Mutagenetix > Incidental Mutation

Incidental Mutation 'R8557:Nedd4l'

660194

Institutional Source

Beutler Lab

Gene Symbol

Nedd4l

Ensembl Gene

ENSMUSG00000024589

Gene Name

neural precursor cell expressed, developmentally down-regulated gene 4-like

Synonyms

Nedd4-2, Nedd4b, 1300012C07Rik

MMRRC Submission

Accession Numbers

Essential gene?

Probably non essential (E-score: 0.201) question?

Stock #

R8557 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

64887705-65217831 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

A to T at 65203915 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Methionine to Leucine at position 678 (M678L)

Ref Sequence

ENSEMBL: ENSMUSP00000153526 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000080418] [ENSMUST00000163516] [ENSMUST00000224347] [ENSMUST00000226058]

AlphaFold

no structure available at present

Predicted Effect

probably benign
Transcript: ENSMUST00000080418
AA Change: M678L

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

SMART Domains

Protein: ENSMUSP00000079280
Gene: ENSMUSG00000024589
AA Change: M678L

Domain	Start	End	E-Value	Type
PDB:3M7F\|B	1	64	2e-21	PDB
WW	73	105	2.32e-13	SMART
low complexity region	139	154	N/A	INTRINSIC
low complexity region	166	178	N/A	INTRINSIC
low complexity region	234	247	N/A	INTRINSIC
WW	266	298	2.08e-15	SMART
low complexity region	355	371	N/A	INTRINSIC
WW	378	410	4.1e-14	SMART
WW	429	461	1.53e-13	SMART
HECTc	518	854	3.04e-183	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000163516
AA Change: M799L

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

SMART Domains

Protein: ENSMUSP00000132838
Gene: ENSMUSG00000024589
AA Change: M799L

Domain	Start	End	E-Value	Type
C2	21	124	1.76e-25	SMART
WW	194	226	2.32e-13	SMART
low complexity region	260	275	N/A	INTRINSIC
low complexity region	287	299	N/A	INTRINSIC
low complexity region	355	368	N/A	INTRINSIC
WW	387	419	2.08e-15	SMART
low complexity region	476	492	N/A	INTRINSIC
WW	499	531	4.1e-14	SMART
WW	550	582	1.53e-13	SMART
HECTc	639	975	3.04e-183	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000224347
AA Change: M658L

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

Predicted Effect

probably benign
Transcript: ENSMUST00000226058
AA Change: M678L

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

Meta Mutation Damage Score

0.0569

Coding Region Coverage

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

Validation Efficiency

100% (60/60)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a member of the Nedd4 family of HECT domain E3 ubiquitin ligases. HECT domain E3 ubiquitin ligases transfer ubiquitin from E2 ubiquitin-conjugating enzymes to protein substrates, thus targeting specific proteins for lysosomal degradation. The encoded protein mediates the ubiquitination of multiple target substrates and plays a critical role in epithelial sodium transport by regulating the cell surface expression of the epithelial sodium channel, ENaC. Single nucleotide polymorphisms in this gene may be associated with essential hypertension. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Mar 2012]
PHENOTYPE: Mice homozygous for a null mutation display salt sensitive hypertension and high salt diet induced cardiac hypertrophy. A spontaneous mutation results in overt diabetes insipidus. Mice homozygous for a knock-out allele exhibit neonatal lethality with primary atelectasis. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 61 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
0610040J01Rik	T	C	5: 63,898,611	V230A	probably benign	Het
Ablim2	A	T	5: 35,828,139	H260L	probably damaging	Het
Acp4	C	T	7: 44,255,848		probably null	Het
Acvr2b	G	T	9: 119,432,588	V416L	probably damaging	Het
Adipoq	A	T	16: 23,146,680		probably benign	Het
Amhr2	A	G	15: 102,454,412	Q538R	probably benign	Het
Apoh	C	T	11: 108,409,236	T237I	probably damaging	Het
Aspm	C	T	1: 139,456,756	T97I	probably benign	Het
Atg16l2	A	T	7: 101,290,656	H499Q	probably benign	Het
Bicdl2	G	A	17: 23,667,562	R375H	probably benign	Het
C3	T	C	17: 57,224,383	T304A	probably benign	Het
Cast	A	T	13: 74,704,182	D647E	probably damaging	Het
Chrm2	T	C	6: 36,524,075	V289A	probably benign	Het
Clock	T	C	5: 76,229,370	D694G	probably damaging	Het
Cyp4a31	C	T	4: 115,570,241	R215C	possibly damaging	Het
Dctn2	T	C	10: 127,278,193	L334P	probably damaging	Het
Dnah11	A	G	12: 117,878,512	I4444T	probably benign	Het
Egf	C	A	3: 129,754,951	R5L	unknown	Het
Ercc1	A	G	7: 19,348,555	N11S	probably benign	Het
Eri3	T	C	4: 117,615,323	S113P	possibly damaging	Het
Fam159a	T	A	4: 108,367,888	N159I	probably benign	Het
Fasn	A	G	11: 120,815,784	V958A	probably benign	Het
Fgf10	A	G	13: 118,781,596	K140R	probably benign	Het
Gfra2	G	A	14: 70,977,297	M163I	probably benign	Het
Gm14403	T	C	2: 177,509,561	I191T	probably damaging	Het
Hdlbp	T	A	1: 93,413,497	E977D	probably damaging	Het
Hectd4	A	G	5: 121,310,651	N354S	possibly damaging	Het
Hpgds	A	T	6: 65,120,015	I170N	probably benign	Het
Limk2	A	G	11: 3,346,379	V356A	possibly damaging	Het
Map4	A	G	9: 110,064,302		probably null	Het
Mettl13	C	T	1: 162,544,352	G316D	possibly damaging	Het
Mia2	T	A	12: 59,101,488	L45I	probably damaging	Het
Mier1	T	A	4: 103,139,346		probably null	Het
Mob3a	G	T	10: 80,691,174	R106S	probably benign	Het
Mug2	T	A	6: 122,063,701	F737I	probably damaging	Het
Myo7a	C	T	7: 98,053,874	A2053T	probably benign	Het
Myrip	A	G	9: 120,417,186	S127G	probably benign	Het
Naaladl2	T	A	3: 24,208,364	K395I	probably benign	Het
Nefh	A	T	11: 4,941,233	I462N	probably damaging	Het
Nfe2	A	G	15: 103,248,598	M322T	probably benign	Het
Ogfr	GGCCAGAGGACCCCAAAAGCCAGGTGGAGCCAGAGGACCCCAAAAGCCAGGTGGAGCCAGAGGACCCCAAAAGCCAGGTGGAGCCAGAGGACCCCAAAAGCCAGGTGGGGCCAGAGGACCCCCAAAGCCAGGTGG	GGCCAGAGGACCCCAAAAGCCAGGTGGAGCCAGAGGACCCCAAAAGCCAGGTGGAGCCAGAGGACCCCAAAAGCCAGGTGGGGCCAGAGGACCCCCAAAGCCAGGTGG	2: 180,595,266		probably benign	Het
Olfr30	T	A	11: 58,455,736	D71V	probably damaging	Het
Olfr657	T	A	7: 104,635,896	V74E	possibly damaging	Het
Pkdcc	A	G	17: 83,221,066	N288S	probably benign	Het
Sacs	G	A	14: 61,207,276	C2257Y	probably damaging	Het
Sec23a	G	T	12: 59,005,270	Q90K	probably damaging	Het
Slc30a6	A	G	17: 74,405,690	T61A	possibly damaging	Het
Slc39a11	C	A	11: 113,250,559	A234S	probably damaging	Het
Smg6	C	A	11: 75,156,238	N1252K	probably damaging	Het
Spata2	A	T	2: 167,484,307	D197E	probably damaging	Het
Spen	C	T	4: 141,470,370	A3396T	probably benign	Het
Spocd1	T	C	4: 129,948,968	F59L	probably damaging	Het
Tectb	T	A	19: 55,192,673		probably benign	Het
Tnnc1	G	A	14: 31,210,605	V82I	probably damaging	Het
Traf7	A	T	17: 24,510,041	V513D	probably damaging	Het
Vmn2r111	A	T	17: 22,571,929	Y129*	probably null	Het
Vrtn	T	A	12: 84,649,916	F480Y	probably benign	Het
Vwa8	A	T	14: 79,009,209	I664F	probably damaging	Het
Vwde	A	T	6: 13,193,137	V401E	probably damaging	Het
Zcchc11	T	A	4: 108,542,711		probably null	Het
Zfp655	A	T	5: 145,244,025	N231I	probably benign	Het

Other mutations in Nedd4l

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00501:Nedd4l	APN	18	65208092	missense	probably damaging	1.00
IGL00931:Nedd4l	APN	18	65172399	missense	possibly damaging	0.57
IGL02306:Nedd4l	APN	18	65172954	missense	possibly damaging	0.64
IGL02363:Nedd4l	APN	18	65208045	splice site	probably benign
IGL02440:Nedd4l	APN	18	65163173	critical splice donor site	probably null
IGL02444:Nedd4l	APN	18	65203957	splice site	probably benign
IGL02700:Nedd4l	APN	18	65209680	missense	probably damaging	1.00
IGL02943:Nedd4l	APN	18	65161652	critical splice donor site	probably null
IGL02999:Nedd4l	APN	18	65198707	missense	probably damaging	1.00
IGL03135:Nedd4l	APN	18	65205670	missense	probably damaging	1.00
IGL03373:Nedd4l	APN	18	65181320	splice site	probably benign
R0036:Nedd4l	UTSW	18	65051123	intron	probably benign
R0396:Nedd4l	UTSW	18	65161654	splice site	probably benign
R0472:Nedd4l	UTSW	18	65208461	missense	probably damaging	1.00
R0494:Nedd4l	UTSW	18	65173021	missense	possibly damaging	0.69
R0513:Nedd4l	UTSW	18	65195185	splice site	probably benign
R0609:Nedd4l	UTSW	18	65208461	missense	probably damaging	1.00
R0631:Nedd4l	UTSW	18	65208503	splice site	probably benign
R1077:Nedd4l	UTSW	18	65167499	splice site	probably benign
R1643:Nedd4l	UTSW	18	65198641	missense	probably damaging	1.00
R1722:Nedd4l	UTSW	18	65157939	missense	probably damaging	1.00
R1806:Nedd4l	UTSW	18	65212791	missense	probably damaging	1.00
R1921:Nedd4l	UTSW	18	65167575	critical splice donor site	probably null
R1986:Nedd4l	UTSW	18	65143803	missense	probably damaging	1.00
R2070:Nedd4l	UTSW	18	65212820	missense	probably damaging	1.00
R2151:Nedd4l	UTSW	18	65210330	missense	probably damaging	1.00
R2152:Nedd4l	UTSW	18	65210330	missense	probably damaging	1.00
R2154:Nedd4l	UTSW	18	65210330	missense	probably damaging	1.00
R2358:Nedd4l	UTSW	18	65209719	missense	possibly damaging	0.51
R2680:Nedd4l	UTSW	18	65163130	missense	possibly damaging	0.85
R3082:Nedd4l	UTSW	18	65178978	missense	probably benign	0.00
R3500:Nedd4l	UTSW	18	65212860	missense	probably damaging	1.00
R3711:Nedd4l	UTSW	18	65209719	missense	possibly damaging	0.51
R3712:Nedd4l	UTSW	18	65209719	missense	possibly damaging	0.51
R3874:Nedd4l	UTSW	18	65167535	missense	probably benign
R4435:Nedd4l	UTSW	18	65212825	missense	possibly damaging	0.84
R4698:Nedd4l	UTSW	18	65203880	missense	probably damaging	1.00
R4757:Nedd4l	UTSW	18	65165605	missense	probably damaging	0.98
R4783:Nedd4l	UTSW	18	65172927	missense	probably damaging	0.99
R4790:Nedd4l	UTSW	18	65203945	missense	possibly damaging	0.94
R4980:Nedd4l	UTSW	18	65080060	nonsense	probably null
R5106:Nedd4l	UTSW	18	65193305	missense	probably damaging	1.00
R5122:Nedd4l	UTSW	18	65191447	missense	probably damaging	1.00
R5605:Nedd4l	UTSW	18	65174244	critical splice donor site	probably null
R6465:Nedd4l	UTSW	18	65155264	missense	probably benign	0.06
R6479:Nedd4l	UTSW	18	65209681	missense	probably damaging	1.00
R6622:Nedd4l	UTSW	18	65174234	missense	probably damaging	0.99
R6773:Nedd4l	UTSW	18	65167551	missense	probably benign	0.36
R7065:Nedd4l	UTSW	18	65195969	missense	probably benign	0.04
R7068:Nedd4l	UTSW	18	65205651	missense	probably damaging	1.00
R7193:Nedd4l	UTSW	18	64997370	missense	probably damaging	1.00
R7496:Nedd4l	UTSW	18	65080018	missense	possibly damaging	0.94
R7903:Nedd4l	UTSW	18	65186367	missense	probably damaging	1.00
R8123:Nedd4l	UTSW	18	65074774	missense	probably damaging	1.00
R8185:Nedd4l	UTSW	18	65209698	missense	probably damaging	1.00
R8282:Nedd4l	UTSW	18	65191489	missense	probably damaging	0.98
R8440:Nedd4l	UTSW	18	64889055	splice site	probably null
R8499:Nedd4l	UTSW	18	65209657	missense	probably damaging	0.98
R8801:Nedd4l	UTSW	18	65155275	missense	probably damaging	1.00
R8896:Nedd4l	UTSW	18	65165617	missense	probably benign
R9025:Nedd4l	UTSW	18	65178924	missense	probably damaging	0.98
R9040:Nedd4l	UTSW	18	65209663	missense	probably damaging	0.99
R9482:Nedd4l	UTSW	18	64887960	unclassified	probably benign
R9498:Nedd4l	UTSW	18	65161652	critical splice donor site	probably null
R9599:Nedd4l	UTSW	18	65210329	missense	probably damaging	1.00
RF013:Nedd4l	UTSW	18	65209680	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- AGAGCCCATTGCCGGAAAATG -3'
(R):5'- CACATTCTCAGTATGCACAAGC -3'

Sequencing Primer
(F):5'- CCCATTGCCGGAAAATGTTTTTG -3'
(R):5'- AGATGGCTCAATTGCTCAAGTGC -3'

Posted On

2021-01-18