Mutagenetix > Incidental Mutations

Incidental Mutation 'R0346:Alas1'

34280

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

038553-MU

Accession Numbers

Is this an essential gene?

Essential (E-score: 1.000) question?

Stock #

R0346 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

106233455-106248654 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

A to T at 106243351 bp

Zygosity

Heterozygous

Amino Acid Change

Serine to Threonine at position 82 (S82T)

Ref Sequence

ENSEMBL: ENSMUSP00000150950 (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: S82T

PolyPhen 2 Score 0.002 (Sensitivity: 0.99; Specificity: 0.30)

SMART Domains

Protein: ENSMUSP00000073725
Gene: ENSMUSG00000032786
AA Change: S82T

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: S82T

PolyPhen 2 Score 0.002 (Sensitivity: 0.99; Specificity: 0.30)

SMART Domains

Protein: ENSMUSP00000108143
Gene: ENSMUSG00000032786
AA Change: S82T

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: S81T

PolyPhen 2 Score 0.384 (Sensitivity: 0.90; Specificity: 0.89)

SMART Domains

Protein: ENSMUSP00000122117
Gene: ENSMUSG00000032786
AA Change: S81T

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: S82T

PolyPhen 2 Score 0.002 (Sensitivity: 0.99; Specificity: 0.30)

SMART Domains

Protein: ENSMUSP00000117014
Gene: ENSMUSG00000032786
AA Change: S82T

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

possibly damaging
Transcript: ENSMUST00000215222
AA Change: S82T

PolyPhen 2 Score 0.778 (Sensitivity: 0.85; Specificity: 0.93)

Predicted Effect

probably benign
Transcript: ENSMUST00000219129
AA Change: S82T

PolyPhen 2 Score 0.020 (Sensitivity: 0.95; Specificity: 0.80)

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000219340

Meta Mutation Damage Score

0.0587

Coding Region Coverage

1x: 99.5%
3x: 98.9%
10x: 97.7%
20x: 96.4%

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: 76 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abca13	A	T	11: 9,566,278	I4406L	probably damaging	Het
Abca16	T	A	7: 120,435,932	C314S	probably damaging	Het
Add3	C	T	19: 53,216,956	R46*	probably null	Het
Alkbh5	C	G	11: 60,538,741	R107G	possibly damaging	Het
Ap3b1	A	T	13: 94,445,971	R365*	probably null	Het
Ass1	A	T	2: 31,514,819	N371Y	probably damaging	Het
AU021092	T	C	16: 5,216,854	D168G	possibly damaging	Het
Bcl2	G	A	1: 106,712,562	R107C	probably damaging	Het
Caln1	C	A	5: 130,822,921	H184N	possibly damaging	Het
Camta1	C	A	4: 151,075,140	R1614L	probably damaging	Het
Ccdc191	T	C	16: 43,938,952	V372A	probably damaging	Het
Ccng2	T	G	5: 93,270,894	I126S	probably damaging	Het
Cep85	A	T	4: 134,132,422	N643K	probably damaging	Het
Clvs2	G	C	10: 33,622,546	S129R	possibly damaging	Het
Cntn1	G	T	15: 92,232,087		probably benign	Het
Cttn	A	T	7: 144,452,539		probably benign	Het
Dedd2	T	C	7: 25,211,269	S161G	possibly damaging	Het
Dnajb13	T	C	7: 100,503,925	D263G	probably damaging	Het
Dppa4	T	A	16: 48,289,324		probably benign	Het
Ear2	A	G	14: 44,102,906	E7G	probably damaging	Het
Eif2b4	A	G	5: 31,188,108		probably benign	Het
Etl4	G	T	2: 20,759,652		probably null	Het
Fbxo15	T	A	18: 84,960,221		probably null	Het
Gm8765	T	C	13: 50,703,310	Y995H	probably benign	Het
Gm9970	A	G	5: 31,240,838		probably benign	Het
Hap1	A	G	11: 100,356,029	S17P	probably benign	Het
Hgd	C	T	16: 37,588,774		probably benign	Het
Inpp5f	T	A	7: 128,690,668	L16Q	probably damaging	Het
Islr2	G	A	9: 58,198,343	R545*	probably null	Het
Itgav	G	T	2: 83,792,609	C675F	probably damaging	Het
Kif13a	T	A	13: 46,814,219	I403L	possibly damaging	Het
Kif14	T	A	1: 136,468,160	I68N	probably damaging	Het
Kif26a	G	T	12: 112,179,348	K1764N	probably null	Het
Lrrd1	C	A	5: 3,850,215	F173L	probably benign	Het
Mroh4	G	C	15: 74,614,292		probably benign	Het
Mrvi1	T	C	7: 110,898,976	D404G	probably damaging	Het
Msh5	A	G	17: 35,029,888	V723A	probably benign	Het
Mybph	T	G	1: 134,197,754	I279S	probably damaging	Het
Myh4	A	T	11: 67,260,326	I1936L	probably benign	Het
Myo1h	A	T	5: 114,355,209	T704S	probably benign	Het
Nav2	C	A	7: 49,604,585	T2377K	probably benign	Het
Nipbl	T	G	15: 8,360,956	Q276H	probably damaging	Het
Nlrp9b	T	C	7: 20,024,515	L559P	probably damaging	Het
Nup210l	T	A	3: 90,189,438	V1318E	probably damaging	Het
Olfr1427	A	T	19: 12,099,439	S67T	probably damaging	Het
Olfr18	A	G	9: 20,314,411	S170P	probably benign	Het
Olfr385	A	G	11: 73,589,457	Y94H	probably damaging	Het
Olfr765	C	A	10: 129,046,473	V197F	possibly damaging	Het
P2ry13	T	C	3: 59,209,566	T264A	possibly damaging	Het
Plekhg5	T	C	4: 152,114,253	L966P	probably benign	Het
Prss35	A	G	9: 86,755,351	K58R	probably benign	Het
Ptafr	T	A	4: 132,580,079	L260*	probably null	Het
Pum1	A	T	4: 130,779,805	T1157S	possibly damaging	Het
Rif1	GCCACCA	GCCA	2: 52,110,324		probably benign	Het
Rnf145	A	G	11: 44,555,164	Y275C	probably damaging	Het
Rpl6	A	T	5: 121,208,491	K218N	possibly damaging	Het
Rps6	T	C	4: 86,855,981	T128A	probably benign	Het
Ryr1	G	T	7: 29,067,588		probably benign	Het
Scel	A	T	14: 103,529,984	Q26H	probably damaging	Het
Sfxn4	A	T	19: 60,858,673	D57E	probably benign	Het
Slc35d1	A	C	4: 103,190,847	L240R	probably damaging	Het
Smcr8	A	G	11: 60,779,750	I575V	probably benign	Het
Syk	G	A	13: 52,640,659	M476I	probably damaging	Het
Tbcel	A	T	9: 42,437,243		probably benign	Het
Tob2	C	A	15: 81,858,223	G65W	probably damaging	Het
Trim16	A	G	11: 62,840,694	N464D	probably benign	Het
Trim36	T	C	18: 46,199,709		probably benign	Het
Trpv4	C	A	5: 114,630,529		probably benign	Het
Tsga10	T	A	1: 37,840,519	T64S	possibly damaging	Het
Ttc26	T	C	6: 38,409,435	C364R	probably damaging	Het
Vars2	A	T	17: 35,664,864		probably benign	Het
Vmn1r72	C	A	7: 11,669,694	V276L	probably benign	Het
Vps13a	T	A	19: 16,677,969	K1898N	probably benign	Het
Vps18	A	G	2: 119,297,164	M823V	probably damaging	Het
Washc2	T	C	6: 116,220,523		probably benign	Het
Zfp763	A	T	17: 33,019,747	H141Q	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
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
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'- TGCTACACAGCCTAGTAGTAGCTCG -3'
(R):5'- TCAGCCCTTCAGAAAGCCACTGTC -3'

Sequencing Primer
(F):5'- CTCGCATATAAACCGGAGGGTC -3'
(R):5'- AGCCACTGTCAGGTGAGG -3'

Posted On

2013-05-09