DDG2P
Gene: PEX6

PEX6 (peroxisomal biogenesis factor 6)
EnsemblGeneIds (GRCh38): ENSG00000124587
EnsemblGeneIds (GRCh37): ENSG00000124587
OMIM: 601498, Gene2Phenotype
PEX6 is in 23 panels

4 reviews

Achchuthan Shanmugasundram (Genomics England Curator)

Green List (high evidence)

The DDG2P confidence category for the disease PEROXISOME BIOGENESIS DISORDER COMPLEMENTATION GROUP 4, OMIM:601498 is definitive. The allelic requirement and mutation consequence are biallelic_autosomal and absent gene product.
Created: 4 Oct 2023, 5:08 p.m. | Last Modified: 4 Oct 2023, 5:08 p.m.

Panel Version: 3.12

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
PEROXISOME BIOGENESIS DISORDER COMPLEMENTATION GROUP 4, OMIM:601498

Created: 4 Oct 2023, 5:08 p.m.
Last Modified: 4 Oct 2023, 5:08 p.m.
Panel version: 3.12

Eleanor Williams (Genomics England Curator)

Removed the GMS review tags for this gene. Although there is evidence for both monoallelic and biallelic variants in this gene being associated with a relevant phenotype, this panel is intended to reflect the DD panel from Gene2Phenotype.

This gene is green with a mode of inheritance of both mono and biallelic on the Intellectual disability panel which is also part of the paediatric disorders super panel and so no variants will be excluded due to the biallelic mode of inheritance here.
Created: 3 Aug 2022, 4:28 p.m. | Last Modified: 3 Aug 2022, 4:28 p.m.

Panel Version: 2.76

Created: 3 Aug 2022, 4:28 p.m.
Last Modified: 3 Aug 2022, 4:28 p.m.
Panel version: 2.76

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, 3:29 p.m. | Last Modified: 1 Apr 2022, 3:31 p.m.

Panel Version: 2.68

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. Incomplete penetrance has been noted, in order to highlight that unaffected parents may also carry rs61753230.
Created: 1 Apr 2022, 3:28 p.m. | Last Modified: 1 Apr 2022, 3:28 p.m.

Panel Version: 2.67

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
29220678

Mode of pathogenicity
Other

Created: 1 Apr 2022, 3:28 p.m.
Last Modified: 1 Apr 2022, 3:31 p.m.
Panel version: 2.67

Rebecca Foulger (Genomics England curator)

I don't know

Original DDG2P rating: confirmed (for all listed disorders).
Created: 19 Nov 2018, 11:30 a.m.

Created: 19 Nov 2018, 11:30 a.m.

Panel version: 0.2

Details

Mode of Inheritance

BIALLELIC, autosomal or pseudoautosomal

Sources

DD-Gene2Phenotype
Expert Review Green

Phenotypes

Heimler syndrome 2, OMIM:616617
Peroxisome biogenesis disorder 4A (Zellweger), OMIM:614862
Peroxisome biogenesis disorder 4B, OMIM:614863

OMIM

601498

Clinvar variants

Variants in PEX6

Penetrance

Incomplete

Publications

29220678

Panels with this gene

History Filter Activity

3 Aug 2022, Gel status: 3

Removed Tag

Eleanor Williams (Genomics England Curator)

Tag Q1_22_MOI was removed from gene: PEX6.

1 Apr 2022, Gel status: 3