Mutagenetix > Incidental Mutation

Incidental Mutation 'R4998:Mmel1'

389629

Institutional Source

Beutler Lab

Gene Symbol

Mmel1

Ensembl Gene

ENSMUSG00000058183

Gene Name

membrane metallo-endopeptidase-like 1

Synonyms

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

MMRRC Submission

042592-MU

Accession Numbers

Essential gene?

Probably non essential (E-score: 0.151) question?

Stock #

R4998 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

154954042-154979985 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 154969967 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Lysine to Arginine at position 177 (K177R)

Ref Sequence

ENSEMBL: ENSMUSP00000101259 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000079269] [ENSMUST00000080559] [ENSMUST00000105634] [ENSMUST00000105635] [ENSMUST00000131758] [ENSMUST00000163732]

AlphaFold

no structure available at present

Predicted Effect

probably benign
Transcript: ENSMUST00000079269
AA Change: K200R

PolyPhen 2 Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)

SMART Domains

Protein: ENSMUSP00000078252
Gene: ENSMUSG00000058183
AA Change: K200R

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 benign
Transcript: ENSMUST00000080559
AA Change: K177R

PolyPhen 2 Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)

SMART Domains

Protein: ENSMUSP00000079399
Gene: ENSMUSG00000058183
AA Change: K177R

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 benign
Transcript: ENSMUST00000105634
AA Change: K177R

PolyPhen 2 Score 0.002 (Sensitivity: 0.99; Specificity: 0.30)

SMART Domains

Protein: ENSMUSP00000101259
Gene: ENSMUSG00000058183
AA Change: K177R

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 benign
Transcript: ENSMUST00000105635
AA Change: K177R

PolyPhen 2 Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)

SMART Domains

Protein: ENSMUSP00000101260
Gene: ENSMUSG00000058183
AA Change: K177R

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

probably benign
Transcript: ENSMUST00000131758
AA Change: K109R

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)

SMART Domains

Protein: ENSMUSP00000121243
Gene: ENSMUSG00000058183
AA Change: K109R

Domain	Start	End	E-Value	Type
Pfam:Peptidase_M13_N	8	150	2.8e-47	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000163732
AA Change: K200R

PolyPhen 2 Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)

SMART Domains

Protein: ENSMUSP00000131753
Gene: ENSMUSG00000058183
AA Change: K200R

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

0.0898

Coding Region Coverage

1x: 99.1%
3x: 98.4%
10x: 96.6%
20x: 93.3%

Validation Efficiency

97% (91/94)

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: 86 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
2310022A10Rik	T	C	7: 27,271,088 (GRCm39)	V135A	probably damaging	Het
Ankrd42	T	C	7: 92,273,282 (GRCm39)	N115S	possibly damaging	Het
Baz1a	T	C	12: 55,021,922 (GRCm39)	E120G	probably damaging	Het
Calcrl	A	T	2: 84,169,658 (GRCm39)	V341E	probably damaging	Het
Card6	T	C	15: 5,129,564 (GRCm39)	R611G	probably benign	Het
Cd70	A	T	17: 57,453,311 (GRCm39)	S118T	probably damaging	Het
Chil5	T	A	3: 105,927,248 (GRCm39)	I188F	probably damaging	Het
Clca4b	C	T	3: 144,621,269 (GRCm39)	V602I	probably benign	Het
Cldn10	G	A	14: 119,025,725 (GRCm39)	G53S	possibly damaging	Het
Col6a4	A	G	9: 105,867,977 (GRCm39)		probably benign	Het
Cox8b	T	C	7: 140,479,001 (GRCm39)	E38G	probably damaging	Het
Cx3cl1	C	G	8: 95,507,053 (GRCm39)	L353V	probably damaging	Het
Cyp2a4	G	T	7: 26,006,786 (GRCm39)	Q48H	probably damaging	Het
Defb8	T	C	8: 19,497,603 (GRCm39)	I3V	probably benign	Het
Dip2a	A	T	10: 76,155,390 (GRCm39)	L65*	probably null	Het
Dnaaf4	A	G	9: 72,867,960 (GRCm39)	T74A	possibly damaging	Het
Dsg2	A	T	18: 20,734,578 (GRCm39)	D852V	probably benign	Het
Edar	T	C	10: 58,441,915 (GRCm39)	R326G	probably damaging	Het
Egfr	A	G	11: 16,831,493 (GRCm39)	E554G	possibly damaging	Het
Eif2b3	A	C	4: 116,923,589 (GRCm39)	K268T	probably benign	Het
Enox1	A	T	14: 77,738,875 (GRCm39)		probably benign	Het
Enpp3	C	A	10: 24,683,436 (GRCm39)	M260I	probably benign	Het
Espn	A	T	4: 152,220,040 (GRCm39)	M361K	possibly damaging	Het
Fam107a	T	C	14: 8,299,514 (GRCm38)	N108S	possibly damaging	Het
Fbn2	A	T	18: 58,205,703 (GRCm39)	V1125D	probably damaging	Het
Fbxo30	T	A	10: 11,166,507 (GRCm39)	S410T	probably damaging	Het
Fchsd1	C	T	18: 38,092,926 (GRCm39)		probably benign	Het
Fcsk	G	A	8: 111,614,435 (GRCm39)	A618V	probably damaging	Het
Gm10715	T	G	9: 3,038,073 (GRCm39)		probably benign	Het
Gm10722	A	C	9: 3,001,041 (GRCm39)	Y39S	probably benign	Het
Gm17416	C	A	2: 152,411,427 (GRCm39)	P57Q	probably damaging	Het
Gm27013	A	T	6: 130,653,501 (GRCm39)	C654S	probably damaging	Het
Gon4l	G	T	3: 88,807,305 (GRCm39)	E1666D	probably damaging	Het
Gypa	T	A	8: 81,222,964 (GRCm39)	S23T	unknown	Het
Gys1	C	A	7: 45,100,968 (GRCm39)		probably benign	Het
Hdac10	T	A	15: 89,008,143 (GRCm39)	Q569L	possibly damaging	Het
Icos	A	G	1: 61,032,941 (GRCm39)	T47A	possibly damaging	Het
Igfn1	T	A	1: 135,882,404 (GRCm39)	I2814F	probably damaging	Het
Kif27	A	G	13: 58,440,957 (GRCm39)	S1153P	probably damaging	Het
Lin28a	A	C	4: 133,746,028 (GRCm39)	F9V	possibly damaging	Het
Lrriq3	T	A	3: 154,893,695 (GRCm39)	N465K	probably benign	Het
Lsm14a	T	C	7: 34,074,799 (GRCm39)	E47G	probably damaging	Het
Ncstn	T	A	1: 171,899,087 (GRCm39)	N348I	possibly damaging	Het
Ninl	A	G	2: 150,795,284 (GRCm39)	I619T	probably damaging	Het
Npb	T	C	11: 120,499,401 (GRCm39)	Y23H	probably damaging	Het
Npepps	A	G	11: 97,096,933 (GRCm39)		probably benign	Het
Or8k30	T	C	2: 86,339,699 (GRCm39)	Y299H	probably benign	Het
Otop1	G	A	5: 38,451,892 (GRCm39)		probably null	Het
Pcdha1	T	C	18: 37,065,469 (GRCm39)	L711P	probably damaging	Het
Pcyt1a	A	G	16: 32,270,660 (GRCm39)		probably benign	Het
Pdpr	G	T	8: 111,841,400 (GRCm39)	V211F	probably damaging	Het
Pip4k2b	T	C	11: 97,613,261 (GRCm39)	N245S	possibly damaging	Het
Platr26	G	A	2: 71,561,214 (GRCm39)		noncoding transcript	Het
Plek	A	G	11: 16,933,194 (GRCm39)		probably null	Het
Potefam3c	G	C	8: 69,906,010 (GRCm39)	N13K	probably benign	Het
Prdm15	A	T	16: 97,595,689 (GRCm39)	D1046E	probably damaging	Het
Prr29	T	G	11: 106,267,779 (GRCm39)	C175G	probably benign	Het
Ptpru	A	G	4: 131,504,196 (GRCm39)	V1097A	probably damaging	Het
Ramp2	T	A	11: 101,138,247 (GRCm39)		probably benign	Het
Rap1gap	A	G	4: 137,455,595 (GRCm39)	D381G	possibly damaging	Het
Rbbp6	T	A	7: 122,589,549 (GRCm39)	D412E	probably benign	Het
Rgs4	C	T	1: 169,572,802 (GRCm39)	V45I	probably benign	Het
Ryr2	C	T	13: 11,658,781 (GRCm39)	R3614Q	probably damaging	Het
Shc3	G	A	13: 51,596,856 (GRCm39)		probably null	Het
Shmt2	A	T	10: 127,354,139 (GRCm39)	C412S	probably damaging	Het
Slc25a45	A	T	19: 5,934,945 (GRCm39)	N265Y	probably damaging	Het
Slc4a10	G	C	2: 62,074,783 (GRCm39)	E316Q	probably benign	Het
Slc5a8	T	C	10: 88,743,919 (GRCm39)		probably null	Het
Snx31	A	G	15: 36,539,513 (GRCm39)	V121A	probably damaging	Het
Socs3	T	C	11: 117,858,542 (GRCm39)	E172G	probably damaging	Het
Tg	A	G	15: 66,545,899 (GRCm39)	D207G	probably damaging	Het
Them4	G	T	3: 94,237,088 (GRCm39)	V183F	probably damaging	Het
Tkt	G	A	14: 30,287,499 (GRCm39)	W136*	probably null	Het
Tlcd3b	C	T	7: 126,426,795 (GRCm39)	R73C	probably damaging	Het
Tmc3	C	A	7: 83,271,529 (GRCm39)	R894S	probably benign	Het
Tmem132a	G	T	19: 10,836,305 (GRCm39)	P742T	probably benign	Het
Tmem202	A	G	9: 59,432,129 (GRCm39)	L66P	probably damaging	Het
Trbc1	G	A	6: 41,516,270 (GRCm39)		probably benign	Het
Trhr2	A	G	8: 123,085,511 (GRCm39)	F158L	probably benign	Het
Ttc13	A	T	8: 125,406,795 (GRCm39)	N595K	probably damaging	Het
Ucp1	A	G	8: 84,024,484 (GRCm39)		probably null	Het
Zbtb4	C	T	11: 69,669,497 (GRCm39)	T740I	probably benign	Het
Zfp69	A	T	4: 120,804,522 (GRCm39)	D116E	possibly damaging	Het
Zfp879	A	G	11: 50,728,796 (GRCm39)	L66S	probably damaging	Het
Zfp955b	T	A	17: 33,524,125 (GRCm39)		probably benign	Het
Zfyve1	T	C	12: 83,594,839 (GRCm39)	I718V	possibly damaging	Het

Other mutations in Mmel1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00971:Mmel1	APN	4	154,972,289 (GRCm39)	splice site	probably benign
IGL01560:Mmel1	APN	4	154,976,967 (GRCm39)	missense	probably null	1.00
IGL01734:Mmel1	APN	4	154,976,408 (GRCm39)	missense	probably benign	0.00
IGL02933:Mmel1	APN	4	154,968,087 (GRCm39)	missense	probably damaging	1.00
IGL03178:Mmel1	APN	4	154,975,311 (GRCm39)	missense	possibly damaging	0.75
R1161:Mmel1	UTSW	4	154,979,671 (GRCm39)	missense	probably damaging	1.00
R1522:Mmel1	UTSW	4	154,979,443 (GRCm39)	missense	probably damaging	1.00
R1566:Mmel1	UTSW	4	154,968,110 (GRCm39)	missense	probably damaging	1.00
R1885:Mmel1	UTSW	4	154,975,333 (GRCm39)	missense	possibly damaging	0.76
R2177:Mmel1	UTSW	4	154,978,560 (GRCm39)	missense	probably damaging	1.00
R3413:Mmel1	UTSW	4	154,974,043 (GRCm39)	missense	probably damaging	1.00
R3432:Mmel1	UTSW	4	154,969,955 (GRCm39)	splice site	probably benign
R3870:Mmel1	UTSW	4	154,968,095 (GRCm39)	missense	probably benign	0.01
R4197:Mmel1	UTSW	4	154,977,761 (GRCm39)	missense	probably damaging	1.00
R4822:Mmel1	UTSW	4	154,972,354 (GRCm39)	missense	probably benign	0.00
R5135:Mmel1	UTSW	4	154,966,781 (GRCm39)	missense	probably benign	0.20
R5225:Mmel1	UTSW	4	154,976,456 (GRCm39)	missense	probably damaging	0.96
R5821:Mmel1	UTSW	4	154,970,044 (GRCm39)	missense	possibly damaging	0.82
R6131:Mmel1	UTSW	4	154,979,475 (GRCm39)	missense	probably damaging	1.00
R6132:Mmel1	UTSW	4	154,979,475 (GRCm39)	missense	probably damaging	1.00
R6133:Mmel1	UTSW	4	154,979,475 (GRCm39)	missense	probably damaging	1.00
R6194:Mmel1	UTSW	4	154,967,673 (GRCm39)	nonsense	probably null
R6223:Mmel1	UTSW	4	154,956,159 (GRCm39)	splice site	probably null
R6786:Mmel1	UTSW	4	154,976,885 (GRCm39)	nonsense	probably null
R6921:Mmel1	UTSW	4	154,966,134 (GRCm39)	missense	probably damaging	0.97
R7272:Mmel1	UTSW	4	154,978,547 (GRCm39)	missense	probably damaging	1.00
R7373:Mmel1	UTSW	4	154,973,665 (GRCm39)	missense	not run
R7685:Mmel1	UTSW	4	154,956,111 (GRCm39)	start codon destroyed	probably null	0.28
R7996:Mmel1	UTSW	4	154,976,912 (GRCm39)	missense	probably benign	0.03
R8683:Mmel1	UTSW	4	154,973,985 (GRCm39)	missense	probably benign	0.13
R8856:Mmel1	UTSW	4	154,969,478 (GRCm39)	missense	possibly damaging	0.84
R8924:Mmel1	UTSW	4	154,974,091 (GRCm39)	missense	probably damaging	1.00
R9364:Mmel1	UTSW	4	154,976,967 (GRCm39)	missense	probably null	1.00
R9594:Mmel1	UTSW	4	154,978,592 (GRCm39)	missense	probably benign	0.15
R9683:Mmel1	UTSW	4	154,977,285 (GRCm39)	missense	probably damaging	1.00
X0025:Mmel1	UTSW	4	154,979,142 (GRCm39)	missense	probably benign	0.06
Z1176:Mmel1	UTSW	4	154,979,665 (GRCm39)	nonsense	probably null
Z1177:Mmel1	UTSW	4	154,978,531 (GRCm39)	critical splice acceptor site	probably null

Predicted Primers

PCR Primer
(F):5'- ACCTATCTCCCTACGGAATACTTG -3'
(R):5'- AGCCATCGTCCTGGTCTATC -3'

Sequencing Primer
(F):5'- CGGAATACTTGGAGAATAGTCCCTC -3'
(R):5'- TTTGCTGCCAAAGTCCAGAG -3'

Posted On

2016-06-06