Incidental Mutation 'R2433:Hmgcr'
| ID |
250504 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Hmgcr
|
| Ensembl Gene |
ENSMUSG00000021670 |
| Gene Name |
3-hydroxy-3-methylglutaryl-Coenzyme A reductase |
| Synonyms |
Red, 3-hydroxy-3-methylglutaryl-CoA reductase, HMG-CoAR |
| MMRRC Submission |
040394-MU
|
| Accession Numbers |
|
| Essential gene? |
Essential
(E-score: 1.000)
|
| Stock # |
R2433 (G1)
|
| Quality Score |
225 |
|
Status
|
Not validated
|
| Chromosome |
13 |
| Chromosomal Location |
96785475-96807444 bp(-) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
A to G
at 96802393 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Leucine to Proline
at position 97
(L97P)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000128939
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000022176]
[ENSMUST00000168855]
[ENSMUST00000169196]
[ENSMUST00000169966]
[ENSMUST00000170287]
[ENSMUST00000171537]
|
| AlphaFold |
Q01237 |
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000022176
AA Change: L97P
PolyPhen 2
Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
|
| SMART Domains |
Protein: ENSMUSP00000022176
Gene: ENSMUSG00000021670
AA Change: L97P
| Domain | Start | End | E-Value | Type |
|---|
|
transmembrane domain
|
20 |
37 |
N/A |
INTRINSIC |
|
Pfam:Patched
|
56 |
342 |
2.7e-11 |
PFAM |
|
Pfam:Sterol-sensing
|
85 |
234 |
3.4e-20 |
PFAM |
|
Pfam:HMG-CoA_red
|
490 |
870 |
2.2e-150 |
PFAM |
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000163201
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000168374
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000168855
|
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000169196
AA Change: L97P
PolyPhen 2
Score 0.996 (Sensitivity: 0.55; Specificity: 0.98)
|
| SMART Domains |
Protein: ENSMUSP00000132749
Gene: ENSMUSG00000021670
AA Change: L97P
| Domain | Start | End | E-Value | Type |
|---|
|
transmembrane domain
|
20 |
37 |
N/A |
INTRINSIC |
|
transmembrane domain
|
57 |
79 |
N/A |
INTRINSIC |
|
Pfam:Sterol-sensing
|
85 |
210 |
4.7e-15 |
PFAM |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000169966
|
| SMART Domains |
Protein: ENSMUSP00000128294
Gene: ENSMUSG00000021670
| Domain | Start | End | E-Value | Type |
|---|
|
transmembrane domain
|
15 |
37 |
N/A |
INTRINSIC |
|
transmembrane domain
|
57 |
79 |
N/A |
INTRINSIC |
|
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000170287
AA Change: L97P
PolyPhen 2
Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
|
| SMART Domains |
Protein: ENSMUSP00000128939
Gene: ENSMUSG00000021670
AA Change: L97P
| Domain | Start | End | E-Value | Type |
|---|
|
transmembrane domain
|
20 |
37 |
N/A |
INTRINSIC |
|
Pfam:Patched
|
56 |
347 |
1.4e-11 |
PFAM |
|
Pfam:Sterol-sensing
|
85 |
234 |
7.4e-20 |
PFAM |
|
Pfam:HMG-CoA_red
|
488 |
819 |
1.3e-148 |
PFAM |
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000172440
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000171537
|
| SMART Domains |
Protein: ENSMUSP00000126959
Gene: ENSMUSG00000021670
| Domain | Start | End | E-Value | Type |
|---|
|
transmembrane domain
|
20 |
42 |
N/A |
INTRINSIC |
|
transmembrane domain
|
67 |
89 |
N/A |
INTRINSIC |
|
| Coding Region Coverage |
- 1x: 99.1%
- 3x: 98.5%
- 10x: 97.1%
- 20x: 94.3%
|
| Validation Efficiency |
|
| MGI Phenotype |
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] HMG-CoA reductase is the rate-limiting enzyme for cholesterol synthesis and is regulated via a negative feedback mechanism mediated by sterols and non-sterol metabolites derived from mevalonate, the product of the reaction catalyzed by reductase. Normally in mammalian cells this enzyme is suppressed by cholesterol derived from the internalization and degradation of low density lipoprotein (LDL) via the LDL receptor. Competitive inhibitors of the reductase induce the expression of LDL receptors in the liver, which in turn increases the catabolism of plasma LDL and lowers the plasma concentration of cholesterol, an important determinant of atherosclerosis. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2008]
PHENOTYPE: Inactivation of both copies of this gene results in early embryonic lethality. [provided by MGI curators]
|
| Allele List at MGI |
|
| Other mutations in this stock |
Total: 26 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Atp6v0a4 |
A |
G |
6: 38,058,964 (GRCm39) |
|
probably null |
Het |
| Bpifb4 |
A |
G |
2: 153,801,597 (GRCm39) |
K573E |
probably damaging |
Het |
| Capn10 |
T |
A |
1: 92,870,247 (GRCm39) |
D244E |
probably benign |
Het |
| Dhrs11 |
C |
A |
11: 84,719,745 (GRCm39) |
|
probably benign |
Het |
| Eipr1 |
G |
A |
12: 28,913,042 (GRCm39) |
G248R |
probably damaging |
Het |
| Fam120a |
A |
C |
13: 49,087,444 (GRCm39) |
D305E |
probably damaging |
Het |
| Htt |
A |
T |
5: 35,064,885 (GRCm39) |
S3033C |
possibly damaging |
Het |
| Igkv10-94 |
T |
C |
6: 68,681,559 (GRCm39) |
T94A |
probably benign |
Het |
| Krtap16-3 |
T |
C |
16: 88,759,533 (GRCm39) |
Y60C |
unknown |
Het |
| Lrp4 |
G |
A |
2: 91,336,360 (GRCm39) |
V1724I |
probably benign |
Het |
| Myo5b |
A |
G |
18: 74,892,158 (GRCm39) |
Y1634C |
probably damaging |
Het |
| Nrxn3 |
A |
G |
12: 89,943,160 (GRCm39) |
Y96C |
probably damaging |
Het |
| Obscn |
A |
T |
11: 58,929,912 (GRCm39) |
|
probably null |
Het |
| Pde3b |
T |
C |
7: 114,126,072 (GRCm39) |
C769R |
probably benign |
Het |
| Phlpp2 |
T |
G |
8: 110,666,634 (GRCm39) |
C1054W |
probably damaging |
Het |
| Pttg1 |
A |
T |
11: 43,311,178 (GRCm39) |
V193D |
probably damaging |
Het |
| Robo1 |
T |
C |
16: 72,767,127 (GRCm39) |
L433S |
probably benign |
Het |
| Sema4f |
A |
T |
6: 82,916,490 (GRCm39) |
C13S |
possibly damaging |
Het |
| Slc12a3 |
T |
C |
8: 95,072,944 (GRCm39) |
L689P |
probably benign |
Het |
| Slc7a6os |
T |
C |
8: 106,931,003 (GRCm39) |
N211S |
possibly damaging |
Het |
| Smurf2 |
T |
A |
11: 106,759,490 (GRCm39) |
I69F |
probably benign |
Het |
| St8sia3 |
A |
T |
18: 64,402,787 (GRCm39) |
H198L |
probably benign |
Het |
| Tacc3 |
A |
G |
5: 33,829,083 (GRCm39) |
K594R |
possibly damaging |
Het |
| Trip12 |
A |
T |
1: 84,721,544 (GRCm39) |
I1396K |
possibly damaging |
Het |
| Ugcg |
A |
G |
4: 59,207,876 (GRCm39) |
T72A |
possibly damaging |
Het |
| Zfp944 |
A |
T |
17: 22,558,193 (GRCm39) |
Y351* |
probably null |
Het |
|
| Other mutations in Hmgcr |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
|---|
|
IGL00557:Hmgcr
|
APN |
13 |
96,795,786 (GRCm39) |
missense |
probably benign |
|
|
IGL01369:Hmgcr
|
APN |
13 |
96,803,030 (GRCm39) |
missense |
probably null |
1.00 |
|
IGL01575:Hmgcr
|
APN |
13 |
96,793,103 (GRCm39) |
missense |
possibly damaging |
0.56 |
|
IGL02183:Hmgcr
|
APN |
13 |
96,799,635 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL02515:Hmgcr
|
APN |
13 |
96,803,020 (GRCm39) |
splice site |
probably benign |
|
|
IGL02716:Hmgcr
|
APN |
13 |
96,796,520 (GRCm39) |
critical splice acceptor site |
probably null |
|
|
IGL03278:Hmgcr
|
APN |
13 |
96,793,270 (GRCm39) |
splice site |
probably benign |
|
|
IGL03367:Hmgcr
|
APN |
13 |
96,802,361 (GRCm39) |
missense |
probably damaging |
0.98 |
|
PIT4131001:Hmgcr
|
UTSW |
13 |
96,795,562 (GRCm39) |
missense |
probably damaging |
1.00 |
|
PIT4504001:Hmgcr
|
UTSW |
13 |
96,799,605 (GRCm39) |
missense |
possibly damaging |
0.95 |
|
R0003:Hmgcr
|
UTSW |
13 |
96,788,653 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R0017:Hmgcr
|
UTSW |
13 |
96,788,597 (GRCm39) |
splice site |
probably benign |
|
|
R0017:Hmgcr
|
UTSW |
13 |
96,788,597 (GRCm39) |
splice site |
probably benign |
|
|
R0217:Hmgcr
|
UTSW |
13 |
96,788,488 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R0511:Hmgcr
|
UTSW |
13 |
96,796,651 (GRCm39) |
splice site |
probably null |
|
|
R0707:Hmgcr
|
UTSW |
13 |
96,787,151 (GRCm39) |
unclassified |
probably benign |
|
|
R1301:Hmgcr
|
UTSW |
13 |
96,795,528 (GRCm39) |
missense |
probably damaging |
0.97 |
|
R2203:Hmgcr
|
UTSW |
13 |
96,793,141 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R2204:Hmgcr
|
UTSW |
13 |
96,793,141 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R2938:Hmgcr
|
UTSW |
13 |
96,799,576 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R3159:Hmgcr
|
UTSW |
13 |
96,802,355 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R3737:Hmgcr
|
UTSW |
13 |
96,787,571 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R3752:Hmgcr
|
UTSW |
13 |
96,799,624 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R3837:Hmgcr
|
UTSW |
13 |
96,795,597 (GRCm39) |
missense |
probably benign |
0.19 |
|
R3838:Hmgcr
|
UTSW |
13 |
96,795,597 (GRCm39) |
missense |
probably benign |
0.19 |
|
R3839:Hmgcr
|
UTSW |
13 |
96,795,597 (GRCm39) |
missense |
probably benign |
0.19 |
|
R4034:Hmgcr
|
UTSW |
13 |
96,787,571 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4035:Hmgcr
|
UTSW |
13 |
96,787,571 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4210:Hmgcr
|
UTSW |
13 |
96,796,729 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4783:Hmgcr
|
UTSW |
13 |
96,802,701 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4820:Hmgcr
|
UTSW |
13 |
96,796,700 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R5090:Hmgcr
|
UTSW |
13 |
96,787,098 (GRCm39) |
missense |
probably benign |
|
|
R5113:Hmgcr
|
UTSW |
13 |
96,793,240 (GRCm39) |
missense |
probably benign |
0.00 |
|
R5209:Hmgcr
|
UTSW |
13 |
96,803,020 (GRCm39) |
splice site |
probably benign |
|
|
R5354:Hmgcr
|
UTSW |
13 |
96,791,404 (GRCm39) |
missense |
probably benign |
0.26 |
|
R5571:Hmgcr
|
UTSW |
13 |
96,803,171 (GRCm39) |
missense |
probably benign |
0.11 |
|
R5804:Hmgcr
|
UTSW |
13 |
96,802,695 (GRCm39) |
missense |
probably damaging |
0.98 |
|
R5886:Hmgcr
|
UTSW |
13 |
96,796,691 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6340:Hmgcr
|
UTSW |
13 |
96,802,366 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6638:Hmgcr
|
UTSW |
13 |
96,795,490 (GRCm39) |
missense |
probably benign |
|
|
R6699:Hmgcr
|
UTSW |
13 |
96,796,717 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7024:Hmgcr
|
UTSW |
13 |
96,795,418 (GRCm39) |
missense |
probably benign |
0.10 |
|
R7061:Hmgcr
|
UTSW |
13 |
96,802,656 (GRCm39) |
missense |
possibly damaging |
0.64 |
|
R7284:Hmgcr
|
UTSW |
13 |
96,789,173 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7286:Hmgcr
|
UTSW |
13 |
96,803,105 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7705:Hmgcr
|
UTSW |
13 |
96,793,231 (GRCm39) |
missense |
probably benign |
0.01 |
|
R7709:Hmgcr
|
UTSW |
13 |
96,799,605 (GRCm39) |
missense |
possibly damaging |
0.95 |
|
R9034:Hmgcr
|
UTSW |
13 |
96,795,885 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9158:Hmgcr
|
UTSW |
13 |
96,792,170 (GRCm39) |
nonsense |
probably null |
|
|
R9253:Hmgcr
|
UTSW |
13 |
96,796,645 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9474:Hmgcr
|
UTSW |
13 |
96,796,403 (GRCm39) |
missense |
probably damaging |
1.00 |
|
| Predicted Primers |
PCR Primer
(F):5'- TAGCAAGTTCATGAAAACTTTCCCC -3'
(R):5'- GCTGGCAGACTTTGGATTTC -3'
Sequencing Primer
(F):5'- CACACACTGGCCTTTACT -3'
(R):5'- GCAGACTTTGGATTTCAGTGCACTAC -3'
|
| Posted On |
2014-11-12 |
Incidental Mutation