Mutagenetix > Incidental Mutation

Incidental Mutation 'R7062:Smpd4'

548370

Institutional Source

Beutler Lab

Gene Symbol

Smpd4

Ensembl Gene

ENSMUSG00000005899

Gene Name

sphingomyelin phosphodiesterase 4

Synonyms

4122402O22Rik, neutral membrane (neutral sphingomyelinase-3)

MMRRC Submission

045158-MU

Accession Numbers

Essential gene?

Probably non essential (E-score: 0.098) question?

Stock #

R7062 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

17437218-17462692 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to A at 17458835 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Aspartic acid to Glutamic Acid at position 519 (D519E)

Ref Sequence

ENSEMBL: ENSMUSP00000006053 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000006053] [ENSMUST00000090159] [ENSMUST00000163476] [ENSMUST00000165363] [ENSMUST00000231436] [ENSMUST00000231627] [ENSMUST00000231722] [ENSMUST00000231792] [ENSMUST00000232021] [ENSMUST00000232116] [ENSMUST00000232271]

AlphaFold

Q6ZPR5

Predicted Effect

probably damaging
Transcript: ENSMUST00000006053
AA Change: D519E

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000006053
Gene: ENSMUSG00000005899
AA Change: D519E

Domain	Start	End	E-Value	Type
Pfam:mit_SMPDase	8	768	N/A	PFAM
transmembrane domain	769	791	N/A	INTRINSIC
transmembrane domain	798	815	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000090159
AA Change: D503E

PolyPhen 2 Score 0.175 (Sensitivity: 0.92; Specificity: 0.87)

SMART Domains

Protein: ENSMUSP00000087620
Gene: ENSMUSG00000005899
AA Change: D503E

Domain	Start	End	E-Value	Type
Pfam:mit_SMPDase	8	288	7.4e-177	PFAM
Pfam:mit_SMPDase	287	752	9.4e-259	PFAM
transmembrane domain	753	775	N/A	INTRINSIC
transmembrane domain	782	799	N/A	INTRINSIC

Predicted Effect

possibly damaging
Transcript: ENSMUST00000163476
AA Change: D490E

PolyPhen 2 Score 0.945 (Sensitivity: 0.80; Specificity: 0.95)

SMART Domains

Protein: ENSMUSP00000131867
Gene: ENSMUSG00000005899
AA Change: D490E

Domain	Start	End	E-Value	Type
Pfam:mit_SMPDase	8	289	6.2e-177	PFAM
Pfam:mit_SMPDase	285	739	9.8e-266	PFAM
transmembrane domain	740	762	N/A	INTRINSIC
transmembrane domain	769	786	N/A	INTRINSIC

Predicted Effect

possibly damaging
Transcript: ENSMUST00000165363
AA Change: D489E

PolyPhen 2 Score 0.929 (Sensitivity: 0.81; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000130720
Gene: ENSMUSG00000005899
AA Change: D489E

Domain	Start	End	E-Value	Type
Pfam:mit_SMPDase	8	289	6.2e-177	PFAM
Pfam:mit_SMPDase	285	738	4.1e-262	PFAM
transmembrane domain	739	761	N/A	INTRINSIC
transmembrane domain	768	785	N/A	INTRINSIC

Predicted Effect

probably damaging
Transcript: ENSMUST00000231436
AA Change: D490E

PolyPhen 2 Score 0.978 (Sensitivity: 0.76; Specificity: 0.96)

Predicted Effect

probably benign
Transcript: ENSMUST00000231627

Predicted Effect

probably benign
Transcript: ENSMUST00000231722

Predicted Effect

probably benign
Transcript: ENSMUST00000231792
AA Change: D269E

PolyPhen 2 Score 0.353 (Sensitivity: 0.90; Specificity: 0.89)

Predicted Effect

possibly damaging
Transcript: ENSMUST00000232021
AA Change: D417E

PolyPhen 2 Score 0.551 (Sensitivity: 0.88; Specificity: 0.91)

Predicted Effect

probably benign
Transcript: ENSMUST00000232116

Predicted Effect

possibly damaging
Transcript: ENSMUST00000232271
AA Change: D195E

PolyPhen 2 Score 0.781 (Sensitivity: 0.85; Specificity: 0.93)

Meta Mutation Damage Score

0.6467

Coding Region Coverage

1x: 100.0%
3x: 99.9%
10x: 99.7%
20x: 99.0%

Validation Efficiency

99% (86/87)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] Sphingomyelinases (EC 3.1.4.12), such as SMPD4, catalyze the hydrolysis of membrane sphingomyelin to form phosphorylcholine and ceramide (Krut et al., 2006 [PubMed 16517606]).[supplied by OMIM, Mar 2008]

Allele List at MGI

Other mutations in this stock

Total: 85 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abcc9	T	A	6: 142,544,872 (GRCm39)	D1370V	probably damaging	Het
Ackr1	A	T	1: 173,159,682 (GRCm39)	I279N	possibly damaging	Het
Adcy10	A	G	1: 165,366,091 (GRCm39)	H536R	probably benign	Het
Adgrb3	T	C	1: 25,865,166 (GRCm39)	T226A	possibly damaging	Het
Apol10b	T	A	15: 77,469,473 (GRCm39)	M235L	probably benign	Het
Arhgap44	T	C	11: 64,902,758 (GRCm39)	T570A	probably benign	Het
Astn1	A	G	1: 158,516,081 (GRCm39)		probably null	Het
Camsap3	A	G	8: 3,657,834 (GRCm39)		probably benign	Het
Ccdc73	C	T	2: 104,782,223 (GRCm39)	A193V	probably damaging	Het
Ccl20	G	A	1: 83,095,535 (GRCm39)	C32Y	probably damaging	Het
Cdk11b	A	G	4: 155,711,268 (GRCm39)	E16G	probably damaging	Het
Celsr2	T	A	3: 108,309,826 (GRCm39)	N1591I	possibly damaging	Het
Col5a2	T	C	1: 45,456,785 (GRCm39)	E306G	probably benign	Het
Cpa1	C	T	6: 30,640,676 (GRCm39)	A106V	probably benign	Het
Ctdspl	G	A	9: 118,866,538 (GRCm39)	R199H	probably damaging	Het
Cyfip2	G	A	11: 46,151,659 (GRCm39)	P547S	probably damaging	Het
Cyp2c37	A	T	19: 39,983,990 (GRCm39)		probably null	Het
Dnajc16	A	G	4: 141,494,001 (GRCm39)	F549L	probably damaging	Het
Dnm3	T	A	1: 161,962,060 (GRCm39)	K50*	probably null	Het
Eci1	C	T	17: 24,645,714 (GRCm39)		probably benign	Het
Eif2b4	C	T	5: 31,350,175 (GRCm39)	C49Y	probably benign	Het
Emc3	A	T	6: 113,499,757 (GRCm39)	I56N	probably damaging	Het
Enthd1	A	G	15: 80,336,745 (GRCm39)	L563P	probably damaging	Het
Ercc4	T	A	16: 12,950,811 (GRCm39)	I635K	probably damaging	Het
Espl1	A	C	15: 102,207,331 (GRCm39)	N265T	probably benign	Het
Fads2	T	C	19: 10,042,962 (GRCm39)		probably null	Het
Fam186a	G	A	15: 99,831,521 (GRCm39)		probably benign	Het
Fastkd1	A	T	2: 69,534,666 (GRCm39)	I368K	possibly damaging	Het
Fat1	G	A	8: 45,403,253 (GRCm39)	M1I	probably null	Het
Foxj1	T	C	11: 116,222,819 (GRCm39)	E328G	probably benign	Het
Gfod2	T	C	8: 106,449,508 (GRCm39)		probably benign	Het
Gm6525	C	T	3: 84,082,198 (GRCm39)	R40C	probably benign	Het
Gna12	G	A	5: 140,771,240 (GRCm39)	T144I	probably benign	Het
Ighv9-3	T	C	12: 114,104,712 (GRCm39)	M11V	probably benign	Het
Kcnj14	T	C	7: 45,467,314 (GRCm39)	Y344C	probably damaging	Het
Lrrc63	A	T	14: 75,323,737 (GRCm39)	S496T	probably benign	Het
Ltn1	T	C	16: 87,224,491 (GRCm39)	T78A	probably damaging	Het
Matr3	T	A	18: 35,712,072 (GRCm39)		probably null	Het
Mcpt4	A	G	14: 56,298,125 (GRCm39)	M142T	probably benign	Het
Mroh7	A	G	4: 106,541,177 (GRCm39)	F1154S	probably damaging	Het
Mrpl1	G	T	5: 96,361,650 (GRCm39)	L12F	probably benign	Het
Myo3b	G	A	2: 70,047,501 (GRCm39)	V308I	probably benign	Het
Nfasc	A	G	1: 132,529,707 (GRCm39)		probably null	Het
Npc1l1	T	A	11: 6,167,807 (GRCm39)	M995L	probably benign	Het
Nvl	A	G	1: 180,939,899 (GRCm39)	I617T	probably benign	Het
Oas1h	C	A	5: 120,999,528 (GRCm39)		probably benign	Het
Oasl2	T	A	5: 115,049,152 (GRCm39)	Y197*	probably null	Het
Or4k1	A	G	14: 50,377,907 (GRCm39)	L63P	probably damaging	Het
Or52ab7	T	C	7: 102,978,293 (GRCm39)	V200A	probably benign	Het
Or5an1c	T	C	19: 12,218,089 (GRCm39)	N312S	probably benign	Het
Or5l13	T	C	2: 87,780,568 (GRCm39)	E3G	probably benign	Het
Or5p70	C	T	7: 107,995,037 (GRCm39)	R237*	probably null	Het
Or8g35	A	T	9: 39,381,353 (GRCm39)	I223N	probably benign	Het
Orc6	T	C	8: 86,029,537 (GRCm39)	V27A	probably damaging	Het
Parp4	A	T	14: 56,852,216 (GRCm39)	R799S	possibly damaging	Het
Pcdhga1	C	A	18: 37,958,130 (GRCm39)	S826R	probably damaging	Het
Phldb1	T	C	9: 44,607,432 (GRCm39)	R1258G	probably damaging	Het
Ppfia1	T	C	7: 144,106,210 (GRCm39)	S21G	probably benign	Het
Ppp1r18	C	A	17: 36,179,103 (GRCm39)	T326K	probably damaging	Het
Psg26	A	G	7: 18,216,521 (GRCm39)	L106P	probably damaging	Het
Rabgap1l	A	T	1: 160,054,220 (GRCm39)	D265E	probably benign	Het
Rasgrp4	T	C	7: 28,849,619 (GRCm39)	L554P	possibly damaging	Het
Rnf17	G	T	14: 56,703,111 (GRCm39)	V621L	probably benign	Het
Sart3	T	C	5: 113,883,663 (GRCm39)	K783R	possibly damaging	Het
Slc23a2	T	A	2: 131,933,189 (GRCm39)	I90F	probably damaging	Het
Slc5a2	A	T	7: 127,869,212 (GRCm39)	M331L	probably damaging	Het
Slc5a7	C	G	17: 54,600,029 (GRCm39)	G128A	probably damaging	Het
Smcr8	A	T	11: 60,671,180 (GRCm39)	Q776L	probably damaging	Het
Smurf1	A	T	5: 144,830,356 (GRCm39)		probably null	Het
Spata18	T	A	5: 73,816,636 (GRCm39)	N125K	probably benign	Het
Spice1	T	A	16: 44,178,259 (GRCm39)	M94K	probably damaging	Het
Stard4	T	C	18: 33,338,587 (GRCm39)		probably null	Het
Stx17	A	G	4: 48,140,442 (GRCm39)	D49G	probably benign	Het
Tbce	T	C	13: 14,194,380 (GRCm39)	D93G	possibly damaging	Het
Tbx21	T	A	11: 96,989,719 (GRCm39)	D491V	probably damaging	Het
Tmbim4	G	T	10: 120,044,731 (GRCm39)		probably benign	Het
Tmem209	C	T	6: 30,502,016 (GRCm39)	R62H	probably damaging	Het
Tmem237	A	T	1: 59,158,771 (GRCm39)		probably null	Het
Tmprss9	T	C	10: 80,730,883 (GRCm39)	I803T	probably benign	Het
Trip4	C	T	9: 65,792,292 (GRCm39)	A7T	probably benign	Het
Unc13a	T	C	8: 72,115,881 (GRCm39)	D107G	probably benign	Het
Uso1	C	A	5: 92,340,599 (GRCm39)	Q672K	possibly damaging	Het
Washc2	T	A	6: 116,196,949 (GRCm39)	N239K	possibly damaging	Het
Zfp661	A	G	2: 127,419,040 (GRCm39)	C367R	probably damaging	Het
Znrf3	T	A	11: 5,231,550 (GRCm39)	E558D	probably damaging	Het

Other mutations in Smpd4

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00944:Smpd4	APN	16	17,460,621 (GRCm39)	missense	probably benign	0.04
IGL01461:Smpd4	APN	16	17,439,370 (GRCm39)	missense	probably damaging	1.00
IGL02051:Smpd4	APN	16	17,444,382 (GRCm39)	missense	probably damaging	1.00
IGL02492:Smpd4	APN	16	17,457,215 (GRCm39)	missense	probably damaging	1.00
IGL03181:Smpd4	APN	16	17,443,671 (GRCm39)	nonsense	probably null
Victim	UTSW	16	17,458,835 (GRCm39)	missense	probably damaging	1.00
weakling	UTSW	16	17,456,350 (GRCm39)	intron	probably benign
G1citation:Smpd4	UTSW	16	17,458,097 (GRCm39)	missense	probably damaging	1.00
R0197:Smpd4	UTSW	16	17,459,461 (GRCm39)	critical splice donor site	probably null
R0549:Smpd4	UTSW	16	17,457,176 (GRCm39)	missense	probably benign	0.15
R0789:Smpd4	UTSW	16	17,443,690 (GRCm39)	missense	probably benign	0.14
R1077:Smpd4	UTSW	16	17,441,833 (GRCm39)	missense	probably damaging	1.00
R1120:Smpd4	UTSW	16	17,456,350 (GRCm39)	intron	probably benign
R1716:Smpd4	UTSW	16	17,460,365 (GRCm39)	missense	probably damaging	1.00
R1758:Smpd4	UTSW	16	17,458,744 (GRCm39)	missense	probably damaging	1.00
R1758:Smpd4	UTSW	16	17,443,872 (GRCm39)	missense	probably damaging	0.99
R1838:Smpd4	UTSW	16	17,460,166 (GRCm39)	splice site	probably null
R2115:Smpd4	UTSW	16	17,444,729 (GRCm39)	missense	probably benign	0.33
R2849:Smpd4	UTSW	16	17,460,076 (GRCm39)	missense	probably damaging	1.00
R4654:Smpd4	UTSW	16	17,459,992 (GRCm39)	intron	probably benign
R6157:Smpd4	UTSW	16	17,458,930 (GRCm39)	splice site	probably null
R6190:Smpd4	UTSW	16	17,449,877 (GRCm39)	missense	probably damaging	1.00
R6822:Smpd4	UTSW	16	17,458,097 (GRCm39)	missense	probably damaging	1.00
R7305:Smpd4	UTSW	16	17,459,647 (GRCm39)	missense	probably damaging	0.99
R7759:Smpd4	UTSW	16	17,456,497 (GRCm39)	missense	probably damaging	1.00
R7853:Smpd4	UTSW	16	17,460,605 (GRCm39)	missense	probably damaging	1.00
R8187:Smpd4	UTSW	16	17,446,999 (GRCm39)	missense	probably damaging	1.00
R8303:Smpd4	UTSW	16	17,457,195 (GRCm39)	missense	probably damaging	1.00
R8518:Smpd4	UTSW	16	17,458,884 (GRCm39)	missense	possibly damaging	0.89
R8735:Smpd4	UTSW	16	17,453,410 (GRCm39)	missense	possibly damaging	0.92
R9075:Smpd4	UTSW	16	17,457,849 (GRCm39)	missense	unknown
R9439:Smpd4	UTSW	16	17,459,451 (GRCm39)	missense	probably benign
Z1176:Smpd4	UTSW	16	17,437,450 (GRCm39)	intron	probably benign
Z1177:Smpd4	UTSW	16	17,439,305 (GRCm39)	critical splice acceptor site	probably benign

Predicted Primers

PCR Primer
(F):5'- TTGCCACGGCTCTTCAGAAG -3'
(R):5'- AGCAGTTATACTTAGAGCACCC -3'

Sequencing Primer
(F):5'- CAGAAGCCAGAGCAAATTTTCTG -3'
(R):5'- TTATACTTAGAGCACCCACTCAATAC -3'

Posted On

2019-05-13