Mutagenetix > Incidental Mutation

Incidental Mutation 'G5030:Usp40'

510

Institutional Source

Beutler Lab

Gene Symbol

Usp40

Ensembl Gene

ENSMUSG00000005501

Gene Name

ubiquitin specific peptidase 40

Synonyms

B230215L03Rik

Accession Numbers

Essential gene?

Non essential (E-score: 0.000) question?

Stock #

G5030 (G3) of strain 560

Quality Score

Status

Validated

Chromosome

Chromosomal Location

87872841-87936273 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to T at 87921941 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Histidine to Glutamine at position 307 (H307Q)

Ref Sequence

ENSEMBL: ENSMUSP00000140107 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000040783] [ENSMUST00000187758] [ENSMUST00000188332]

AlphaFold

Q8BWR4

Predicted Effect

probably damaging
Transcript: ENSMUST00000040783
AA Change: H307Q

PolyPhen 2 Score 0.996 (Sensitivity: 0.55; Specificity: 0.98)

SMART Domains

Protein: ENSMUSP00000038533
Gene: ENSMUSG00000005501
AA Change: H307Q

Domain	Start	End	E-Value	Type
Pfam:UCH	40	344	1.1e-31	PFAM
Pfam:UCH_1	41	320	1.2e-20	PFAM
low complexity region	641	650	N/A	INTRINSIC

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000186315

Predicted Effect

probably damaging
Transcript: ENSMUST00000187758
AA Change: H307Q

PolyPhen 2 Score 0.996 (Sensitivity: 0.55; Specificity: 0.98)

SMART Domains

Protein: ENSMUSP00000140107
Gene: ENSMUSG00000005501
AA Change: H307Q

Domain	Start	End	E-Value	Type
Pfam:UCH	40	346	8.7e-41	PFAM
Pfam:UCH_1	41	319	2.4e-22	PFAM
low complexity region	641	650	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000188332

SMART Domains

Protein: ENSMUSP00000140574
Gene: ENSMUSG00000005501

Domain	Start	End	E-Value	Type
Pfam:UCH	40	70	5.9e-6	PFAM

Meta Mutation Damage Score

0.5251

Coding Region Coverage

1x: 81.1%
3x: 60.2%

Het Detection Efficiency

35.6%

Validation Efficiency

87% (206/237)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] Modification of cellular proteins by ubiquitin is an essential regulatory mechanism controlled by the coordinated action of multiple ubiquitin-conjugating and deubiquitinating enzymes. USP40 belongs to a large family of cysteine proteases that function as deubiquitinating enzymes (Quesada et al., 2004 [PubMed 14715245]).[supplied by OMIM, Mar 2008]

Allele List at MGI

All alleles(4) : Targeted, other(2) Gene trapped(2)

Other mutations in this stock

Total: 30 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abca8a	T	A	11: 109,961,165 (GRCm39)	I585F	probably damaging	Het
Adam18	C	G	8: 25,141,872 (GRCm39)	L232F	probably benign	Homo
Atp13a4	A	G	16: 29,274,306 (GRCm39)	I385T	probably damaging	Homo
Ccdc17	T	A	4: 116,455,699 (GRCm39)	S277T	probably benign	Het
Ccng1	A	G	11: 40,644,629 (GRCm39)		probably benign	Het
Ces1f	T	C	8: 94,000,847 (GRCm39)	D99G	probably benign	Het
Clec16a	G	A	16: 10,389,425 (GRCm39)	R187Q	probably damaging	Homo
Cryl1	C	T	14: 57,579,595 (GRCm39)		probably benign	Het
Cryzl2	C	T	1: 157,292,580 (GRCm39)	Q48*	probably null	Het
Dtx4	A	G	19: 12,446,943 (GRCm39)	L583P	probably benign	Het
Ephx4	A	T	5: 107,577,693 (GRCm39)	D339V	probably damaging	Het
Eri2	A	T	7: 119,385,601 (GRCm39)	V300E	possibly damaging	Het
F3	T	A	3: 121,518,648 (GRCm39)	N37K	probably damaging	Homo
Fpr1	A	T	17: 18,097,068 (GRCm39)	L307H	probably damaging	Het
Fv1	T	A	4: 147,953,618 (GRCm39)	N61K	possibly damaging	Het
Gm5548	T	C	3: 112,961,512 (GRCm39)		noncoding transcript	Homo
Il1r1	A	G	1: 40,352,323 (GRCm39)	K498E	possibly damaging	Homo
Myh11	T	C	16: 14,068,443 (GRCm39)	I192M	probably damaging	Homo
Nckap5	T	C	1: 125,953,591 (GRCm39)	K923R	probably damaging	Het
Nmbr	A	T	10: 14,642,747 (GRCm39)	Y102F	possibly damaging	Het
Or6c75	A	G	10: 129,337,406 (GRCm39)	T218A	probably benign	Homo
Pde1a	C	T	2: 79,718,180 (GRCm39)		probably benign	Het
Pex6	T	C	17: 47,026,382 (GRCm39)		probably benign	Het
Rtn2	T	C	7: 19,027,099 (GRCm39)	S305P	probably damaging	Homo
Saal1	G	A	7: 46,342,207 (GRCm39)	T412I	probably damaging	Homo
Slc46a2	A	T	4: 59,913,867 (GRCm39)	I352N	probably damaging	Het
Trim37	A	T	11: 87,033,967 (GRCm39)	H99L	probably damaging	Het
Tubgcp4	C	T	2: 121,014,815 (GRCm39)	R242C	probably damaging	Het
Twf2	C	A	9: 106,084,141 (GRCm39)	L27I	possibly damaging	Het
Zfhx3	T	G	8: 109,678,091 (GRCm39)	V3047G	possibly damaging	Het

Other mutations in Usp40

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00264:Usp40	APN	1	87,931,960 (GRCm39)	splice site	probably benign
IGL00828:Usp40	APN	1	87,906,028 (GRCm39)	unclassified	probably benign
IGL01090:Usp40	APN	1	87,890,187 (GRCm39)	missense	probably benign	0.01
IGL01123:Usp40	APN	1	87,913,845 (GRCm39)	missense	probably benign	0.01
IGL01401:Usp40	APN	1	87,921,920 (GRCm39)	missense	probably damaging	1.00
IGL02506:Usp40	APN	1	87,909,738 (GRCm39)	missense	probably damaging	0.98
IGL02580:Usp40	APN	1	87,908,688 (GRCm39)	splice site	probably null
IGL02625:Usp40	APN	1	87,877,739 (GRCm39)	missense	probably benign	0.19
IGL02811:Usp40	APN	1	87,923,458 (GRCm39)	missense	probably damaging	1.00
IGL02958:Usp40	APN	1	87,906,207 (GRCm39)	missense	probably damaging	0.99
Brink	UTSW	1	87,908,755 (GRCm39)	missense	probably benign	0.11
void	UTSW	1	87,923,435 (GRCm39)	nonsense	probably null
R0019:Usp40	UTSW	1	87,906,133 (GRCm39)	missense	probably benign	0.00
R0282:Usp40	UTSW	1	87,908,680 (GRCm39)	splice site	probably benign
R0453:Usp40	UTSW	1	87,874,320 (GRCm39)	makesense	probably null
R0646:Usp40	UTSW	1	87,906,244 (GRCm39)	missense	probably benign	0.00
R1440:Usp40	UTSW	1	87,909,808 (GRCm39)	missense	probably benign	0.01
R1490:Usp40	UTSW	1	87,916,687 (GRCm39)	nonsense	probably null
R1620:Usp40	UTSW	1	87,921,947 (GRCm39)	missense	probably damaging	1.00
R1881:Usp40	UTSW	1	87,921,993 (GRCm39)	missense	probably benign	0.08
R1903:Usp40	UTSW	1	87,909,778 (GRCm39)	missense	probably benign	0.15
R1912:Usp40	UTSW	1	87,874,368 (GRCm39)	missense	probably benign	0.00
R1919:Usp40	UTSW	1	87,923,564 (GRCm39)	missense	possibly damaging	0.75
R1976:Usp40	UTSW	1	87,906,258 (GRCm39)	missense	probably benign	0.00
R2111:Usp40	UTSW	1	87,877,936 (GRCm39)	missense	probably benign	0.17
R2112:Usp40	UTSW	1	87,877,936 (GRCm39)	missense	probably benign	0.17
R2163:Usp40	UTSW	1	87,923,580 (GRCm39)	splice site	probably benign
R2432:Usp40	UTSW	1	87,909,804 (GRCm39)	missense	probably benign
R2865:Usp40	UTSW	1	87,877,701 (GRCm39)	nonsense	probably null
R3885:Usp40	UTSW	1	87,894,991 (GRCm39)	missense	probably damaging	1.00
R4360:Usp40	UTSW	1	87,880,083 (GRCm39)	missense	probably damaging	1.00
R4370:Usp40	UTSW	1	87,925,597 (GRCm39)	missense	probably benign
R4496:Usp40	UTSW	1	87,923,459 (GRCm39)	missense	possibly damaging	0.69
R4714:Usp40	UTSW	1	87,894,901 (GRCm39)	splice site	probably null
R4888:Usp40	UTSW	1	87,913,923 (GRCm39)	critical splice acceptor site	probably null
R4944:Usp40	UTSW	1	87,880,077 (GRCm39)	missense	probably benign	0.10
R5269:Usp40	UTSW	1	87,923,504 (GRCm39)	missense	probably benign	0.01
R5629:Usp40	UTSW	1	87,908,731 (GRCm39)	missense	probably benign
R5696:Usp40	UTSW	1	87,923,474 (GRCm39)	missense	probably benign	0.27
R5756:Usp40	UTSW	1	87,879,413 (GRCm39)	missense	possibly damaging	0.66
R5887:Usp40	UTSW	1	87,927,592 (GRCm39)	missense	probably damaging	1.00
R5910:Usp40	UTSW	1	87,896,122 (GRCm39)	nonsense	probably null
R6014:Usp40	UTSW	1	87,907,738 (GRCm39)	missense	probably damaging	1.00
R6044:Usp40	UTSW	1	87,917,872 (GRCm39)	missense	probably benign
R6083:Usp40	UTSW	1	87,906,281 (GRCm39)	missense	probably benign	0.01
R6299:Usp40	UTSW	1	87,925,649 (GRCm39)	missense	probably damaging	0.99
R6625:Usp40	UTSW	1	87,894,935 (GRCm39)	missense	probably benign	0.01
R6757:Usp40	UTSW	1	87,907,759 (GRCm39)	missense	probably damaging	0.99
R6810:Usp40	UTSW	1	87,908,755 (GRCm39)	missense	probably benign	0.11
R7110:Usp40	UTSW	1	87,913,884 (GRCm39)	missense	probably benign	0.11
R7573:Usp40	UTSW	1	87,913,794 (GRCm39)	missense	probably benign	0.09
R7575:Usp40	UTSW	1	87,877,682 (GRCm39)	missense	probably damaging	1.00
R7634:Usp40	UTSW	1	87,890,152 (GRCm39)	nonsense	probably null
R7756:Usp40	UTSW	1	87,894,922 (GRCm39)	missense	probably damaging	0.99
R7767:Usp40	UTSW	1	87,909,900 (GRCm39)	missense	probably benign	0.01
R7861:Usp40	UTSW	1	87,909,852 (GRCm39)	missense	probably damaging	0.99
R7881:Usp40	UTSW	1	87,923,435 (GRCm39)	nonsense	probably null
R7896:Usp40	UTSW	1	87,906,201 (GRCm39)	missense	possibly damaging	0.77
R8119:Usp40	UTSW	1	87,895,400 (GRCm39)	splice site	probably null
R8354:Usp40	UTSW	1	87,908,694 (GRCm39)	missense	probably benign	0.00
R8358:Usp40	UTSW	1	87,908,770 (GRCm39)	missense	possibly damaging	0.71
R8425:Usp40	UTSW	1	87,887,558 (GRCm39)	missense	probably benign
R8446:Usp40	UTSW	1	87,906,190 (GRCm39)	missense	probably benign
R8454:Usp40	UTSW	1	87,908,694 (GRCm39)	missense	probably benign	0.00
R8744:Usp40	UTSW	1	87,911,491 (GRCm39)	missense	probably benign
R9002:Usp40	UTSW	1	87,935,063 (GRCm39)	missense	probably benign
R9033:Usp40	UTSW	1	87,923,499 (GRCm39)	utr 3 prime	probably benign
R9210:Usp40	UTSW	1	87,885,035 (GRCm39)	missense	possibly damaging	0.90
R9245:Usp40	UTSW	1	87,878,009 (GRCm39)	missense	probably benign
R9331:Usp40	UTSW	1	87,901,828 (GRCm39)	missense	probably damaging	1.00
R9378:Usp40	UTSW	1	87,885,032 (GRCm39)	missense	probably damaging	1.00
R9379:Usp40	UTSW	1	87,881,889 (GRCm39)	missense	probably benign
R9501:Usp40	UTSW	1	87,925,557 (GRCm39)	missense	probably benign	0.01
R9535:Usp40	UTSW	1	87,935,161 (GRCm39)	start gained	probably benign
R9537:Usp40	UTSW	1	87,935,117 (GRCm39)	missense	probably benign	0.01
RF006:Usp40	UTSW	1	87,894,917 (GRCm39)	missense	possibly damaging	0.47
Z1177:Usp40	UTSW	1	87,896,136 (GRCm39)	missense	probably damaging	1.00

Nature of Mutation

DNA sequencing using the SOLiD technique identified a T to A transversion at position 1054 of the Usp40 transcript in exon 8 of 28 total exons. Two transcripts of the Usp40 gene are displayed on Ensembl. The mutated nucleotide causes a histidine to glutamine substitution at amino acid 307 of the encoded protein. The mutation has been confirmed by DNA sequencing using the Sanger method (Figure 1).

Protein Function and Prediction

The Usp40 gene encodes a 1235 amino acid protein that belongs to a large family of cysteine proteases that function as deubiquitinating enzymes. These enzymes catalyze the thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin. Cys 50 (the nucleophile) and His 305 (the proton acceptor) are key catalytical residues. Several isoforms of this protein have been reported (Uniprot Q8BWR4).

The H307Q change occurs close to the key catalytic histidine (His 305), and is predicted to be probably damaging by the PolyPhen program (see report).

Posted On

2010-10-26