PEX13 - dismech genes

Normal function · from ai-gene-review (Q92968, commit 79fe13b38970) · AI-generated, not KB evidence

PEX13 (Peroxin-13) is an integral peroxisomal membrane protein that functions as a core component of the PEX13-PEX14 docking/translocation module (DTM) required for import of peroxisomal matrix proteins. PEX13 contains an N-terminal YG-rich intrinsically disordered region (IDR) that forms a selective phase reminiscent of nucleoporin FG repeats, and a C-terminal SH3 domain that mediates interactions with PEX5 (PTS1 receptor) via WxxxF/Y motifs. A proximal FxxxF motif autoinhibits the SH3 domain; PEX14 NTD binding to FxxxF releases this autoinhibition, creating a dynamic interaction network that tunes matrix protein import. PEX13 is essential for both PTS1 and PTS2 protein import. Loss of PEX13 causes Zellweger spectrum disorders (complementation group 13). PEX13 also functions in peroxisome quality control by preventing inappropriate pexophagy through regulation of PEX5 ubiquitination state and peroxisomal ROS levels.

PEX13 is the SH3-domain peroxin of the peroxisomal docking/translocation module (DTM). Its cytoplasmically oriented C-terminal SH3 domain engages the diaromatic WxxxF/Y motifs of the PTS1 receptor PEX5 and, through a non-canonical surface regulated by a proximal intramolecular FxxxF motif, also engages PEX14, so that PEX13 physically couples the cargo-loaded receptor to the rest of the translocon. This adaptor role is what makes PEX13 rate-limiting for docking: loss of Pex13p reduces peroxisome-associated Pex5p ~40-fold and abolishes import of both PTS1 and PTS2 cargo while leaving PMP insertion untouched, showing the defect is in receptor engagement rather than in membrane assembly.

molecular function: protein-macromolecule adaptor activity · contributes to molecular function: protein transmembrane transporter activity · directly involved in: protein import into peroxisome matrix; protein import into peroxisome matrix, docking; protein import into peroxisome matrix, translocation · locations: peroxisomal membrane · in complex: peroxisomal importomer 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 11A (Zellweger)	causative
Peroxisome Biogenesis Disorder 11B	causative partial loss of function	mechanism: PEX13 Hypomorphic Deficiency
Peroxisome Biogenesis Disorder	untyped Pathogenic Variants	mechanism: Peroxisome Biogenesis Defect
Zellweger Spectrum Disorders	untyped Autosomal recessive causal pathogenic variant. Peroxisomal matrix protein import depends on PEX13, whose SH3 domain binds the import receptor PEX5.	mechanism: Docking and Translocation Module Failure subtype: PEX13-ZSD scoped to subtype: PEX13-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 2019-10-04	Peroxisome Biogenesis Disorder untyped