Incidental Mutation 'R8453:Alas1'
| ID |
654865 |
| 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 |
067904-MU
|
| Accession Numbers |
|
| Essential gene? |
Essential
(E-score: 1.000)
|
| Stock # |
R8453 (G1)
|
| Quality Score |
225.009 |
|
Status
|
Validated
|
| Chromosome |
9 |
| Chromosomal Location |
106110654-106125153 bp(-) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
C to T
at 106113721 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Arginine to Glutamine
at position 508
(R508Q)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000108143
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000074082]
[ENSMUST00000112524]
[ENSMUST00000133617]
[ENSMUST00000141118]
[ENSMUST00000143125]
[ENSMUST00000214989]
[ENSMUST00000219129]
|
| AlphaFold |
Q8VC19 |
| Predicted Effect |
possibly damaging
Transcript: ENSMUST00000074082
AA Change: R507Q
PolyPhen 2
Score 0.830 (Sensitivity: 0.84; Specificity: 0.93)
|
| SMART Domains |
Protein: ENSMUSP00000073725
Gene: ENSMUSG00000032786
AA Change: R507Q
| 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 |
possibly damaging
Transcript: ENSMUST00000112524
AA Change: R508Q
PolyPhen 2
Score 0.830 (Sensitivity: 0.84; Specificity: 0.93)
|
| SMART Domains |
Protein: ENSMUSP00000108143
Gene: ENSMUSG00000032786
AA Change: R508Q
| 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 |
possibly damaging
Transcript: ENSMUST00000141118
AA Change: R508Q
PolyPhen 2
Score 0.830 (Sensitivity: 0.84; Specificity: 0.93)
|
| SMART Domains |
Protein: ENSMUSP00000117014
Gene: ENSMUSG00000032786
AA Change: R508Q
| 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: R102Q
PolyPhen 2
Score 0.043 (Sensitivity: 0.94; Specificity: 0.83)
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000219129
|
| Coding Region Coverage |
- 1x: 100.0%
- 3x: 100.0%
- 10x: 99.7%
- 20x: 99.2%
|
| Validation Efficiency |
100% (68/68) |
| 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 |
|---|
| 9630041A04Rik |
G |
T |
9: 101,815,884 (GRCm39) |
C23F |
possibly damaging |
Het |
| Adam29 |
T |
C |
8: 56,326,196 (GRCm39) |
H86R |
possibly damaging |
Het |
| Albfm1 |
A |
T |
5: 90,714,360 (GRCm39) |
R123S |
possibly damaging |
Het |
| Ark2n |
T |
C |
18: 77,761,604 (GRCm39) |
E236G |
probably damaging |
Het |
| Bmp3 |
G |
A |
5: 99,003,282 (GRCm39) |
|
probably null |
Het |
| Bud13 |
A |
G |
9: 46,199,499 (GRCm39) |
T287A |
probably benign |
Het |
| C3 |
T |
C |
17: 57,519,643 (GRCm39) |
E1203G |
probably benign |
Het |
| Carmil2 |
A |
C |
8: 106,416,843 (GRCm39) |
Q476P |
probably damaging |
Het |
| Ccdc187 |
T |
A |
2: 26,166,458 (GRCm39) |
T707S |
probably damaging |
Het |
| Cfap43 |
A |
T |
19: 47,735,086 (GRCm39) |
V1435E |
probably damaging |
Het |
| Chrm3 |
A |
T |
13: 9,927,267 (GRCm39) |
*590K |
probably null |
Het |
| Commd1 |
C |
T |
11: 22,928,503 (GRCm39) |
|
probably benign |
Het |
| Creb3l1 |
A |
T |
2: 91,821,274 (GRCm39) |
Y314* |
probably null |
Het |
| Ctc1 |
T |
A |
11: 68,913,275 (GRCm39) |
S90R |
probably benign |
Het |
| Dixdc1 |
T |
C |
9: 50,596,186 (GRCm39) |
Q413R |
probably benign |
Het |
| Dlg5 |
T |
C |
14: 24,208,213 (GRCm39) |
T998A |
probably benign |
Het |
| Dnai4 |
A |
G |
4: 102,917,113 (GRCm39) |
I577T |
possibly damaging |
Het |
| Eif1ad14 |
C |
T |
12: 87,886,323 (GRCm39) |
S102N |
probably benign |
Het |
| Fam89b |
A |
G |
19: 5,778,903 (GRCm39) |
S99P |
possibly damaging |
Het |
| Fbxo30 |
A |
G |
10: 11,166,479 (GRCm39) |
I400M |
probably benign |
Het |
| Gad1 |
A |
T |
2: 70,431,057 (GRCm39) |
M567L |
probably benign |
Het |
| Gemin5 |
T |
C |
11: 58,016,065 (GRCm39) |
S1314G |
probably benign |
Het |
| Gm9195 |
T |
G |
14: 72,678,201 (GRCm39) |
I2323L |
probably benign |
Het |
| Gria1 |
T |
A |
11: 57,133,877 (GRCm39) |
F585L |
probably damaging |
Het |
| Hbs1l |
A |
T |
10: 21,185,178 (GRCm39) |
H200L |
probably benign |
Het |
| Igsf5 |
A |
G |
16: 96,222,996 (GRCm39) |
Q360R |
probably benign |
Het |
| Il31ra |
A |
T |
13: 112,660,717 (GRCm39) |
V624E |
probably damaging |
Het |
| Iqsec3 |
T |
C |
6: 121,364,779 (GRCm39) |
R837G |
probably damaging |
Het |
| Itprid2 |
T |
C |
2: 79,475,129 (GRCm39) |
S363P |
probably benign |
Het |
| Lpl |
A |
G |
8: 69,348,433 (GRCm39) |
I221V |
probably damaging |
Het |
| Mcf2l |
T |
C |
8: 13,034,956 (GRCm39) |
|
probably null |
Het |
| Mink1 |
T |
A |
11: 70,501,154 (GRCm39) |
D887E |
possibly damaging |
Het |
| Mmp10 |
T |
G |
9: 7,508,203 (GRCm39) |
F443C |
probably damaging |
Het |
| Mmrn1 |
T |
A |
6: 60,965,361 (GRCm39) |
Y1131N |
probably damaging |
Het |
| Mrc2 |
T |
A |
11: 105,223,137 (GRCm39) |
V460E |
probably damaging |
Het |
| Nicn1 |
T |
A |
9: 108,170,572 (GRCm39) |
F57Y |
probably damaging |
Het |
| Nlrp4b |
A |
G |
7: 10,449,528 (GRCm39) |
Y577C |
probably damaging |
Het |
| Nrap |
T |
C |
19: 56,312,352 (GRCm39) |
T1535A |
probably damaging |
Het |
| Opa1 |
G |
A |
16: 29,439,686 (GRCm39) |
R755H |
probably damaging |
Het |
| P4htm |
C |
T |
9: 108,457,566 (GRCm39) |
|
probably benign |
Het |
| Phldb2 |
A |
G |
16: 45,645,385 (GRCm39) |
S354P |
probably benign |
Het |
| Phykpl |
T |
C |
11: 51,489,121 (GRCm39) |
S316P |
probably damaging |
Het |
| Pnpla1 |
T |
A |
17: 29,077,873 (GRCm39) |
D11E |
probably benign |
Het |
| Pold2 |
A |
G |
11: 5,825,104 (GRCm39) |
F98L |
probably damaging |
Het |
| Prph |
G |
A |
15: 98,954,657 (GRCm39) |
R241Q |
probably benign |
Het |
| Rcl1 |
T |
C |
19: 29,093,159 (GRCm39) |
I58T |
possibly damaging |
Het |
| Rps6ka2 |
A |
G |
17: 7,514,151 (GRCm39) |
N117D |
probably benign |
Het |
| Sars1 |
G |
A |
3: 108,336,029 (GRCm39) |
S331L |
probably benign |
Het |
| Scfd1 |
A |
C |
12: 51,459,374 (GRCm39) |
K312Q |
possibly damaging |
Het |
| Senp5 |
A |
G |
16: 31,808,166 (GRCm39) |
C363R |
probably benign |
Het |
| Senp7 |
A |
G |
16: 56,008,691 (GRCm39) |
I1024V |
probably damaging |
Het |
| Sh2b1 |
TGGGGACCAGCTCAGCCACGGGGACCAGCTC |
TGGGGACCAGCTCAGCCACGGGGACCAGCTCAGCCACGGGGACCAGCTC |
7: 126,066,742 (GRCm39) |
|
probably benign |
Het |
| Sptbn4 |
A |
G |
7: 27,103,663 (GRCm39) |
L1191P |
probably damaging |
Het |
| Stk40 |
A |
G |
4: 126,022,766 (GRCm39) |
E180G |
probably damaging |
Het |
| Stxbp5 |
A |
T |
10: 9,684,792 (GRCm39) |
V536E |
probably benign |
Het |
| Suco |
A |
T |
1: 161,650,586 (GRCm39) |
|
probably benign |
Het |
| Tex15 |
G |
T |
8: 34,066,899 (GRCm39) |
E2110* |
probably null |
Het |
| Thbs4 |
G |
A |
13: 92,927,325 (GRCm39) |
P55S |
probably benign |
Het |
| Tmem115 |
T |
C |
9: 107,411,997 (GRCm39) |
V107A |
probably benign |
Het |
| Tnfaip6 |
A |
C |
2: 51,945,879 (GRCm39) |
I242L |
probably benign |
Het |
| Trabd |
G |
T |
15: 88,969,616 (GRCm39) |
A270S |
possibly damaging |
Het |
| Trim30d |
T |
A |
7: 104,136,947 (GRCm39) |
I86F |
probably damaging |
Het |
| Trpc7 |
A |
G |
13: 56,970,372 (GRCm39) |
V404A |
probably benign |
Het |
| Vmn1r61 |
A |
G |
7: 5,613,886 (GRCm39) |
Y143H |
probably benign |
Het |
| Vmn2r18 |
T |
A |
5: 151,485,373 (GRCm39) |
D707V |
probably damaging |
Het |
| Vnn3 |
G |
A |
10: 23,745,443 (GRCm39) |
R464H |
probably benign |
Het |
| Wdr27 |
T |
C |
17: 15,112,751 (GRCm39) |
T652A |
probably benign |
Het |
| Yeats2 |
C |
T |
16: 20,041,637 (GRCm39) |
R1176* |
probably null |
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 |
|
R8928:Alas1
|
UTSW |
9 |
106,118,513 (GRCm39) |
missense |
probably benign |
|
|
R9015:Alas1
|
UTSW |
9 |
106,113,670 (GRCm39) |
missense |
probably benign |
0.17 |
|
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'- TGGCTACAGTCTGAACACCAG -3'
(R):5'- GACTTCTCCTCCCAGGTAAAGC -3'
Sequencing Primer
(F):5'- GTCTGAACACCAGCCCTG -3'
(R):5'- TCCTCCCAGGTAAAGCGTTCG -3'
|
| Posted On |
2020-10-20 |
Incidental Mutation