Incidental Mutation 'R6316:Smpd1'
| ID |
509987 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Smpd1
|
| Ensembl Gene |
ENSMUSG00000037049 |
| Gene Name |
sphingomyelin phosphodiesterase 1, acid lysosomal |
| Synonyms |
ASM, A-SMase, Zn-SMase, aSMase, acid sphingomyelinase |
| MMRRC Submission |
044416-MU
|
| Accession Numbers |
|
| Essential gene? |
Possibly non essential
(E-score: 0.305)
|
| Stock # |
R6316 (G1)
|
| Quality Score |
225.009 |
|
Status
|
Validated
|
| Chromosome |
7 |
| Chromosomal Location |
105203567-105207596 bp(+) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
T to C
at 105204709 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Valine to Alanine
at position 196
(V196A)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000042187
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000046983]
[ENSMUST00000081165]
[ENSMUST00000186814]
[ENSMUST00000187057]
[ENSMUST00000188001]
[ENSMUST00000188368]
[ENSMUST00000189072]
[ENSMUST00000191601]
[ENSMUST00000189265]
[ENSMUST00000189378]
[ENSMUST00000190369]
[ENSMUST00000191011]
|
| AlphaFold |
Q04519 |
| Predicted Effect |
probably benign
Transcript: ENSMUST00000046983
AA Change: V196A
PolyPhen 2
Score 0.190 (Sensitivity: 0.92; Specificity: 0.87)
|
| SMART Domains |
Protein: ENSMUSP00000042187
Gene: ENSMUSG00000037049
AA Change: V196A
| Domain | Start | End | E-Value | Type |
|---|
|
transmembrane domain
|
30 |
52 |
N/A |
INTRINSIC |
|
SapB
|
85 |
163 |
1.05e-7 |
SMART |
|
low complexity region
|
177 |
196 |
N/A |
INTRINSIC |
|
Pfam:Metallophos
|
197 |
459 |
4.4e-21 |
PFAM |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000081165
|
| SMART Domains |
Protein: ENSMUSP00000079932
Gene: ENSMUSG00000037032
| Domain | Start | End | E-Value | Type |
|---|
|
low complexity region
|
146 |
184 |
N/A |
INTRINSIC |
|
WW
|
254 |
285 |
6.23e-5 |
SMART |
|
low complexity region
|
287 |
299 |
N/A |
INTRINSIC |
|
PTB
|
365 |
512 |
4.16e-38 |
SMART |
|
PTB
|
538 |
667 |
1.76e-36 |
SMART |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000186814
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000187057
|
| SMART Domains |
Protein: ENSMUSP00000139899
Gene: ENSMUSG00000037032
| Domain | Start | End | E-Value | Type |
|---|
|
WW
|
31 |
62 |
3.7e-7 |
SMART |
|
low complexity region
|
64 |
76 |
N/A |
INTRINSIC |
|
PTB
|
142 |
287 |
3.8e-41 |
SMART |
|
PTB
|
313 |
442 |
9.5e-39 |
SMART |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000188001
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000188368
|
| SMART Domains |
Protein: ENSMUSP00000139788
Gene: ENSMUSG00000037032
| Domain | Start | End | E-Value | Type |
|---|
|
WW
|
31 |
62 |
3.7e-7 |
SMART |
|
low complexity region
|
64 |
76 |
N/A |
INTRINSIC |
|
PTB
|
142 |
289 |
1.8e-40 |
SMART |
|
PTB
|
315 |
444 |
9.5e-39 |
SMART |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000189072
|
| SMART Domains |
Protein: ENSMUSP00000139575
Gene: ENSMUSG00000037032
| Domain | Start | End | E-Value | Type |
|---|
|
Pfam:WW
|
1 |
24 |
8.1e-5 |
PFAM |
|
low complexity region
|
28 |
40 |
N/A |
INTRINSIC |
|
PTB
|
106 |
253 |
1.8e-40 |
SMART |
|
PTB
|
279 |
408 |
9.5e-39 |
SMART |
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000210934
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000211614
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000191601
|
| SMART Domains |
Protein: ENSMUSP00000140116
Gene: ENSMUSG00000037032
| Domain | Start | End | E-Value | Type |
|---|
|
low complexity region
|
146 |
184 |
N/A |
INTRINSIC |
|
WW
|
254 |
285 |
3.7e-7 |
SMART |
|
low complexity region
|
287 |
299 |
N/A |
INTRINSIC |
|
PTB
|
365 |
512 |
1.8e-40 |
SMART |
|
PTB
|
538 |
667 |
9.5e-39 |
SMART |
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000211307
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000189265
|
| SMART Domains |
Protein: ENSMUSP00000140137
Gene: ENSMUSG00000037032
| Domain | Start | End | E-Value | Type |
|---|
|
Pfam:PID
|
1 |
34 |
2.3e-6 |
PFAM |
|
PTB
|
63 |
192 |
9.5e-39 |
SMART |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000189378
|
| SMART Domains |
Protein: ENSMUSP00000140979
Gene: ENSMUSG00000037032
| Domain | Start | End | E-Value | Type |
|---|
|
low complexity region
|
146 |
184 |
N/A |
INTRINSIC |
|
WW
|
254 |
285 |
6.23e-5 |
SMART |
|
low complexity region
|
287 |
299 |
N/A |
INTRINSIC |
|
PTB
|
365 |
510 |
6.86e-39 |
SMART |
|
PTB
|
536 |
665 |
1.76e-36 |
SMART |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000190369
|
| SMART Domains |
Protein: ENSMUSP00000140486
Gene: ENSMUSG00000037032
| Domain | Start | End | E-Value | Type |
|---|
|
Pfam:WW
|
1 |
24 |
8.1e-5 |
PFAM |
|
low complexity region
|
28 |
40 |
N/A |
INTRINSIC |
|
PTB
|
106 |
253 |
1.8e-40 |
SMART |
|
PTB
|
279 |
408 |
9.5e-39 |
SMART |
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000191250
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000191011
|
| SMART Domains |
Protein: ENSMUSP00000140973
Gene: ENSMUSG00000037032
| Domain | Start | End | E-Value | Type |
|---|
|
low complexity region
|
146 |
184 |
N/A |
INTRINSIC |
|
WW
|
254 |
285 |
6.23e-5 |
SMART |
|
low complexity region
|
287 |
299 |
N/A |
INTRINSIC |
|
PTB
|
365 |
510 |
6.86e-39 |
SMART |
|
PTB
|
536 |
665 |
1.76e-36 |
SMART |
|
| Meta Mutation Damage Score |
0.0689 |
| Coding Region Coverage |
- 1x: 100.0%
- 3x: 99.9%
- 10x: 99.3%
- 20x: 98.0%
|
| Validation Efficiency |
97% (38/39) |
| MGI Phenotype |
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The protein encoded by this gene is a lysosomal acid sphingomyelinase that converts sphingomyelin to ceramide. The encoded protein also has phospholipase C activity. Defects in this gene are a cause of Niemann-Pick disease type A (NPA) and Niemann-Pick disease type B (NPB). Multiple transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2010]
PHENOTYPE: Nullizygous mutations cause tremors, ataxia, altered lipid homeostasis, increased foam cell number, Purkinje cell loss and premature death, and may lead to hepatosplenomegaly, hunched posture, reduced weight, abnormal apoptosis, sperm defects, dyspnea, and high susceptibility to bacterial infection. [provided by MGI curators]
|
| Allele List at MGI |
|
| Other mutations in this stock |
Total: 38 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Abca12 |
T |
C |
1: 71,353,118 (GRCm39) |
T775A |
probably benign |
Het |
| Adam6a |
A |
T |
12: 113,509,196 (GRCm39) |
N523I |
probably benign |
Het |
| Adgrv1 |
T |
C |
13: 81,647,187 (GRCm39) |
T3118A |
possibly damaging |
Het |
| Arhgef4 |
G |
A |
1: 34,762,558 (GRCm39) |
A605T |
unknown |
Het |
| Asxl3 |
A |
G |
18: 22,655,839 (GRCm39) |
Y1283C |
probably damaging |
Het |
| Btbd2 |
T |
A |
10: 80,480,612 (GRCm39) |
I319F |
probably damaging |
Het |
| Eno4 |
G |
A |
19: 58,948,723 (GRCm39) |
|
probably null |
Het |
| Glis2 |
T |
A |
16: 4,431,700 (GRCm39) |
|
probably benign |
Het |
| Grin2b |
A |
T |
6: 135,757,277 (GRCm39) |
C395S |
probably benign |
Het |
| H1f8 |
T |
C |
6: 115,925,876 (GRCm39) |
|
probably null |
Het |
| Kansl1l |
T |
A |
1: 66,774,744 (GRCm39) |
Y694F |
probably benign |
Het |
| Kcnj1 |
A |
T |
9: 32,308,632 (GRCm39) |
E332V |
probably damaging |
Het |
| Klhdc7a |
T |
C |
4: 139,694,113 (GRCm39) |
E278G |
probably benign |
Het |
| Krt33a |
T |
C |
11: 99,905,027 (GRCm39) |
N160D |
probably damaging |
Het |
| Ksr2 |
A |
G |
5: 117,823,567 (GRCm39) |
N448S |
probably damaging |
Het |
| Lpar6 |
A |
G |
14: 73,476,774 (GRCm39) |
Y245C |
probably damaging |
Het |
| Magel2 |
T |
C |
7: 62,028,467 (GRCm39) |
I457T |
possibly damaging |
Het |
| Manf |
A |
G |
9: 106,766,385 (GRCm39) |
L132P |
probably damaging |
Het |
| Moxd2 |
T |
C |
6: 40,860,481 (GRCm39) |
D321G |
probably damaging |
Het |
| Mtmr12 |
T |
A |
15: 12,236,199 (GRCm39) |
C153S |
probably null |
Het |
| Muc16 |
T |
C |
9: 18,553,115 (GRCm39) |
T4393A |
probably benign |
Het |
| Notch3 |
T |
C |
17: 32,356,787 (GRCm39) |
|
probably null |
Het |
| Or9e1 |
A |
G |
11: 58,732,768 (GRCm39) |
Y276C |
probably damaging |
Het |
| Pirb |
T |
A |
7: 3,720,822 (GRCm39) |
K225N |
probably damaging |
Het |
| Plch1 |
C |
T |
3: 63,688,811 (GRCm39) |
W131* |
probably null |
Het |
| Rilpl2 |
A |
G |
5: 124,615,943 (GRCm39) |
V69A |
probably damaging |
Het |
| Smdt1 |
T |
C |
15: 82,232,210 (GRCm39) |
V99A |
probably damaging |
Het |
| Supt20 |
TCAGCAGCAGCAGCAGCAGCAGCA |
TCAGCAGCAGCAGCAGCAGCAGCAGCA |
3: 54,635,069 (GRCm39) |
|
probably benign |
Het |
| Tcte1 |
A |
G |
17: 45,845,786 (GRCm39) |
H130R |
probably benign |
Het |
| Tead1 |
C |
A |
7: 112,491,046 (GRCm39) |
Q296K |
probably damaging |
Het |
| Thoc2l |
G |
C |
5: 104,667,595 (GRCm39) |
G706R |
probably damaging |
Het |
| Tmem163 |
C |
T |
1: 127,479,102 (GRCm39) |
S139N |
probably benign |
Het |
| Tor1aip2 |
G |
T |
1: 155,937,840 (GRCm39) |
D192Y |
probably damaging |
Het |
| Trgv2 |
G |
A |
13: 19,520,912 (GRCm39) |
Q61* |
probably null |
Het |
| Trib1 |
T |
C |
15: 59,521,264 (GRCm39) |
S85P |
probably benign |
Het |
| Trrap |
T |
A |
5: 144,750,336 (GRCm39) |
N1581K |
probably benign |
Het |
| Vmn1r181 |
G |
A |
7: 23,684,183 (GRCm39) |
R216Q |
probably benign |
Het |
| Xrn2 |
A |
G |
2: 146,883,930 (GRCm39) |
Y563C |
probably damaging |
Het |
|
| Other mutations in Smpd1 |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
|---|
|
IGL00493:Smpd1
|
APN |
7 |
105,205,848 (GRCm39) |
missense |
probably damaging |
0.99 |
|
IGL01147:Smpd1
|
APN |
7 |
105,204,943 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL01526:Smpd1
|
APN |
7 |
105,203,982 (GRCm39) |
missense |
probably benign |
0.01 |
|
IGL01541:Smpd1
|
APN |
7 |
105,205,033 (GRCm39) |
missense |
possibly damaging |
0.48 |
|
IGL01619:Smpd1
|
APN |
7 |
105,204,549 (GRCm39) |
missense |
possibly damaging |
0.89 |
|
IGL01924:Smpd1
|
APN |
7 |
105,204,655 (GRCm39) |
missense |
probably benign |
0.01 |
|
IGL03004:Smpd1
|
APN |
7 |
105,205,881 (GRCm39) |
missense |
possibly damaging |
0.82 |
|
R0782:Smpd1
|
UTSW |
7 |
105,204,550 (GRCm39) |
missense |
possibly damaging |
0.80 |
|
R1445:Smpd1
|
UTSW |
7 |
105,205,881 (GRCm39) |
missense |
possibly damaging |
0.82 |
|
R1489:Smpd1
|
UTSW |
7 |
105,205,761 (GRCm39) |
splice site |
probably null |
|
|
R3683:Smpd1
|
UTSW |
7 |
105,204,609 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R3685:Smpd1
|
UTSW |
7 |
105,204,609 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R3977:Smpd1
|
UTSW |
7 |
105,205,108 (GRCm39) |
missense |
probably benign |
0.29 |
|
R4850:Smpd1
|
UTSW |
7 |
105,205,192 (GRCm39) |
missense |
probably benign |
|
|
R5084:Smpd1
|
UTSW |
7 |
105,206,185 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6429:Smpd1
|
UTSW |
7 |
105,206,135 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6672:Smpd1
|
UTSW |
7 |
105,204,480 (GRCm39) |
missense |
probably benign |
|
|
R7156:Smpd1
|
UTSW |
7 |
105,203,693 (GRCm39) |
unclassified |
probably benign |
|
|
R7883:Smpd1
|
UTSW |
7 |
105,206,192 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8261:Smpd1
|
UTSW |
7 |
105,204,520 (GRCm39) |
missense |
probably benign |
0.01 |
|
R9287:Smpd1
|
UTSW |
7 |
105,204,442 (GRCm39) |
missense |
probably benign |
0.14 |
|
R9406:Smpd1
|
UTSW |
7 |
105,203,750 (GRCm39) |
missense |
possibly damaging |
0.62 |
|
R9461:Smpd1
|
UTSW |
7 |
105,204,789 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9496:Smpd1
|
UTSW |
7 |
105,205,202 (GRCm39) |
critical splice donor site |
probably null |
|
|
X0021:Smpd1
|
UTSW |
7 |
105,206,852 (GRCm39) |
missense |
probably damaging |
1.00 |
|
| Predicted Primers |
PCR Primer
(F):5'- AGCACCACTAGATGTGTGCC -3'
(R):5'- TTTCTAGCGTTCGCAAGGGC -3'
Sequencing Primer
(F):5'- ACCACTAGATGTGTGCCAGTCAG -3'
(R):5'- GCAGGTCACACTTGCTGTAC -3'
|
| Posted On |
2018-04-02 |
Incidental Mutation