Fetal anomalies
Gene: PEX6

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

3 reviews

Arina Puzriakova (Genomics England Curator)

The mode of inheritance of this gene has been updated to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Created: 30 Jan 2023, 4:26 p.m. | Last Modified: 30 Jan 2023, 4:26 p.m.

Panel Version: 2.10

Created: 30 Jan 2023, 4:26 p.m.
Last Modified: 30 Jan 2023, 4:26 p.m.
Panel version: 2.10

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, 3:35 p.m. | Last Modified: 1 Apr 2022, 3:35 p.m.

Panel Version: 1.847

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, 3:33 p.m. | Last Modified: 1 Apr 2022, 3:33 p.m.

Panel Version: 1.845

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Mode of pathogenicity
Other

Created: 1 Apr 2022, 3:33 p.m.
Last Modified: 1 Apr 2022, 3:33 p.m.
Panel version: 1.847

Rebecca Foulger (Genomics England curator)

Green List (high evidence)

This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in March 2019. Clinical review and curation was performed by Lyn Chitty, Anna de Burca, Rhiannon Mellis, Richard Scott, Ellen McDonagh and Rebecca Foulger. Outcome of review: Confirmed that phenotype is fetally-relevant: keep on the Fetal anomalies panel as a Green gene.
Created: 4 Apr 2019, 10:28 a.m.

DDG2P rating in original PAGE list: Confirmed for ZELLWEGER SYNDROME and Confirmed for PEROXISOME BIOGENESIS DISORDER COMPLEMENTATION GROUP 4.
Created: 11 Dec 2018, 9:05 a.m.

Created: 11 Dec 2018, 9:05 a.m.

Panel version: 0.153

Details

Mode of Inheritance

BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Sources

NHS GMS
PAGE 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

30 Jan 2023, Gel status: 3

Removed Tag

Arina Puzriakova (Genomics England Curator)

Tag Q1_22_MOI was removed from gene: PEX6.

30 Jan 2023, Gel status: 3

Added New Source, Set mode of inheritance

Arina Puzriakova (Genomics England Curator)

Source NHS GMS was added to PEX6. Mode of inheritance for gene PEX6 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal

1 Apr 2022, Gel status: 3