Incidental Mutation 'R4884:Hecw2'
ID 375482
Institutional Source Beutler Lab
Gene Symbol Hecw2
Ensembl Gene ENSMUSG00000042807
Gene Name HECT, C2 and WW domain containing E3 ubiquitin protein ligase 2
Synonyms A730039N16Rik, Nedl2, D030049F17Rik
MMRRC Submission 041978-MU
Accession Numbers
Essential gene? Probably non essential (E-score: 0.180) question?
Stock # R4884 (G1)
Quality Score 225
Status Not validated
Chromosome 1
Chromosomal Location 53846031-54234193 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to A at 53990000 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Isoleucine to Phenylalanine at position 125 (I125F)
Ref Sequence ENSEMBL: ENSMUSP00000113283 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000087659] [ENSMUST00000097741] [ENSMUST00000120904]
AlphaFold Q6I6G8
Predicted Effect probably benign
Transcript: ENSMUST00000087659
AA Change: I125F

PolyPhen 2 Score 0.031 (Sensitivity: 0.95; Specificity: 0.82)
SMART Domains Protein: ENSMUSP00000084942
Gene: ENSMUSG00000042807
AA Change: I125F

DomainStartEndE-ValueType
Pfam:HECW_N 45 164 4.6e-62 PFAM
low complexity region 165 178 N/A INTRINSIC
C2 186 297 2.19e-12 SMART
low complexity region 577 596 N/A INTRINSIC
low complexity region 716 735 N/A INTRINSIC
low complexity region 746 755 N/A INTRINSIC
low complexity region 769 786 N/A INTRINSIC
WW 814 846 1.21e-11 SMART
coiled coil region 853 880 N/A INTRINSIC
low complexity region 913 925 N/A INTRINSIC
WW 992 1024 2.12e-7 SMART
Blast:HECTc 1111 1183 2e-23 BLAST
HECTc 1241 1578 8.02e-183 SMART
Predicted Effect probably benign
Transcript: ENSMUST00000097741
AA Change: I125F

PolyPhen 2 Score 0.031 (Sensitivity: 0.95; Specificity: 0.82)
SMART Domains Protein: ENSMUSP00000095348
Gene: ENSMUSG00000042807
AA Change: I125F

DomainStartEndE-ValueType
PDB:2LFE|A 42 162 1e-87 PDB
low complexity region 165 178 N/A INTRINSIC
C2 186 292 5.92e-9 SMART
Predicted Effect probably benign
Transcript: ENSMUST00000120904
AA Change: I125F

PolyPhen 2 Score 0.031 (Sensitivity: 0.95; Specificity: 0.82)
SMART Domains Protein: ENSMUSP00000113283
Gene: ENSMUSG00000042807
AA Change: I125F

DomainStartEndE-ValueType
PDB:2LFE|A 42 162 6e-80 PDB
low complexity region 165 178 N/A INTRINSIC
C2 186 297 2.19e-12 SMART
low complexity region 577 596 N/A INTRINSIC
low complexity region 716 735 N/A INTRINSIC
low complexity region 746 755 N/A INTRINSIC
low complexity region 769 786 N/A INTRINSIC
WW 814 846 1.21e-11 SMART
coiled coil region 853 880 N/A INTRINSIC
low complexity region 913 925 N/A INTRINSIC
WW 992 1024 2.12e-7 SMART
Blast:HECTc 1111 1183 2e-23 BLAST
HECTc 1241 1578 8.02e-183 SMART
Predicted Effect noncoding transcript
Transcript: ENSMUST00000146850
Coding Region Coverage
  • 1x: 99.1%
  • 3x: 98.4%
  • 10x: 96.7%
  • 20x: 93.5%
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 a family of E3 ubiquitin ligases which plays an important role in the proliferation, migration and differentiation of neural crest cells as a regulator of glial cell line-derived neurotrophic factor (GDNF)/Ret signaling. This gene also plays an important role in angiogenesis through stabilization of endothelial cell-to-cell junctions as a regulator of angiomotin-like 1 stability. The encoded protein contains an N-terminal calcium/lipid-binding (C2) domain involved in membrane targeting, two-four WW domains responsible for cellular localization and substrate recognition, and a C-terminal homologous with E6-associated protein C-terminus (HECT) catalytic domain. Naturally occurring mutations in this gene are associated with neurodevelopmental delay, hypotonia, and epilepsy. The decreased expression of this gene in the aganglionic colon is associated with Hirschsprung's disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2017]
Allele List at MGI
Other mutations in this stock
Total: 113 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
2700049A03Rik G T 12: 71,211,320 (GRCm39) E685* probably null Het
2700049A03Rik A T 12: 71,211,321 (GRCm39) E685V possibly damaging Het
Aadat C T 8: 60,979,663 (GRCm39) P175L probably damaging Het
Acot7 G T 4: 152,270,664 (GRCm39) probably benign Het
Adad1 T G 3: 37,130,813 (GRCm39) F259V possibly damaging Het
Adora2a A G 10: 75,161,879 (GRCm39) Y6C probably null Het
Ahnak A G 19: 8,990,118 (GRCm39) probably benign Het
Ankar A T 1: 72,737,966 (GRCm39) M72K probably damaging Het
Ankrd45 A G 1: 160,988,270 (GRCm39) K176R possibly damaging Het
Ap3m2 T C 8: 23,293,997 (GRCm39) K18E probably damaging Het
Apol10b C T 15: 77,473,006 (GRCm39) R16Q possibly damaging Het
Atp2b2 T A 6: 113,819,147 (GRCm39) T49S possibly damaging Het
B3gntl1 T G 11: 121,520,795 (GRCm39) Y206S possibly damaging Het
BC061237 G A 14: 44,738,666 (GRCm39) E22K possibly damaging Het
Bmp1 A G 14: 70,712,655 (GRCm39) V959A probably benign Het
Cep295 T C 9: 15,263,056 (GRCm39) E169G probably damaging Het
Cfap20dc G A 14: 8,578,394 (GRCm38) T116I probably damaging Het
Cfap65 T G 1: 74,942,283 (GRCm39) E1757A possibly damaging Het
Cgrrf1 T A 14: 47,090,912 (GRCm39) I216N possibly damaging Het
Clstn2 T A 9: 97,681,448 (GRCm39) D64V probably damaging Het
Col27a1 T A 4: 63,194,197 (GRCm39) D851E possibly damaging Het
Coq9 C T 8: 95,579,822 (GRCm39) P259L probably benign Het
Cps1 A G 1: 67,216,183 (GRCm39) N836S probably benign Het
Cracd A T 5: 76,996,682 (GRCm39) I47F probably damaging Het
Crebbp T C 16: 3,906,239 (GRCm39) K1588E probably damaging Het
Cspg4 T C 9: 56,805,353 (GRCm39) W2055R probably benign Het
Cyp3a44 A T 5: 145,714,792 (GRCm39) M453K probably damaging Het
Dhx36 T G 3: 62,391,681 (GRCm39) D555A probably damaging Het
Dock2 A T 11: 34,216,248 (GRCm39) Y1219N probably damaging Het
Dpy19l2 A T 9: 24,539,476 (GRCm39) C492* probably null Het
Dusp22 A G 13: 30,852,813 (GRCm39) N16S probably benign Het
Epha1 A G 6: 42,337,668 (GRCm39) M805T probably damaging Het
Espl1 C T 15: 102,232,505 (GRCm39) A2071V possibly damaging Het
Fbxo11 T A 17: 88,299,761 (GRCm39) D863V probably damaging Het
Fbxo7 T A 10: 85,865,014 (GRCm39) Y106N probably damaging Het
Fhip1a A C 3: 85,590,918 (GRCm39) C178G probably damaging Het
Fst A G 13: 114,590,920 (GRCm39) V282A probably damaging Het
Gfra3 T A 18: 34,844,304 (GRCm39) M79L probably benign Het
Glp1r T C 17: 31,155,240 (GRCm39) V409A probably damaging Het
Gm10799 T A 2: 103,898,552 (GRCm39) D51V probably damaging Het
Gm572 C A 4: 148,751,819 (GRCm39) T228N possibly damaging Het
Grip1 C T 10: 119,911,211 (GRCm39) T643M probably damaging Het
Hdgfl2 C T 17: 56,403,265 (GRCm39) R222C possibly damaging Het
Hipk1 A G 3: 103,651,338 (GRCm39) S1153P possibly damaging Het
Insm2 T C 12: 55,646,546 (GRCm39) S97P probably damaging Het
Iqca1 A G 1: 90,067,759 (GRCm39) V164A probably benign Het
Kcna6 T C 6: 126,715,689 (GRCm39) D400G probably benign Het
Kctd1 T C 18: 15,107,311 (GRCm39) Y122C probably damaging Het
Klk14 G A 7: 43,341,501 (GRCm39) C51Y probably damaging Het
Klra2 T C 6: 131,207,165 (GRCm39) Y148C probably damaging Het
Krtap31-1 G A 11: 99,799,310 (GRCm39) C171Y unknown Het
Ldlrap1 C T 4: 134,486,282 (GRCm39) R59Q probably benign Het
Ltb T C 17: 35,414,234 (GRCm39) I3T probably benign Het
Macf1 T C 4: 123,348,802 (GRCm39) I2477V probably benign Het
Mpdz A T 4: 81,279,713 (GRCm39) I39N probably damaging Het
Mtcl3 A T 10: 29,072,537 (GRCm39) N610Y probably damaging Het
Mycbp2 A G 14: 103,448,731 (GRCm39) I1776T probably damaging Het
Myof T A 19: 37,930,805 (GRCm39) E994V probably damaging Het
Myom3 A G 4: 135,510,366 (GRCm39) E553G possibly damaging Het
Mysm1 A T 4: 94,847,185 (GRCm39) C504S probably damaging Het
Nectin3 A T 16: 46,269,249 (GRCm39) H384Q probably benign Het
Net1 G A 13: 3,934,252 (GRCm39) R482* probably null Het
Nit1 T C 1: 171,171,263 (GRCm39) K193R probably null Het
Nlgn1 A G 3: 25,966,838 (GRCm39) V205A probably damaging Het
Nr3c2 A T 8: 77,635,438 (GRCm39) I180F possibly damaging Het
Nup50l A T 6: 96,141,793 (GRCm39) M417K probably damaging Het
Nup62 T A 7: 44,478,289 (GRCm39) S101R probably damaging Het
Or13c7 T C 4: 43,854,890 (GRCm39) S194P probably damaging Het
Or1l8 G T 2: 36,818,024 (GRCm39) T34K possibly damaging Het
Or4c3 A G 2: 89,851,987 (GRCm39) V141A probably benign Het
Or51b17 T A 7: 103,542,862 (GRCm39) I27F probably benign Het
Or56b2j T A 7: 104,353,068 (GRCm39) I98N probably damaging Het
Or5b111 A T 19: 13,291,034 (GRCm39) I205N probably benign Het
Or5b124 A T 19: 13,611,391 (GRCm39) K305N probably benign Het
Or5p80 A T 7: 108,229,819 (GRCm39) I207F probably damaging Het
Osbpl6 A T 2: 76,379,883 (GRCm39) I158F probably damaging Het
Pcbp4 A G 9: 106,339,301 (GRCm39) T103A probably benign Het
Pcdha2 T A 18: 37,073,953 (GRCm39) L528Q probably damaging Het
Pcdhga5 T C 18: 37,827,680 (GRCm39) S43P probably damaging Het
Pdgfra C A 5: 75,349,973 (GRCm39) N952K probably benign Het
Pla2r1 A G 2: 60,365,328 (GRCm39) S81P probably damaging Het
Rabggtb A T 3: 153,617,568 (GRCm39) D43E possibly damaging Het
Rexo5 T A 7: 119,424,774 (GRCm39) C43* probably null Het
Robo1 T A 16: 72,701,639 (GRCm39) D168E probably damaging Het
Saxo4 A T 19: 10,451,865 (GRCm39) *428R probably null Het
Scimp A G 11: 70,688,865 (GRCm39) M49T unknown Het
Sema3e T A 5: 14,275,579 (GRCm39) V228E probably damaging Het
Sema6d A G 2: 124,498,738 (GRCm39) probably null Het
Serpinb6d A T 13: 33,850,428 (GRCm39) D85V possibly damaging Het
Slc24a2 C T 4: 86,909,745 (GRCm39) V658I probably damaging Het
Snd1 T C 6: 28,526,911 (GRCm39) I198T possibly damaging Het
Snx33 C T 9: 56,833,464 (GRCm39) V202M probably damaging Het
Srcap A G 7: 127,121,189 (GRCm39) E174G probably damaging Het
Srgap2 C A 1: 131,220,314 (GRCm39) probably null Het
Stxbp5 A T 10: 9,688,085 (GRCm39) Y405* probably null Het
Thsd4 C T 9: 59,895,320 (GRCm39) R710H probably benign Het
Trp53inp1 T A 4: 11,165,130 (GRCm39) D51E probably benign Het
Ttc41 A G 10: 86,566,882 (GRCm39) D516G probably benign Het
Tut7 A T 13: 59,937,266 (GRCm39) L775H probably damaging Het
Uap1l1 A G 2: 25,252,840 (GRCm39) V400A probably damaging Het
Vit T C 17: 78,932,182 (GRCm39) S430P probably damaging Het
Vmn1r9 T A 6: 57,048,294 (GRCm39) M123K possibly damaging Het
Vmn2r14 A T 5: 109,369,384 (GRCm39) probably null Het
Vwa3a A G 7: 120,390,924 (GRCm39) T746A probably benign Het
Wdfy4 G T 14: 32,710,852 (GRCm39) Y2578* probably null Het
Wdr53 A T 16: 32,075,796 (GRCm39) K334* probably null Het
Xpot G T 10: 121,442,713 (GRCm39) H495Q probably damaging Het
Zfp109 T C 7: 23,928,570 (GRCm39) T288A probably benign Het
Zfp277 T A 12: 40,413,152 (GRCm39) E276V probably damaging Het
Zfp703 A G 8: 27,468,729 (GRCm39) D131G probably benign Het
Zfp985 T A 4: 147,667,801 (GRCm39) I223N probably benign Het
Zrsr2-ps1 T C 11: 22,923,805 (GRCm39) V193A possibly damaging Het
Zscan20 A G 4: 128,481,958 (GRCm39) I568T possibly damaging Het
Other mutations in Hecw2
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00092:Hecw2 APN 1 53,869,896 (GRCm39) missense probably damaging 1.00
IGL00338:Hecw2 APN 1 53,867,040 (GRCm39) splice site probably benign
IGL00530:Hecw2 APN 1 53,892,439 (GRCm39) missense probably damaging 1.00
IGL01343:Hecw2 APN 1 53,866,135 (GRCm39) missense probably damaging 0.96
IGL01503:Hecw2 APN 1 53,866,120 (GRCm39) missense probably damaging 1.00
IGL01989:Hecw2 APN 1 53,879,951 (GRCm39) missense probably damaging 1.00
IGL02016:Hecw2 APN 1 53,870,702 (GRCm39) missense possibly damaging 0.73
IGL02052:Hecw2 APN 1 53,965,670 (GRCm39) missense probably benign
IGL02085:Hecw2 APN 1 53,981,961 (GRCm39) critical splice acceptor site probably null
IGL02302:Hecw2 APN 1 53,972,407 (GRCm39) missense probably damaging 1.00
IGL02310:Hecw2 APN 1 53,963,075 (GRCm39) missense probably null 0.38
IGL02388:Hecw2 APN 1 53,964,858 (GRCm39) missense probably benign 0.17
IGL02499:Hecw2 APN 1 53,965,647 (GRCm39) missense probably benign
IGL02695:Hecw2 APN 1 53,965,368 (GRCm39) missense possibly damaging 0.94
IGL02732:Hecw2 APN 1 53,965,847 (GRCm39) splice site probably benign
IGL03100:Hecw2 APN 1 53,870,815 (GRCm39) missense probably damaging 1.00
IGL03175:Hecw2 APN 1 53,965,416 (GRCm39) missense possibly damaging 0.51
IGL03253:Hecw2 APN 1 53,871,875 (GRCm39) missense possibly damaging 0.85
IGL03356:Hecw2 APN 1 53,966,217 (GRCm39) splice site probably benign
Memoriam UTSW 1 53,965,215 (GRCm39) missense probably benign
recollect UTSW 1 53,943,581 (GRCm39) missense possibly damaging 0.88
ANU74:Hecw2 UTSW 1 53,964,853 (GRCm39) missense probably benign 0.01
R0077:Hecw2 UTSW 1 53,907,990 (GRCm39) splice site probably benign
R0133:Hecw2 UTSW 1 53,869,899 (GRCm39) missense probably damaging 1.00
R0268:Hecw2 UTSW 1 53,965,857 (GRCm39) splice site probably benign
R1303:Hecw2 UTSW 1 54,079,552 (GRCm39) missense probably benign 0.00
R1460:Hecw2 UTSW 1 53,852,404 (GRCm39) missense probably damaging 0.96
R1524:Hecw2 UTSW 1 53,890,777 (GRCm39) missense probably damaging 1.00
R1533:Hecw2 UTSW 1 53,965,704 (GRCm39) splice site probably null
R1828:Hecw2 UTSW 1 53,965,182 (GRCm39) missense probably benign
R2170:Hecw2 UTSW 1 53,981,956 (GRCm39) missense probably damaging 0.99
R2338:Hecw2 UTSW 1 53,943,581 (GRCm39) missense possibly damaging 0.88
R3016:Hecw2 UTSW 1 53,869,839 (GRCm39) missense probably damaging 1.00
R3872:Hecw2 UTSW 1 53,871,916 (GRCm39) splice site probably benign
R3892:Hecw2 UTSW 1 53,965,280 (GRCm39) missense probably benign 0.01
R4086:Hecw2 UTSW 1 53,870,815 (GRCm39) missense probably damaging 1.00
R4247:Hecw2 UTSW 1 53,871,804 (GRCm39) missense probably damaging 1.00
R4248:Hecw2 UTSW 1 53,871,804 (GRCm39) missense probably damaging 1.00
R4249:Hecw2 UTSW 1 53,871,804 (GRCm39) missense probably damaging 1.00
R4545:Hecw2 UTSW 1 53,852,381 (GRCm39) makesense probably null
R4805:Hecw2 UTSW 1 53,880,018 (GRCm39) missense probably damaging 1.00
R4834:Hecw2 UTSW 1 53,869,911 (GRCm39) missense probably damaging 1.00
R4983:Hecw2 UTSW 1 53,871,830 (GRCm39) missense probably benign 0.42
R5168:Hecw2 UTSW 1 53,952,459 (GRCm39) missense probably damaging 1.00
R5482:Hecw2 UTSW 1 53,965,360 (GRCm39) missense probably benign 0.09
R5549:Hecw2 UTSW 1 53,964,850 (GRCm39) missense possibly damaging 0.91
R5623:Hecw2 UTSW 1 53,871,782 (GRCm39) missense probably null 1.00
R5740:Hecw2 UTSW 1 53,926,762 (GRCm39) missense probably benign 0.12
R5919:Hecw2 UTSW 1 53,976,249 (GRCm39) missense probably damaging 0.99
R6058:Hecw2 UTSW 1 53,963,135 (GRCm39) missense possibly damaging 0.67
R6460:Hecw2 UTSW 1 53,907,992 (GRCm39) splice site probably null
R6875:Hecw2 UTSW 1 53,976,291 (GRCm39) missense probably benign 0.01
R7097:Hecw2 UTSW 1 53,904,283 (GRCm39) missense possibly damaging 0.88
R7131:Hecw2 UTSW 1 53,904,280 (GRCm39) missense probably damaging 1.00
R7291:Hecw2 UTSW 1 53,953,753 (GRCm39) missense probably damaging 1.00
R7401:Hecw2 UTSW 1 53,943,502 (GRCm39) missense probably damaging 1.00
R7482:Hecw2 UTSW 1 54,079,629 (GRCm39) missense probably damaging 0.99
R7501:Hecw2 UTSW 1 53,953,031 (GRCm39) critical splice acceptor site probably null
R7520:Hecw2 UTSW 1 53,965,215 (GRCm39) missense probably benign
R7611:Hecw2 UTSW 1 53,952,459 (GRCm39) missense probably damaging 1.00
R8184:Hecw2 UTSW 1 54,079,546 (GRCm39) missense probably benign 0.37
R8286:Hecw2 UTSW 1 53,879,928 (GRCm39) missense probably damaging 1.00
R8300:Hecw2 UTSW 1 53,926,775 (GRCm39) missense probably null 0.07
R8354:Hecw2 UTSW 1 53,964,467 (GRCm39) critical splice donor site probably null
R8362:Hecw2 UTSW 1 54,079,650 (GRCm39) start codon destroyed probably null 0.51
R8691:Hecw2 UTSW 1 53,904,223 (GRCm39) missense probably benign 0.26
R8745:Hecw2 UTSW 1 53,972,330 (GRCm39) missense probably damaging 1.00
R8769:Hecw2 UTSW 1 53,952,507 (GRCm39) missense probably benign 0.00
R8830:Hecw2 UTSW 1 53,930,305 (GRCm39) missense probably damaging 1.00
R8842:Hecw2 UTSW 1 53,990,033 (GRCm39) missense
R8874:Hecw2 UTSW 1 53,943,608 (GRCm39) splice site probably benign
R9064:Hecw2 UTSW 1 53,866,045 (GRCm39) missense probably benign 0.08
R9326:Hecw2 UTSW 1 54,079,369 (GRCm39) missense probably damaging 1.00
R9450:Hecw2 UTSW 1 53,878,188 (GRCm39) nonsense probably null
R9486:Hecw2 UTSW 1 53,852,466 (GRCm39) missense probably damaging 1.00
R9763:Hecw2 UTSW 1 53,963,074 (GRCm39) missense probably damaging 1.00
R9766:Hecw2 UTSW 1 53,904,287 (GRCm39) missense probably damaging 1.00
Z1177:Hecw2 UTSW 1 53,963,102 (GRCm39) missense possibly damaging 0.95
Predicted Primers PCR Primer
(F):5'- TCACAACATTGAACTCTCTGATTCC -3'
(R):5'- AGTGTTCACTGATGGTCTGCC -3'

Sequencing Primer
(F):5'- CTCCAGTGAACATTTTCTAAACAAC -3'
(R):5'- ACTGATGGTCTGCCTTCTTTATC -3'
Posted On 2016-03-17