Curated summary · agent-written · kb/genes/curated/hgnc_8851.md

All 20 claims checked against the KB draft

PEX10 across dismech

PEX10 (peroxisomal biogenesis factor 10) is named by 4 disorder entries.

Normal function

ai-gene-review gives PEX10's core molecular function as ubiquitin protein ligase activity at the peroxisomal membrane, acting in protein import into peroxisome matrix. The upstream review is being updated to also list receptor recycling as a directly involved process; the pinned ingest does not carry that yet.

Causative records

Two entries type PEX10 as causative, and both record a germline origin: Peroxisome Biogenesis Disorder 6A (Zellweger); and Peroxisome Biogenesis Disorder 6B. They divide the allelic series by residual function. Peroxisome Biogenesis Disorder 6A (Zellweger) records a loss of function on the node Biallelic Severe PEX10 Genotype, and Peroxisome Biogenesis Disorder 6B a partial loss of function on Biallelic Hypomorphic PEX10 Genotype.

Grouping-level records

The broader entries also name PEX10, including Zellweger Spectrum Disorders; and Peroxisome Biogenesis Disorder; Zellweger Spectrum Disorders places it on RING Ubiquitin Ligase Retrotranslocation Failure. Their genetic records are untyped and untyped respectively.

Where the layers disagree

ClinGen classifies PEX10 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 PEX10 mechanism nodes are annotated with protein import into peroxisome matrix, receptor recycling, the more specific child of the process the pinned ai-gene-review ingest records, so the two share 0 GO terms by exact 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 (O60683, commit 79fe13b38970) · AI-generated, not KB evidence

PEX10 (Peroxisome biogenesis factor 10) is an integral peroxisomal membrane protein containing a C-terminal C3HC4 RING finger domain. It is a component of the PEX2-PEX10-PEX12 E3 ubiquitin ligase complex that forms a retrotranslocation channel in the peroxisomal membrane. PEX10 functions as an E3 ubiquitin-protein ligase (EC 2.3.2.27) that, together with PEX12, catalyzes monoubiquitination of the PTS1 receptor PEX5 at its conserved N-terminal cysteine (Cys11), an essential step for PEX5 recycling back to the cytosol during peroxisomal matrix protein import. When recycling is compromised, PEX10 participates in polyubiquitination of PEX5 leading to proteasomal degradation (RADAR pathway). The cryo-EM structure reveals that PEX10 contributes five transmembrane segments to the retrotranslocation channel, with its RING finger (RF10) forming part of the cytosolic tower positioned to facilitate ubiquitin transfer. Biallelic mutations in PEX10 cause Zellweger spectrum disorders (complementation group 7).

PEX10 functions as an E3 ubiquitin-protein ligase via its C-terminal C3HC4 RING finger domain. Together with PEX12, PEX10 monoubiquitinates the PTS1 receptor PEX5 at Cys11, which is essential for PEX5 recycling and continued peroxisomal matrix protein import. PEX10 also contributes to the retrotranslocation channel through which PEX5 is exported from the peroxisomal membrane back to the cytosol.

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

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 6A (Zellweger)	causative germline loss of function	mechanism: Biallelic Severe PEX10 Genotype; Loss of Peroxin-10 RING Ligase Function
Peroxisome Biogenesis Disorder 6B	causative germline partial loss of function	mechanism: Biallelic Hypomorphic PEX10 Genotype; Partial Loss of Peroxin-10 RING Function
Peroxisome Biogenesis Disorder	untyped Pathogenic Variants	mechanism: Peroxisome Biogenesis Defect
Zellweger Spectrum Disorders	untyped Autosomal recessive causal pathogenic variant. PEX10 is a RING finger peroxin of the membrane-embedded ubiquitin ligase complex that recycles the matrix protein import receptor.	mechanism: RING Ubiquitin Ligase Retrotranslocation Failure subtype: PEX10-ZSD scoped to subtype: PEX10-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 2019-12-06	Peroxisome Biogenesis Disorder untyped