Mutagenetix > Incidental Mutation

Incidental Mutation 'R8286:Hecw2'

638441

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

067708-MU

Accession Numbers

Essential gene?

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

Stock #

R8286 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

53846031-54234193 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 53879928 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Threonine to Alanine at position 1294 (T1294A)

Ref Sequence

ENSEMBL: ENSMUSP00000084942 (fasta)

Gene Model

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

AlphaFold

Q6I6G8

Predicted Effect

probably damaging
Transcript: ENSMUST00000087659
AA Change: T1294A

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000084942
Gene: ENSMUSG00000042807
AA Change: T1294A

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: ENSMUST00000120904
AA Change: T1294A

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000113283
Gene: ENSMUSG00000042807
AA Change: T1294A

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

Coding Region Coverage

1x: 100.0%
3x: 99.9%
10x: 99.6%
20x: 98.8%

Validation Efficiency

100% (42/42)

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: 44 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abcb1b	A	T	5: 8,914,119 (GRCm39)	Y1163F	probably damaging	Het
Abcd4	A	G	12: 84,649,920 (GRCm39)	V589A	probably benign	Het
Adam26b	T	A	8: 43,972,998 (GRCm39)	N668I	probably benign	Het
Atp2b2	T	C	6: 113,819,275 (GRCm39)	N6S	possibly damaging	Het
Cacna2d2	A	G	9: 107,392,063 (GRCm39)	Y468C	probably damaging	Het
Cngb1	A	T	8: 96,002,252 (GRCm39)	V52D		Het
Cped1	A	T	6: 22,254,601 (GRCm39)	Y998F	probably benign	Het
Csmd1	A	G	8: 16,039,188 (GRCm39)	V2390A	probably benign	Het
Ctsj	A	T	13: 61,148,330 (GRCm39)	C321*	probably null	Het
Dip2a	A	C	10: 76,122,297 (GRCm39)	I139S	probably benign	Het
Dnaaf9	T	C	2: 130,559,248 (GRCm39)	I937V	probably damaging	Het
Eif1	A	G	11: 100,210,795 (GRCm39)		probably benign	Het
Exoc1	T	C	5: 76,711,087 (GRCm39)	I662T	probably benign	Het
Flt4	A	G	11: 49,528,089 (GRCm39)	R971G	probably benign	Het
Herc2	T	G	7: 55,879,410 (GRCm39)	V4676G	possibly damaging	Het
Hif1a	A	G	12: 73,992,022 (GRCm39)		probably benign	Het
Icam5	C	A	9: 20,946,822 (GRCm39)	A450E	possibly damaging	Het
Map3k21	T	A	8: 126,637,498 (GRCm39)	M28K	probably benign	Het
Mars1	C	A	10: 127,141,348 (GRCm39)	R347L	probably benign	Het
Mctp1	A	T	13: 76,905,174 (GRCm39)	I426F	probably benign	Het
Mdn1	T	C	4: 32,731,960 (GRCm39)	S3007P	possibly damaging	Het
Mical3	T	C	6: 120,998,149 (GRCm39)	R65G	possibly damaging	Het
Ncald	G	T	15: 37,397,505 (GRCm39)	Y58*	probably null	Het
Neil2	A	T	14: 63,426,154 (GRCm39)	I72K	probably benign	Het
Or8b35	C	A	9: 37,904,401 (GRCm39)	Y204*	probably null	Het
Or8k23	A	G	2: 86,186,691 (GRCm39)	F12L	probably damaging	Het
Pan2	A	G	10: 128,154,189 (GRCm39)	D1086G	probably damaging	Het
Plxnb1	A	G	9: 108,935,870 (GRCm39)	T1087A	probably damaging	Het
Prpf39	A	G	12: 65,103,132 (GRCm39)	M469V	probably benign	Het
Ptprk	A	T	10: 28,444,323 (GRCm39)	S905C	probably damaging	Het
Rassf5	T	C	1: 131,140,067 (GRCm39)	D164G	possibly damaging	Het
Setd1a	T	C	7: 127,385,356 (GRCm39)	W688R	possibly damaging	Het
Sfswap	C	T	5: 129,616,783 (GRCm39)	T409I	probably damaging	Het
Slc50a1	G	A	3: 89,177,710 (GRCm39)		probably null	Het
Slfn9	G	C	11: 82,872,095 (GRCm39)	N880K	probably damaging	Het
Sprr1b	T	C	3: 92,344,720 (GRCm39)	K52R	probably benign	Het
Tfb2m	T	C	1: 179,356,770 (GRCm39)	D388G	probably damaging	Het
Tmem234	T	C	4: 129,500,881 (GRCm39)		probably benign	Het
Traj43	A	G	14: 54,412,201 (GRCm39)	N1D		Het
Trmt1l	T	A	1: 151,333,543 (GRCm39)	I682N	probably damaging	Het
Trp53rka	T	C	2: 165,333,445 (GRCm39)	D148G	probably damaging	Het
Vmn2r86	A	G	10: 130,285,855 (GRCm39)	V440A	probably benign	Het
Vxn	C	T	1: 9,683,613 (GRCm39)	T67I	probably benign	Het
Wdfy3	C	T	5: 102,085,287 (GRCm39)	V736I	probably benign	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
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
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
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'- GGGGCTGCCTGTAGAATTAG -3'
(R):5'- CTGTAGTGAGCATCCTCTACAATG -3'

Sequencing Primer
(F):5'- GCCTGTAGAATTAGGTTTGACAAGC -3'
(R):5'- GTGAGCATCCTCTACAATGTTAAAC -3'

Posted On

2020-07-28