PEX13

Summary

PEX13 (peroxisomal biogenesis factor 13, HGNC:8855) is a protein-coding gene on chromosome 2p15, encoding Peroxisomal membrane protein PEX13 (Q92968). Component of the PEX13-PEX14 docking complex, a translocon channel that specifically mediates the import of peroxisomal cargo proteins bound to PEX5 receptor.

This gene encodes a peroxisomal membrane protein that binds the type 1 peroxisomal targeting signal receptor via a SH3 domain located in the cytoplasm. Mutations and deficiencies in peroxisomal protein importing and peroxisome assembly lead to peroxisomal biogenesis disorders, an example of which is Zellweger syndrome.

Source: NCBI Gene 5194 — RefSeq curated summary.

At a glance

• Gene–disease (curated): peroxisome biogenesis disorder (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 2
• Clinical variants (ClinVar): 616 total — 33 pathogenic, 10 likely-pathogenic
• Phenotypes (HPO): 105
• MANE Select transcript: NM_002618

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8855
Approved symbol	PEX13
Name	peroxisomal biogenesis factor 13
Location	2p15
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000162928
Ensembl biotype	protein_coding
OMIM	601789
Entrez	5194

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 9 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000295030, ENST00000401576, ENST00000414712, ENST00000444100, ENST00000472678, ENST00000902277, ENST00000902278, ENST00000920043, ENST00000920044, ENST00000971318

RefSeq mRNA: 1 — MANE Select: NM_002618 NM_002618

CCDS: CCDS1866

Canonical transcript exons

ENST00000295030 — 4 exons

Exon	Start	End
ENSE00001069927	61045726	61045851
ENSE00001069928	61048472	61051990
ENSE00001069929	61031419	61032113
ENSE00001560425	61017720	61017851

Expression profiles

Bgee: expression breadth ubiquitous, 264 present calls, max score 95.59.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 14.5738 / max 94.4020, expressed in 1794 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
20468	14.5738	1794

Top tissues by expression

287 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	95.59	gold quality
sperm	CL:0000019	94.66	gold quality
oocyte	CL:0000023	93.67	gold quality
buccal mucosa cell	CL:0002336	92.76	gold quality
male germ cell	CL:0000015	91.81	gold quality
esophagus squamous epithelium	UBERON:0006920	91.75	gold quality
epithelium of nasopharynx	UBERON:0001951	90.11	gold quality
germinal epithelium of ovary	UBERON:0001304	89.44	gold quality
epithelium of esophagus	UBERON:0001976	88.42	gold quality
visceral pleura	UBERON:0002401	87.99	gold quality
calcaneal tendon	UBERON:0003701	86.97	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.96	gold quality
cortical plate	UBERON:0005343	86.89	gold quality
mucosa of paranasal sinus	UBERON:0005030	86.87	gold quality
ventricular zone	UBERON:0003053	86.85	gold quality
gingival epithelium	UBERON:0001949	86.77	gold quality
parietal pleura	UBERON:0002400	86.62	gold quality
palpebral conjunctiva	UBERON:0001812	86.37	gold quality
adrenal tissue	UBERON:0018303	86.17	gold quality
ganglionic eminence	UBERON:0004023	86.15	gold quality
amniotic fluid	UBERON:0000173	85.94	gold quality
eye	UBERON:0000970	85.90	gold quality
jejunal mucosa	UBERON:0000399	85.81	gold quality
pleura	UBERON:0000977	85.50	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.31	gold quality
hindlimb stylopod muscle	UBERON:0004252	85.00	gold quality
liver	UBERON:0002107	84.85	gold quality
gastrocnemius	UBERON:0001388	84.82	gold quality
squamous epithelium	UBERON:0006914	84.80	gold quality
muscle of leg	UBERON:0001383	84.76	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

168 targeting PEX13, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4713-3P	100.00	65.92	505
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345

Literature-anchored findings (GeneRIF, showing 9)

• Pex13p has a role in determining the peroxisomal localization of Pex14p (PMID:14715663)
• analysis of PEX13 substitution of Ile326 by threonine in a patient with peroxisomal biogenesis disorder [case report] (PMID:16006427)
• Zellweger syndrome caused by PEX13 deficiency: report of two novel mutations. (PMID:19449432)
• Results show PEX13 interacts with itself in peroxisomes in living cells and the import of PTS1 (peroxisomal targeting signal 1) proteins is specifically disrupted when homooligomerization of PEX13 is interrupted. (PMID:23716570)
• our results demonstrate that PEX13 is required for selective autophagy, and suggest that dysregulation of PEX13-mediated mitophagy may contribute to ZSS pathogenesis. (PMID:27827795)
• Data suggest that soluble/cytosolic PEX5 interacts with PEX14/PEX13 complex, a model for the docking/translocation module (DTM) of the peroxisomal matrix protein translocon; PEX14/PEX13 complex appears to function in peroxisomal membrane as large cavity into which cytosolic PEX5 can enter to release its cargo. (PEX = peroxisomal biogenesis factor) (PMID:28765278)
• Hepatocyte-specific deletion of peroxisomal protein PEX13 results in disrupted iron homeostasis. (PMID:32565019)
• Genotype-phenotype correlations and disease mechanisms in PEX13-related Zellweger spectrum disorders. (PMID:35854306)
• Modulation of peroxisomal import by the PEX13 SH3 domain and a proximal FxxxF binding motif. (PMID:38632234)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	pex13	ENSDARG00000071037
mus_musculus	Pex13	ENSMUSG00000020283
rattus_norvegicus	Pex13	ENSRNOG00000054896
drosophila_melanogaster	Pex13	FBGN0033812
caenorhabditis_elegans		WBGENE00004198

Protein

Protein identifiers

Peroxisomal membrane protein PEX13 — Q92968 (reviewed: Q92968)

Alternative names: Peroxin-13

All UniProt accessions (4): B5MBY9, D3YTD3, Q92968, G5E9N6

UniProt curated annotations — full annotation on UniProt →

Function. Component of the PEX13-PEX14 docking complex, a translocon channel that specifically mediates the import of peroxisomal cargo proteins bound to PEX5 receptor. The PEX13-PEX14 docking complex forms a large import pore which can be opened to a diameter of about 9 nm. Mechanistically, PEX5 receptor along with cargo proteins associates with the PEX14 subunit of the PEX13-PEX14 docking complex in the cytosol, leading to the insertion of the receptor into the organelle membrane with the concomitant translocation of the cargo into the peroxisome matrix. Involved in the import of PTS1- and PTS2-type containing proteins.

Subunit / interactions. Interacts (via SH3 domain) with PEX14 (via SH3-binding motif); forming the PEX13-PEX14 docking complex. Interacts with PEX19.

Subcellular location. Peroxisome membrane.

Disease relevance. Peroxisome biogenesis disorder complementation group 13 (PBD-CG13) [MIM:614883] A peroxisomal disorder arising from a failure of protein import into the peroxisomal membrane or matrix. The peroxisome biogenesis disorders (PBD group) are genetically heterogeneous with at least 14 distinct genetic groups as concluded from complementation studies. Include disorders are: Zellweger syndrome (ZWS), neonatal adrenoleukodystrophy (NALD), infantile Refsum disease (IRD), and classical rhizomelic chondrodysplasia punctata (RCDP). ZWS, NALD and IRD are distinct from RCDP and constitute a clinical continuum of overlapping phenotypes known as the Zellweger spectrum (PBD-ZSS). The disease is caused by variants affecting the gene represented in this entry. Peroxisome biogenesis disorder 11A (PBD11A) [MIM:614883] A fatal peroxisome biogenesis disorder belonging to the Zellweger disease spectrum and clinically characterized by severe neurologic dysfunction with profound psychomotor retardation, severe hypotonia and neonatal seizures, craniofacial abnormalities, liver dysfunction, and biochemically by the absence of peroxisomes. Additional features include cardiovascular and skeletal defects, renal cysts, ocular abnormalities, and hearing impairment. Most severely affected individuals with the classic form of the disease (classic Zellweger syndrome) die within the first year of life. The disease is caused by variants affecting the gene represented in this entry. Peroxisome biogenesis disorder 11B (PBD11B) [MIM:614885] A peroxisome biogenesis disorder that includes neonatal adrenoleukodystrophy (NALD) and infantile Refsum disease (IRD), two milder manifestations of the Zellweger disease spectrum. The clinical course of patients with the NALD and IRD presentation is variable and may include developmental delay, hypotonia, liver dysfunction, sensorineural hearing loss, retinal dystrophy and vision impairment. Children with the NALD presentation may reach their teens, while patients with the IRD presentation may reach adulthood. The clinical conditions are often slowly progressive in particular with respect to loss of hearing and vision. The biochemical abnormalities include accumulation of phytanic acid, very long chain fatty acids (VLCFA), di- and trihydroxycholestanoic acid and pipecolic acid. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the peroxin-13 family.

RefSeq proteins (1): NP_002609* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001452	SH3_domain	Domain
IPR007223	Peroxin-13_N	Domain
IPR035463	Pex13	Family
IPR036028	SH3-like_dom_sf	Homologous_superfamily

Pfam: PF04088, PF14604

UniProt features (26 total): strand 5, topological domain 4, region of interest 3, transmembrane region 3, helix 3, compositionally biased region 2, sequence variant 2, chain 1, modified residue 1, turn 1, domain 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
7Z0I	X-RAY DIFFRACTION	1.8
7Z0J	X-RAY DIFFRACTION	2.3
7Z0K	X-RAY DIFFRACTION	2.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q92968-F1	65.62	0.16

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 354

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-8866654	E3 ubiquitin ligases ubiquitinate target proteins
R-HSA-9033241	Peroxisomal protein import
R-HSA-9603798	Class I peroxisomal membrane protein import

MSigDB gene sets: 421 (showing top): RNGTGGGC_UNKNOWN, GOBP_LIPID_MODIFICATION, GOBP_FATTY_ACID_CATABOLIC_PROCESS, HORIUCHI_WTAP_TARGETS_DN, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_10, GOBP_BEHAVIOR, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, FISCHER_G1_S_CELL_CYCLE, GOBP_SUCKLING_BEHAVIOR, MENSE_HYPOXIA_UP, GOBP_NEUROGENESIS, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND

GO Biological Process (15): fatty acid alpha-oxidation (GO:0001561), neuron migration (GO:0001764), suckling behavior (GO:0001967), locomotory behavior (GO:0007626), protein import into peroxisome matrix, docking (GO:0016560), protein import into peroxisome matrix, translocation (GO:0016561), cerebral cortex cell migration (GO:0021795), cellular response to reactive oxygen species (GO:0034614), microtubule-based peroxisome localization (GO:0060152), protein monoubiquitination (GO:0006513), protein transport (GO:0015031), protein import into peroxisome matrix (GO:0016558), protein import into peroxisome matrix, receptor recycling (GO:0016562), protein unfolding (GO:0043335), protein import into peroxisome matrix, substrate release (GO:0044721)

GO Molecular Function (2): transmembrane protein transporter activity (GO:0008320), protein binding (GO:0005515)

GO Cellular Component (5): peroxisome (GO:0005777), peroxisomal membrane (GO:0005778), cytosol (GO:0005829), membrane (GO:0016020), peroxisomal importomer complex (GO:1990429)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Protein localization	2
Protein ubiquitination	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein import into peroxisome matrix	4
intracellular protein localization	2
cellular anatomical structure	2
fatty acid catabolic process	1
fatty acid oxidation	1
cell migration	1
generation of neurons	1
feeding behavior	1
behavior	1
intracellular protein transmembrane transport	1
cerebral cortex development	1
telencephalon cell migration	1
response to reactive oxygen species	1
cellular response to oxidative stress	1
cellular response to oxygen-containing compound	1
microtubule-based process	1
peroxisome localization	1
protein ubiquitination	1
transport	1
establishment of protein localization	1
peroxisomal membrane transport	1
protein transmembrane import into intracellular organelle	1
protein localization to peroxisome	1
establishment of protein localization to peroxisome	1
receptor recycling	1
cellular process	1
protein-containing complex disassembly	1
macromolecule transmembrane transporter activity	1
protein transmembrane transport	1
protein transporter activity	1
binding	1
microbody	1
peroxisome	1
microbody membrane	1
cytoplasm	1
transporter complex	1

Protein interactions and networks

STRING

1021 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PEX13	PEX14	O75381	999
PEX13	PEX5	P50542	999
PEX13	PEX12	O00623	997
PEX13	PEX10	O60683	995
PEX13	PEX7	O00628	992
PEX13	PEX2	P28328	984
PEX13	PEX19	P40855	983
PEX13	PEX3	P56589	976
PEX13	PEX6	Q13608	973
PEX13	PEX16	Q9Y5Y5	957
PEX13	PEX26	Q7Z412	931
PEX13	PEX5L	Q8IYB4	888
PEX13	PEX1	O43933	872
PEX13	PEX11A	O75192	847
PEX13	AGPS	O00116	817

IntAct

45 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
PEX19	PEX13	psi-mi:“MI:0915”(physical association)	0.710
PEX19	PEX13	psi-mi:“MI:0407”(direct interaction)	0.710
PEX13	PEX19	psi-mi:“MI:0407”(direct interaction)	0.710
PEX13	CEP19	psi-mi:“MI:0915”(physical association)	0.560
PEX14	PEX13	psi-mi:“MI:0915”(physical association)	0.550
LPAR1	TMEM223	psi-mi:“MI:0914”(association)	0.530
C3AR1	TMEM120B	psi-mi:“MI:0914”(association)	0.530
BTN3A2	BTN3A3	psi-mi:“MI:0914”(association)	0.530
PEX7	TCP1	psi-mi:“MI:0914”(association)	0.530
LPAR1	TMEM120B	psi-mi:“MI:0914”(association)	0.530
PEX7	TXNDC9	psi-mi:“MI:0914”(association)	0.530
ATP5PF	SLC19A2	psi-mi:“MI:0914”(association)	0.530
ADAM10	PEX13	psi-mi:“MI:0407”(direct interaction)	0.440
PRRG4	PEX13	psi-mi:“MI:0407”(direct interaction)	0.440
GRB2	PEX13	psi-mi:“MI:0915”(physical association)	0.400
PEX13	Mbp	psi-mi:“MI:0915”(physical association)	0.400
TRAF1	ECI2	psi-mi:“MI:0914”(association)	0.350
	TMEM223	psi-mi:“MI:0914”(association)	0.350

BioGRID (61): SPRR2A (Reconstituted Complex), PEX13 (Affinity Capture-MS), PEX13 (Affinity Capture-MS), PEX5 (Two-hybrid), PEX13 (Affinity Capture-MS), PEX13 (Affinity Capture-MS), PEX13 (Affinity Capture-MS), PEX13 (Affinity Capture-MS), PEX13 (Affinity Capture-MS), PEX13 (Affinity Capture-MS), PEX13 (Affinity Capture-MS), PEX13 (Reconstituted Complex), PEX13 (Affinity Capture-MS), CEP19 (Two-hybrid), PEX13 (Affinity Capture-MS)

ESM2 similar proteins: A0A1N7SYS3, A1A619, A3LP48, A9ULX8, B0BN56, D4A2Y9, F1NVK6, F6UF99, O04326, P40508, P82908, P82925, P92204, Q02854, Q04935, Q0P5B1, Q1LVV0, Q28GQ3, Q28HF6, Q28X44, Q2UDY8, Q3SYY7, Q3V0J1, Q56VL3, Q5I030, Q5R891, Q5XI29, Q61733, Q659C4, Q66IE4, Q68EU0, Q6AZH0, Q6BI17, Q6CHT7, Q6CJX5, Q6DFB7, Q6DFJ8, Q6NYD7, Q6PFM4, Q75D23

Diamond homologs: A7MBI0, D4A2Y9, O43281, P29355, P56945, Q0P5B1, Q19951, Q61140, Q63767, Q64355, Q92968, Q99JB8, Q9D0K1, Q9UKS6, Q9UNF0, A0A8I3PDQ1, A2QW93, A5GFW5, O35177, O43586, O60504, P10569, P34109, P38753, P62993, P62994, P87379, P97814, Q07883, Q08EC4, Q0CJU8, Q14511, Q557J6, Q5BBL4, Q5I1X5, Q5R4J7, Q5TCX8, Q60631, Q66II3, Q6FN49

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
PEX14	“up-regulates activity”	PEX13	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 37 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Peroxisomal protein import	7	41.8×	5e-08

Disease & clinical

Clinical variants and AI predictions

ClinVar

616 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	33
Likely pathogenic	10
Uncertain significance	328
Likely benign	190
Benign	13

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1372243	NM_002618.4(PEX13):c.46C>T (p.Arg16Ter)	Pathogenic
1387888	NM_002618.4(PEX13):c.499del (p.His167fs)	Pathogenic
1411346	NM_002618.4(PEX13):c.367G>T (p.Glu123Ter)	Pathogenic
1426245	NM_002618.4(PEX13):c.201dup (p.Val68fs)	Pathogenic
1428939	NM_002618.4(PEX13):c.829dup (p.Ala277fs)	Pathogenic
1453426	NM_002618.4(PEX13):c.159_160del (p.Pro54fs)	Pathogenic
1705035	NM_002618.4(PEX13):c.391C>T (p.Gln131Ter)	Pathogenic
1897669	NM_002618.4(PEX13):c.913+1G>T	Pathogenic
1993651	NM_002618.4(PEX13):c.148del (p.Arg50fs)	Pathogenic
2031148	NM_002618.4(PEX13):c.633G>A (p.Trp211Ter)	Pathogenic
2109668	NM_002618.4(PEX13):c.759_760del (p.Leu254fs)	Pathogenic
2584448	NM_002618.4(PEX13):c.573_582del (p.Arg193fs)	Pathogenic
2722852	NM_002618.4(PEX13):c.744C>G (p.Tyr248Ter)	Pathogenic
2727059	NM_002618.4(PEX13):c.676C>T (p.Arg226Ter)	Pathogenic
2742993	NM_002618.4(PEX13):c.855del (p.Val286fs)	Pathogenic
2754296	NM_002618.4(PEX13):c.27del (p.Lys10fs)	Pathogenic
2757683	NM_002618.4(PEX13):c.431del (p.Ser144fs)	Pathogenic
2762794	NM_002618.4(PEX13):c.596T>G (p.Leu199Ter)	Pathogenic
2805185	NM_002618.4(PEX13):c.20dup (p.Pro8fs)	Pathogenic
2834166	NM_002618.4(PEX13):c.801G>A (p.Trp267Ter)	Pathogenic
2834722	NM_002618.4(PEX13):c.145dup (p.Thr49fs)	Pathogenic
2859713	NM_002618.4(PEX13):c.871del (p.Ile291fs)	Pathogenic
3649968	NM_002618.4(PEX13):c.213del (p.Phe71fs)	Pathogenic
3651137	NM_002618.4(PEX13):c.294T>G (p.Tyr98Ter)	Pathogenic
3673489	NM_002618.4(PEX13):c.107del (p.Gly36fs)	Pathogenic
375270	NM_002618.4(PEX13):c.937T>G (p.Trp313Gly)	Pathogenic
4722094	NM_002618.4(PEX13):c.544_545insAAT (p.Phe182Ter)	Pathogenic
4733096	NM_002618.4(PEX13):c.592del (p.Met198fs)	Pathogenic
4795152	NM_002618.4(PEX13):c.296del (p.Gly99fs)	Pathogenic
573201	NM_002618.4(PEX13):c.586C>T (p.Gln196Ter)	Pathogenic

SpliceAI

1121 predictions. Top by Δscore:

Variant	Effect	Δscore
2:61017849:CCAG:C	donor_loss	1.0000
2:61017850:CAG:C	donor_loss	1.0000
2:61017851:AG:A	donor_loss	1.0000
2:61017852:G:GG	donor_gain	1.0000
2:61017852:GT:G	donor_loss	1.0000
2:61017853:T:A	donor_loss	1.0000
2:61031517:G:GT	donor_gain	1.0000
2:61045724:A:AG	acceptor_gain	1.0000
2:61045725:G:GA	acceptor_gain	1.0000
2:61045725:GA:G	acceptor_gain	1.0000
2:61045725:GAC:G	acceptor_gain	1.0000
2:61045725:GACA:G	acceptor_gain	1.0000
2:61045828:A:AG	donor_gain	1.0000
2:61045847:CAAAG:C	donor_loss	1.0000
2:61045848:AAAGG:A	donor_loss	1.0000
2:61045849:AAGG:A	donor_loss	1.0000
2:61045850:AGGT:A	donor_loss	1.0000
2:61045852:G:GC	donor_loss	1.0000
2:61048467:A:AG	acceptor_gain	1.0000
2:61048468:T:G	acceptor_gain	1.0000
2:61048468:TCA:T	acceptor_loss	1.0000
2:61048469:CAGA:C	acceptor_loss	1.0000
2:61048470:A:AG	acceptor_gain	1.0000
2:61048470:A:C	acceptor_loss	1.0000
2:61048471:G:GA	acceptor_gain	1.0000
2:61048471:GA:G	acceptor_gain	1.0000
2:61048471:GAA:G	acceptor_gain	1.0000
2:61048471:GAAC:G	acceptor_gain	1.0000
2:61048471:GAACA:G	acceptor_gain	1.0000
2:61017847:TTCCA:T	donor_gain	0.9900

AlphaMissense

2614 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:61031754:T:A	V143D	1.000
2:61031771:G:C	A149P	1.000
2:61031795:A:C	S157R	1.000
2:61031797:T:A	S157R	1.000
2:61031797:T:G	S157R	1.000
2:61048550:T:A	V331D	1.000
2:61031691:C:A	A122D	0.999
2:61031702:A:C	S126R	0.999
2:61031704:C:A	S126R	0.999
2:61031704:C:G	S126R	0.999
2:61031714:T:C	F130L	0.999
2:61031715:T:C	F130S	0.999
2:61031715:T:G	F130C	0.999
2:61031716:T:A	F130L	0.999
2:61031716:T:G	F130L	0.999
2:61031733:T:A	I136N	0.999
2:61031741:G:C	A139P	0.999
2:61031750:T:C	S142P	0.999
2:61031756:A:C	S144R	0.999
2:61031758:T:A	S144R	0.999
2:61031758:T:G	S144R	0.999
2:61031763:T:A	M146K	0.999
2:61031763:T:G	M146R	0.999
2:61031783:G:C	A153P	0.999
2:61031784:C:A	A153D	0.999
2:61031787:T:A	V154D	0.999
2:61031798:T:C	F158L	0.999
2:61031800:C:A	F158L	0.999
2:61031800:C:G	F158L	0.999
2:61031804:G:C	A160P	0.999

dbSNP variants (sampled 300 via entrez): RS1000055423 (2:61026211 C>G,T), RS1000059081 (2:61039255 A>C), RS1000097749 (2:61019459 G>A), RS1000412409 (2:61042691 C>T), RS1000584322 (2:61028560 T>C), RS1000640653 (2:61022021 A>G), RS1000654655 (2:61027349 A>C,T), RS1000683394 (2:61039509 A>G), RS1000702048 (2:61018327 C>G,T), RS1000776465 (2:61022236 T>C), RS1000788989 (2:61028371 G>A), RS1000858616 (2:61050207 C>A,G), RS1000943176 (2:61027172 A>C), RS1000962535 (2:61043898 G>A), RS1001001113 (2:61038946 T>C)

Disease associations

OMIM: gene MIM:601789 | disease phenotypes: MIM:614883, MIM:614885, MIM:214100, MIM:614862

GenCC curated gene-disease

Disease	Classification	Inheritance
peroxisome biogenesis disorder 11A (Zellweger)	Definitive	Autosomal recessive
peroxisome biogenesis disorder 11B	Definitive	Autosomal recessive
peroxisome biogenesis disorder	Strong	Autosomal recessive
Zellweger spectrum disorders	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
peroxisome biogenesis disorder	Definitive	AR

Mondo (5): peroxisome biogenesis disorder 11A (Zellweger) (MONDO:0013949), peroxisome biogenesis disorder 11B (MONDO:0013950), peroxisome biogenesis disorder (MONDO:0019234), peroxisome biogenesis disorder 4A (Zellweger) (MONDO:0013930), Zellweger spectrum disorders (MONDO:0019609)

Orphanet (3): Zellweger syndrome (Orphanet:912), Neonatal adrenoleukodystrophy (Orphanet:44), Peroxisome biogenesis disorder (Orphanet:79189)

HPO phenotypes

105 total (30 of 105 shown, HPO-id order):

HPO	Term
HP:0000003	Multicystic kidney dysplasia
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000047	Hypospadias
HP:0000107	Renal cyst
HP:0000126	Hydronephrosis
HP:0000157	Abnormality of the tongue
HP:0000174	Abnormal palate morphology
HP:0000218	High palate
HP:0000239	Large fontanelles
HP:0000252	Microcephaly
HP:0000256	Macrocephaly
HP:0000260	Wide anterior fontanel
HP:0000268	Dolichocephaly
HP:0000271	Abnormality of the face
HP:0000286	Epicanthus
HP:0000325	Triangular face
HP:0000347	Micrognathia
HP:0000348	High forehead
HP:0000358	Posteriorly rotated ears
HP:0000365	Hearing impairment
HP:0000377	Abnormal pinna morphology
HP:0000407	Sensorineural hearing impairment
HP:0000431	Wide nasal bridge
HP:0000463	Anteverted nares
HP:0000474	Thickened nuchal skin fold
HP:0000486	Strabismus
HP:0000501	Glaucoma
HP:0000505	Visual impairment
HP:0000508	Ptosis

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST001438_15	Crohn’s disease	5.000000e-09
GCST006956_8	Erectile dysfunction	8.000000e-06

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D015211	Zellweger Syndrome	C06.552.970; C10.228.140.163.100.968; C12.050.351.968.419.978; C12.200.777.419.978; C12.950.419.978; C16.131.077.970; C16.320.565.189.968; C16.320.565.663.970; C18.452.132.100.968; C18.452.648.189.968; C18.452.648.663.970
C563301	Peroxisome Biogenesis Disorder, Complementation Group 4 (supp.)
C536664	Peroxisome biogenesis disorders (supp.)
C531857	Zellweger leukodystrophy (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

36 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
trichostatin A	affects cotreatment, decreases expression, affects expression	4
methylmercuric chloride	decreases expression	3
Valproic Acid	affects cotreatment, decreases expression, increases expression	3
mercuric bromide	affects cotreatment, decreases expression	2
entinostat	decreases expression, affects cotreatment	2
Acetaminophen	decreases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
bisphenol F	affects cotreatment, increases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, increases expression	1
avobenzone	increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
belinostat	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Vorinostat	increases expression	1
Leflunomide	increases expression	1
Caffeine	decreases phosphorylation	1
Calcitriol	increases expression, affects cotreatment	1
Cisplatin	affects cotreatment, decreases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Hydrogen Peroxide	affects expression	1
Indomethacin	affects cotreatment, increases expression	1
Methyl Methanesulfonate	increases expression	1
Phenobarbital	affects expression	1
Plant Extracts	affects cotreatment, increases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_TC93	HAP1 PEX13 (-) 1	Cancer cell line	Male
CVCL_TC94	HAP1 PEX13 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

10 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00007020	PHASE3	COMPLETED	Compassionate Treatment of Patients With Inborn Errors of Bile Acid Metabolism With Cholic Acid
NCT01838941	PHASE3	COMPLETED	Betaine and Peroxisome Biogenesis Disorders
NCT02171104	PHASE2	ACTIVE_NOT_RECRUITING	MT2013-31: Allo HCT for Metabolic Disorders and Severe Osteopetrosis
NCT03856866	PHASE2	COMPLETED	Hydroxychloroquine Administration for Reduction of Pexophagy
NCT00004442	Not specified	TERMINATED	Study of Bile Acids in Patients With Peroxisomal Disorders
NCT02699190	Not specified	COMPLETED	LeukoSEQ: Whole Genome Sequencing as a First-Line Diagnostic Tool for Leukodystrophies
NCT03047369	Not specified	RECRUITING	The Myelin Disorders Biorepository Project
NCT01668186	Not specified	RECRUITING	Longitudinal Natural History Study of Patients With Peroxisome Biogenesis Disorders (PBD)
NCT03440905	Not specified	COMPLETED	Proxy-Reported Symptoms and Quality of Life Survey in Zellweger Spectrum Disorders
NCT06190626	Not specified	RECRUITING	Longitudinal Prospective Natural History Study of Retinopathy in Zellweger Spectrum Disorder