T	C	10: 18,039,148 (GRCm39)	T429A	probably benign	Het
Eif3c	G	T	7: 126,155,538 (GRCm39)	H577N	probably damaging	Het
Erg	A	G	16: 95,162,126 (GRCm39)	S334P	possibly damaging	Het
Faf2	A	G	13: 54,796,139 (GRCm39)	S127G	probably benign	Het
Fbxl3	T	A	14: 103,329,790 (GRCm39)	T141S	possibly damaging	Het
Fbxw4	T	A	19: 45,624,874 (GRCm39)	M122L	probably benign	Het
Fgd4	T	C	16: 16,271,941 (GRCm39)	M476V	probably damaging	Het
Flvcr2	A	T	12: 85,829,779 (GRCm39)	I263F	probably benign	Het
Gadl1	A	T	9: 115,794,705 (GRCm39)	R293S	probably benign	Het
Gm11983	G	T	11: 6,787,033 (GRCm39)	F31L	unknown	Het
Gmnn	A	T	13: 24,940,638 (GRCm39)	N70K	probably benign	Het
Gpr3	A	G	4: 132,938,390 (GRCm39)	V94A	possibly damaging	Het
Greb1l	A	G	18: 10,541,675 (GRCm39)	S1141G	probably benign	Het
Helz2	A	T	2: 180,870,792 (GRCm39)	V2892E	probably damaging	Het
Hivep1	T	A	13: 42,311,849 (GRCm39)	M1363K	probably benign	Het
Hk1	T	A	10: 62,128,118 (GRCm39)	T336S	possibly damaging	Het
Hpgds	A	T	6: 65,115,229 (GRCm39)	I18N	possibly damaging	Het
Insrr	T	A	3: 87,720,910 (GRCm39)	L1056Q	probably damaging	Het
Ints10	A	G	8: 69,260,139 (GRCm39)	M288V	probably benign	Het
Itgb6	T	C	2: 60,485,032 (GRCm39)	D237G	probably damaging	Het
Kcnf1	A	G	12: 17,225,303 (GRCm39)	I306T	probably damaging	Het
Kdm3b	G	A	18: 34,963,212 (GRCm39)	G1556D	probably damaging	Het
Kif5b	A	G	18: 6,216,892 (GRCm39)	L477P	probably damaging	Het
Klf5	T	G	14: 99,540,919 (GRCm39)	*310G	probably null	Het
Lnx1	A	G	5: 74,780,783 (GRCm39)	V246A	probably benign	Het
Ly75	C	T	2: 60,146,442 (GRCm39)	E1279K	probably benign	Het
Lztr1	T	A	16: 17,337,305 (GRCm39)	C233S	probably benign	Het
Mfsd6l	T	G	11: 68,447,536 (GRCm39)	I129S	probably benign	Het
Mrgprx2	T	A	7: 48,148,938 (GRCm39)		probably benign	Het
Ncapd2	A	T	6: 125,145,285 (GRCm39)		probably benign	Het
Or10ag53	T	A	2: 87,082,546 (GRCm39)	Y88*	probably null	Het
Or12e9	T	A	2: 87,202,485 (GRCm39)	M203K	possibly damaging	Het
Or2a25	G	T	6: 42,888,825 (GRCm39)	V123L	possibly damaging	Het
Or8g30	A	C	9: 39,230,019 (GRCm39)	V297G	probably damaging	Het
Pde6a	A	G	18: 61,397,047 (GRCm39)	H631R	probably damaging	Het
Pfkl	C	T	10: 77,824,794 (GRCm39)	G665D	probably damaging	Het
Pik3ap1	T	A	19: 41,270,430 (GRCm39)	E753V	probably damaging	Het
Pik3cd	G	T	4: 149,740,055 (GRCm39)	R502S	probably benign	Het
Piwil2	T	A	14: 70,627,984 (GRCm39)	I762L	probably benign	Het
Pkd1	T	A	17: 24,784,636 (GRCm39)	L394*	probably null	Het
Plekhb2	A	G	1: 34,916,046 (GRCm39)	D195G	probably benign	Het
Plppr5	T	C	3: 117,456,103 (GRCm39)	M208T	probably damaging	Het
Polr2i	G	A	7: 29,932,513 (GRCm39)	V115I	unknown	Het
Prkacb	T	C	3: 146,456,239 (GRCm39)	S187G	probably null	Het
Prkag3	G	T	1: 74,780,353 (GRCm39)	H437Q	probably benign	Het
Prlr	T	A	15: 10,319,352 (GRCm39)	Y94N	probably damaging	Het
Prmt6	T	C	3: 110,157,214 (GRCm39)	I358M	probably benign	Het
Psd4	A	G	2: 24,287,492 (GRCm39)	R475G		Het
Rad51b	G	A	12: 79,347,417 (GRCm39)	C27Y	probably damaging	Het
Scfd2	A	G	5: 74,691,625 (GRCm39)	L219P	probably damaging	Het
Scn5a	G	A	9: 119,381,142 (GRCm39)		probably benign	Het
Sec24d	T	C	3: 123,121,287 (GRCm39)	V391A	probably benign	Het
Selenbp2	T	A	3: 94,607,332 (GRCm39)	L251Q	probably damaging	Het
Sh3rf1	T	C	8: 61,827,202 (GRCm39)	V652A	probably benign	Het
Slc11a2	A	G	15: 100,301,186 (GRCm39)	V289A	probably benign	Het
Smim29	T	C	17: 27,783,223 (GRCm39)	D48G	probably benign	Het
Sox8	T	A	17: 25,789,135 (GRCm39)	Y121F	probably damaging	Het
Taar7a	A	T	10: 23,868,733 (GRCm39)	I216N	probably damaging	Het
Tanc1	T	A	2: 59,622,224 (GRCm39)	S448T	probably benign	Het
Tas2r119	G	A	15: 32,178,226 (GRCm39)	G264D	probably damaging	Het
Trav7-6	A	G	14: 53,954,604 (GRCm39)	K65E	probably benign	Het
Trim17	A	G	11: 58,856,057 (GRCm39)	E38G	probably damaging	Het
Trub2	A	T	2: 29,668,276 (GRCm39)		probably benign	Het
Ttn	T	A	2: 76,571,964 (GRCm39)	M26310L	probably damaging	Het
Unc13c	T	G	9: 73,453,322 (GRCm39)	I1823L	probably benign	Het
Vav2	C	A	2: 27,160,151 (GRCm39)	E728*	probably null	Het
Virma	A	G	4: 11,540,494 (GRCm39)	D1465G	probably benign	Het
Vmn2r72	T	G	7: 85,398,388 (GRCm39)	M531L	probably benign	Het
Vwa3b	G	A	1: 37,203,597 (GRCm39)	V59I	possibly damaging	Het
Xrcc1	G	A	7: 24,271,642 (GRCm39)	E542K	probably benign	Het
Zdhhc6	T	G	19: 55,287,318 (GRCm39)	T381P	probably benign	Het
Zdhhc8	T	C	16: 18,041,141 (GRCm39)	S740G	probably damaging	Het
Zfp106	T	C	2: 120,364,019 (GRCm39)	K819R	probably damaging	Het

Other mutations in Alas1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00911:Alas1	APN	9	106,113,671 (GRCm39)	missense	probably benign	0.17
IGL02165:Alas1	APN	9	106,115,982 (GRCm39)	missense	probably damaging	1.00
IGL02355:Alas1	APN	9	106,113,838 (GRCm39)	missense	probably damaging	1.00
IGL02362:Alas1	APN	9	106,113,838 (GRCm39)	missense	probably damaging	1.00
IGL02499:Alas1	APN	9	106,118,520 (GRCm39)	missense	probably damaging	1.00
IGL02606:Alas1	APN	9	106,118,309 (GRCm39)	unclassified	probably benign
IGL03121:Alas1	APN	9	106,124,113 (GRCm39)	missense	probably damaging	0.99
R0115:Alas1	UTSW	9	106,115,451 (GRCm39)	splice site	probably null
R0294:Alas1	UTSW	9	106,118,455 (GRCm39)	missense	probably damaging	1.00
R0333:Alas1	UTSW	9	106,118,480 (GRCm39)	missense	probably benign	0.08
R0346:Alas1	UTSW	9	106,120,550 (GRCm39)	missense	possibly damaging	0.78
R1700:Alas1	UTSW	9	106,116,845 (GRCm39)	missense	possibly damaging	0.46
R1982:Alas1	UTSW	9	106,115,384 (GRCm39)	missense	probably damaging	1.00
R2056:Alas1	UTSW	9	106,118,489 (GRCm39)	missense	probably damaging	1.00
R2058:Alas1	UTSW	9	106,118,489 (GRCm39)	missense	probably damaging	1.00
R2059:Alas1	UTSW	9	106,118,489 (GRCm39)	missense	probably damaging	1.00
R2355:Alas1	UTSW	9	106,113,673 (GRCm39)	missense	probably damaging	0.96
R2516:Alas1	UTSW	9	106,115,859 (GRCm39)	missense	probably damaging	1.00
R3896:Alas1	UTSW	9	106,119,000 (GRCm39)	splice site	probably null
R4091:Alas1	UTSW	9	106,119,000 (GRCm39)	splice site	probably null
R4093:Alas1	UTSW	9	106,119,000 (GRCm39)	splice site	probably null
R4095:Alas1	UTSW	9	106,119,000 (GRCm39)	splice site	probably null
R4673:Alas1	UTSW	9	106,113,676 (GRCm39)	missense	probably damaging	1.00
R4948:Alas1	UTSW	9	106,124,077 (GRCm39)	nonsense	probably null
R5165:Alas1	UTSW	9	106,118,454 (GRCm39)	missense	probably damaging	1.00
R5215:Alas1	UTSW	9	106,120,574 (GRCm39)	missense	probably benign	0.05
R5420:Alas1	UTSW	9	106,111,358 (GRCm39)	missense	probably benign	0.13
R5993:Alas1	UTSW	9	106,111,328 (GRCm39)	missense	probably benign	0.11
R6033:Alas1	UTSW	9	106,118,403 (GRCm39)	missense	probably damaging	1.00
R6033:Alas1	UTSW	9	106,118,403 (GRCm39)	missense	probably damaging	1.00
R7489:Alas1	UTSW	9	106,118,833 (GRCm39)	critical splice donor site	probably null
R7726:Alas1	UTSW	9	106,124,150 (GRCm39)	missense	probably benign	0.00
R8012:Alas1	UTSW	9	106,123,962 (GRCm39)	missense	probably benign
R8036:Alas1	UTSW	9	106,112,721 (GRCm39)	missense	probably benign	0.19
R8353:Alas1	UTSW	9	106,113,721 (GRCm39)	missense	possibly damaging	0.83
R8453:Alas1	UTSW	9	106,113,721 (GRCm39)	missense	possibly damaging	0.83
R8928:Alas1	UTSW	9	106,118,513 (GRCm39)	missense	probably benign
R9259:Alas1	UTSW	9	106,118,835 (GRCm39)	missense	probably benign	0.01
R9475:Alas1	UTSW	9	106,111,261 (GRCm39)	missense	probably benign	0.08
R9516:Alas1	UTSW	9	106,115,840 (GRCm39)	critical splice donor site	probably null
R9797:Alas1	UTSW	9	106,113,842 (GRCm39)	missense	probably damaging	1.00
Z1176:Alas1	UTSW	9	106,120,566 (GRCm39)	missense	probably benign	0.00
Z1176:Alas1	UTSW	9	106,115,968 (GRCm39)	missense	probably benign	0.42

Predicted Primers

PCR Primer
(F):5'- CAAGCCAGACAGCTGAAGTCAG -3'
(R):5'- GCACGAGTTTGCTGATCGAC -3'

Sequencing Primer
(F):5'- CCAGACAGCTGAAGTCAGAGAGAC -3'
(R):5'- GAGTTTGCTGATCGACACCGTC -3'

Posted On

2021-10-11