Mutagenetix > Incidental Mutations

Incidental Mutation 'R6131:Mmel1'

487123

Institutional Source

Beutler Lab

Gene Symbol

Mmel1

Ensembl Gene

ENSMUSG00000058183

Gene Name

membrane metallo-endopeptidase-like 1

Synonyms

Nep2, Mell1, Nl1, NEPLP gamma, NEPLP beta, NEPLP alpha, SEP

MMRRC Submission

044278-MU

Accession Numbers

Is this an essential gene?

Probably non essential (E-score: 0.192) question?

Stock #

R6131 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

154869585-154895528 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

C to T at 154895018 bp

Zygosity

Heterozygous

Amino Acid Change

Histidine to Tyrosine at position 728 (H728Y)

Ref Sequence

ENSEMBL: ENSMUSP00000131753 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000030935] [ENSMUST00000079269] [ENSMUST00000080559] [ENSMUST00000105634] [ENSMUST00000105635] [ENSMUST00000132281] [ENSMUST00000163732]

Predicted Effect

probably benign
Transcript: ENSMUST00000030935

SMART Domains

Protein: ENSMUSP00000030935
Gene: ENSMUSG00000029059

Domain	Start	End	E-Value	Type
Pfam:AhpC-TSA_2	53	166	9.9e-25	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000079269
AA Change: H728Y

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

SMART Domains

Protein: ENSMUSP00000078252
Gene: ENSMUSG00000058183
AA Change: H728Y

Domain	Start	End	E-Value	Type
transmembrane domain	20	42	N/A	INTRINSIC
Pfam:Peptidase_M13_N	99	498	1.7e-135	PFAM
Pfam:Peptidase_M13	559	767	1.2e-68	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000080559
AA Change: H742Y

PolyPhen 2 Score 0.974 (Sensitivity: 0.76; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000079399
Gene: ENSMUSG00000058183
AA Change: H742Y

Domain	Start	End	E-Value	Type
transmembrane domain	20	42	N/A	INTRINSIC
Pfam:Peptidase_M13_N	76	512	4.8e-131	PFAM
Pfam:Peptidase_M13	573	779	3.4e-71	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000105634
AA Change: H742Y

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

SMART Domains

Protein: ENSMUSP00000101259
Gene: ENSMUSG00000058183
AA Change: H742Y

Domain	Start	End	E-Value	Type
transmembrane domain	20	42	N/A	INTRINSIC
Pfam:Peptidase_M13_N	76	512	1.4e-105	PFAM
Pfam:Peptidase_M13	573	781	4e-74	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000105635
AA Change: H705Y

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

SMART Domains

Protein: ENSMUSP00000101260
Gene: ENSMUSG00000058183
AA Change: H705Y

Domain	Start	End	E-Value	Type
transmembrane domain	20	42	N/A	INTRINSIC
Pfam:Peptidase_M13_N	76	475	1.6e-135	PFAM
Pfam:Peptidase_M13	536	744	1.2e-68	PFAM

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000123513

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000129623

Predicted Effect

probably benign
Transcript: ENSMUST00000132281

SMART Domains

Protein: ENSMUSP00000116611
Gene: ENSMUSG00000029059

Domain	Start	End	E-Value	Type
Pfam:AhpC-TSA_2	9	114	4.2e-25	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000163732
AA Change: H728Y

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

SMART Domains

Protein: ENSMUSP00000131753
Gene: ENSMUSG00000058183
AA Change: H728Y

Domain	Start	End	E-Value	Type
transmembrane domain	20	42	N/A	INTRINSIC
Pfam:Peptidase_M13_N	99	498	1.7e-135	PFAM
Pfam:Peptidase_M13	559	765	3.3e-71	PFAM

Meta Mutation Damage Score

0.7652

Coding Region Coverage

1x: 99.9%
3x: 99.7%
10x: 98.5%
20x: 95.8%

Validation Efficiency

96% (50/52)

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 member of the neutral endopeptidase (NEP) or membrane metallo-endopeptidase (MME) family. Family members play important roles in pain perception, arterial pressure regulation, phosphate metabolism and homeostasis. This protein is a type II transmembrane protein and is thought to be expressed as a secreted protein. This gene is expressed mainly in testis with weak expression in the brain, kidney, and heart. [provided by RefSeq, Jul 2008]
PHENOTYPE: Homozygous null mice display impaired male fertility. Female fertility is not affected. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 51 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
5031439G07Rik	A	T	15: 84,960,592	W75R	probably damaging	Het
Abca15	T	C	7: 120,340,205	V274A	probably benign	Het
Afg3l2	G	T	18: 67,421,259	L458M	probably damaging	Het
Ap1m2	T	C	9: 21,296,501	Y396C	probably damaging	Het
Apob	T	C	12: 8,015,874	S405P	probably benign	Het
Arhgap26	G	T	18: 39,286,585	G533*	probably null	Het
Atxn2l	T	C	7: 126,503,165		probably benign	Het
Ccdc88c	A	T	12: 100,941,128	L995H	probably damaging	Het
Cep192	A	G	18: 67,837,997	H1023R	possibly damaging	Het
Cog5	T	A	12: 31,886,221	M589K	possibly damaging	Het
Col25a1	C	A	3: 130,535,465	P337Q	probably damaging	Het
Cyfip1	T	G	7: 55,873,480	V51G	possibly damaging	Het
Dnah7b	A	T	1: 46,253,466	I3004F	probably damaging	Het
Dsg3	A	T	18: 20,538,512	D758V	probably damaging	Het
Dsg3	A	G	18: 20,520,477		probably null	Het
Eml5	A	T	12: 98,861,251	H573Q	probably damaging	Het
Erp27	T	C	6: 136,908,203	D199G	probably damaging	Het
Flnb	A	G	14: 7,894,635	Y811C	possibly damaging	Het
G6pd2	A	T	5: 61,809,250	S123C	probably benign	Het
Gm17677	T	A	9: 35,741,544	C27*	probably null	Het
Gm1818	T	A	12: 48,555,536		noncoding transcript	Het
Gm29340	C	T	2: 116,968,038		noncoding transcript	Het
Gm8298	A	G	3: 59,868,903	K165R	possibly damaging	Het
Hcn2	G	T	10: 79,733,908	G581W	probably damaging	Het
Hist1h2bf	C	A	13: 23,574,136		probably benign	Het
Kidins220	T	C	12: 24,992,314		probably null	Het
Lonp1	T	C	17: 56,614,457	E926G	probably benign	Het
Lrp1	T	C	10: 127,560,157	I2415V	probably benign	Het
Mmp10	A	G	9: 7,503,632		probably null	Het
Myo16	T	A	8: 10,569,877	I1476N	probably benign	Het
Nectin3	G	T	16: 46,395,152	H76N	probably damaging	Het
Nov	A	G	15: 54,749,360	D255G	probably benign	Het
Nphs2	G	A	1: 156,325,951	R204Q	probably damaging	Het
Olfr194	T	C	16: 59,119,893	Y59C	probably damaging	Het
Olfr883	ATTGCTGTTT	ATTGCTGTTTGCTGTTT	9: 38,026,540		probably null	Het
Olfr920	T	A	9: 38,756,066	I126N	probably damaging	Het
Otx1	A	T	11: 21,999,406	L24H	probably damaging	Het
Psme2b	T	C	11: 48,945,925	D65G	probably damaging	Het
Rlf	T	C	4: 121,154,975	K214E	probably damaging	Het
Rnasel	A	T	1: 153,754,460	T241S	probably damaging	Het
Samd9l	C	G	6: 3,377,252	G3A	probably benign	Het
Smg7	A	G	1: 152,845,211		probably null	Het
Spag16	A	G	1: 70,725,083		probably null	Het
Spata31d1c	T	A	13: 65,035,671	D342E	probably benign	Het
Stab2	A	G	10: 86,883,778		probably null	Het
Taar7b	A	T	10: 24,000,717	Y260F	probably benign	Het
Vcpip1	T	C	1: 9,747,292	I289V	probably damaging	Het
Vmn2r39	A	G	7: 9,014,964	V791A	probably damaging	Het
Vmn2r66	T	A	7: 84,995,016	I729F	probably damaging	Het
Vmn2r-ps130	C	T	17: 23,063,655	A103V	probably benign	Het
Zfp536	T	A	7: 37,569,712	D93V	probably damaging	Het

Other mutations in Mmel1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00971:Mmel1	APN	4	154887832	splice site	probably benign
IGL01560:Mmel1	APN	4	154892510	missense	probably null	1.00
IGL01734:Mmel1	APN	4	154891951	missense	probably benign	0.00
IGL02933:Mmel1	APN	4	154883630	missense	probably damaging	1.00
IGL03178:Mmel1	APN	4	154890854	missense	possibly damaging	0.75
R1161:Mmel1	UTSW	4	154895214	missense	probably damaging	1.00
R1522:Mmel1	UTSW	4	154894986	missense	probably damaging	1.00
R1566:Mmel1	UTSW	4	154883653	missense	probably damaging	1.00
R1885:Mmel1	UTSW	4	154890876	missense	possibly damaging	0.76
R2177:Mmel1	UTSW	4	154894103	missense	probably damaging	1.00
R3413:Mmel1	UTSW	4	154889586	missense	probably damaging	1.00
R3432:Mmel1	UTSW	4	154885498	splice site	probably benign
R3870:Mmel1	UTSW	4	154883638	missense	probably benign	0.01
R4197:Mmel1	UTSW	4	154893304	missense	probably damaging	1.00
R4822:Mmel1	UTSW	4	154887897	missense	probably benign	0.00
R4998:Mmel1	UTSW	4	154885510	missense	probably benign	0.00
R5135:Mmel1	UTSW	4	154882324	missense	probably benign	0.20
R5225:Mmel1	UTSW	4	154891999	missense	probably damaging	0.96
R5821:Mmel1	UTSW	4	154885587	missense	possibly damaging	0.82
R6132:Mmel1	UTSW	4	154895018	missense	probably damaging	1.00
R6133:Mmel1	UTSW	4	154895018	missense	probably damaging	1.00
R6194:Mmel1	UTSW	4	154883216	nonsense	probably null
R6223:Mmel1	UTSW	4	154871702	splice site	probably null
R6786:Mmel1	UTSW	4	154892428	nonsense	probably null
R6921:Mmel1	UTSW	4	154881677	missense	probably damaging	0.97
R7272:Mmel1	UTSW	4	154894090	missense	probably damaging	1.00
R7373:Mmel1	UTSW	4	154889208	missense	not run
R7685:Mmel1	UTSW	4	154871654	start codon destroyed	probably null	0.28
R7996:Mmel1	UTSW	4	154892455	missense	probably benign	0.03
X0025:Mmel1	UTSW	4	154894685	missense	probably benign	0.06
Z1176:Mmel1	UTSW	4	154895208	nonsense	probably null
Z1177:Mmel1	UTSW	4	154894074	critical splice acceptor site	probably null

Predicted Primers

PCR Primer
(F):5'- GACCTGTTGGCCTCCATATC -3'
(R):5'- ATAGCTCAGCCTTGGCTACCAG -3'

Sequencing Primer
(F):5'- CCTCATCTTACAAACAGCTGTTTAGG -3'
(R):5'- TTGGCTACCAGATGCGACATC -3'

Posted On

2017-10-10