Incidental Mutation 'R5165:Alas1'
| ID |
395655 |
| 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 |
042746-MU
|
| Accession Numbers |
|
| Essential gene? |
Essential
(E-score: 1.000)
|
| Stock # |
R5165 (G1)
|
| Quality Score |
225 |
|
Status
|
Validated
|
| Chromosome |
9 |
| Chromosomal Location |
106110654-106125153 bp(-) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
T to C
at 106118454 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Threonine to Alanine
at position 223
(T223A)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000151891
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000074082]
[ENSMUST00000112524]
[ENSMUST00000133617]
[ENSMUST00000141118]
[ENSMUST00000219129]
[ENSMUST00000215222]
[ENSMUST00000143125]
[ENSMUST00000214989]
|
| AlphaFold |
Q8VC19 |
| Predicted Effect |
possibly damaging
Transcript: ENSMUST00000074082
AA Change: T223A
PolyPhen 2
Score 0.828 (Sensitivity: 0.84; Specificity: 0.93)
|
| SMART Domains |
Protein: ENSMUSP00000073725
Gene: ENSMUSG00000032786
AA Change: T223A
| 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: T223A
PolyPhen 2
Score 0.828 (Sensitivity: 0.84; Specificity: 0.93)
|
| SMART Domains |
Protein: ENSMUSP00000108143
Gene: ENSMUSG00000032786
AA Change: T223A
| 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: ENSMUST00000123115
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000123601
|
| 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 |
noncoding transcript
Transcript: ENSMUST00000134053
|
| Predicted Effect |
possibly damaging
Transcript: ENSMUST00000141118
AA Change: T223A
PolyPhen 2
Score 0.828 (Sensitivity: 0.84; Specificity: 0.93)
|
| SMART Domains |
Protein: ENSMUSP00000117014
Gene: ENSMUSG00000032786
AA Change: T223A
| 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 damaging
Transcript: ENSMUST00000219129
AA Change: T223A
PolyPhen 2
Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000215222
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000214249
|
| 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: ENSMUST00000219340
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000214989
|
| Meta Mutation Damage Score |
0.1284 |
| Coding Region Coverage |
- 1x: 99.2%
- 3x: 98.5%
- 10x: 96.9%
- 20x: 94.3%
|
| Validation Efficiency |
98% (58/59) |
| 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: 53 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Actg2 |
T |
A |
6: 83,503,814 (GRCm39) |
I77F |
probably benign |
Het |
| Actl6a |
G |
A |
3: 32,774,357 (GRCm39) |
V285I |
probably benign |
Het |
| Adam9 |
A |
T |
8: 25,457,190 (GRCm39) |
I646N |
possibly damaging |
Het |
| Ahnak |
T |
C |
19: 8,993,029 (GRCm39) |
I4771T |
possibly damaging |
Het |
| Apc2 |
A |
G |
10: 80,151,684 (GRCm39) |
E2246G |
probably damaging |
Het |
| Atp1a1 |
A |
G |
3: 101,489,105 (GRCm39) |
I795T |
probably benign |
Het |
| Ccn3 |
A |
G |
15: 54,612,585 (GRCm39) |
D198G |
probably damaging |
Het |
| Cdhr4 |
T |
C |
9: 107,874,829 (GRCm39) |
L633P |
probably damaging |
Het |
| Cep350 |
A |
G |
1: 155,804,114 (GRCm39) |
S990P |
probably damaging |
Het |
| Cplx2 |
A |
G |
13: 54,526,789 (GRCm39) |
I66V |
possibly damaging |
Het |
| Cx3cl1 |
T |
C |
8: 95,506,504 (GRCm39) |
S170P |
probably benign |
Het |
| Cyth1 |
T |
C |
11: 118,059,908 (GRCm39) |
N353S |
possibly damaging |
Het |
| Dapp1 |
T |
C |
3: 137,644,976 (GRCm39) |
|
probably null |
Het |
| Dmwd |
G |
A |
7: 18,811,960 (GRCm39) |
|
probably benign |
Het |
| Dsg1c |
A |
G |
18: 20,410,080 (GRCm39) |
H516R |
probably damaging |
Het |
| Efemp2 |
T |
C |
19: 5,525,439 (GRCm39) |
C39R |
probably damaging |
Het |
| Fnbp4 |
C |
G |
2: 90,608,001 (GRCm39) |
Q908E |
possibly damaging |
Het |
| Foxred2 |
A |
G |
15: 77,840,212 (GRCm39) |
V26A |
probably damaging |
Het |
| Gkap1 |
A |
G |
13: 58,411,010 (GRCm39) |
|
probably null |
Het |
| Gstcd |
A |
C |
3: 132,790,440 (GRCm39) |
V109G |
probably damaging |
Het |
| Hoxc9 |
T |
A |
15: 102,892,432 (GRCm39) |
M215K |
probably damaging |
Het |
| Igkv4-80 |
A |
C |
6: 68,993,649 (GRCm39) |
S81A |
probably benign |
Het |
| Kcnj9 |
A |
T |
1: 172,150,724 (GRCm39) |
D296E |
probably benign |
Het |
| Kctd18 |
T |
C |
1: 57,998,395 (GRCm39) |
Y68C |
probably damaging |
Het |
| Kif21a |
A |
T |
15: 90,840,579 (GRCm39) |
M1179K |
probably benign |
Het |
| Lrfn5 |
T |
C |
12: 61,886,410 (GRCm39) |
I66T |
possibly damaging |
Het |
| Lrp12 |
A |
G |
15: 39,735,857 (GRCm39) |
S692P |
probably benign |
Het |
| Lrrc10 |
A |
T |
10: 116,881,965 (GRCm39) |
N213I |
probably benign |
Het |
| Nceh1 |
G |
A |
3: 27,295,677 (GRCm39) |
V313I |
probably benign |
Het |
| Nkx6-3 |
T |
A |
8: 23,643,759 (GRCm39) |
H53Q |
probably damaging |
Het |
| Ntmt2 |
A |
G |
1: 163,550,092 (GRCm39) |
I53T |
probably benign |
Het |
| Or14j7 |
A |
G |
17: 38,235,252 (GRCm39) |
D265G |
probably benign |
Het |
| Or2y16 |
A |
G |
11: 49,335,203 (GRCm39) |
H175R |
probably damaging |
Het |
| Or4f53 |
T |
A |
2: 111,087,568 (GRCm39) |
V36E |
possibly damaging |
Het |
| Or5b97 |
A |
T |
19: 12,878,564 (GRCm39) |
N193K |
probably benign |
Het |
| Oxct1 |
A |
T |
15: 4,083,251 (GRCm39) |
T157S |
possibly damaging |
Het |
| Pcdhga3 |
A |
G |
18: 37,808,723 (GRCm39) |
E392G |
possibly damaging |
Het |
| Polr1a |
T |
G |
6: 71,944,909 (GRCm39) |
Y1322D |
probably damaging |
Het |
| Prkdc |
T |
A |
16: 15,496,136 (GRCm39) |
S776T |
probably damaging |
Het |
| Ralgapb |
A |
G |
2: 158,307,832 (GRCm39) |
I1047V |
possibly damaging |
Het |
| Sertad4 |
A |
T |
1: 192,529,130 (GRCm39) |
S229T |
possibly damaging |
Het |
| Shank2 |
T |
A |
7: 143,963,373 (GRCm39) |
V327D |
possibly damaging |
Het |
| Skint6 |
A |
T |
4: 112,722,865 (GRCm39) |
V904E |
possibly damaging |
Het |
| Slfn8 |
A |
T |
11: 82,907,953 (GRCm39) |
Y197N |
probably damaging |
Het |
| Smo |
T |
A |
6: 29,736,077 (GRCm39) |
L23Q |
unknown |
Het |
| Snx29 |
T |
A |
16: 11,238,639 (GRCm39) |
M23K |
probably damaging |
Het |
| Synrg |
T |
C |
11: 83,881,761 (GRCm39) |
S366P |
probably benign |
Het |
| Tomm40 |
A |
G |
7: 19,447,592 (GRCm39) |
|
probably null |
Het |
| Tpcn1 |
T |
C |
5: 120,696,010 (GRCm39) |
E81G |
probably damaging |
Het |
| Trappc1 |
A |
G |
11: 69,215,060 (GRCm39) |
Q26R |
probably benign |
Het |
| Ttn |
T |
A |
2: 76,606,900 (GRCm39) |
|
probably null |
Het |
| Usp25 |
T |
A |
16: 76,873,293 (GRCm39) |
D450E |
possibly damaging |
Het |
| Zmynd19 |
T |
A |
2: 24,848,201 (GRCm39) |
Y132* |
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 |
|
|
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 |
|
|
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'- AGTCCTGCCAAATAACGCCTG -3'
(R):5'- GTGTGCCACACATTCTAGTCC -3'
Sequencing Primer
(F):5'- CTGCCAAATAACGCCTGTGGTAG -3'
(R):5'- GTTTGTTTGCACTTCAGCT -3'
|
| Posted On |
2016-06-21 |
Incidental Mutation