Incidental Mutation 'R4247:Hecw2'
ID 320448
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 041063-MU
Accession Numbers
Essential gene? Probably non essential (E-score: 0.180) question?
Stock # R4247 (G1)
Quality Score 225
Status Validated
Chromosome 1
Chromosomal Location 53846031-54234193 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) C to T at 53871804 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Valine to Methionine at position 1381 (V1381M)
Ref Sequence ENSEMBL: ENSMUSP00000113283 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000087659] [ENSMUST00000120904]
AlphaFold Q6I6G8
Predicted Effect probably damaging
Transcript: ENSMUST00000087659
AA Change: V1381M

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000084942
Gene: ENSMUSG00000042807
AA Change: V1381M

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 damaging
Transcript: ENSMUST00000120904
AA Change: V1381M

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000113283
Gene: ENSMUSG00000042807
AA Change: V1381M

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: ENSMUST00000150677
Meta Mutation Damage Score 0.5933 question?
Coding Region Coverage
  • 1x: 99.3%
  • 3x: 98.7%
  • 10x: 97.5%
  • 20x: 95.9%
Validation Efficiency 98% (41/42)
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: 39 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Adam22 T C 5: 8,195,626 (GRCm39) I305V probably benign Het
Aga T A 8: 53,964,865 (GRCm39) L9Q possibly damaging Het
Akna C T 4: 63,313,409 (GRCm39) G238D probably benign Het
Arhgap23 G A 11: 97,354,525 (GRCm39) E813K probably damaging Het
Atp13a2 T C 4: 140,719,539 (GRCm39) probably null Het
Atp8a1 C T 5: 67,824,917 (GRCm39) G820S probably damaging Het
Ccdc97 T G 7: 25,415,459 (GRCm39) H68P possibly damaging Het
Dclre1b A C 3: 103,711,400 (GRCm39) probably null Het
Erap1 T C 13: 74,823,414 (GRCm39) I816T probably damaging Het
Fubp1 G A 3: 151,937,573 (GRCm39) A103T possibly damaging Het
Gnal C G 18: 67,221,654 (GRCm39) P19R unknown Het
Gtf3c5 T C 2: 28,461,196 (GRCm39) D306G probably damaging Het
Hsdl2 A T 4: 59,594,417 (GRCm39) N16I probably damaging Het
Kif14 G T 1: 136,401,126 (GRCm39) M492I possibly damaging Het
Kif27 A G 13: 58,435,731 (GRCm39) V1354A probably damaging Het
Kif9 G T 9: 110,325,027 (GRCm39) probably null Het
Lmtk3 G A 7: 45,443,486 (GRCm39) C723Y possibly damaging Het
Lrrc24 A G 15: 76,602,176 (GRCm39) I193T possibly damaging Het
Or2bd2 A G 7: 6,441,901 (GRCm39) probably benign Het
Or52b1 T C 7: 104,979,355 (GRCm39) I15V probably benign Het
Pkd1l1 C T 11: 8,815,543 (GRCm39) R1456K possibly damaging Het
Pramel52-ps A G 5: 94,531,446 (GRCm39) D110G possibly damaging Het
Ranbp2 A G 10: 58,314,686 (GRCm39) D1802G possibly damaging Het
Resf1 T A 6: 149,227,041 (GRCm39) M29K possibly damaging Het
Satl1 A G X: 111,316,033 (GRCm39) S141P probably benign Het
Scn11a C T 9: 119,636,952 (GRCm39) V250M probably damaging Het
Slitrk1 A G 14: 109,149,994 (GRCm39) V239A possibly damaging Het
Slitrk6 T A 14: 110,988,171 (GRCm39) D512V probably damaging Het
Snx8 A G 5: 140,341,800 (GRCm39) L121P probably damaging Het
Sumf1 A C 6: 108,131,974 (GRCm39) V156G probably damaging Het
Tamalin G T 15: 101,122,418 (GRCm39) R79L possibly damaging Het
Trp73 A G 4: 154,149,089 (GRCm39) probably null Het
Tsen2 A G 6: 115,524,785 (GRCm39) probably benign Het
Upp1 T C 11: 9,084,815 (GRCm39) I178T probably benign Het
Vmn2r73 A T 7: 85,521,883 (GRCm39) L152Q probably damaging Het
Vmn2r97 T C 17: 19,167,542 (GRCm39) S599P possibly damaging Het
Wrnip1 T C 13: 32,990,866 (GRCm39) L375P probably damaging Het
Zfp945 C T 17: 23,069,583 (GRCm39) G793D probably damaging Het
Zfyve9 C A 4: 108,576,389 (GRCm39) A231S 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
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
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'- TGTAGTTGGCAGAATTTTGCAC -3'
(R):5'- CTTGTCATGAAGCCTGAGCCTC -3'

Sequencing Primer
(F):5'- CTATATGCCTTTAGCTTTAGTTGCAG -3'
(R):5'- ATGAAGCCTGAGCCTCCTTCC -3'
Posted On 2015-06-12