Curated summary · agent-written · kb/genes/curated/hgnc_9717.md

All 18 claims checked against the KB draft

PEX2 across dismech

PEX2 (peroxisomal biogenesis factor 2) is named by 3 disorder entries.

Normal function

ai-gene-review gives PEX2's core molecular function as ubiquitin protein ligase activity at the peroxisomal membrane, acting in protein import into peroxisome matrix; protein import into peroxisome matrix, receptor recycling; pexophagy; and negative regulation of triglyceride catabolic process. PEX2 is one of the three RING peroxins of the membrane ligase that monoubiquitinates the matrix-import receptor PEX5 so that it can be recycled.

Causative records

Peroxisome Biogenesis Disorder 5B types PEX2 as causative, with a germline origin and a partial loss of function impact. The gene sits on the node Biallelic PEX2 Genotype With Residual Peroxin-2 Function, which leads to a partial loss of the RING ligase activity and from there to partial failure of matrix-protein import.

Grouping-level records

The broader entries also name PEX2, including Zellweger Spectrum Disorders; and Peroxisome Biogenesis Disorder. Zellweger Spectrum Disorders places it on RING Ubiquitin Ligase Retrotranslocation Failure, and Peroxisome Biogenesis Disorder on Peroxisome Biogenesis Defect. Nodes naming PEX2 conform to the module peroxisomal_metabolic_failure.

Where the layers disagree

ClinGen classifies PEX2 for 1 disease, peroxisome biogenesis disorder as a whole, rated definitive; the dismech entry matched to it that does not type the gene is Peroxisome Biogenesis Disorder.

The KB's PEX2 nodes and ai-gene-review share protein import into peroxisome matrix, receptor recycling by exact GO identifier.

Underlined values are claims re-computed from the knowledge base each time this page is built. The tables below are the source of truth.

Normal function · from ai-gene-review (P28328, commit 79fe13b38970) · AI-generated, not KB evidence

PEX2 (Peroxisome biogenesis factor 2 / Peroxin-2) is an integral peroxisomal membrane protein containing a RING-type zinc finger domain. It functions as an E3 ubiquitin ligase subunit of the PEX2-PEX10-PEX12 retrotranslocation channel complex. This complex catalyzes monoubiquitination of the PTS1 receptor PEX5 at Cys-11, a modification required for ATP-dependent receptor recycling to the cytosol. Each subunit contributes five transmembrane segments that co-assemble into an open channel through which PEX5 is exported. PEX2 also independently mediates ubiquitination of peroxisomal membrane proteins (PEX5, PMP70/ABCD3) during amino acid starvation to induce pexophagy, and ubiquitinates ATGL/PNPLA2 for proteasomal degradation in response to ROS, thereby regulating lipolysis. Mutations in PEX2 cause Zellweger spectrum disorders (complementation group 10).

PEX2 is a RING-finger E3 ubiquitin ligase subunit of the heterotrimeric PEX2-PEX10-PEX12 complex embedded in the peroxisomal membrane. The complex forms a retrotranslocation channel for the PTS1 receptor PEX5, and the PEX2 RING finger (RF2) is positioned above the channel pore to monoubiquitinate the N-terminal cysteine (Cys11) of PEX5 as it is threaded through, licensing ATP-dependent extraction of the receptor to the cytosol by PEX1-PEX6. This receptor-recycling step is essential for sustained peroxisomal matrix protein import, and its loss causes Zellweger spectrum disorders.

molecular function: ubiquitin protein ligase activity · directly involved in: protein import into peroxisome matrix, receptor recycling; protein import into peroxisome matrix · locations: peroxisomal membrane · in complex: ubiquitin ligase complex

Independently of its receptor-recycling role, PEX2 is the E3 ubiquitin ligase that triggers pexophagy: during amino acid starvation (via mTORC1 downregulation) PEX2 is upregulated and ubiquitinates peroxisomal membrane proteins including PEX5 and PMP70, marking peroxisomes for NBR1-dependent autophagic degradation. PEX2, but not PEX10 or PEX12, is rate-limiting for this process.

molecular function: ubiquitin protein ligase activity · directly involved in: pexophagy · locations: peroxisomal membrane

PEX2 links peroxisomal beta-oxidation to lipid droplet lipolysis: acting as a sensor of peroxisome-derived ROS (which stabilize PEX2 protein via disulfide bond formation), PEX2 polyubiquitinates the lipase ATGL/PNPLA2 at Lys92 with K48-linked chains, targeting it for proteasomal degradation and thereby downregulating lipolysis.

molecular function: ubiquitin protein ligase activity · directly involved in: negative regulation of triglyceride catabolic process · locations: peroxisomal membrane

In the knowledge base · computed from kb/ at build time

Disorders

Relationship is the entry's genetic[].relationship_type. untyped means the entry has a genetic record for the gene but does not type it; its free-text association is shown instead.

Disorder	Relationship	Where the gene appears
Peroxisome Biogenesis Disorder 5B	causative germline partial loss of function	mechanism: Biallelic PEX2 Genotype With Residual Peroxin-2 Function subtype: Ataxic form; NALD-IRD
Peroxisome Biogenesis Disorder	untyped Pathogenic Variants	mechanism: Peroxisome Biogenesis Defect
Zellweger Spectrum Disorders	untyped Autosomal recessive causal pathogenic variant. PEX2 is a RING finger peroxin of the membrane-embedded ubiquitin ligase complex that monoubiquitinates the peroxisomal matrix protein import receptor.	mechanism: RING Ubiquitin Ligase Retrotranslocation Failure subtype: PEX2-ZSD scoped to subtype: PEX2-ZSD

ClinGen gene–disease validity · snapshot 2026-10-03 · matched to entries by MONDO

An entry matches when ClinGen's MONDO disease is the entry's own disease term, a subtype term, or an exact-match mapping. An amber status marks an entry ClinGen supports the gene for (Definitive, Strong or Moderate) whose own record does not type it. A Limited, Disputed or Refuted tier on such an entry is not a gap.

ClinGen disease	MOI	Classification	dismech entry
peroxisome biogenesis disorder MONDO:0019234	AR	Definitive 2020-02-07	Peroxisome Biogenesis Disorder untyped

Mechanism modules · computed from kb/

peroxisomal_metabolic_failure via Peroxisome Biogenesis Disorder 5B