Mutagenetix > Incidental Mutations

Incidental Mutation 'G5030:Dtx4'

483

Institutional Source

Beutler Lab

Gene Symbol

Dtx4

Ensembl Gene

ENSMUSG00000039982

Gene Name

deltex 4, E3 ubiquitin ligase

Synonyms

RNF155

Accession Numbers

Genbank: NM_001047855

Is this an essential gene?

Possibly essential (E-score: 0.548) question?

Stock #

G5030 (G3) of strain 560

Quality Score

Status

Validated

Chromosome

Chromosomal Location

12466341-12501996 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 12469579 bp

Zygosity

Heterozygous

Amino Acid Change

Leucine to Proline at position 583 (L583P)

Ref Sequence

ENSEMBL: ENSMUSP00000040229 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000045521] [ENSMUST00000081035]

Predicted Effect

probably benign
Transcript: ENSMUST00000045521
AA Change: L583P

PolyPhen 2 Score 0.074 (Sensitivity: 0.93; Specificity: 0.85)

SMART Domains

Protein: ENSMUSP00000040229
Gene: ENSMUSG00000039982
AA Change: L583P

Domain	Start	End	E-Value	Type
WWE	5	86	1.38e-38	SMART
WWE	88	163	6.72e-28	SMART
low complexity region	175	192	N/A	INTRINSIC
low complexity region	372	386	N/A	INTRINSIC
RING	406	464	2.2e-6	SMART
Blast:RING	510	532	3e-7	BLAST

Predicted Effect

probably benign
Transcript: ENSMUST00000081035

SMART Domains

Protein: ENSMUSP00000108573
Gene: ENSMUSG00000046805

Domain	Start	End	E-Value	Type
signal peptide	1	26	N/A	INTRINSIC
MACPF	151	350	2.13e-58	SMART
transmembrane domain	661	683	N/A	INTRINSIC
low complexity region	685	698	N/A	INTRINSIC

Meta Mutation Damage Score

0.3772

Coding Region Coverage

1x: 81.1%
3x: 60.2%

Het Detection Efficiency

35.6%

Validation Efficiency

87% (206/237)

Allele List at MGI

All alleles(1) : Gene trapped(1)

Other mutations in this stock

Total: 30 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abca8a	T	A	11: 110,070,339	I585F	probably damaging	Het
Adam18	C	G	8: 24,651,856	L232F	probably benign	Homo
Atp13a4	A	G	16: 29,455,488	I385T	probably damaging	Homo
Ccdc17	T	A	4: 116,598,502	S277T	probably benign	Het
Ccng1	A	G	11: 40,753,802		probably benign	Het
Ces1f	T	C	8: 93,274,219	D99G	probably benign	Het
Clec16a	G	A	16: 10,571,561	R187Q	probably damaging	Homo
Cryl1	C	T	14: 57,342,138		probably benign	Het
Cryzl2	C	T	1: 157,465,010	Q48*	probably null	Het
Ephx4	A	T	5: 107,429,827	D339V	probably damaging	Het
Eri2	A	T	7: 119,786,378	V300E	possibly damaging	Het
F3	T	A	3: 121,724,999	N37K	probably damaging	Homo
Fpr1	A	T	17: 17,876,806	L307H	probably damaging	Het
Fv1	T	A	4: 147,869,161	N61K	possibly damaging	Het
Gm5548	T	C	3: 113,054,196		noncoding transcript	Homo
Il1r1	A	G	1: 40,313,163	K498E	possibly damaging	Homo
Myh11	T	C	16: 14,250,579	I192M	probably damaging	Homo
Nckap5	T	C	1: 126,025,854	K923R	probably damaging	Het
Nmbr	A	T	10: 14,767,003	Y102F	possibly damaging	Het
Olfr790	A	G	10: 129,501,537	T218A	probably benign	Homo
Pde1a	C	T	2: 79,887,836		probably benign	Het
Pex6	T	C	17: 46,715,456		probably benign	Het
Rtn2	T	C	7: 19,293,174	S305P	probably damaging	Homo
Saal1	G	A	7: 46,692,783	T412I	probably damaging	Homo
Slc46a2	A	T	4: 59,913,867	I352N	probably damaging	Het
Trim37	A	T	11: 87,143,141	H99L	probably damaging	Het
Tubgcp4	C	T	2: 121,184,334	R242C	probably damaging	Het
Twf2	C	A	9: 106,206,942	L27I	possibly damaging	Het
Usp40	A	T	1: 87,994,219	H307Q	probably damaging	Het
Zfhx3	T	G	8: 108,951,459	V3047G	possibly damaging	Het

Other mutations in Dtx4

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL01533:Dtx4	APN	19	12478215	missense	possibly damaging	0.88
IGL02173:Dtx4	APN	19	12473257	nonsense	probably null
IGL03127:Dtx4	APN	19	12486500	splice site	probably benign
R0143:Dtx4	UTSW	19	12486482	missense	probably damaging	0.98
R0932:Dtx4	UTSW	19	12492151	missense	probably benign
R1066:Dtx4	UTSW	19	12501009	missense	probably damaging	0.98
R2155:Dtx4	UTSW	19	12485282	nonsense	probably null
R2182:Dtx4	UTSW	19	12483107	missense	probably null	0.75
R2362:Dtx4	UTSW	19	12492535	missense	probably damaging	1.00
R3880:Dtx4	UTSW	19	12486456	missense	probably benign	0.01
R4108:Dtx4	UTSW	19	12501123	missense	probably damaging	0.96
R4361:Dtx4	UTSW	19	12485296	missense	probably benign	0.04
R4943:Dtx4	UTSW	19	12501060	missense	probably damaging	1.00
R5361:Dtx4	UTSW	19	12485262	critical splice donor site	probably null
R5440:Dtx4	UTSW	19	12492317	missense	probably damaging	1.00
R5613:Dtx4	UTSW	19	12485403	missense	probably damaging	0.97
R5614:Dtx4	UTSW	19	12482183	missense	probably damaging	1.00
R5703:Dtx4	UTSW	19	12482210	missense	possibly damaging	0.84
R5994:Dtx4	UTSW	19	12501153	missense	probably damaging	1.00
R6695:Dtx4	UTSW	19	12473235	nonsense	probably null
R7107:Dtx4	UTSW	19	12473260	nonsense	probably null
R7208:Dtx4	UTSW	19	12482073	critical splice donor site	probably null
R7231:Dtx4	UTSW	19	12469658	nonsense	probably null
R7521:Dtx4	UTSW	19	12492497	missense	probably benign	0.30
R7609:Dtx4	UTSW	19	12492281	missense	probably damaging	1.00
R7721:Dtx4	UTSW	19	12482136	missense	probably benign	0.09
R7775:Dtx4	UTSW	19	12492010	missense	probably benign	0.02
Z1176:Dtx4	UTSW	19	12491909	missense	probably benign	0.00

Nature of Mutation

DNA sequencing using the SOLiD technique identified a T to C transition at position 863 of the Dtx4transcript. According to the Genbank record, the Pex6 gene contains 17 total exons. The mutated nucleotide causes a leucine to phenylalanine substitution at amino acid 583 of the encoded protein. The mutation has been confirmed by DNA sequencing using the Sanger method (Figure 1).

Protein Function and Prediction

The Dtx4 gene encodes a 616 amino acid regulator of Notch signaling, a signaling pathway involved in cell-cell communications that regulates a broad spectrum of cell-fate determinations. The protein belongs to the Deltex family and contains a RING-type zinc finger at residues 406-465 and two WWE domains at residues 1-78 and 79-155. The WWE domains are thought to mediate some protein-protein interaction, and are frequently found in ubiquitin ligases (Uniprot Q6PDK8).

The L583P change is predicted to be probably damaging by the PolyPhen program.

Posted On

2010-10-27