Mutagenetix > Incidental Mutation

Incidental Mutation 'R8261:Smpd1'

639927

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

067686-MU

Accession Numbers

Essential gene?

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

Stock #

R8261 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

105203567-105207596 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 105204520 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Valine to Alanine at position 133 (V133A)

Ref Sequence

ENSEMBL: ENSMUSP00000042187 (fasta)

Gene Model

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

AlphaFold

Q04519

Predicted Effect

probably benign
Transcript: ENSMUST00000046983
AA Change: V133A

PolyPhen 2 Score 0.006 (Sensitivity: 0.97; Specificity: 0.75)

SMART Domains

Protein: ENSMUSP00000042187
Gene: ENSMUSG00000037049
AA Change: V133A

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

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

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: 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: ENSMUST00000211614

Coding Region Coverage

1x: 100.0%
3x: 100.0%
10x: 99.8%
20x: 99.3%

Validation Efficiency

100% (76/76)

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: 77 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
4933412E24Rik	T	C	15: 59,888,425 (GRCm39)	E5G	probably benign	Het
Adam23	T	C	1: 63,567,957 (GRCm39)	V202A	noncoding transcript	Het
Adamtsl1	A	C	4: 86,195,120 (GRCm39)	E512D	probably damaging	Het
Ahnak	A	T	19: 8,982,817 (GRCm39)	D1367V	probably damaging	Het
Angpt4	A	T	2: 151,769,084 (GRCm39)	Q198L	probably benign	Het
Apcdd1	T	A	18: 63,066,974 (GRCm39)	H29Q	possibly damaging	Het
Cdh16	T	A	8: 105,341,811 (GRCm39)	K755*	probably null	Het
Cdk6	T	G	5: 3,440,685 (GRCm39)	F80V	probably benign	Het
Chd1	T	C	17: 17,607,804 (GRCm39)	S451P	probably benign	Het
Chd6	A	G	2: 160,799,002 (GRCm39)	L2361P	probably damaging	Het
Chst8	A	G	7: 34,447,579 (GRCm39)	M13T	possibly damaging	Het
Cntnap2	T	C	6: 47,072,627 (GRCm39)	L1065P	probably damaging	Het
Dctn4	T	C	18: 60,659,343 (GRCm39)	V14A	possibly damaging	Het
Dicer1	A	T	12: 104,657,865 (GRCm39)	V1903D	probably damaging	Het
E2f2	A	G	4: 135,911,791 (GRCm39)		silent	Het
Eif4g3	T	A	4: 137,898,429 (GRCm39)	S902T	possibly damaging	Het
Emid1	G	T	11: 5,084,353 (GRCm39)	A152D	probably benign	Het
Fer1l6	T	A	15: 58,432,345 (GRCm39)	N297K	possibly damaging	Het
Fes	T	C	7: 80,032,902 (GRCm39)	D281G	probably null	Het
Frmpd2	T	C	14: 33,224,934 (GRCm39)	V133A	probably benign	Het
Fry	A	G	5: 150,369,372 (GRCm39)	Y2282C	probably damaging	Het
Gm10377	C	T	14: 42,616,664 (GRCm39)		probably null	Het
Gm1527	A	G	3: 28,974,749 (GRCm39)	T521A	probably damaging	Het
Gpr141	T	A	13: 19,936,013 (GRCm39)	H254L	probably benign	Het
Gpr160	A	G	3: 30,950,096 (GRCm39)	E56G	probably benign	Het
Grid2ip	T	G	5: 143,367,695 (GRCm39)		probably null	Het
Grin2a	A	G	16: 9,481,382 (GRCm39)	F473S	probably damaging	Het
Igkv1-131	T	C	6: 67,743,102 (GRCm39)	T94A	probably damaging	Het
Inava	T	A	1: 136,153,215 (GRCm39)	N226Y	probably damaging	Het
Iqgap2	A	G	13: 95,772,078 (GRCm39)	L1367P	probably damaging	Het
Kdm5d	T	A	Y: 936,929 (GRCm39)	M856K	probably damaging	Het
Kirrel1	T	C	3: 86,995,309 (GRCm39)		probably benign	Het
Lad1	T	C	1: 135,755,500 (GRCm39)	S259P	probably damaging	Het
Lalba	A	T	15: 98,379,992 (GRCm39)	F86Y	possibly damaging	Het
Lrfn5	G	A	12: 61,886,323 (GRCm39)	C37Y	probably damaging	Het
Man2c1	A	G	9: 57,046,942 (GRCm39)	T665A	probably benign	Het
Ms4a20	T	A	19: 11,087,707 (GRCm39)	S75C	probably damaging	Het
Myh11	T	C	16: 14,041,867 (GRCm39)	I719V		Het
Nbl1	A	T	4: 138,812,832 (GRCm39)	C34S	probably damaging	Het
Ncapg	T	A	5: 45,844,730 (GRCm39)	I575N	possibly damaging	Het
Nlgn1	T	C	3: 25,487,816 (GRCm39)	T840A	possibly damaging	Het
Nrdc	T	C	4: 108,873,876 (GRCm39)	S231P	possibly damaging	Het
Nrg2	T	C	18: 36,165,428 (GRCm39)	K395E	probably benign	Het
Nrip1	A	T	16: 76,088,949 (GRCm39)	N869K	possibly damaging	Het
Or2a14	T	A	6: 43,130,242 (GRCm39)	M1K	probably null	Het
Or4c12	A	G	2: 89,773,716 (GRCm39)	F248L	probably benign	Het
Or8s16	A	T	15: 98,210,546 (GRCm39)	M295K	probably benign	Het
Otub2	G	T	12: 103,369,161 (GRCm39)		probably null	Het
Paxbp1	T	C	16: 90,834,303 (GRCm39)	D161G	probably benign	Het
Pcnx3	C	T	19: 5,715,412 (GRCm39)	G1946E	probably damaging	Het
Per2	T	A	1: 91,361,170 (GRCm39)	Q495L	possibly damaging	Het
Plxna2	T	A	1: 194,431,724 (GRCm39)	V571E	probably damaging	Het
Prr7	C	A	13: 55,620,735 (GRCm39)	P248T	possibly damaging	Het
Ptprr	A	T	10: 116,073,169 (GRCm39)	T464S	possibly damaging	Het
Rapgef2	A	G	3: 78,993,325 (GRCm39)	V721A	probably benign	Het
Rfx1	A	T	8: 84,819,479 (GRCm39)	Y625F	probably benign	Het
Rps6kb2	G	T	19: 4,211,195 (GRCm39)	A110D	possibly damaging	Het
Setdb2	A	T	14: 59,651,141 (GRCm39)		probably benign	Het
Slc25a31	T	C	3: 40,679,351 (GRCm39)	I272T	probably damaging	Het
Sorl1	T	C	9: 41,925,777 (GRCm39)	D1185G	probably damaging	Het
Spag6	T	A	2: 18,750,301 (GRCm39)	L449H	probably benign	Het
Sptb	C	A	12: 76,668,036 (GRCm39)	R687L	probably benign	Het
Sptbn5	A	T	2: 119,877,616 (GRCm39)	V1012E	noncoding transcript	Het
Tmem192	A	G	8: 65,416,972 (GRCm39)	I188V	probably benign	Het
Tmem253	G	A	14: 52,256,708 (GRCm39)	V194M	probably benign	Het
Tph1	A	G	7: 46,303,173 (GRCm39)		silent	Het
Trak1	A	G	9: 121,280,733 (GRCm39)	E374G	probably damaging	Het
Trpv1	A	T	11: 73,145,593 (GRCm39)		probably null	Het
Trub2	T	C	2: 29,667,725 (GRCm39)	H305R	probably benign	Het
Ttn	A	G	2: 76,747,768 (GRCm39)	V4427A	probably benign	Het
Vasn	A	G	16: 4,466,160 (GRCm39)	T36A	probably damaging	Het
Vmn1r8	A	T	6: 57,013,158 (GRCm39)	I70F	probably benign	Het
Vps13c	A	T	9: 67,862,262 (GRCm39)	I2960L	probably damaging	Het
Zdhhc4	C	A	5: 143,307,588 (GRCm39)	M144I	probably benign	Het
Zfp273	T	A	13: 67,974,070 (GRCm39)	N399K	probably benign	Het
Zfp976	T	A	7: 42,262,125 (GRCm39)	T572S	unknown	Het
Zmym4	A	G	4: 126,798,360 (GRCm39)	C756R	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
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
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'- TTAGACATGGAAGCCTGTGG -3'
(R):5'- GTCCCAGTGTAGATCAGTAAGG -3'

Sequencing Primer
(F):5'- CATGGAAGCCTGTGGAGTGG -3'
(R):5'- TCCCAGTGTAGATCAGTAAGGAAGAG -3'

Posted On

2020-07-28