Incidental Mutation 'R7097:Hecw2'
ID 550532
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 045189-MU
Accession Numbers
Essential gene? Probably non essential (E-score: 0.180) question?
Stock # R7097 (G1)
Quality Score 225.009
Status Validated
Chromosome 1
Chromosomal Location 53846031-54234193 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to A at 53904283 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Tyrosine to Phenylalanine at position 1155 (Y1155F)
Ref Sequence ENSEMBL: ENSMUSP00000084942 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000087659] [ENSMUST00000120904]
AlphaFold Q6I6G8
Predicted Effect possibly damaging
Transcript: ENSMUST00000087659
AA Change: Y1155F

PolyPhen 2 Score 0.882 (Sensitivity: 0.82; Specificity: 0.94)
SMART Domains Protein: ENSMUSP00000084942
Gene: ENSMUSG00000042807
AA Change: Y1155F

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 possibly damaging
Transcript: ENSMUST00000120904
AA Change: Y1155F

PolyPhen 2 Score 0.882 (Sensitivity: 0.82; Specificity: 0.94)
SMART Domains Protein: ENSMUSP00000113283
Gene: ENSMUSG00000042807
AA Change: Y1155F

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
Meta Mutation Damage Score 0.0864 question?
Coding Region Coverage
  • 1x: 100.0%
  • 3x: 100.0%
  • 10x: 99.7%
  • 20x: 99.1%
Validation Efficiency 99% (75/76)
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: 75 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
1700010I14Rik A G 17: 9,224,052 (GRCm39) N435S probably damaging Het
Aip A T 19: 4,165,381 (GRCm39) V195E probably benign Het
Amer3 A T 1: 34,627,869 (GRCm39) I703F probably benign Het
Amfr T C 8: 94,738,637 (GRCm39) E7G probably benign Het
Angel1 A G 12: 86,773,158 (GRCm39) S4P probably damaging Het
Atp2c1 A G 9: 105,341,850 (GRCm39) I146T probably damaging Het
Atp6v0e A G 17: 26,914,390 (GRCm39) T72A probably benign Het
Bahcc1 T C 11: 120,163,472 (GRCm39) V590A possibly damaging Het
Bcl6 A G 16: 23,791,364 (GRCm39) V330A possibly damaging Het
Bcl6 T C 16: 23,791,652 (GRCm39) D234G probably damaging Het
Btaf1 C T 19: 36,926,502 (GRCm39) T58I probably damaging Het
Ccdc175 A T 12: 72,175,183 (GRCm39) probably null Het
Cdca4 C A 12: 112,785,189 (GRCm39) V180L probably benign Het
Ces1g C A 8: 94,043,665 (GRCm39) G425C possibly damaging Het
Chl1 T C 6: 103,683,409 (GRCm39) L745P probably damaging Het
Clec4g T A 8: 3,769,518 (GRCm39) T42S possibly damaging Het
Ctsg A C 14: 56,337,489 (GRCm39) I238S probably damaging Het
Cyb5rl A T 4: 106,944,513 (GRCm39) E41V unknown Het
Dcdc2a A G 13: 25,291,681 (GRCm39) E222G probably benign Het
Dnaaf1 G T 8: 120,323,538 (GRCm39) G509V possibly damaging Het
Dnah5 A G 15: 28,453,410 (GRCm39) I4394V probably benign Het
Dot1l T G 10: 80,626,560 (GRCm39) S1260R probably damaging Het
Dst T G 1: 34,208,341 (GRCm39) I1089S probably damaging Het
Efcab3 A T 11: 104,899,787 (GRCm39) I4350F possibly damaging Het
Eps8l3 A G 3: 107,791,801 (GRCm39) probably null Het
Fam135b A G 15: 71,493,917 (GRCm39) V4A possibly damaging Het
Fnip2 T C 3: 79,388,313 (GRCm39) E806G probably benign Het
Fryl T A 5: 73,231,251 (GRCm39) I1609F probably benign Het
Gdi1 G A X: 73,350,461 (GRCm39) R55H probably benign Het
Gsn A T 2: 35,185,061 (GRCm39) K339* probably null Het
Kif20b T A 19: 34,951,892 (GRCm39) N1723K probably damaging Het
Kif2b T C 11: 91,467,650 (GRCm39) D211G probably benign Het
Lhfpl4 C T 6: 113,153,632 (GRCm39) V140I probably benign Het
Med16 C T 10: 79,739,177 (GRCm39) G203D probably damaging Het
Mrgpra3 T A 7: 47,239,389 (GRCm39) Y179F probably benign Het
Muc6 AGGCGCAGAAACCCTGGC AGGC 7: 141,214,363 (GRCm39) probably null Het
Myo18b A G 5: 113,022,271 (GRCm39) S374P unknown Het
Myoz1 A G 14: 20,699,477 (GRCm39) I287T possibly damaging Het
Ncoa6 T C 2: 155,279,983 (GRCm39) D11G probably benign Het
Nlrp9c A G 7: 26,085,046 (GRCm39) Y178H probably damaging Het
Nmur1 T C 1: 86,315,230 (GRCm39) T212A probably damaging Het
Oacyl A G 18: 65,853,323 (GRCm39) D143G probably benign Het
Obox5 A G 7: 15,492,732 (GRCm39) Y229C probably damaging Het
Or10d1c A T 9: 38,893,914 (GRCm39) M142K probably benign Het
Or1j12 A G 2: 36,342,702 (GRCm39) Y35C probably damaging Het
Or1j18 G T 2: 36,624,436 (GRCm39) M34I probably benign Het
Or1x2 C A 11: 50,918,428 (GRCm39) L200I probably benign Het
Or8c13 A T 9: 38,091,632 (GRCm39) C162* probably null Het
Pcdhb17 A C 18: 37,619,566 (GRCm39) N452T probably benign Het
Pear1 T G 3: 87,658,752 (GRCm39) H901P probably benign Het
Peds1 C G 2: 167,503,398 (GRCm39) A7P probably benign Het
Pi16 A G 17: 29,545,313 (GRCm39) Y192C probably damaging Het
Pip5k1b T G 19: 24,335,424 (GRCm39) E362D probably damaging Het
Pla2g5 T C 4: 138,531,830 (GRCm39) D58G probably damaging Het
Pole T A 5: 110,472,968 (GRCm39) probably null Het
Prdm16 G T 4: 154,429,925 (GRCm39) T348K probably damaging Het
Prkdc T A 16: 15,507,207 (GRCm39) F896I probably damaging Het
Prmt7 T C 8: 106,961,732 (GRCm39) F215S unknown Het
Prss23 T A 7: 89,159,392 (GRCm39) T226S probably damaging Het
Ptpn14 G A 1: 189,595,595 (GRCm39) W739* probably null Het
Rfx5 G T 3: 94,863,850 (GRCm39) G135C probably damaging Het
Scmh1 A G 4: 120,382,252 (GRCm39) H573R probably benign Het
Serpina5 G T 12: 104,068,554 (GRCm39) probably null Het
Sh3rf2 G A 18: 42,237,227 (GRCm39) probably null Het
Slc38a2 T C 15: 96,591,182 (GRCm39) M229V probably damaging Het
Slc6a17 C G 3: 107,400,464 (GRCm39) G222R probably damaging Het
Sp110 C T 1: 85,507,406 (GRCm39) G367D possibly damaging Het
Srcap C A 7: 127,138,213 (GRCm39) L1128M probably damaging Het
Tpra1 T A 6: 88,885,276 (GRCm39) I76N probably damaging Het
Trav6-4 A T 14: 53,692,049 (GRCm39) Y52F probably benign Het
Trp63 C A 16: 25,639,227 (GRCm39) H138Q probably damaging Het
Trub2 A G 2: 29,669,838 (GRCm39) V177A possibly damaging Het
Ugt2a2 T C 5: 87,608,255 (GRCm39) D528G possibly damaging Het
Wnk2 C A 13: 49,256,314 (GRCm39) R269L possibly damaging Het
Zc3h12c T A 9: 52,027,226 (GRCm39) Q731L 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
R4884:Hecw2 UTSW 1 53,990,000 (GRCm39) missense probably benign 0.03
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
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'- TGAACTTACAAGGAAGCGAGCTAC -3'
(R):5'- GCACGGATGTTTCTGAGTATGAAAC -3'

Sequencing Primer
(F):5'- CGAGCTACTTAAAAAGGCAGC -3'
(R):5'- GTTTCTGAGTATGAAACTATGGAAGG -3'
Posted On 2019-05-15