Mutagenetix > Incidental Mutation

Incidental Mutation 'R8955:Enpp1'

681943

Institutional Source

Beutler Lab

Gene Symbol

Enpp1

Ensembl Gene

ENSMUSG00000037370

Gene Name

ectonucleotide pyrophosphatase/phosphodiesterase 1

Synonyms

PC-1, Npps, E-NPP1, Pca-1, twy, NPP1, 4833416E15Rik, Pdnp1, Pca, CD203c, Ly-41

MMRRC Submission

Accession Numbers

Essential gene?

Possibly non essential (E-score: 0.278) question?

Stock #

R8955 (G1)

Quality Score

225.009

Status

Not validated

Chromosome

Chromosomal Location

24637914-24712159 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

T to A at 24669028 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Isoleucine to Phenylalanine at position 318 (I318F)

Ref Sequence

ENSEMBL: ENSMUSP00000046090 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000039882] [ENSMUST00000105520] [ENSMUST00000135846]

AlphaFold

no structure available at present

Predicted Effect

probably benign
Transcript: ENSMUST00000039882
AA Change: I318F

PolyPhen 2 Score 0.014 (Sensitivity: 0.96; Specificity: 0.79)

SMART Domains

Protein: ENSMUSP00000046090
Gene: ENSMUSG00000037370
AA Change: I318F

Domain	Start	End	E-Value	Type
low complexity region	22	34	N/A	INTRINSIC
low complexity region	59	69	N/A	INTRINSIC
SO	86	126	2.17e-14	SMART
SO	127	170	1.51e-13	SMART
Pfam:Phosphodiest	194	358	1e-44	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000105520
AA Change: I318F

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

SMART Domains

Protein: ENSMUSP00000101159
Gene: ENSMUSG00000037370
AA Change: I318F

Domain	Start	End	E-Value	Type
low complexity region	22	34	N/A	INTRINSIC
transmembrane domain	57	79	N/A	INTRINSIC
SO	86	126	2.17e-14	SMART
SO	127	170	1.51e-13	SMART
Pfam:Phosphodiest	194	520	1.8e-87	PFAM
Endonuclease_NS	655	873	5.33e-15	SMART
NUC	656	887	3.62e-107	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000135846
AA Change: I318F

PolyPhen 2 Score 0.003 (Sensitivity: 0.98; Specificity: 0.44)

SMART Domains

Protein: ENSMUSP00000114273
Gene: ENSMUSG00000037370
AA Change: I318F

Domain	Start	End	E-Value	Type
low complexity region	22	34	N/A	INTRINSIC
transmembrane domain	57	79	N/A	INTRINSIC
SO	86	126	2.17e-14	SMART
SO	127	170	1.51e-13	SMART
Pfam:Phosphodiest	194	520	4.2e-91	PFAM
Endonuclease_NS	656	874	5.33e-15	SMART
NUC	657	888	3.62e-107	SMART

Coding Region Coverage

1x: 100.0%
3x: 99.9%
10x: 99.6%
20x: 98.7%

Validation Efficiency

MGI Phenotype

FUNCTION: This gene encodes a member of the nucleoside pyrophosphatase/phosphodiesterase family of enzymes that catalyzes the hydrolysis of pyrophosphate and phosphodiester bonds in nucleotide triphosphates and oligonucleotides, respectively, to generate nucleoside 5'-monophosphates. The encoded protein is a type II transmembrane glycoprotein that negatively regulates bone mineralization. Mice harboring a nonsense mutation in this gene, termed tiptoe walking (ttw), exhibit ectopic ossification of the spinal ligaments. The encoded protein binds to the insulin receptor, inhibits downstream signaling events and induces insulin resistance and glucose tolerance. This gene is located adjacent to a paralog on chromosome 10. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Apr 2015]
PHENOTYPE: Mice homozygous for a null allele develop hyperostosis leading to ossific intervertebral fusion, peripheral joint ankylosis and tendon calcification, and display spontaneous arterial and articular cartilage calcification, and altered adipocyte maturation. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 87 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Adcy8	C	T	15: 64,704,705	V1003I	possibly damaging	Het
Adgra3	T	A	5: 49,961,389	Y939F	probably benign	Het
Adra2b	T	C	2: 127,363,584	V2A	probably benign	Het
Aga	T	A	8: 53,521,129	Y296N	possibly damaging	Het
Apc	A	G	18: 34,268,317	Q52R	probably damaging	Het
Arfgef1	A	T	1: 10,199,837	S362R	probably benign	Het
Arhgef7	C	T	8: 11,758,451		probably benign	Het
Bmp5	A	T	9: 75,898,553	M446L	probably damaging	Het
Carmil3	C	T	14: 55,496,077	T350I	probably damaging	Het
Cd44	T	A	2: 102,853,018	T224S	probably damaging	Het
Cep112	A	T	11: 108,752,434	I7F	possibly damaging	Het
Chrna2	G	A	14: 66,142,232	A7T	probably benign	Het
Cldn16	G	A	16: 26,482,520	V193I	probably benign	Het
Clec4a3	G	A	6: 122,966,520	E100K	possibly damaging	Het
Cntln	C	T	4: 85,067,873	T1026I	possibly damaging	Het
Cyp4v3	T	A	8: 45,308,527	I420F	probably benign	Het
Dcbld2	G	A	16: 58,450,762	A301T		Het
Dnah1	A	T	14: 31,285,993	D2152E	probably benign	Het
Dpy19l4	A	G	4: 11,290,195	V179A	probably benign	Het
Dusp4	T	A	8: 34,817,308	I259N	probably damaging	Het
Entpd6	T	C	2: 150,753,085	V15A	possibly damaging	Het
Epb41l1	C	G	2: 156,522,003	Q811E	probably benign	Het
Epb41l5	T	C	1: 119,642,562	H32R	probably damaging	Het
Fam135b	C	T	15: 71,462,214	V1044I	possibly damaging	Het
Fat4	A	T	3: 38,983,629	H3810L	probably benign	Het
Fbxw28	T	A	9: 109,338,789		probably null	Het
Flnb	T	G	14: 7,892,874	V648G	probably damaging	Het
Flnb	T	A	14: 7,904,688	Y1030*	probably null	Het
Fndc3a	T	C	14: 72,556,970	T787A	probably benign	Het
Gli2	T	A	1: 118,855,457	H106L	probably damaging	Het
Gm10283	T	A	8: 60,501,356		probably null	Het
Gm3336	C	T	8: 70,721,896	R67*	probably null	Het
Gsr	T	G	8: 33,693,908	I399M	possibly damaging	Het
Gtf2ird2	T	A	5: 134,216,754	M618K	probably damaging	Het
Gtf3c3	T	A	1: 54,423,563	D347V	probably benign	Het
H2afy2	A	T	10: 61,757,831	I22N	probably damaging	Het
Hspa12a	T	C	19: 58,799,626	Y588C	probably damaging	Het
Il20ra	A	G	10: 19,759,412	E467G	possibly damaging	Het
Inf2	A	G	12: 112,610,564	I991V	unknown	Het
Irx6	T	C	8: 92,678,412	C303R	probably damaging	Het
Kcnmb4	T	A	10: 116,473,476	K16*	probably null	Het
Kirrel3	T	C	9: 34,944,442	L86P	probably damaging	Het
Lipo5	A	C	19: 33,473,130	F21V		Het
Lrmp	A	T	6: 145,171,664	M376L	probably benign	Het
Lrrc31	T	A	3: 30,679,118	R482S	probably benign	Het
Lrrc3b	C	T	14: 15,358,159	C149Y	probably damaging	Het
Lrrk1	A	G	7: 66,269,825	M446T	probably benign	Het
Mettl14	C	T	3: 123,374,044	D222N	probably benign	Het
Mfsd4b3	G	A	10: 39,948,076	H63Y	probably benign	Het
Myo16	T	C	8: 10,376,175	W311R	probably damaging	Het
Nccrp1	A	T	7: 28,546,203	N151K	probably benign	Het
Obsl1	T	C	1: 75,503,849	D377G	probably damaging	Het
Olfr1356	G	T	10: 78,847,742	P58T	probably damaging	Het
Olfr1447	T	A	19: 12,901,214	T189S	probably benign	Het
Olfr371	T	A	8: 85,231,284	I263N	probably benign	Het
Olfr508	T	A	7: 108,630,299	C102*	probably null	Het
Pigb	T	C	9: 73,038,701	N63S	probably damaging	Het
Plch2	T	C	4: 154,992,566	E577G	probably benign	Het
Prkab2	T	C	3: 97,666,627	V194A	probably benign	Het
Psd3	T	C	8: 67,963,809	I479V	probably benign	Het
Ralgapb	C	A	2: 158,437,344	P117T	probably benign	Het
Ralgapb	C	G	2: 158,495,469	T1116R	probably damaging	Het
Rpap2	T	A	5: 107,620,495	S400T	possibly damaging	Het
Rpgrip1l	C	A	8: 91,280,828	W378L	possibly damaging	Het
Rps20	T	A	4: 3,834,617	M82L	probably benign	Het
Rps5	T	C	7: 12,925,513	M77T	possibly damaging	Het
Scaf11	A	G	15: 96,420,490	S398P	probably damaging	Het
Sdf2	T	A	11: 78,254,937	D153E	probably benign	Het
Selplg	GTCTGCCTCCATGGGTGCTGGCTGCGAGGTCTCTGCCTCCATGGGTGCTGGCTGCGAGGTCTCTGCCTCCATGGGTGCTGGCTGCGAGGTCTCTGCCTCCATGGGTGCTGGCTGCGAGGTCTCT	GTCTGCCTCCATGGGTGCTGGCTGCGAGGTCTCTGCCTCCATGGGTGCTGGCTGCGAGGTCTCTGCCTCCATGGGTGCTGGCTGCGAGGTCTCT	5: 113,819,695		probably benign	Het
Slc12a9	T	C	5: 137,331,008	N128S	probably damaging	Het
Slc25a32	C	A	15: 39,097,551	G246C	probably damaging	Het
Slc38a4	C	T	15: 97,016,781	A64T	probably benign	Het
Slit3	T	C	11: 35,698,380	V1254A	probably damaging	Het
Slx4	T	C	16: 3,990,247	K481R	probably benign	Het
Tcea1	A	G	1: 4,889,509	T136A	probably benign	Het
Thra	A	G	11: 98,753,623	D13G	possibly damaging	Het
Tmed9	G	A	13: 55,596,962	S227N	probably benign	Het
Trim80	C	A	11: 115,440,712	T20K	probably benign	Het
Trmt61a	G	T	12: 111,682,822	V276L	probably benign	Het
Trpc4ap	T	C	2: 155,666,251	D160G	possibly damaging	Het
Ubr5	C	T	15: 38,029,581	E467K		Het
Vars2	C	A	17: 35,661,649	G26W	probably damaging	Het
Vmn1r226	G	T	17: 20,688,025	R173L	possibly damaging	Het
Vmn1r29	G	T	6: 58,307,299	M1I	probably null	Het
Vmn2r3	G	T	3: 64,261,382	P578Q	possibly damaging	Het
Vmn2r57	A	T	7: 41,400,147	I726N	possibly damaging	Het
Zfp39	A	T	11: 58,890,120	Y605*	probably null	Het

Other mutations in Enpp1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00392:Enpp1	APN	10	24645427	missense	possibly damaging	0.93
IGL00966:Enpp1	APN	10	24654031	missense	probably damaging	1.00
IGL01364:Enpp1	APN	10	24664614	missense	probably damaging	1.00
IGL02040:Enpp1	APN	10	24655856	missense	probably damaging	1.00
IGL02143:Enpp1	APN	10	24677974	missense	probably damaging	1.00
IGL02631:Enpp1	APN	10	24641961	missense	probably damaging	1.00
IGL02655:Enpp1	APN	10	24677974	missense	probably damaging	1.00
IGL02677:Enpp1	APN	10	24679185	splice site	probably benign
IGL02691:Enpp1	APN	10	24711892	missense	probably damaging	0.99
IGL02966:Enpp1	APN	10	24660274	missense	probably damaging	1.00
IGL03087:Enpp1	APN	10	24655881	splice site	probably benign
IGL03330:Enpp1	APN	10	24664906	splice site	probably benign
IGL03365:Enpp1	APN	10	24669025	missense	probably damaging	1.00
IGL03377:Enpp1	APN	10	24660283	critical splice acceptor site	probably null
PIT4651001:Enpp1	UTSW	10	24653950	missense	probably benign	0.16
R0011:Enpp1	UTSW	10	24670002	nonsense	probably null
R0201:Enpp1	UTSW	10	24653917	missense	probably benign	0.00
R0496:Enpp1	UTSW	10	24672052	missense	probably benign	0.18
R1228:Enpp1	UTSW	10	24645412	missense	probably benign	0.30
R1536:Enpp1	UTSW	10	24641834	missense	probably benign	0.27
R1927:Enpp1	UTSW	10	24654888	missense	possibly damaging	0.65
R2051:Enpp1	UTSW	10	24711804	critical splice donor site	probably null
R2057:Enpp1	UTSW	10	24660192	missense	probably damaging	0.98
R2353:Enpp1	UTSW	10	24651341	missense	probably benign	0.24
R4077:Enpp1	UTSW	10	24669007	critical splice donor site	probably null
R4079:Enpp1	UTSW	10	24669007	critical splice donor site	probably null
R4739:Enpp1	UTSW	10	24679248	missense	probably null	0.99
R4740:Enpp1	UTSW	10	24679248	missense	probably null	0.99
R4761:Enpp1	UTSW	10	24641951	missense	possibly damaging	0.94
R4822:Enpp1	UTSW	10	24661935	missense	possibly damaging	0.74
R4919:Enpp1	UTSW	10	24648085	missense	probably benign	0.01
R5140:Enpp1	UTSW	10	24652852	missense	possibly damaging	0.51
R5302:Enpp1	UTSW	10	24651390	missense	probably benign
R5421:Enpp1	UTSW	10	24669757	missense	probably damaging	1.00
R5695:Enpp1	UTSW	10	24654908	missense	probably damaging	0.99
R5735:Enpp1	UTSW	10	24654919	missense	possibly damaging	0.92
R5789:Enpp1	UTSW	10	24647239	missense	probably benign
R5942:Enpp1	UTSW	10	24676068	nonsense	probably null
R6048:Enpp1	UTSW	10	24660254	missense	probably damaging	1.00
R6053:Enpp1	UTSW	10	24657126	missense	possibly damaging	0.93
R6305:Enpp1	UTSW	10	24641882	missense	probably damaging	1.00
R6319:Enpp1	UTSW	10	24648031	missense	probably damaging	1.00
R6624:Enpp1	UTSW	10	24669755	nonsense	probably null
R6793:Enpp1	UTSW	10	24655825	missense	probably damaging	1.00
R6936:Enpp1	UTSW	10	24651339	missense	probably benign	0.30
R7255:Enpp1	UTSW	10	24645315	missense	possibly damaging	0.95
R7285:Enpp1	UTSW	10	24660161	missense	probably benign	0.01
R7401:Enpp1	UTSW	10	24645282	missense	probably damaging	1.00
R7429:Enpp1	UTSW	10	24711950	missense	probably benign	0.00
R7430:Enpp1	UTSW	10	24711950	missense	probably benign	0.00
R7526:Enpp1	UTSW	10	24674410	splice site	probably null
R7532:Enpp1	UTSW	10	24675987	missense	probably benign	0.29
R7789:Enpp1	UTSW	10	24654083	splice site	probably null
R8073:Enpp1	UTSW	10	24679244	missense	possibly damaging	0.50
R8283:Enpp1	UTSW	10	24674656	missense	probably benign	0.25
R9494:Enpp1	UTSW	10	24651336	missense	probably benign
Z1177:Enpp1	UTSW	10	24661942	missense	probably damaging	0.96

Predicted Primers

PCR Primer
(F):5'- TTCAGCACCATCTAAGACTCTG -3'
(R):5'- TACCTCATATACAGGGTTATTGTAGCC -3'

Sequencing Primer
(F):5'- TCAGCACCATCTAAGACTCTGTAAAG -3'
(R):5'- TCCTGTCACTGAAGATGAATGCG -3'

Posted On

2021-08-31