Incidental Mutation 'R5740:Hecw2'
ID 444730
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 043196-MU
Accession Numbers
Essential gene? Probably non essential (E-score: 0.180) question?
Stock # R5740 (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 C at 53926762 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Tyrosine to Cysteine at position 1079 (Y1079C)
Ref Sequence ENSEMBL: ENSMUSP00000113283 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000087659] [ENSMUST00000120904]
AlphaFold Q6I6G8
Predicted Effect probably benign
Transcript: ENSMUST00000087659
AA Change: Y1079C

PolyPhen 2 Score 0.117 (Sensitivity: 0.93; Specificity: 0.86)
SMART Domains Protein: ENSMUSP00000084942
Gene: ENSMUSG00000042807
AA Change: Y1079C

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: ENSMUST00000120904
AA Change: Y1079C

PolyPhen 2 Score 0.117 (Sensitivity: 0.93; Specificity: 0.86)
SMART Domains Protein: ENSMUSP00000113283
Gene: ENSMUSG00000042807
AA Change: Y1079C

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: ENSMUST00000157324
Coding Region Coverage
  • 1x: 99.2%
  • 3x: 98.6%
  • 10x: 97.2%
  • 20x: 95.3%
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 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: 38 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
4921513I03Rik G A 10: 120,614,413 (GRCm39) probably benign Het
Arrdc5 T A 17: 56,604,838 (GRCm39) N150Y probably benign Het
Bag1 T C 4: 40,941,526 (GRCm39) Q269R probably null Het
C7 T C 15: 5,086,522 (GRCm39) N40D probably benign Het
Ccnt1 T C 15: 98,442,381 (GRCm39) I296V probably benign Het
Col19a1 C T 1: 24,376,996 (GRCm39) G450S probably damaging Het
F13a1 T C 13: 37,082,178 (GRCm39) T509A probably benign Het
Fgg A T 3: 82,918,832 (GRCm39) T282S probably benign Het
Fzd7 A G 1: 59,522,839 (GRCm39) M241V probably benign Het
Gja1 G A 10: 56,264,285 (GRCm39) V215M probably damaging Het
Golgb1 T C 16: 36,739,362 (GRCm39) L2567P probably damaging Het
Grik2 T C 10: 48,989,573 (GRCm39) N819D probably damaging Het
Grik4 C T 9: 42,719,863 (GRCm39) R3H possibly damaging Het
Hivep3 A G 4: 119,953,220 (GRCm39) E512G possibly damaging Het
Ino80 T C 2: 119,261,510 (GRCm39) D718G probably damaging Het
Ints10 G A 8: 69,257,574 (GRCm39) R258K probably damaging Het
Jak2 A G 19: 29,239,824 (GRCm39) K73E possibly damaging Het
Lrba A G 3: 86,235,649 (GRCm39) I918V probably damaging Het
M1ap T C 6: 82,958,903 (GRCm39) V178A probably damaging Het
Mcub A T 3: 129,712,374 (GRCm39) M167K probably benign Het
Mgat4c A T 10: 102,225,182 (GRCm39) K465N possibly damaging Het
Naip1 T A 13: 100,569,009 (GRCm39) probably null Het
Ncbp3 T A 11: 72,944,323 (GRCm39) N108K possibly damaging Het
Npepps A T 11: 97,126,894 (GRCm39) D455E possibly damaging Het
Or5b101 T C 19: 13,004,926 (GRCm39) M256V probably benign Het
Pan2 G A 10: 128,144,033 (GRCm39) G128S probably damaging Het
Ppp3cb A T 14: 20,551,664 (GRCm39) I489N possibly damaging Het
Sdccag8 A G 1: 176,658,716 (GRCm39) T134A probably benign Het
Sh3tc1 T C 5: 35,864,399 (GRCm39) E596G probably benign Het
Shank1 T C 7: 44,003,164 (GRCm39) S1619P possibly damaging Het
Slc46a3 A T 5: 147,816,643 (GRCm39) C387* probably null Het
Slc5a5 G T 8: 71,341,561 (GRCm39) probably null Het
Ttn T C 2: 76,721,718 (GRCm39) probably benign Het
Vangl1 T C 3: 102,091,450 (GRCm39) D212G probably damaging Het
Vmn1r52 T A 6: 90,156,176 (GRCm39) I160N probably benign Het
Vmn2r118 C T 17: 55,900,103 (GRCm39) M600I probably benign Het
Vmn2r7 T C 3: 64,614,654 (GRCm39) I387V probably benign Het
Zfp369 A G 13: 65,444,581 (GRCm39) R575G probably benign 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
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'- AGAAGCTCTCTGGGACTCAAG -3'
(R):5'- AGCACCTGTTCTGATCAGTTGG -3'

Sequencing Primer
(F):5'- TCTCTGGGACTCAAGGACAG -3'
(R):5'- ATCAGTTGGTCATTTTCTGTGATAAG -3'
Posted On 2016-11-21