Mutagenetix > Incidental Mutations

Incidental Mutation 'R4983:Hecw2'

385678

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

042577-MU

Accession Numbers

Is this an essential gene?

Possibly essential (E-score: 0.619) question?

Stock #

R4983 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

53806876-54195168 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 53832671 bp

Zygosity

Heterozygous

Amino Acid Change

Histidine to Arginine at position 1372 (H1372R)

Ref Sequence

ENSEMBL: ENSMUSP00000113283 (fasta)

Gene Model

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

Predicted Effect

probably benign
Transcript: ENSMUST00000087659
AA Change: H1372R

PolyPhen 2 Score 0.422 (Sensitivity: 0.89; Specificity: 0.90)

SMART Domains

Protein: ENSMUSP00000084942
Gene: ENSMUSG00000042807
AA Change: H1372R

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 benign
Transcript: ENSMUST00000120904
AA Change: H1372R

PolyPhen 2 Score 0.422 (Sensitivity: 0.89; Specificity: 0.90)

SMART Domains

Protein: ENSMUSP00000113283
Gene: ENSMUSG00000042807
AA Change: H1372R

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: ENSMUST00000150677

Meta Mutation Damage Score

0.0676

Coding Region Coverage

1x: 99.2%
3x: 98.5%
10x: 96.8%
20x: 94.0%

Validation Efficiency

97% (103/106)

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: 94 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
4933411K16Rik	T	G	19: 42,053,076	S215R	possibly damaging	Het
9130011E15Rik	T	C	19: 45,950,707	T335A	probably benign	Het
Abcc9	T	C	6: 142,682,141	M388V	probably benign	Het
Acbd6	A	C	1: 155,601,529	T154P	probably benign	Het
Ago1	T	C	4: 126,453,654	D434G	probably damaging	Het
Ankib1	A	T	5: 3,769,652	M89K	probably benign	Het
Arap2	A	T	5: 62,676,525	H866Q	probably damaging	Het
BC017158	C	T	7: 128,276,473		probably benign	Het
Capn12	A	T	7: 28,890,370	H622L	probably benign	Het
Capns2	T	G	8: 92,901,902	F140V	probably damaging	Het
Catsper1	T	G	19: 5,335,963	F75V	probably benign	Het
Ccdc24	T	C	4: 117,872,100	N16S	probably benign	Het
Cdkn2aip	A	T	8: 47,712,929	L114Q	probably damaging	Het
Cenpe	T	A	3: 135,234,928	S649R	probably damaging	Het
Chgb	A	T	2: 132,793,682	R515W	probably damaging	Het
Chrnb1	A	G	11: 69,793,978	F123S	probably damaging	Het
Copz2	A	T	11: 96,857,551		probably null	Het
Cspp1	T	A	1: 10,126,463	N900K	probably damaging	Het
Daw1	C	A	1: 83,187,998	A178E	probably benign	Het
Dnase1l1	C	T	X: 74,277,038		probably null	Homo
Epb41l5	T	C	1: 119,555,071	D629G	probably benign	Het
Erap1	A	G	13: 74,690,710	E925G	probably benign	Het
Exoc7	A	C	11: 116,289,269	F657V	probably damaging	Het
Fam210b	G	C	2: 172,345,665	A2P	probably damaging	Homo
Fry	A	G	5: 150,398,254	E1018G	probably damaging	Het
Galc	A	T	12: 98,242,768	L15*	probably null	Het
Gm11232	T	A	4: 71,756,901	K121N	possibly damaging	Het
Gm17677	T	G	9: 35,742,169	F90V	probably benign	Het
Hectd1	A	T	12: 51,784,262	D931E	probably benign	Het
Ighv3-2	T	A	12: 114,033,986		noncoding transcript	Het
Kcns2	T	G	15: 34,839,605	S371R	probably damaging	Het
Kif23	T	C	9: 61,936,703	K175E	probably benign	Het
Kmt2c	G	A	5: 25,295,511	R436W	possibly damaging	Het
Lama5	A	G	2: 180,193,449	S1317P	probably benign	Het
Lce1e	T	C	3: 92,707,828	S71G	unknown	Het
Lrrc37a	T	A	11: 103,497,618	E2327V	unknown	Het
Map3k20	A	G	2: 72,402,067	M356V	probably benign	Het
Med12l	C	T	3: 59,261,929	A1580V	probably damaging	Het
Metap2	G	T	10: 93,889,600	T30K	possibly damaging	Het
Mysm1	T	A	4: 94,972,970	T53S	probably benign	Het
Nasp	A	T	4: 116,602,185	D717E	probably damaging	Het
Ndnf	G	A	6: 65,703,571	R278H	possibly damaging	Het
Neb	A	T	2: 52,216,261	N4205K	probably damaging	Het
Nebl	A	T	2: 17,375,271	I764N	possibly damaging	Het
Nucb1	A	G	7: 45,498,889	Y131H	probably damaging	Het
Olfr1157	G	T	2: 87,962,698	H65N	probably benign	Het
Olfr292	A	C	7: 86,694,479	T8P	probably benign	Het
Olfr381	A	G	11: 73,486,797	I9T	probably benign	Het
Oscp1	T	A	4: 126,076,762	C115S	probably benign	Het
Paip2	C	T	18: 35,613,359	R59C	possibly damaging	Het
Pcdhga4	G	A	18: 37,686,519	D374N	probably damaging	Het
Pcolce	G	T	5: 137,605,674		probably benign	Het
Pcyox1l	T	C	18: 61,699,397	E193G	probably damaging	Het
Pde6b	A	T	5: 108,425,330	Q522L	probably benign	Het
Peg10	T	TCCG	6: 4,756,451		probably benign	Het
Phf11a	A	G	14: 59,284,438	F95L	probably benign	Het
Pja2	A	C	17: 64,309,058	S281A	probably benign	Het
Plekhm2	A	G	4: 141,634,376	F272S	probably damaging	Het
Pom121l2	T	C	13: 21,983,814	S752P	probably benign	Het
Ppl	T	C	16: 5,088,718	T1238A	possibly damaging	Het
Prmt7	A	G	8: 106,250,363	Y569C	probably damaging	Het
Prss37	G	A	6: 40,516,136	T132I	probably benign	Het
Psmf1	A	T	2: 151,729,457		probably benign	Het
Ptprj	A	C	2: 90,460,532	I528S	probably damaging	Het
Reg1	A	G	6: 78,428,213	T140A	possibly damaging	Het
Rtn4	A	G	11: 29,707,217	N457S	probably benign	Het
Scn9a	T	C	2: 66,566,270	K93R	probably benign	Het
Sec16a	A	G	2: 26,439,519	V828A	probably benign	Het
Sec23b	T	A	2: 144,581,953	D507E	probably benign	Het
Sirt4	A	T	5: 115,482,791	F107L	probably benign	Het
Slc14a2	A	T	18: 78,150,401	L862Q	probably damaging	Het
Slc16a4	T	C	3: 107,300,860	S229P	probably benign	Het
Slc37a3	A	T	6: 39,352,717	C185*	probably null	Het
Slc5a2	A	T	7: 128,271,810	*154C	probably null	Het
Snx17	A	G	5: 31,195,794	S42G	possibly damaging	Het
Tgm6	T	C	2: 130,141,193	V234A	probably damaging	Het
Thbs4	A	G	13: 92,790,699	M94T	probably benign	Het
Thtpa	A	G	14: 55,072,148		probably benign	Het
Tie1	T	C	4: 118,483,755	E343G	probably damaging	Het
Tmem145	A	G	7: 25,308,602	I238V	probably benign	Het
Tmprss11f	T	C	5: 86,537,999	S170G	probably benign	Het
Tnk2	T	A	16: 32,680,465	D865E	probably damaging	Het
Ttll8	T	C	15: 88,925,582	E337G	probably benign	Het
Ttn	G	A	2: 76,867,446		probably benign	Het
Tubgcp6	T	C	15: 89,106,291	E710G	probably damaging	Het
Txndc2	T	A	17: 65,638,060	H374L	probably benign	Het
Unc80	G	T	1: 66,674,732		probably null	Het
Vmn2r23	G	A	6: 123,733,349	C537Y	probably damaging	Het
Vmn2r45	A	G	7: 8,483,117	F391L	probably damaging	Het
Vstm4	A	T	14: 32,919,245	T262S	probably benign	Het
Zfp180	C	T	7: 24,106,078	R641C	probably damaging	Het
Zfp979	A	T	4: 147,613,914	S113T	possibly damaging	Het
Zswim4	C	T	8: 84,226,667		probably null	Het
Zswim5	T	A	4: 116,985,686	M876K	possibly damaging	Het

Other mutations in Hecw2

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00092:Hecw2	APN	1	53830737	missense	probably damaging	1.00
IGL00338:Hecw2	APN	1	53827881	splice site	probably benign
IGL00530:Hecw2	APN	1	53853280	missense	probably damaging	1.00
IGL01343:Hecw2	APN	1	53826976	missense	probably damaging	0.96
IGL01503:Hecw2	APN	1	53826961	missense	probably damaging	1.00
IGL01989:Hecw2	APN	1	53840792	missense	probably damaging	1.00
IGL02016:Hecw2	APN	1	53831543	missense	possibly damaging	0.73
IGL02052:Hecw2	APN	1	53926511	missense	probably benign
IGL02085:Hecw2	APN	1	53942802	critical splice acceptor site	probably null
IGL02302:Hecw2	APN	1	53933248	missense	probably damaging	1.00
IGL02310:Hecw2	APN	1	53923916	missense	probably null	0.38
IGL02388:Hecw2	APN	1	53925699	missense	probably benign	0.17
IGL02499:Hecw2	APN	1	53926488	missense	probably benign
IGL02695:Hecw2	APN	1	53926209	missense	possibly damaging	0.94
IGL02732:Hecw2	APN	1	53926688	splice site	probably benign
IGL03100:Hecw2	APN	1	53831656	missense	probably damaging	1.00
IGL03175:Hecw2	APN	1	53926257	missense	possibly damaging	0.51
IGL03253:Hecw2	APN	1	53832716	missense	possibly damaging	0.85
IGL03356:Hecw2	APN	1	53927058	splice site	probably benign
Memoriam	UTSW	1	53926056	missense	probably benign
recollect	UTSW	1	53904422	missense	possibly damaging	0.88
ANU74:Hecw2	UTSW	1	53925694	missense	probably benign	0.01
R0077:Hecw2	UTSW	1	53868831	splice site	probably benign
R0133:Hecw2	UTSW	1	53830740	missense	probably damaging	1.00
R0268:Hecw2	UTSW	1	53926698	splice site	probably benign
R1303:Hecw2	UTSW	1	54040393	missense	probably benign	0.00
R1460:Hecw2	UTSW	1	53813245	missense	probably damaging	0.96
R1524:Hecw2	UTSW	1	53851618	missense	probably damaging	1.00
R1533:Hecw2	UTSW	1	53926545	splice site	probably null
R1828:Hecw2	UTSW	1	53926023	missense	probably benign
R2170:Hecw2	UTSW	1	53942797	missense	probably damaging	0.99
R2338:Hecw2	UTSW	1	53904422	missense	possibly damaging	0.88
R3016:Hecw2	UTSW	1	53830680	missense	probably damaging	1.00
R3872:Hecw2	UTSW	1	53832757	splice site	probably benign
R3892:Hecw2	UTSW	1	53926121	missense	probably benign	0.01
R4086:Hecw2	UTSW	1	53831656	missense	probably damaging	1.00
R4247:Hecw2	UTSW	1	53832645	missense	probably damaging	1.00
R4248:Hecw2	UTSW	1	53832645	missense	probably damaging	1.00
R4249:Hecw2	UTSW	1	53832645	missense	probably damaging	1.00
R4545:Hecw2	UTSW	1	53813222	makesense	probably null
R4805:Hecw2	UTSW	1	53840859	missense	probably damaging	1.00
R4834:Hecw2	UTSW	1	53830752	missense	probably damaging	1.00
R4884:Hecw2	UTSW	1	53950841	missense	probably benign	0.03
R5168:Hecw2	UTSW	1	53913300	missense	probably damaging	1.00
R5482:Hecw2	UTSW	1	53926201	missense	probably benign	0.09
R5549:Hecw2	UTSW	1	53925691	missense	possibly damaging	0.91
R5623:Hecw2	UTSW	1	53832623	missense	probably null	1.00
R5740:Hecw2	UTSW	1	53887603	missense	probably benign	0.12
R5919:Hecw2	UTSW	1	53937090	missense	probably damaging	0.99
R6058:Hecw2	UTSW	1	53923976	missense	possibly damaging	0.67
R6460:Hecw2	UTSW	1	53868833	splice site	probably null
R6875:Hecw2	UTSW	1	53937132	missense	probably benign	0.01
R7097:Hecw2	UTSW	1	53865124	missense	possibly damaging	0.88
R7131:Hecw2	UTSW	1	53865121	missense	probably damaging	1.00
R7291:Hecw2	UTSW	1	53914594	missense	probably damaging	1.00
R7401:Hecw2	UTSW	1	53904343	missense	probably damaging	1.00
R7482:Hecw2	UTSW	1	54040470	missense	probably damaging	0.99
R7501:Hecw2	UTSW	1	53913872	critical splice acceptor site	probably null
R7520:Hecw2	UTSW	1	53926056	missense	probably benign
R7611:Hecw2	UTSW	1	53913300	missense	probably damaging	1.00
R8184:Hecw2	UTSW	1	54040387	missense	probably benign	0.37
R8286:Hecw2	UTSW	1	53840769	missense	probably damaging	1.00
R8300:Hecw2	UTSW	1	53887616	missense	probably null	0.07
R8362:Hecw2	UTSW	1	54040491	start codon destroyed	probably null	0.51
Z1177:Hecw2	UTSW	1	53923943	missense	possibly damaging	0.95

Predicted Primers

PCR Primer
(F):5'- TCTGTAGTTGGCAGAATTTTGCAC -3'
(R):5'- TGTCATGAAGCCTGAGCCTC -3'

Sequencing Primer
(F):5'- CTATATGCCTTTAGCTTTAGTTGCAG -3'
(R):5'- ATGAAGCCTGAGCCTCCTTCC -3'

Posted On

2016-05-10