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Intellectual disability

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

4 reviews

Sarah Leigh (Genomics England Curator)

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, 4:13 p.m. | Last Modified: 1 Apr 2022, 4:13 p.m.
Panel Version: 3.1533
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, 4:08 p.m. | Last Modified: 1 Apr 2022, 4:08 p.m.
Panel Version: 3.1530

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Mode of pathogenicity
Other

Caroline Wright (Sanger)

Green List (high evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
ZELLWEGER SYNDROME (ZWS)

Publications

  • 0

BRIDGE consortium (NIHRBR-RD)

Green List (high evidence)

This is a pertinent gene from the NIHR BioResource - Rare Diseases Study (NIHRBR-RD) BRIDGE Study : SPEED (Specialist Pathology: Evaluating Exomes in Diagnostics) which covers epilepsies, movement and microcephaly disorders, this gene is on the SPEED_NEURO_20170705 gene list. Evidences used for SPEED NEURO gene list: in_ddg2p_20141118_conf;in_ddg2p_20141118_conf;in_ddg2p_201507;in_ddg2p_201507_conf;in_ddg2p_2_4_2017;in_ddg2p_2_4_2017_conf;in_movement_disorder_list;in_UKGTN_v12 . Main mutation mechanism : Loss of function
Created: 27 Jul 2017, 7:59 p.m.
Evidences key, gene present in following gene lists and main mutation mechanism : ddg2p_20141118; ddg2p_20141118_conf; ddg2p_201507; ddg2p_201507_conf; manju_list; UKGTN_v12; Nijmegen_ID_diagnostic; Nijmegen_ID_candidates; GEL_ID_green_20160217; neuro_20160418_strict; Loss of function. This is a pertinent gene from the BRIDGE Study : SPEED (Specialist Pathology: Evaluating Exomes in Diagnostics) which covers epilepsies, movement and microcephaly disorders, this gene comes from the SPEED_NEURO_v3.0_20170404 gene list. The following experts from the BRIDGE consortium NIHRBR-RD contributed to this panel: - Professor F. Lucy Raymond, Cambridge Institute for Medical Research, University of Cambridge - Manju Kurian, Paediatric neurologist, Great Ormond Street Hosptial - Keren Carss, NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust - Alba Sanchis-Juan, NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust - Marie Erwood NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust - Louise Daugherty, NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust
Created: 19 Jul 2017, 1:04 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

  • 25529582
  • Personal communication with NIHRBRRD BRIDGE SPEED
  • Version 12 ukgtn.nhs.uk

Lu Raymond (university of cambridge )

Green List (high evidence)

History Filter Activity

1 Apr 2022, Gel status: 3

Set penetrance

Sarah Leigh (Genomics England Curator)

Penetrance for gene PEX6 was set from to Complete

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 (Zellweger), 614862Peroxisome biogenesis disorder 4B, 614863; ZELLWEGER SYNDROME (ZWS) 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

1 Apr 2022, Gel status: 3

Added Tag

Sarah Leigh (Genomics England Curator)

Tag Q1_22_MOI tag was added to gene: PEX6.

12 Mar 2018, Gel status: 3

Panel promoted to version 2.0

Ellen McDonagh (Genomics England Curator)

12.03.2018: Due to major updates completed (Phase 1, 2 and 3), this panel was promoted to Version 2 in order to reflect the major updates since November 2017 which have resulted in reviews for 836 genes added by Genomics England Curators and the Clinical Team, 130 new Green genes added to the interpretation pipeline (from 751 to 881 Green genes), and the gene total has increased from 1879 to 1927.

13 Nov 2015, Gel status: 4

gel status update

GEL ()

The Gel status was updated for this whole panel

13 Nov 2015, Gel status: 4

gel status update

GEL ()

The Gel status was updated for this whole panel

13 Nov 2015, Gel status: 1

Set Mode of Inheritance, Added New Source

Ellen McDonagh (Genomics England Curator)

PEX6 was added to Intellectual disabilitypanel. Source: Expert Review Green Model of inheritance for gene PEX6 was set to BIALLELIC, autosomal or pseudoautosomal

24 Jun 2015, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

PEX6 was added to Intellectual disabilitypanel. Sources: Radboud University Medical Center, Nijmegen