Incidental Mutation 'R7068:Nedd4l'
ID 548717
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 045164-MU
Accession Numbers
Essential gene? Probably non essential (E-score: 0.196) question?
Stock # R7068 (G1)
Quality Score 225.009
Status Not validated
Chromosome 18
Chromosomal Location 65020776-65350899 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to T at 65338722 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Arginine to Serine at position 695 (R695S)
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 damaging
Transcript: ENSMUST00000080418
AA Change: R695S

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000079280
Gene: ENSMUSG00000024589
AA Change: R695S

DomainStartEndE-ValueType
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: R816S

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000132838
Gene: ENSMUSG00000024589
AA Change: R816S

DomainStartEndE-ValueType
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 damaging
Transcript: ENSMUST00000224347
AA Change: R675S

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
Predicted Effect probably damaging
Transcript: ENSMUST00000226058
AA Change: R695S

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
Coding Region Coverage
  • 1x: 100.0%
  • 3x: 99.9%
  • 10x: 99.6%
  • 20x: 98.9%
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: 57 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Acsm1 A G 7: 119,221,803 (GRCm39) H24R probably benign Het
Ago2 A T 15: 73,018,299 (GRCm39) F46L probably damaging Het
Amd1 A G 10: 40,166,508 (GRCm39) F123L probably benign Het
Arhgef10 T C 8: 15,008,639 (GRCm39) F546L probably damaging Het
Asic2 G A 11: 81,043,081 (GRCm39) H71Y probably benign Het
Asphd1 A G 7: 126,547,850 (GRCm39) V151A probably benign Het
Best3 T C 10: 116,824,543 (GRCm39) V3A probably damaging Het
C4b A G 17: 34,952,451 (GRCm39) L1196P probably damaging Het
Cd22 A G 7: 30,577,504 (GRCm39) V3A probably benign Het
Cdkl3 T C 11: 51,902,154 (GRCm39) probably null Het
Clcnka A T 4: 141,114,421 (GRCm39) V631E probably damaging Het
Cmya5 A G 13: 93,229,205 (GRCm39) V1961A possibly damaging Het
Dnah14 A G 1: 181,597,355 (GRCm39) E3559G probably benign Het
Emsy A T 7: 98,259,968 (GRCm39) D39E probably benign Het
Fbxl16 G T 17: 26,038,485 (GRCm39) V477F possibly damaging Het
Flt1 A T 5: 147,610,444 (GRCm39) I393N probably damaging Het
Gabra4 A T 5: 71,729,402 (GRCm39) N433K probably benign Het
Gatad1 T C 5: 3,693,540 (GRCm39) R210G probably benign Het
Ghsr T A 3: 27,425,986 (GRCm39) V14D probably benign Het
Glb1l A G 1: 75,179,381 (GRCm39) Y183H probably damaging Het
Hycc1 A G 5: 24,169,793 (GRCm39) S519P possibly damaging Het
Ighv3-4 T C 12: 114,217,274 (GRCm39) T106A probably damaging Het
Ik T G 18: 36,888,518 (GRCm39) F439V possibly damaging Het
Itih5 T C 2: 10,254,115 (GRCm39) S789P probably damaging Het
Kcnj8 T C 6: 142,511,965 (GRCm39) D214G probably damaging Het
Kdm5a C A 6: 120,407,176 (GRCm39) H1464N probably benign Het
Klb A T 5: 65,536,683 (GRCm39) Y671F probably damaging Het
Kremen2 C A 17: 23,960,859 (GRCm39) R421L possibly damaging Het
Mroh9 T A 1: 162,866,750 (GRCm39) D662V probably damaging Het
Mtmr12 T G 15: 12,257,756 (GRCm39) M278R probably null Het
Ndufa8 T C 2: 35,934,447 (GRCm39) M44V possibly damaging Het
Nuf2 G A 1: 169,349,988 (GRCm39) P97S probably damaging Het
Or14c46 A C 7: 85,918,745 (GRCm39) L84R probably damaging Het
Or2ah1 T C 2: 85,653,396 (GRCm39) V27A probably benign Het
Or5ac24 T C 16: 59,165,567 (GRCm39) T166A possibly damaging Het
P4ha2 A G 11: 54,001,820 (GRCm39) T33A probably benign Het
Parp1 A G 1: 180,416,233 (GRCm39) H544R probably damaging Het
Plec A G 15: 76,061,969 (GRCm39) L2678P probably damaging Het
Rad1 T A 15: 10,490,379 (GRCm39) Y85* probably null Het
Sema6d A G 2: 124,499,741 (GRCm39) I309V probably benign Het
Skint2 T C 4: 112,481,548 (GRCm39) V137A probably damaging Het
Slc23a3 T C 1: 75,109,877 (GRCm39) N130S probably benign Het
Slc35f1 T C 10: 52,938,596 (GRCm39) F176S probably damaging Het
Slc44a2 T A 9: 21,232,144 (GRCm39) Y10N probably benign Het
Smarcc1 A G 9: 110,014,952 (GRCm39) T506A probably damaging Het
Smchd1 A T 17: 71,694,087 (GRCm39) S1219R probably benign Het
Smco1 A G 16: 32,092,929 (GRCm39) N200S probably benign Het
Srcap A G 7: 127,141,115 (GRCm39) T1571A probably benign Het
Strip2 C T 6: 29,932,207 (GRCm39) T459I probably benign Het
Tarbp1 C T 8: 127,153,773 (GRCm39) A1560T probably damaging Het
Tcl1b1 T A 12: 105,125,952 (GRCm39) probably benign Het
Tdrd5 T C 1: 156,111,841 (GRCm39) E436G probably damaging Het
Trim31 T A 17: 37,209,408 (GRCm39) C55S probably damaging Het
Tsr1 G T 11: 74,794,745 (GRCm39) E467* probably null Het
Tulp4 T A 17: 6,235,564 (GRCm39) D178E probably damaging Het
Vmn1r30 A G 6: 58,411,995 (GRCm39) V279A possibly damaging Het
Vmn2r98 A G 17: 19,285,575 (GRCm39) R132G probably benign Het
Other mutations in Nedd4l
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00501:Nedd4l APN 18 65,341,163 (GRCm39) missense probably damaging 1.00
IGL00931:Nedd4l APN 18 65,305,470 (GRCm39) missense possibly damaging 0.57
IGL02306:Nedd4l APN 18 65,306,025 (GRCm39) missense possibly damaging 0.64
IGL02363:Nedd4l APN 18 65,341,116 (GRCm39) splice site probably benign
IGL02440:Nedd4l APN 18 65,296,244 (GRCm39) critical splice donor site probably null
IGL02444:Nedd4l APN 18 65,337,028 (GRCm39) splice site probably benign
IGL02700:Nedd4l APN 18 65,342,751 (GRCm39) missense probably damaging 1.00
IGL02943:Nedd4l APN 18 65,294,723 (GRCm39) critical splice donor site probably null
IGL02999:Nedd4l APN 18 65,331,778 (GRCm39) missense probably damaging 1.00
IGL03135:Nedd4l APN 18 65,338,741 (GRCm39) missense probably damaging 1.00
IGL03373:Nedd4l APN 18 65,314,391 (GRCm39) splice site probably benign
R0036:Nedd4l UTSW 18 65,184,194 (GRCm39) intron probably benign
R0396:Nedd4l UTSW 18 65,294,725 (GRCm39) splice site probably benign
R0472:Nedd4l UTSW 18 65,341,532 (GRCm39) missense probably damaging 1.00
R0494:Nedd4l UTSW 18 65,306,092 (GRCm39) missense possibly damaging 0.69
R0513:Nedd4l UTSW 18 65,328,256 (GRCm39) splice site probably benign
R0609:Nedd4l UTSW 18 65,341,532 (GRCm39) missense probably damaging 1.00
R0631:Nedd4l UTSW 18 65,341,574 (GRCm39) splice site probably benign
R1077:Nedd4l UTSW 18 65,300,570 (GRCm39) splice site probably benign
R1643:Nedd4l UTSW 18 65,331,712 (GRCm39) missense probably damaging 1.00
R1722:Nedd4l UTSW 18 65,291,010 (GRCm39) missense probably damaging 1.00
R1806:Nedd4l UTSW 18 65,345,862 (GRCm39) missense probably damaging 1.00
R1921:Nedd4l UTSW 18 65,300,646 (GRCm39) critical splice donor site probably null
R1986:Nedd4l UTSW 18 65,276,874 (GRCm39) missense probably damaging 1.00
R2070:Nedd4l UTSW 18 65,345,891 (GRCm39) missense probably damaging 1.00
R2151:Nedd4l UTSW 18 65,343,401 (GRCm39) missense probably damaging 1.00
R2152:Nedd4l UTSW 18 65,343,401 (GRCm39) missense probably damaging 1.00
R2154:Nedd4l UTSW 18 65,343,401 (GRCm39) missense probably damaging 1.00
R2358:Nedd4l UTSW 18 65,342,790 (GRCm39) missense possibly damaging 0.51
R2680:Nedd4l UTSW 18 65,296,201 (GRCm39) missense possibly damaging 0.85
R3082:Nedd4l UTSW 18 65,312,049 (GRCm39) missense probably benign 0.00
R3500:Nedd4l UTSW 18 65,345,931 (GRCm39) missense probably damaging 1.00
R3711:Nedd4l UTSW 18 65,342,790 (GRCm39) missense possibly damaging 0.51
R3712:Nedd4l UTSW 18 65,342,790 (GRCm39) missense possibly damaging 0.51
R3874:Nedd4l UTSW 18 65,300,606 (GRCm39) missense probably benign
R4435:Nedd4l UTSW 18 65,345,896 (GRCm39) missense possibly damaging 0.84
R4698:Nedd4l UTSW 18 65,336,951 (GRCm39) missense probably damaging 1.00
R4757:Nedd4l UTSW 18 65,298,676 (GRCm39) missense probably damaging 0.98
R4783:Nedd4l UTSW 18 65,305,998 (GRCm39) missense probably damaging 0.99
R4790:Nedd4l UTSW 18 65,337,016 (GRCm39) missense possibly damaging 0.94
R4980:Nedd4l UTSW 18 65,213,131 (GRCm39) nonsense probably null
R5106:Nedd4l UTSW 18 65,326,376 (GRCm39) missense probably damaging 1.00
R5122:Nedd4l UTSW 18 65,324,518 (GRCm39) missense probably damaging 1.00
R5605:Nedd4l UTSW 18 65,307,315 (GRCm39) critical splice donor site probably null
R6465:Nedd4l UTSW 18 65,288,335 (GRCm39) missense probably benign 0.06
R6479:Nedd4l UTSW 18 65,342,752 (GRCm39) missense probably damaging 1.00
R6622:Nedd4l UTSW 18 65,307,305 (GRCm39) missense probably damaging 0.99
R6773:Nedd4l UTSW 18 65,300,622 (GRCm39) missense probably benign 0.36
R7065:Nedd4l UTSW 18 65,329,040 (GRCm39) missense probably benign 0.04
R7193:Nedd4l UTSW 18 65,130,441 (GRCm39) missense probably damaging 1.00
R7496:Nedd4l UTSW 18 65,213,089 (GRCm39) missense possibly damaging 0.94
R7903:Nedd4l UTSW 18 65,319,438 (GRCm39) missense probably damaging 1.00
R8123:Nedd4l UTSW 18 65,207,845 (GRCm39) missense probably damaging 1.00
R8185:Nedd4l UTSW 18 65,342,769 (GRCm39) missense probably damaging 1.00
R8282:Nedd4l UTSW 18 65,324,560 (GRCm39) missense probably damaging 0.98
R8440:Nedd4l UTSW 18 65,022,126 (GRCm39) splice site probably null
R8499:Nedd4l UTSW 18 65,342,728 (GRCm39) missense probably damaging 0.98
R8557:Nedd4l UTSW 18 65,336,986 (GRCm39) missense probably benign 0.00
R8801:Nedd4l UTSW 18 65,288,346 (GRCm39) missense probably damaging 1.00
R8896:Nedd4l UTSW 18 65,298,688 (GRCm39) missense probably benign
R9025:Nedd4l UTSW 18 65,311,995 (GRCm39) missense probably damaging 0.98
R9040:Nedd4l UTSW 18 65,342,734 (GRCm39) missense probably damaging 0.99
R9482:Nedd4l UTSW 18 65,021,031 (GRCm39) unclassified probably benign
R9498:Nedd4l UTSW 18 65,294,723 (GRCm39) critical splice donor site probably null
R9599:Nedd4l UTSW 18 65,343,400 (GRCm39) missense probably damaging 1.00
RF013:Nedd4l UTSW 18 65,342,751 (GRCm39) missense probably damaging 1.00
Predicted Primers PCR Primer
(F):5'- AGGAATGCAGGGCTTCACAG -3'
(R):5'- ATACAGGTGGGAAGCCAGTC -3'

Sequencing Primer
(F):5'- AGGGCTTCACAGTGGGC -3'
(R):5'- TATAATCCTAGCCCCAGGAGGCTG -3'
Posted On 2019-05-13