Mutagenetix > Incidental Mutation

Incidental Mutation 'R3685:Smpd1'

269502

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

Accession Numbers

Essential gene?

Possibly non essential (E-score: 0.305) question?

Stock #

R3685 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

105203567-105207596 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to A at 105204609 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Cysteine to Serine at position 163 (C163S)

Ref Sequence

ENSEMBL: ENSMUSP00000042187 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000046983] [ENSMUST00000081165] [ENSMUST00000186814] [ENSMUST00000187057] [ENSMUST00000188001] [ENSMUST00000188368] [ENSMUST00000189072] [ENSMUST00000189378] [ENSMUST00000190369] [ENSMUST00000191601] [ENSMUST00000191011] [ENSMUST00000189265]

AlphaFold

Q04519

Predicted Effect

probably damaging
Transcript: ENSMUST00000046983
AA Change: C163S

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000042187
Gene: ENSMUSG00000037049
AA Change: C163S

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

noncoding transcript
Transcript: ENSMUST00000191250

Predicted Effect

probably benign
Transcript: ENSMUST00000211614

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000211307

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

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

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

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

Coding Region Coverage

1x: 99.1%
3x: 98.5%
10x: 97.1%
20x: 94.4%

Validation Efficiency

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: 20 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Ahdc1	T	C	4: 132,793,013 (GRCm39)	L1418P	possibly damaging	Het
Atp13a5	G	C	16: 29,135,573 (GRCm39)	L340V	probably damaging	Het
Cdon	A	G	9: 35,400,328 (GRCm39)	E1014G	possibly damaging	Het
Cyp2c40	A	G	19: 39,775,223 (GRCm39)	M343T	possibly damaging	Het
Dmrtc2	T	C	7: 24,573,687 (GRCm39)	V174A	probably benign	Het
Ggta1	T	A	2: 35,298,000 (GRCm39)	T162S	probably benign	Het
Gm9637	A	G	14: 19,401,950 (GRCm38)		noncoding transcript	Het
Gpbp1	T	C	13: 111,603,405 (GRCm39)	T15A	probably benign	Het
Itih5	A	T	2: 10,243,435 (GRCm39)	N391Y	possibly damaging	Het
Klhl40	A	G	9: 121,611,724 (GRCm39)	E579G	probably damaging	Het
Or4a73	C	A	2: 89,421,099 (GRCm39)	R120L	probably damaging	Het
Or4c118	A	T	2: 88,975,364 (GRCm39)	M1K	probably null	Het
Or5d37	T	A	2: 87,923,603 (GRCm39)	I226F	probably damaging	Het
Prr16	C	A	18: 51,435,892 (GRCm39)	P124T	probably damaging	Het
Ribc2	A	G	15: 85,019,535 (GRCm39)	T106A	possibly damaging	Het
Slc37a1	C	A	17: 31,544,667 (GRCm39)	T253N	probably benign	Het
Tacc2	A	G	7: 130,226,800 (GRCm39)	S1162G	probably benign	Het
Tenm2	C	A	11: 35,942,644 (GRCm39)	V1342L	probably benign	Het
Trim34a	T	C	7: 103,909,333 (GRCm39)		probably null	Het
Zfand6	G	A	7: 84,283,570 (GRCm39)	P11S	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
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
R6316:Smpd1	UTSW	7	105,204,709 (GRCm39)	missense	probably benign	0.19
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'- TGGCCAGGGTTCACTTGTTC -3'
(R):5'- GATCTGCACAGTAAGGGTCTG -3'

Sequencing Primer
(F):5'- ATTGGTTCCTTCCACCACAGAAG -3'
(R):5'- GGGTCTGTGCCCTCCAG -3'

Posted On

2015-02-19