Mutagenetix > Incidental Mutation

Incidental Mutation 'R2170:Hecw2'

237408

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

Accession Numbers

Essential gene?

Probably non essential (E-score: 0.180) question?

Stock #

R2170 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

53846031-54234193 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to A at 53981956 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Glutamic Acid to Valine at position 135 (E135V)

Ref Sequence

ENSEMBL: ENSMUSP00000113283 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000087659] [ENSMUST00000097741] [ENSMUST00000120904]

AlphaFold

Q6I6G8

Predicted Effect

probably damaging
Transcript: ENSMUST00000087659
AA Change: E135V

PolyPhen 2 Score 0.994 (Sensitivity: 0.69; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000084942
Gene: ENSMUSG00000042807
AA Change: E135V

Domain	Start	End	E-Value	Type
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: ENSMUST00000097741
AA Change: E135V

PolyPhen 2 Score 0.994 (Sensitivity: 0.69; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000095348
Gene: ENSMUSG00000042807
AA Change: E135V

Domain	Start	End	E-Value	Type
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 damaging
Transcript: ENSMUST00000120904
AA Change: E135V

PolyPhen 2 Score 0.994 (Sensitivity: 0.69; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000113283
Gene: ENSMUSG00000042807
AA Change: E135V

Domain	Start	End	E-Value	Type
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: 99.2%
3x: 98.7%
10x: 97.5%
20x: 95.6%

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: 37 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
1700030J22Rik	A	G	8: 117,697,896 (GRCm39)	S404P	probably damaging	Het
4933434E20Rik	T	A	3: 89,963,611 (GRCm39)	L89Q	probably benign	Het
Atxn2l	T	A	7: 126,102,411 (GRCm39)		probably benign	Het
Bcl6	A	G	16: 23,793,680 (GRCm39)	F89S	probably damaging	Het
Ccdc168	A	T	1: 44,095,168 (GRCm39)	S1977T	probably benign	Het
Ccr1l1	C	A	9: 123,778,172 (GRCm39)	V92F	possibly damaging	Het
Cdh15	G	A	8: 123,588,763 (GRCm39)	R279Q	probably damaging	Het
Chrne	T	C	11: 70,509,323 (GRCm39)	N86S	probably damaging	Het
Copg2	CCTCATC	CC	6: 30,789,757 (GRCm39)		probably null	Het
Elapor2	A	G	5: 9,529,206 (GRCm39)	D221G	probably damaging	Het
Eps8l2	T	C	7: 140,921,984 (GRCm39)	S21P	probably benign	Het
Glb1	CCTCTCTCTCTCTCTCTCTCTCTCTCTCTCT	CCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCT	9: 114,302,873 (GRCm39)		probably benign	Het
Gngt2	A	G	11: 95,728,071 (GRCm39)		probably benign	Het
Hmcn2	G	A	2: 31,270,293 (GRCm39)	A1177T	probably benign	Het
Itga10	T	C	3: 96,557,773 (GRCm39)	V272A	probably damaging	Het
Kif17	A	G	4: 138,015,682 (GRCm39)	I418M	probably benign	Het
Knl1	T	C	2: 118,918,075 (GRCm39)		probably null	Het
Lamc1	C	T	1: 153,124,888 (GRCm39)	A628T	probably benign	Het
Mag	A	T	7: 30,608,412 (GRCm39)	L234*	probably null	Het
Muc5ac	T	A	7: 141,366,084 (GRCm39)	V2080E	possibly damaging	Het
Myo18b	T	C	5: 112,871,724 (GRCm39)	D2119G	probably benign	Het
Ncam1	C	T	9: 49,709,981 (GRCm39)	A17T	probably benign	Het
Nipbl	A	G	15: 8,322,702 (GRCm39)	Y2570H	probably damaging	Het
Oasl2	T	C	5: 115,044,861 (GRCm39)	V129A	probably damaging	Het
Or14a257	T	A	7: 86,137,778 (GRCm39)	H327L	probably benign	Het
Or4k47	C	T	2: 111,451,945 (GRCm39)	S158N	possibly damaging	Het
Podn	A	T	4: 107,879,730 (GRCm39)	L85Q	probably damaging	Het
Ppp1r12c	A	T	7: 4,485,805 (GRCm39)	D680E	possibly damaging	Het
Prdm14	G	A	1: 13,192,684 (GRCm39)	L352F	probably damaging	Het
Prob1	G	T	18: 35,787,790 (GRCm39)	Q155K	probably benign	Het
Rin2	C	T	2: 145,702,366 (GRCm39)	T354I	probably benign	Het
Shoc1	A	G	4: 59,069,215 (GRCm39)	L737S	possibly damaging	Het
Stard5	A	G	7: 83,282,366 (GRCm39)	T60A	probably benign	Het
Syt7	A	G	19: 10,416,744 (GRCm39)	K402E	probably damaging	Het
Tll2	T	A	19: 41,171,714 (GRCm39)	D69V	probably damaging	Het
Vmn1r40	T	C	6: 89,691,957 (GRCm39)	F258S	probably benign	Het
Zfp759	T	A	13: 67,284,812 (GRCm39)	Y19N	possibly damaging	Het

Other mutations in Hecw2

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH 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
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
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'- ATGACTCTGACAGGGTAGCC -3'
(R):5'- CTTACGGAGTTTCAGCAAAGC -3'

Sequencing Primer
(F):5'- CCAGGCAGAAATAGAACTCTTCG -3'
(R):5'- TGAGCCACATAGTGAGCTTC -3'

Posted On

2014-10-02