Incidental Mutation 'R2516:Alas1'
ID |
253815 |
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 |
040420-MU
|
Accession Numbers |
|
Essential gene? |
Essential
(E-score: 1.000)
|
Stock # |
R2516 (G1)
|
Quality Score |
225 |
Status
|
Validated
|
Chromosome |
9 |
Chromosomal Location |
106110654-106125153 bp(-) (GRCm39) |
Type of Mutation |
missense |
DNA Base Change (assembly) |
G to A
at 106115859 bp (GRCm39)
|
Zygosity |
Heterozygous |
Amino Acid Change |
Threonine to Isoleucine
at position 385
(T385I)
|
Ref Sequence |
ENSEMBL: ENSMUSP00000117014
(fasta)
|
Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000074082]
[ENSMUST00000112524]
[ENSMUST00000133617]
[ENSMUST00000141118]
[ENSMUST00000143125]
[ENSMUST00000214989]
[ENSMUST00000219129]
[ENSMUST00000215222]
|
AlphaFold |
Q8VC19 |
Predicted Effect |
probably damaging
Transcript: ENSMUST00000074082
AA Change: T385I
PolyPhen 2
Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
|
SMART Domains |
Protein: ENSMUSP00000073725 Gene: ENSMUSG00000032786 AA Change: T385I
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 damaging
Transcript: ENSMUST00000112524
AA Change: T385I
PolyPhen 2
Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
|
SMART Domains |
Protein: ENSMUSP00000108143 Gene: ENSMUSG00000032786 AA Change: T385I
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 |
probably damaging
Transcript: ENSMUST00000141118
AA Change: T385I
PolyPhen 2
Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
|
SMART Domains |
Protein: ENSMUSP00000117014 Gene: ENSMUSG00000032786 AA Change: T385I
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: ENSMUST00000143125
AA Change: T24I
PolyPhen 2
Score 0.998 (Sensitivity: 0.27; Specificity: 0.99)
|
SMART Domains |
Protein: ENSMUSP00000119968 Gene: ENSMUSG00000032786 AA Change: T24I
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 damaging
Transcript: ENSMUST00000214989
AA Change: T34I
PolyPhen 2
Score 0.992 (Sensitivity: 0.70; Specificity: 0.97)
|
Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000219340
|
Predicted Effect |
probably benign
Transcript: ENSMUST00000219129
|
Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000214249
|
Predicted Effect |
probably benign
Transcript: ENSMUST00000215222
|
Meta Mutation Damage Score |
0.8460 |
Coding Region Coverage |
- 1x: 99.2%
- 3x: 98.6%
- 10x: 97.3%
- 20x: 95.1%
|
Validation Efficiency |
98% (65/66) |
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: 66 list
Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
Abcb11 |
A |
T |
2: 69,159,673 (GRCm39) |
I6N |
possibly damaging |
Het |
Aen |
T |
C |
7: 78,555,616 (GRCm39) |
V188A |
probably damaging |
Het |
Afg3l1 |
A |
G |
8: 124,228,693 (GRCm39) |
E753G |
probably damaging |
Het |
Alms1 |
C |
A |
6: 85,644,945 (GRCm39) |
|
probably benign |
Het |
Ankrd65 |
A |
G |
4: 155,875,868 (GRCm39) |
T30A |
possibly damaging |
Het |
App |
T |
C |
16: 84,775,117 (GRCm39) |
S582G |
probably damaging |
Het |
Arfgef1 |
A |
T |
1: 10,223,879 (GRCm39) |
V1473E |
possibly damaging |
Het |
Arhgap21 |
G |
A |
2: 20,859,809 (GRCm39) |
P1196S |
probably damaging |
Het |
Arhgap24 |
A |
G |
5: 103,039,776 (GRCm39) |
T238A |
probably benign |
Het |
Atf7 |
T |
C |
15: 102,437,439 (GRCm39) |
|
probably benign |
Het |
Best1 |
G |
T |
19: 9,970,675 (GRCm39) |
S55* |
probably null |
Het |
Capn11 |
A |
G |
17: 45,944,725 (GRCm39) |
V514A |
probably damaging |
Het |
Cep104 |
T |
A |
4: 154,073,603 (GRCm39) |
M52K |
probably damaging |
Het |
Clca3a1 |
C |
T |
3: 144,443,619 (GRCm39) |
|
probably null |
Het |
Cyp3a25 |
T |
C |
5: 145,939,837 (GRCm39) |
|
probably null |
Het |
Dmxl2 |
G |
A |
9: 54,307,378 (GRCm39) |
P2197S |
probably damaging |
Het |
Drosha |
T |
C |
15: 12,859,551 (GRCm39) |
|
probably null |
Het |
Exosc9 |
A |
G |
3: 36,617,311 (GRCm39) |
K355R |
probably benign |
Het |
Fut1 |
A |
C |
7: 45,268,622 (GRCm39) |
H192P |
probably benign |
Het |
Gm572 |
T |
A |
4: 148,748,841 (GRCm39) |
V166D |
possibly damaging |
Het |
Gm9966 |
C |
T |
7: 95,607,735 (GRCm39) |
P19S |
unknown |
Het |
Gmds |
C |
T |
13: 32,284,456 (GRCm39) |
V219I |
probably damaging |
Het |
Gsn |
G |
A |
2: 35,173,965 (GRCm39) |
E25K |
probably benign |
Het |
Il4i1 |
T |
C |
7: 44,489,315 (GRCm39) |
F368S |
probably damaging |
Het |
Irak1bp1 |
T |
C |
9: 82,712,373 (GRCm39) |
L98P |
probably damaging |
Het |
Khdrbs3 |
T |
C |
15: 68,896,544 (GRCm39) |
|
probably benign |
Het |
Kndc1 |
T |
C |
7: 139,501,738 (GRCm39) |
I925T |
probably damaging |
Het |
Laptm4a |
T |
C |
12: 8,988,151 (GRCm39) |
I296T |
probably benign |
Het |
Lpl |
A |
T |
8: 69,340,170 (GRCm39) |
H55L |
probably benign |
Het |
Lrrk2 |
C |
A |
15: 91,640,130 (GRCm39) |
N1558K |
probably benign |
Het |
Mfsd2a |
A |
G |
4: 122,844,280 (GRCm39) |
L289P |
probably damaging |
Het |
Mmrn2 |
T |
A |
14: 34,120,759 (GRCm39) |
M543K |
probably benign |
Het |
Mnat1 |
T |
C |
12: 73,228,550 (GRCm39) |
|
probably benign |
Het |
Msto1 |
A |
T |
3: 88,819,200 (GRCm39) |
|
probably null |
Het |
Mtus1 |
A |
G |
8: 41,535,776 (GRCm39) |
Y647H |
probably damaging |
Het |
Nars1 |
A |
T |
18: 64,638,087 (GRCm39) |
V289E |
probably damaging |
Het |
Oit3 |
T |
A |
10: 59,264,167 (GRCm39) |
K322N |
probably damaging |
Het |
Oit3 |
G |
A |
10: 59,277,507 (GRCm39) |
|
probably benign |
Het |
Or4k1 |
T |
C |
14: 50,377,440 (GRCm39) |
I219V |
probably benign |
Het |
Or5b113 |
T |
A |
19: 13,342,557 (GRCm39) |
C188* |
probably null |
Het |
Or5m12 |
A |
G |
2: 85,734,900 (GRCm39) |
I166T |
probably benign |
Het |
Or6c211 |
G |
A |
10: 129,506,155 (GRCm39) |
R78W |
probably damaging |
Het |
Pecr |
A |
T |
1: 72,316,469 (GRCm39) |
C79S |
probably damaging |
Het |
Plekhn1 |
T |
C |
4: 156,307,116 (GRCm39) |
D478G |
probably damaging |
Het |
Pls1 |
A |
T |
9: 95,658,616 (GRCm39) |
M264K |
probably benign |
Het |
Ptprj |
C |
A |
2: 90,305,340 (GRCm39) |
|
probably benign |
Het |
Pygm |
A |
G |
19: 6,447,631 (GRCm39) |
D646G |
probably benign |
Het |
Rif1 |
GCCACCA |
GCCA |
2: 52,000,336 (GRCm39) |
|
probably benign |
Het |
Scn8a |
T |
C |
15: 100,867,043 (GRCm39) |
V283A |
probably benign |
Het |
Shisa5 |
T |
C |
9: 108,885,575 (GRCm39) |
|
probably null |
Het |
Slc10a4 |
A |
G |
5: 73,165,848 (GRCm39) |
I246V |
possibly damaging |
Het |
Slc1a1 |
A |
T |
19: 28,870,312 (GRCm39) |
I104F |
probably benign |
Het |
Slc22a8 |
A |
G |
19: 8,587,559 (GRCm39) |
Y511C |
probably benign |
Het |
Slc6a5 |
A |
G |
7: 49,606,210 (GRCm39) |
N706S |
probably benign |
Het |
Sos2 |
T |
C |
12: 69,697,433 (GRCm39) |
K96E |
probably damaging |
Het |
Stom |
G |
A |
2: 35,205,977 (GRCm39) |
R251* |
probably null |
Het |
Sycp1 |
T |
C |
3: 102,752,382 (GRCm39) |
E800G |
probably benign |
Het |
Tab2 |
G |
A |
10: 7,783,245 (GRCm39) |
P679L |
probably damaging |
Het |
Tiam2 |
G |
A |
17: 3,503,657 (GRCm39) |
V945I |
probably damaging |
Het |
Trpm5 |
G |
T |
7: 142,628,254 (GRCm39) |
P1007Q |
probably damaging |
Het |
Uchl1 |
T |
G |
5: 66,839,956 (GRCm39) |
I139S |
probably damaging |
Het |
Vmn1r232 |
A |
G |
17: 21,134,288 (GRCm39) |
I104T |
possibly damaging |
Het |
Vmn2r97 |
G |
A |
17: 19,167,814 (GRCm39) |
M689I |
probably benign |
Het |
Zc3h18 |
A |
T |
8: 123,129,904 (GRCm39) |
|
probably benign |
Het |
Zfhx4 |
C |
T |
3: 5,468,418 (GRCm39) |
P2859S |
probably benign |
Het |
Zfp456 |
T |
C |
13: 67,510,491 (GRCm39) |
K99R |
probably benign |
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 |
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 |
|
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'- TCTCAATTACAGAGTCCCAGTGC -3'
(R):5'- GCCTCTGCCATTAAGTAGCAC -3'
Sequencing Primer
(F):5'- AAAAATGCCAAACCAAAAGGAAAC -3'
(R):5'- AAGTAGCACTTTTCTCATGTCAGGC -3'
|
Posted On |
2014-12-04 |