Mutagenetix > Incidental Mutation

Incidental Mutation 'R1722:Nedd4l'

191582

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

039754-MU

Accession Numbers

Essential gene?

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

Stock #

R1722 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

64887705-65217831 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

T to A at 65157939 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Valine to Glutamic Acid at position 203 (V203E)

Ref Sequence

ENSEMBL: ENSMUSP00000132838 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000080418] [ENSMUST00000163516] [ENSMUST00000224347] [ENSMUST00000224385] [ENSMUST00000225057] [ENSMUST00000225261] [ENSMUST00000226058]

AlphaFold

no structure available at present

Predicted Effect

probably damaging
Transcript: ENSMUST00000080418
AA Change: V82E

PolyPhen 2 Score 0.984 (Sensitivity: 0.74; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000079280
Gene: ENSMUSG00000024589
AA Change: V82E

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 damaging
Transcript: ENSMUST00000163516
AA Change: V203E

PolyPhen 2 Score 0.995 (Sensitivity: 0.68; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000132838
Gene: ENSMUSG00000024589
AA Change: V203E

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: V82E

PolyPhen 2 Score 0.143 (Sensitivity: 0.92; Specificity: 0.86)

Predicted Effect

probably benign
Transcript: ENSMUST00000224385

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000224663

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000224890

Predicted Effect

probably benign
Transcript: ENSMUST00000225057

Predicted Effect

probably damaging
Transcript: ENSMUST00000225261
AA Change: V82E

PolyPhen 2 Score 0.988 (Sensitivity: 0.73; Specificity: 0.96)

Predicted Effect

probably damaging
Transcript: ENSMUST00000226058
AA Change: V82E

PolyPhen 2 Score 0.984 (Sensitivity: 0.74; Specificity: 0.96)

Coding Region Coverage

1x: 99.2%
3x: 98.5%
10x: 96.9%
20x: 94.3%

Validation Efficiency

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: 60 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
4931422A03Rik	A	T	2: 103,993,928		probably null	Het
Adssl1	A	T	12: 112,636,481	I346F	possibly damaging	Het
Ahnak	T	A	19: 9,010,655	L3101H	probably damaging	Het
Aldh3b3	A	G	19: 3,964,871	I123V	possibly damaging	Het
Angptl1	C	T	1: 156,857,085	P275S	possibly damaging	Het
Apoa5	C	T	9: 46,270,549	Q308*	probably null	Het
Arhgef12	T	C	9: 43,020,717	*106W	probably null	Het
Atp2c1	A	G	9: 105,439,400	Y485H	probably benign	Het
Atp6v1b1	C	T	6: 83,743,092	T3I	possibly damaging	Het
Btbd7	A	T	12: 102,812,654	I451N	possibly damaging	Het
Clasp1	T	G	1: 118,590,464	L1080R	probably damaging	Het
Clec4f	A	G	6: 83,646,933	V408A	probably benign	Het
Clint1	T	A	11: 45,906,406	M438K	possibly damaging	Het
Cuzd1	A	T	7: 131,311,644	Y415N	probably damaging	Het
Ddias	A	G	7: 92,860,042	F222L	possibly damaging	Het
Efcab7	A	T	4: 99,900,618	T321S	probably benign	Het
Elp3	A	T	14: 65,551,397	D393E	probably benign	Het
Fbn2	T	C	18: 58,048,052		probably null	Het
Fcgr3	T	C	1: 171,054,119	R146G	possibly damaging	Het
Fkrp	G	A	7: 16,810,794	A381V	probably benign	Het
Gatad2b	T	G	3: 90,355,679	I476S	probably damaging	Het
Gm1527	C	T	3: 28,921,634	H557Y	probably benign	Het
Gm2431	A	T	7: 142,257,862	C102S	unknown	Het
Hoxd13	A	G	2: 74,670,045	N310S	probably benign	Het
Il9	T	A	13: 56,479,395	T135S	probably benign	Het
Ints4	A	C	7: 97,513,579	N476T	probably benign	Het
Kcnq4	A	C	4: 120,702,427	D525E	probably benign	Het
Kncn	A	T	4: 115,885,899	Y57F	probably damaging	Het
Lpl	TGG	TG	8: 68,896,602		probably null	Het
Lrrfip2	A	G	9: 111,199,761	T351A	probably damaging	Het
Madd	T	C	2: 91,167,637	E682G	probably benign	Het
March7	A	C	2: 60,234,182	R267S	probably damaging	Het
Mmp16	T	A	4: 18,051,767	L252Q	probably damaging	Het
Mri1	A	T	8: 84,253,925	V296D	possibly damaging	Het
Myo3a	A	G	2: 22,399,827	T665A	probably benign	Het
N4bp2	T	C	5: 65,806,882	V758A	probably benign	Het
Nbea	T	C	3: 55,665,695	D2489G	probably damaging	Het
Neb	T	C	2: 52,256,745	T2836A	probably damaging	Het
Nkpd1	C	A	7: 19,523,921	Q392K	possibly damaging	Het
Nploc4	G	T	11: 120,382,569	A576E	probably benign	Het
Nxph1	T	A	6: 9,247,516	N162K	probably damaging	Het
Olfr1356	T	A	10: 78,846,971	T315S	probably benign	Het
Olfr410	T	C	11: 74,334,445	Y262C	probably damaging	Het
Pabpc2	T	G	18: 39,775,116	I478S	probably benign	Het
Pde7b	G	T	10: 20,436,244	H190Q	probably damaging	Het
Plekha2	A	T	8: 25,042,960	S332T	probably benign	Het
Rapgef6	TG	TGG	11: 54,546,397		probably null	Het
Rasl11a	A	T	5: 146,845,242	H9L	probably benign	Het
Rer1	A	T	4: 155,075,001	F177I	probably damaging	Het
Rinl	T	C	7: 28,792,244	L74P	probably damaging	Het
Rsf1	CG	CGACGGCGGTG	7: 97,579,908		probably benign	Het
Rttn	T	C	18: 88,973,531	V78A	probably benign	Het
Skint5	A	T	4: 113,846,311		probably null	Het
Tenm2	A	C	11: 36,008,103	Y2743D	probably damaging	Het
Tmem101	T	C	11: 102,154,693	Y110C	probably damaging	Het
Trim9	T	C	12: 70,248,374	N658S	probably benign	Het
Ucp1	A	T	8: 83,290,688	T36S	probably benign	Het
Vmn2r43	A	G	7: 8,255,068	I382T	probably damaging	Het
Zfp142	C	T	1: 74,569,776	R1620Q	probably damaging	Het
Zfp386	T	C	12: 116,059,906	S380P	probably damaging	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
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
R8557:Nedd4l	UTSW	18	65203915	missense	probably benign	0.00
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'- GGCTTGCTTGTCAGCACACATACTC -3'
(R):5'- CCAAACTTGTCCTGGAACTGCCAC -3'

Sequencing Primer
(F):5'- tggagaggaactctagctcag -3'
(R):5'- TGGAACTGCCACCCATTG -3'

Posted On

2014-05-14