Mutagenetix > Incidental Mutation

Incidental Mutation 'F5493:Pex1'

568

Institutional Source

Beutler Lab

Gene Symbol

Pex1

Ensembl Gene

ENSMUSG00000005907

Gene Name

peroxisomal biogenesis factor 1

Synonyms

peroxisome biogenesis factor 1, 5430414H02Rik, E330005K07Rik, ZWS1

Accession Numbers

Essential gene?

Possibly essential (E-score: 0.503) question?

Stock #

F5493 (G1)

Quality Score

Status

Validated

Chromosome

Chromosomal Location

3646066-3687230 bp(+) (GRCm39)

Type of Mutation

critical splice donor site (2 bp from exon)

DNA Base Change (assembly)

T to G at 3685912 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Ref Sequence

ENSEMBL: ENSMUSP00000113304 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000006061] [ENSMUST00000007559] [ENSMUST00000121291] [ENSMUST00000140871]

AlphaFold

Q5BL07

Predicted Effect

probably null
Transcript: ENSMUST00000006061

SMART Domains

Protein: ENSMUSP00000006061
Gene: ENSMUSG00000005907

Domain	Start	End	E-Value	Type
Pfam:PEX-2N	14	99	2.4e-53	PFAM
Pfam:PEX-1N	103	179	8.6e-27	PFAM
low complexity region	508	527	N/A	INTRINSIC
AAA	552	702	1.39e-10	SMART
low complexity region	754	765	N/A	INTRINSIC
AAA	834	970	4.07e-17	SMART
low complexity region	1024	1044	N/A	INTRINSIC
low complexity region	1051	1061	N/A	INTRINSIC
low complexity region	1065	1078	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000007559

SMART Domains

Protein: ENSMUSP00000007559
Gene: ENSMUSG00000007415

Domain	Start	End	E-Value	Type
SCOP:d1gnf__	7	33	9e-5	SMART
low complexity region	34	83	N/A	INTRINSIC

Predicted Effect

probably null
Transcript: ENSMUST00000121291

SMART Domains

Protein: ENSMUSP00000113304
Gene: ENSMUSG00000005907

Domain	Start	End	E-Value	Type
Pfam:PEX-2N	17	98	8.7e-38	PFAM
Pfam:PEX-1N	104	179	1.4e-27	PFAM
low complexity region	548	567	N/A	INTRINSIC
AAA	592	742	1.39e-10	SMART
low complexity region	794	805	N/A	INTRINSIC
AAA	874	1010	4.07e-17	SMART
low complexity region	1064	1084	N/A	INTRINSIC
low complexity region	1091	1101	N/A	INTRINSIC
low complexity region	1105	1118	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000140871

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000196432

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000197167

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000199213

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000199632

Meta Mutation Damage Score

0.9500

Coding Region Coverage

1x: 76.6%
3x: 51.4%

Het Detection Efficiency

27.8%

Validation Efficiency

67% (74/111)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a member of the AAA ATPase family, a large group of ATPases associated with diverse cellular activities. This protein is cytoplasmic but is often anchored to a peroxisomal membrane where it forms a heteromeric complex and plays a role in the import of proteins into peroxisomes and peroxisome biogenesis. Mutations in this gene have been associated with complementation group 1 peroxisomal disorders such as neonatal adrenoleukodystrophy, infantile Refsum disease, and Zellweger syndrome. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2013]
PHENOTYPE: Mice homozygous for a knock-in allele display premature death, postnatal growth retardation, fatty livers, a bile acid defect associated with intestinal lipid malabsorption and cholestasis, and a retinopathy associated with retinal cone cell degenerationand abnormal cone and rod electrophysiology. [provided by MGI curators]

Allele List at MGI

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

Other mutations in this stock

Total: 10 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Cars1	T	A	7: 143,123,608 (GRCm39)	T448S	probably damaging	Het
Cdca2	T	A	14: 67,915,141 (GRCm39)	N706I	probably damaging	Het
Fat1	A	G	8: 45,478,517 (GRCm39)	E2521G	probably damaging	Het
Fmo2	C	A	1: 162,708,101 (GRCm39)	V345L	probably benign	Het
Frrs1l	T	C	4: 56,968,293 (GRCm39)	M160V	probably benign	Het
Nckap5	A	T	1: 125,953,564 (GRCm39)	M996K	probably benign	Het
Nlrp4d	A	T	7: 10,115,011 (GRCm39)	D568E	possibly damaging	Het
Ptprd	A	G	4: 76,002,645 (GRCm39)	L17P	probably damaging	Het
Tnfsf13b	T	A	8: 10,056,916 (GRCm39)	V25E	probably damaging	Het
Zfp386	T	C	12: 116,023,922 (GRCm39)	Y512H	probably damaging	Het

Other mutations in Pex1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL01287:Pex1	APN	5	3,656,027 (GRCm39)	missense	probably benign	0.00
IGL01315:Pex1	APN	5	3,659,975 (GRCm39)	missense	probably damaging	1.00
IGL01671:Pex1	APN	5	3,674,088 (GRCm39)	missense	probably benign	0.00
IGL01863:Pex1	APN	5	3,656,066 (GRCm39)	missense	probably benign	0.01
IGL01933:Pex1	APN	5	3,683,789 (GRCm39)	missense	probably damaging	1.00
IGL01960:Pex1	APN	5	3,677,588 (GRCm39)	unclassified	probably benign
IGL02347:Pex1	APN	5	3,653,350 (GRCm39)	missense	probably damaging	0.98
IGL02374:Pex1	APN	5	3,685,481 (GRCm39)	missense	probably benign	0.01
IGL02392:Pex1	APN	5	3,655,952 (GRCm39)	nonsense	probably null
IGL02597:Pex1	APN	5	3,685,865 (GRCm39)	missense	possibly damaging	0.50
IGL02703:Pex1	APN	5	3,665,120 (GRCm39)	missense	probably benign	0.24
IGL02815:Pex1	APN	5	3,686,797 (GRCm39)	missense	probably damaging	0.97
IGL02862:Pex1	APN	5	3,655,424 (GRCm39)	intron	probably benign
IGL03005:Pex1	APN	5	3,680,292 (GRCm39)	missense	probably null	0.96
E0370:Pex1	UTSW	5	3,681,614 (GRCm39)	splice site	probably null
R0014:Pex1	UTSW	5	3,676,141 (GRCm39)	unclassified	probably benign
R0014:Pex1	UTSW	5	3,676,141 (GRCm39)	unclassified	probably benign
R0401:Pex1	UTSW	5	3,683,759 (GRCm39)	missense	probably damaging	1.00
R0480:Pex1	UTSW	5	3,656,444 (GRCm39)	splice site	probably null
R0555:Pex1	UTSW	5	3,656,130 (GRCm39)	missense	possibly damaging	0.89
R0976:Pex1	UTSW	5	3,683,943 (GRCm39)	missense	probably benign	0.00
R1200:Pex1	UTSW	5	3,656,411 (GRCm39)	critical splice donor site	probably null
R1672:Pex1	UTSW	5	3,676,085 (GRCm39)	missense	probably damaging	1.00
R1753:Pex1	UTSW	5	3,680,044 (GRCm39)	missense	probably damaging	1.00
R1880:Pex1	UTSW	5	3,655,770 (GRCm39)	missense	probably benign
R1953:Pex1	UTSW	5	3,680,038 (GRCm39)	missense	probably damaging	1.00
R2054:Pex1	UTSW	5	3,653,341 (GRCm39)	missense	possibly damaging	0.78
R2081:Pex1	UTSW	5	3,674,132 (GRCm39)	critical splice donor site	probably null
R2237:Pex1	UTSW	5	3,668,915 (GRCm39)	critical splice donor site	probably null
R3946:Pex1	UTSW	5	3,676,084 (GRCm39)	missense	probably damaging	1.00
R4528:Pex1	UTSW	5	3,681,712 (GRCm39)	missense	probably damaging	1.00
R4579:Pex1	UTSW	5	3,668,880 (GRCm39)	missense	probably benign	0.03
R4585:Pex1	UTSW	5	3,683,885 (GRCm39)	missense	probably damaging	1.00
R4586:Pex1	UTSW	5	3,683,885 (GRCm39)	missense	probably damaging	1.00
R4656:Pex1	UTSW	5	3,654,880 (GRCm39)	critical splice donor site	probably null
R4789:Pex1	UTSW	5	3,680,270 (GRCm39)	missense	probably damaging	0.98
R4850:Pex1	UTSW	5	3,674,426 (GRCm39)	missense	probably benign
R4963:Pex1	UTSW	5	3,659,924 (GRCm39)	missense	probably benign	0.01
R5005:Pex1	UTSW	5	3,672,310 (GRCm39)	missense	probably damaging	1.00
R5015:Pex1	UTSW	5	3,670,597 (GRCm39)	missense	probably damaging	1.00
R5019:Pex1	UTSW	5	3,672,331 (GRCm39)	missense	probably damaging	1.00
R5937:Pex1	UTSW	5	3,674,487 (GRCm39)	missense	possibly damaging	0.94
R5942:Pex1	UTSW	5	3,660,277 (GRCm39)	missense	probably benign	0.04
R5995:Pex1	UTSW	5	3,657,704 (GRCm39)	missense	possibly damaging	0.53
R6434:Pex1	UTSW	5	3,680,196 (GRCm39)	nonsense	probably null
R6552:Pex1	UTSW	5	3,673,953 (GRCm39)	missense	probably damaging	1.00
R6777:Pex1	UTSW	5	3,672,358 (GRCm39)	missense	probably benign	0.01
R6877:Pex1	UTSW	5	3,685,505 (GRCm39)	missense	probably benign	0.19
R6948:Pex1	UTSW	5	3,655,994 (GRCm39)	missense	probably benign	0.00
R7317:Pex1	UTSW	5	3,668,875 (GRCm39)	missense	probably damaging	1.00
R7408:Pex1	UTSW	5	3,680,222 (GRCm39)	missense	probably damaging	1.00
R7658:Pex1	UTSW	5	3,646,244 (GRCm39)	unclassified	probably benign
R8062:Pex1	UTSW	5	3,655,656 (GRCm39)	missense	probably benign
R8354:Pex1	UTSW	5	3,681,707 (GRCm39)	missense	probably damaging	1.00
R8366:Pex1	UTSW	5	3,676,007 (GRCm39)	missense	probably benign	0.00
R8482:Pex1	UTSW	5	3,662,923 (GRCm39)	missense	probably benign	0.00
R8673:Pex1	UTSW	5	3,685,886 (GRCm39)	missense	possibly damaging	0.65
R8812:Pex1	UTSW	5	3,681,614 (GRCm39)	missense	probably benign	0.00
R9004:Pex1	UTSW	5	3,662,914 (GRCm39)	missense	probably benign	0.01
R9031:Pex1	UTSW	5	3,686,844 (GRCm39)	missense	probably damaging	1.00
R9080:Pex1	UTSW	5	3,655,476 (GRCm39)	missense	probably damaging	1.00
R9586:Pex1	UTSW	5	3,676,047 (GRCm39)	missense	probably damaging	0.98
R9655:Pex1	UTSW	5	3,655,653 (GRCm39)	missense	probably damaging	1.00
R9758:Pex1	UTSW	5	3,685,876 (GRCm39)	missense	probably damaging	0.96
X0019:Pex1	UTSW	5	3,655,653 (GRCm39)	missense	probably damaging	1.00
X0027:Pex1	UTSW	5	3,680,270 (GRCm39)	missense	probably damaging	0.98
Z1088:Pex1	UTSW	5	3,656,075 (GRCm39)	missense	probably benign	0.06

Nature of Mutation

DNA sequencing using the SOLiD technique identified a T to G transversion at base pair 3635912 in the Genbank genomic region NC_000071(Build 37.1) for the Pex1 gene on Chromosome 5 (GTAAGTAACC ->GGAAGTAACC). The mutation is located within intron 22 from the ATG exon, two nucleotides from the previous exon. The Pex1 gene contains 23 total exons (Genbank record NM_027777). Multiple transcripts of the Pex1 gene are displayed on Ensembl and Vega. The mutation has been confirmed by DNA sequencing using the Sanger method (see related file).

Protein Function and Prediction

The Pex1 gene encodes a 1284amino acid protein that is a member of the AAA ATPase family and is involved in peroxisome biosynthesis. Two isoforms are produced by alternative splicing. PEX1 is required for stability of PEX5 and protein import into the peroxisome matrix. The protein is anchored by PEX26 to peroxisome membranes, possibly to form heteromeric AAA ATPase complexes required for the import of proteins into peroxisomes. PEX1 directly interacts with PEX6. ATP binding occurs at residues 600-607 and 745-752 (Uniprot Q5BL07). In humans, mutations in the PEX1 gene cause peroxisomal biogenesis disorders (PBDs; OMIM 601539).

Posted On

2010-11-29