Incidental Mutation 'R5420:Alas1'
| ID |
427992 |
| 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 |
042988-MU
|
| Accession Numbers |
|
| Essential gene? |
Essential
(E-score: 1.000)
|
| Stock # |
R5420 (G1)
|
| Quality Score |
225 |
|
Status
|
Validated
|
| Chromosome |
9 |
| Chromosomal Location |
106110654-106125153 bp(-) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
G to T
at 106111358 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Leucine to Isoleucine
at position 603
(L603I)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000117014
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000074082]
[ENSMUST00000112524]
[ENSMUST00000133617]
[ENSMUST00000141118]
[ENSMUST00000143125]
[ENSMUST00000214989]
|
| AlphaFold |
Q8VC19 |
| Predicted Effect |
probably benign
Transcript: ENSMUST00000074082
AA Change: L602I
PolyPhen 2
Score 0.134 (Sensitivity: 0.92; Specificity: 0.86)
|
| SMART Domains |
Protein: ENSMUSP00000073725
Gene: ENSMUSG00000032786
AA Change: L602I
| 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: L603I
PolyPhen 2
Score 0.134 (Sensitivity: 0.92; Specificity: 0.86)
|
| SMART Domains |
Protein: ENSMUSP00000108143
Gene: ENSMUSG00000032786
AA Change: L603I
| 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 benign
Transcript: ENSMUST00000141118
AA Change: L603I
PolyPhen 2
Score 0.134 (Sensitivity: 0.92; Specificity: 0.86)
|
| SMART Domains |
Protein: ENSMUSP00000117014
Gene: ENSMUSG00000032786
AA Change: L603I
| 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 |
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 |
probably benign
Transcript: ENSMUST00000214989
|
| Meta Mutation Damage Score |
0.0898 |
| Coding Region Coverage |
- 1x: 99.2%
- 3x: 98.6%
- 10x: 97.0%
- 20x: 94.7%
|
| Validation Efficiency |
97% (66/68) |
| 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: 59 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Actn3 |
TGCGCAGC |
T |
19: 4,915,372 (GRCm39) |
|
probably null |
Het |
| Adamts1 |
A |
T |
16: 85,596,497 (GRCm39) |
C117* |
probably null |
Het |
| Adgrg6 |
A |
T |
10: 14,302,730 (GRCm39) |
Y894* |
probably null |
Het |
| Arhgap21 |
G |
T |
2: 20,885,897 (GRCm39) |
R427S |
probably damaging |
Het |
| Arhgef25 |
A |
T |
10: 127,023,143 (GRCm39) |
V88D |
probably benign |
Het |
| Bdp1 |
T |
C |
13: 100,202,551 (GRCm39) |
Q691R |
possibly damaging |
Het |
| Bpifa6 |
T |
A |
2: 153,831,250 (GRCm39) |
I272N |
probably damaging |
Het |
| Cacybp |
T |
C |
1: 160,035,914 (GRCm39) |
|
probably benign |
Het |
| Capn3 |
T |
C |
2: 120,325,777 (GRCm39) |
|
probably benign |
Het |
| Ccdc47 |
C |
T |
11: 106,101,176 (GRCm39) |
R162Q |
probably benign |
Het |
| Cideb |
A |
C |
14: 55,995,748 (GRCm39) |
M1R |
probably null |
Het |
| Clec16a |
G |
A |
16: 10,549,543 (GRCm39) |
C872Y |
probably damaging |
Het |
| Crebbp |
C |
T |
16: 3,925,322 (GRCm39) |
R760H |
probably damaging |
Het |
| Cyp2c23 |
A |
C |
19: 44,004,103 (GRCm39) |
|
probably null |
Het |
| Cyp3a13 |
T |
G |
5: 137,897,243 (GRCm39) |
D357A |
probably damaging |
Het |
| Dip2b |
C |
T |
15: 100,103,054 (GRCm39) |
|
probably benign |
Het |
| Ecm2 |
A |
T |
13: 49,681,210 (GRCm39) |
R448S |
possibly damaging |
Het |
| Edil3 |
T |
C |
13: 89,279,891 (GRCm39) |
Y190H |
probably damaging |
Het |
| Eps8l1 |
T |
G |
7: 4,473,160 (GRCm39) |
|
probably null |
Het |
| Eps8l3 |
A |
T |
3: 107,791,301 (GRCm39) |
K280* |
probably null |
Het |
| Fam184a |
A |
G |
10: 53,509,753 (GRCm39) |
F1137L |
probably damaging |
Het |
| Fmn2 |
A |
T |
1: 174,526,344 (GRCm39) |
R1388* |
probably null |
Het |
| Glt8d2 |
T |
C |
10: 82,488,516 (GRCm39) |
K318R |
probably benign |
Het |
| Herc2 |
A |
T |
7: 55,853,578 (GRCm39) |
K3690I |
probably damaging |
Het |
| Ifi206 |
T |
A |
1: 173,308,599 (GRCm39) |
I466F |
possibly damaging |
Het |
| Jade2 |
T |
C |
11: 51,709,434 (GRCm39) |
K525R |
probably benign |
Het |
| Kmt2a |
A |
T |
9: 44,759,633 (GRCm39) |
F772I |
probably damaging |
Het |
| Lipi |
A |
G |
16: 75,352,757 (GRCm39) |
V360A |
possibly damaging |
Het |
| Mbl1 |
C |
T |
14: 40,879,153 (GRCm39) |
S108L |
possibly damaging |
Het |
| Mmp1b |
T |
C |
9: 7,384,897 (GRCm39) |
I251V |
possibly damaging |
Het |
| Mrpl23 |
A |
G |
7: 142,089,874 (GRCm39) |
T25A |
probably damaging |
Het |
| Mto1 |
T |
A |
9: 78,360,109 (GRCm39) |
M199K |
probably benign |
Het |
| Nes |
A |
T |
3: 87,884,309 (GRCm39) |
N812I |
probably damaging |
Het |
| Nfkbie |
T |
A |
17: 45,871,132 (GRCm39) |
D261E |
probably benign |
Het |
| Or7e173 |
T |
C |
9: 19,938,355 (GRCm39) |
Y293C |
probably damaging |
Het |
| Pakap |
G |
A |
4: 57,856,062 (GRCm39) |
V505I |
probably benign |
Het |
| Pakap |
T |
A |
4: 57,856,434 (GRCm39) |
Y588N |
probably damaging |
Het |
| Papola |
A |
G |
12: 105,772,754 (GRCm39) |
I114V |
possibly damaging |
Het |
| Pappa |
T |
G |
4: 65,254,017 (GRCm39) |
|
probably null |
Het |
| Pcdh7 |
T |
A |
5: 57,877,529 (GRCm39) |
D361E |
probably damaging |
Het |
| Pick1 |
A |
G |
15: 79,133,040 (GRCm39) |
T367A |
probably benign |
Het |
| Plbd2 |
A |
G |
5: 120,632,547 (GRCm39) |
Y152H |
probably damaging |
Het |
| Ppfia2 |
A |
T |
10: 106,671,562 (GRCm39) |
E424D |
possibly damaging |
Het |
| Rab7b |
C |
T |
1: 131,626,164 (GRCm39) |
T64I |
probably damaging |
Het |
| Rarb |
T |
A |
14: 16,434,249 (GRCm38) |
I310F |
possibly damaging |
Het |
| Rdh16f2 |
C |
T |
10: 127,712,943 (GRCm39) |
P314S |
possibly damaging |
Het |
| Rpain |
A |
T |
11: 70,868,516 (GRCm39) |
|
probably null |
Het |
| Rufy3 |
T |
C |
5: 88,788,518 (GRCm39) |
*488Q |
probably null |
Het |
| Sash1 |
G |
A |
10: 8,621,950 (GRCm39) |
T398I |
probably damaging |
Het |
| Scara5 |
CG |
C |
14: 65,997,111 (GRCm39) |
|
probably null |
Het |
| Scrn1 |
T |
A |
6: 54,489,048 (GRCm39) |
I358F |
probably benign |
Het |
| Stam2 |
G |
A |
2: 52,626,305 (GRCm39) |
|
probably benign |
Het |
| Thbs1 |
G |
T |
2: 117,943,636 (GRCm39) |
D85Y |
possibly damaging |
Het |
| Thoc2l |
T |
A |
5: 104,666,225 (GRCm39) |
I249N |
probably damaging |
Het |
| Trp53 |
T |
C |
11: 69,479,146 (GRCm39) |
|
probably benign |
Het |
| Ttn |
A |
T |
2: 76,641,587 (GRCm39) |
L5176Q |
possibly damaging |
Het |
| Vmn1r223 |
A |
G |
13: 23,433,675 (GRCm39) |
R90G |
probably benign |
Het |
| Zfp521 |
A |
T |
18: 13,977,144 (GRCm39) |
Y1090N |
probably damaging |
Het |
| Zfp677 |
T |
C |
17: 21,618,175 (GRCm39) |
C411R |
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 |
|
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'- CTACTATGTGGGTATGGTAATGGCC -3'
(R):5'- CCTCCTGAATGCTAGCTCTG -3'
Sequencing Primer
(F):5'- AATGGCCTGGGGTTTGTGAATAAC -3'
(R):5'- ACTCTGATTCTCTTGGGC -3'
|
| Posted On |
2016-09-01 |
Incidental Mutation