Genes in panel

Hereditary ataxia - adult onset

Gene: PEX6

Green List (high evidence)

PEX6 (peroxisomal biogenesis factor 6)
EnsemblGeneIds (GRCh38): ENSG00000124587
EnsemblGeneIds (GRCh37): ENSG00000124587
OMIM: 601498, Gene2Phenotype
PEX6 is in 24 panels

3 reviews

Sarah Leigh (Genomics England Curator)

For Peroxisome biogenesis disorder 4B (OMIM:614863), Falkenberg et al (PMID: 29220678) has identified Allelic Expression Imbalance (AEI) as a mechanism responsible for the condition. Affected patients (7 unrelated cases) were monoallelic for rs61753230 (c.2578C>T, p.Arg860Trp) and rs144286892 (c.∗442_445 delTAAA), with these variants being on the same chromosome (cis). It would appear that rs144286892 causes the over expression of the allele that it is on, resulting in over expression of rs61753230. The unaffected parents analysed were monoallelic for rs61753230 and biallelic for rs144286892, resulting in overexpression of both rs61753230 and wild type alleles (PMID: 29220678). Experimental evidence revealed that rs61753230 has a dominant-negative effect on the function of the PEX1- PEX6 complex in peroxisomal matrix protein import (PMID: 29220678).
Created: 1 Apr 2022, 3:55 p.m. | Last Modified: 1 Apr 2022, 3:55 p.m.
Panel Version: 2.153
Comment on mode of inheritance: The Q1_22_MOI tag has been added to this gene. The mode of inheritance for PEX6 should be set to: BOTH monoallelic and biallelic, autosomal or pseudoautosomal, in order to detect the dominant Peroxisome biogenesis disorder 4B (OMIM:614863). Incomplete penetrance has been noted, in order to highlight that unaffected parents may also carry rs61753230.
Created: 1 Apr 2022, 3:54 p.m. | Last Modified: 1 Apr 2022, 3:54 p.m.
Panel Version: 2.153

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Mode of pathogenicity
Other

Louise Daugherty (Genomics England Curator)

I don't know

Review and rating from Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group.
Created: 15 Apr 2019, 10:21 a.m.

Tracy Lester (Genetics laboratory, Oxford UK)

Green List (high evidence)

Lots of cases in lit, ataxia seems to be associated with type 4B. PMID 26669662 also reports a homozygous missense variant in associated with spinocerebellar ataxia with blindness and deafness (no other cases that I can find)
Created: 15 Apr 2019, 10:06 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Peroxisome biogenesis disorder 4A, 614862 and 4B, 614863

History Filter Activity

1 Apr 2022, Gel status: 3

Set mode of pathogenicity, Set penetrance

Sarah Leigh (Genomics England Curator)

Mode of pathogenicity for gene PEX6 was changed from to Other Penetrance for gene PEX6 was set from to None

1 Apr 2022, Gel status: 3

Added Tag

Sarah Leigh (Genomics England Curator)

Tag Q1_22_MOI tag was added to gene: PEX6.

1 Apr 2022, Gel status: 3

Set mode of inheritance

Sarah Leigh (Genomics England Curator)

Mode of inheritance for gene: PEX6 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal

1 Apr 2022, Gel status: 3

Set Phenotypes

Sarah Leigh (Genomics England Curator)

Phenotypes for gene: PEX6 were changed from Peroxisome biogenesis disorder 4A, 614862; Peroxisome biogenesis disorder 4B, 614863 to Peroxisome biogenesis disorder 4A (Zellweger), OMIM:614862; Peroxisome biogenesis disorder 4B, OMIM:614863

1 Apr 2022, Gel status: 3

Set publications

Sarah Leigh (Genomics England Curator)

Publications for gene: PEX6 were set to

27 Apr 2019, Gel status: 3

Set mode of inheritance

Louise Daugherty (Genomics England Curator)

Mode of inheritance for gene: PEX6 was changed from to BIALLELIC, autosomal or pseudoautosomal

27 Apr 2019, Gel status: 3

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: pex6 has been classified as Green List (High Evidence).

15 Apr 2019, Gel status: 1

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Added phenotypes Peroxisome biogenesis disorder 4A, 614862; Peroxisome biogenesis disorder 4B, 614863 for gene: PEX6

14 Apr 2019, Gel status: 1

Added New Source

Louise Daugherty (Genomics England Curator)

Source NHS GMS was added to PEX6.

14 Apr 2019, Gel status: 1

Created, Added New Source, Set mode of inheritance

Louise Daugherty (Genomics England Curator)

gene: PEX6 was added gene: PEX6 was added to Hereditary ataxia - adult onset. Sources: Wessex and West Midlands GLH Mode of inheritance for gene: PEX6 was set to