PEX10

Summary

PEX10 (peroxisomal biogenesis factor 10, HGNC:8851) is a protein-coding gene on chromosome 1p36.32, encoding Peroxisome biogenesis factor 10 (O60683). E3 ubiquitin-protein ligase component of a retrotranslocation channel required for peroxisome organization by mediating export of the PEX5 receptor from peroxisomes to the cytosol, thereby promoting PEX5 recycling.

This gene encodes a protein involved in import of peroxisomal matrix proteins. This protein localizes to the peroxisomal membrane. Mutations in this gene result in phenotypes within the Zellweger spectrum of peroxisomal biogenesis disorders, ranging from neonatal adrenoleukodystrophy to Zellweger syndrome. Alternative splicing results in two transcript variants encoding different isoforms.

Source: NCBI Gene 5192 — RefSeq curated summary.

At a glance

• Gene–disease (curated): peroxisome biogenesis disorder (Definitive, ClinGen) — +4 more curated relationships
• GWAS associations: 4
• Clinical variants (ClinVar): 875 total — 66 pathogenic, 50 likely-pathogenic
• Phenotypes (HPO): 134
• MANE Select transcript: NM_002617

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8851
Approved symbol	PEX10
Name	peroxisomal biogenesis factor 10
Location	1p36.32
Locus type	gene with protein product
Status	Approved
Aliases	RNF69
Ensembl gene	ENSG00000157911
Ensembl biotype	protein_coding
OMIM	602859
Entrez	5192

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 6 protein_coding, 4 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000288774, ENST00000447513, ENST00000502666, ENST00000507596, ENST00000508384, ENST00000510434, ENST00000514502, ENST00000515760, ENST00000650293, ENST00000874692, ENST00000874693

RefSeq mRNA: 5 — MANE Select: NM_002617 NM_001374425, NM_001374426, NM_001374427, NM_002617, NM_153818

CCDS: CCDS41, CCDS44045

Canonical transcript exons

ENST00000447513 — 6 exons

Exon	Start	End
ENSE00001035830	2406484	2406619
ENSE00001035832	2408452	2408858
ENSE00001207524	2403974	2405834
ENSE00003514210	2410371	2410451
ENSE00003687915	2406720	2406895
ENSE00003901586	2412391	2412564

Expression profiles

Bgee: expression breadth ubiquitous, 266 present calls, max score 92.13.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.9241 / max 73.7123, expressed in 1798 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
9898	11.6239	1797
9900	0.1949	108
9899	0.1053	50

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
parotid gland	UBERON:0001831	92.13	gold quality
tendon of biceps brachii	UBERON:0008188	91.01	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	90.56	gold quality
right adrenal gland cortex	UBERON:0035827	90.22	gold quality
right adrenal gland	UBERON:0001233	90.09	gold quality
left adrenal gland	UBERON:0001234	89.04	gold quality
spinal cord	UBERON:0002240	88.91	gold quality
left adrenal gland cortex	UBERON:0035825	88.90	gold quality
amygdala	UBERON:0001876	88.67	gold quality
medial globus pallidus	UBERON:0002477	88.57	gold quality
left testis	UBERON:0004533	88.47	gold quality
right testis	UBERON:0004534	88.28	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	88.25	gold quality
adrenal cortex	UBERON:0001235	88.19	gold quality
nucleus accumbens	UBERON:0001882	88.13	gold quality
putamen	UBERON:0001874	88.10	gold quality
inferior olivary complex	UBERON:0002127	88.10	silver quality
caudate nucleus	UBERON:0001873	87.67	gold quality
right frontal lobe	UBERON:0002810	87.52	gold quality
ventricular zone	UBERON:0003053	87.35	gold quality
testis	UBERON:0000473	87.15	gold quality
cingulate cortex	UBERON:0003027	87.11	gold quality
adrenal gland	UBERON:0002369	87.10	gold quality
anterior cingulate cortex	UBERON:0009835	86.91	gold quality
globus pallidus	UBERON:0001875	86.34	gold quality
apex of heart	UBERON:0002098	85.84	gold quality
substantia nigra	UBERON:0002038	85.82	gold quality
prefrontal cortex	UBERON:0000451	85.41	gold quality
adenohypophysis	UBERON:0002196	85.33	gold quality
Brodmann (1909) area 9	UBERON:0013540	85.03	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.49

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

37 targeting PEX10, 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-3185	99.99	68.12	1959
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-3682-5P	99.93	67.97	1163
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-548A-3P	99.76	70.58	3524
HSA-MIR-200A-5P	99.76	69.10	949
HSA-MIR-200B-5P	99.76	69.05	948
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-1200	99.71	70.42	1838
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-3182	99.40	68.15	2454
HSA-MIR-4652-3P	99.33	70.02	2742
HSA-MIR-128-1-5P	99.33	60.46	332
HSA-MIR-128-2-5P	99.33	60.83	311
HSA-MIR-3922-3P	99.25	64.96	1136
HSA-MIR-4324	99.04	70.14	1569
HSA-MIR-1227-5P	98.65	65.32	1549
HSA-MIR-3135B	98.61	65.33	1470
HSA-MIR-619-3P	98.38	65.58	693
HSA-MIR-450A-2-3P	97.91	67.56	1459
HSA-MIR-490-3P	97.79	65.54	606

Literature-anchored findings (GeneRIF, showing 7)

• Genetic heterogeneity in Japanese patients with peroxisome biogenesis disorders and evidence for a founder haplotype for the most common mutation in PEX10 gene. (PMID:14713216)
• the relative fraction of disease-causing alleles that occur in the coding and splice junction sequences of PEX10 gene. (PMID:19105186)
• child and an adult of normal intelligence with progressive ataxia, axonal motor neuropathy, decreased vibration sense and cerebellar atrophy; 2 mutations in PEX10 found in child, c.992G>A and c.764_765insA, and in the adult, c.2T>C and c.790C>T (PMID:20695019)
• abnormal expression of PEX10 gene resulting from copy number variations of 1p36 region may be associated with the epilepsy phenotype (PMID:25636090)
• This study demonstrated that two mutations in PEX10 were found in the three peroxisomal biogenesis disorders patients: c.827G>T (novel) causing the missense change p.Cys276Phe and c.932G>A causing the missense change p.Arg311Gln. (PMID:27230853)
• Collectively, the rs2477686 in PEX10 , rs6080550 in SIRPA-SIRPG, and rs10842262 in SOX5 gene may indeed be the genetic risk factors for nonobstructive azoospermia (NOA), which requires further investigation using larger independent sets of samples in different ethnic populations. (PMID:30863997)
• Effect and in silico characterization of genetic variants associated with severe spermatogenic disorders in a large Iberian cohort. (PMID:33784440)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	pex10	ENSDARG00000041511
mus_musculus	Pex10	ENSMUSG00000029047
rattus_norvegicus	Pex10	ENSRNOG00000024012
drosophila_melanogaster	Pex10	FBGN0035233
caenorhabditis_elegans		WBGENE00016318

Protein

Protein identifiers

Peroxisome biogenesis factor 10 — O60683 (reviewed: O60683)

Alternative names: Peroxin-10, Peroxisomal biogenesis factor 10, Peroxisome assembly protein 10, RING finger protein 69

All UniProt accessions (7): A0A3B3ITN6, D6RA89, D6RBB0, D6RIF5, O60683, J3KRE0, J3QRM4

UniProt curated annotations — full annotation on UniProt →

Function. E3 ubiquitin-protein ligase component of a retrotranslocation channel required for peroxisome organization by mediating export of the PEX5 receptor from peroxisomes to the cytosol, thereby promoting PEX5 recycling. The retrotranslocation channel is composed of PEX2, PEX10 and PEX12; each subunit contributing transmembrane segments that coassemble into an open channel that specifically allows the passage of PEX5 through the peroxisomal membrane. PEX10 also regulates PEX5 recycling by acting as a E3 ubiquitin-protein ligase. When PEX5 recycling is compromised, PEX10 catalyzes polyubiquitination of PEX5 during its passage through the retrotranslocation channel, leading to its degradation.

Subunit / interactions. Component of the PEX2-PEX10-PEX12 retrotranslocation channel, composed of PEX2, PEX10 and PEX12. Interacts with PEX19.

Subcellular location. Peroxisome membrane.

Disease relevance. Peroxisome biogenesis disorder complementation group 7 (PBD-CG7) [MIM:614870] 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 6A (PBD6A) [MIM:614870] 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 6B (PBD6B) [MIM:614871] 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.

Activity regulation. The E3 ubiquitin-protein ligase activity is stimulated by PEX12.

Domain organisation. The three subunits of the retrotranslocation channel (PEX2, PEX10 and PEX12) coassemble in the membrane into a channel with an open 10 Angstrom pore. The RING-type zinc-fingers that catalyze PEX5 receptor ubiquitination are positioned above the pore on the cytosolic side of the complex.

Pathway. Protein modification; protein ubiquitination.

Similarity. Belongs to the pex2/pex10/pex12 family.

Isoforms (2)

UniProt ID	Names	Canonical?
O60683-1	1	yes
O60683-2	2

RefSeq proteins (5): NP_001361354, NP_001361355, NP_001361356, NP_002608, NP_722540 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001841	Znf_RING	Domain
IPR006845	Pex_N	Domain
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR017907	Znf_RING_CS	Conserved_site
IPR025654	PEX2/10	Family

Pfam: PF04757, PF13639

UniProt features (31 total): binding site 8, sequence variant 7, topological domain 6, transmembrane region 5, mutagenesis site 2, chain 1, zinc finger region 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O60683-F1	82.81	0.44

Functional residue map

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

Ligand- & substrate-binding residues (8): 273; 276; 288; 290; 293; 296; 307; 310

Mutagenesis-validated functional residues (2):

Position	Phenotype
273	abolished e3 ubiquitin-protein ligase activity.
310	abolished e3 ubiquitin-protein ligase activity.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-8866654	E3 ubiquitin ligases ubiquitinate target proteins
R-HSA-9033241	Peroxisomal protein import

MSigDB gene sets: 375 (showing top): GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, KESHELAVA_MULTIPLE_DRUG_RESISTANCE, GOBP_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_RECEPTOR_METABOLIC_PROCESS, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, GOBP_PROTEIN_POLYUBIQUITINATION, GOBP_PEROXISOMAL_TRANSPORT, GOBP_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOCC_MICROBODY_MEMBRANE, GOBP_PROTEIN_TRANSMEMBRANE_TRANSPORT, E12_Q6, GOBP_PROTEASOMAL_PROTEIN_CATABOLIC_PROCESS

GO Biological Process (13): protein polyubiquitination (GO:0000209), protein quality control for misfolded or incompletely synthesized proteins (GO:0006515), peroxisome organization (GO:0007031), protein import into peroxisome matrix (GO:0016558), protein import into peroxisome matrix, receptor recycling (GO:0016562), cellular response to reactive oxygen species (GO:0034614), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161), protein import into peroxisome matrix, substrate release (GO:0044721), pexophagy (GO:0000425), protein monoubiquitination (GO:0006513), protein transport (GO:0015031), protein ubiquitination (GO:0016567), protein unfolding (GO:0043335)

GO Molecular Function (6): zinc ion binding (GO:0008270), transmembrane protein transporter activity (GO:0008320), ubiquitin protein ligase activity (GO:0061630), protein binding (GO:0005515), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (3): peroxisome (GO:0005777), peroxisomal membrane (GO:0005778), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Protein ubiquitination	1
Protein localization	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein ubiquitination	2
protein import into peroxisome matrix	2
protein catabolic process	1
organelle organization	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
response to reactive oxygen species	1
cellular response to oxidative stress	1
cellular response to oxygen-containing compound	1
ubiquitin-dependent protein catabolic process	1
proteasomal protein catabolic process	1
protein-containing complex disassembly	1
macroautophagy	1
autophagy of peroxisome	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
protein modification by small protein conjugation	1
cellular process	1
transition metal ion binding	1
macromolecule transmembrane transporter activity	1
protein transmembrane transport	1
protein transporter activity	1
ubiquitin-protein transferase activity	1
ubiquitin-like protein ligase activity	1
binding	1
catalytic activity	1
cation binding	1
microbody	1
peroxisome	1
microbody membrane	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1036 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PEX10	PEX12	O00623	999
PEX10	PEX2	P28328	999
PEX10	PEX13	Q92968	995
PEX10	PEX5	P50542	975
PEX10	PEX19	P40855	973
PEX10	PEX6	Q13608	973
PEX10	PEX7	O00628	972
PEX10	PEX3	P56589	963
PEX10	PEX16	Q9Y5Y5	962
PEX10	GABARAPL2	P60520	952
PEX10	PEX14	O75381	946
PEX10	PEX26	Q7Z412	943
PEX10	F5GZY7	F5GZY7	923
PEX10	PEX1	O43933	895
PEX10	PEX5L	Q8IYB4	895

IntAct

22 interactions, top by confidence:

A	B	Type	Score
SCN3B	ABCC5	psi-mi:“MI:0914”(association)	0.530
PEX10	UBE2I	psi-mi:“MI:0915”(physical association)	0.370
PEX10	PEX10	psi-mi:“MI:0915”(physical association)	0.370
PEX10	MKRN3	psi-mi:“MI:0915”(physical association)	0.370
CGRRF1	PEX10	psi-mi:“MI:0915”(physical association)	0.370
PEX10	PCGF6	psi-mi:“MI:0915”(physical association)	0.370
PEX19	PEX10	psi-mi:“MI:0915”(physical association)	0.370
	TMEM223	psi-mi:“MI:0914”(association)	0.350
PEX5	AGPS	psi-mi:“MI:0914”(association)	0.350
TTYH1	TMEM223	psi-mi:“MI:0914”(association)	0.350
LDLRAD1	GXYLT2	psi-mi:“MI:0914”(association)	0.350
ATP2A1	TMEM120B	psi-mi:“MI:0914”(association)	0.350
PIPSL	C1orf226	psi-mi:“MI:0914”(association)	0.350
FTL	SH3PXD2B	psi-mi:“MI:0914”(association)	0.350
SAAL1	QSOX1	psi-mi:“MI:0914”(association)	0.350
EIF2B5	GOLIM4	psi-mi:“MI:0914”(association)	0.350
PEX14	PEX12	psi-mi:“MI:0914”(association)	0.350
MFSD10	NDUFS8	psi-mi:“MI:0914”(association)	0.350
SLC30A7	ESYT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (59): PEX10 (Affinity Capture-MS), PEX10 (Affinity Capture-MS), PEX10 (Affinity Capture-MS), PEX10 (Affinity Capture-MS), PEX10 (Affinity Capture-MS), PEX10 (Affinity Capture-MS), PEX10 (Affinity Capture-MS), PEX10 (Affinity Capture-MS), PEX10 (Affinity Capture-MS), PEX10 (Two-hybrid), PEX10 (Two-hybrid), PEX10 (Affinity Capture-RNA), PEX10 (Affinity Capture-MS), PEX10 (Affinity Capture-MS), PEX10 (Affinity Capture-MS)

ESM2 similar proteins: A0A1L8FG46, A0A1L8FM16, A0A1L8H814, A0A8I6ASZ5, A1L1L2, A4FUD4, A4FV45, A5D7N3, B0BN86, B0JYZ2, B1AUE5, E7F4V8, F1MX48, O00623, O60683, O88177, O95870, P17152, Q1JPD2, Q2YD98, Q4FZX0, Q4QRH7, Q4R8P0, Q5R6S0, Q5RAS8, Q5SYH2, Q5T197, Q5T1A1, Q5ZJY9, Q6DFK1, Q6INN0, Q6MG55, Q6NUQ4, Q6P6M5, Q810S1, Q86XJ0, Q8BK08, Q8BM55, Q8HXW8, Q8IUH8

Diamond homologs: A0A1L8FG46, A0A1L8FM16, B1AUE5, E7FDW2, O35445, O60683, O64425, P68907, P87176, Q09463, Q2KHN1, Q2TBT8, Q54S31, Q568Y3, Q5M807, Q5RFK9, Q5ZIR9, Q69ZS0, Q6PC78, Q8HXW8, Q91YT2, Q96GF1, Q99942, Q9P3U8, Q9SYU4, Q9UPQ7, Q9UUF0, Q9V8P9, O76064, P09309, Q2HJ46, Q4KLN8, Q5R4I2, Q803C1, Q80Z37, Q8VC56, Q9NS56, P90990, Q5M7Z0, Q6NTV1

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
Ub:E2	“up-regulates activity”	PEX10	ubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	66
Likely pathogenic	50
Uncertain significance	328
Likely benign	326
Benign	22

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1070795	NM_002617.4(PEX10):c.601-4dup	Pathogenic
1071642	NM_002617.4(PEX10):c.506_507del (p.Gln169fs)	Pathogenic
1071671	NM_002617.4(PEX10):c.504_507del (p.Gln169fs)	Pathogenic
1071782	NM_002617.4(PEX10):c.387del (p.Ser130fs)	Pathogenic
1073376	NM_002617.4(PEX10):c.486_496del (p.Ala163fs)	Pathogenic
1347847	NC_000001.10:g.(?2337205)(2338414_?)del	Pathogenic
1406389	NM_002617.4(PEX10):c.747G>A (p.Trp249Ter)	Pathogenic
1410903	NM_002617.4(PEX10):c.1A>T (p.Met1Leu)	Pathogenic
1440916	NM_002617.4(PEX10):c.475del (p.Ala159fs)	Pathogenic
1454209	NM_002617.4(PEX10):c.211G>T (p.Glu71Ter)	Pathogenic
1455721	NM_002617.4(PEX10):c.727C>T (p.Gln243Ter)	Pathogenic
1456172	NM_002617.4(PEX10):c.601-14del	Pathogenic
1457525	NM_002617.4(PEX10):c.430_439del (p.Trp144fs)	Pathogenic
162431	NM_002617.4(PEX10):c.337del (p.Leu113fs)	Pathogenic
162434	NM_002617.4(PEX10):c.2T>C (p.Met1Thr)	Pathogenic
162435	NM_002617.4(PEX10):c.730C>T (p.Arg244Ter)	Pathogenic
1686018	NM_002617.4(PEX10):c.827G>C (p.Cys276Ser)	Pathogenic
1804978	NM_002617.4(PEX10):c.637dup (p.Ala213fs)	Pathogenic
197886	NM_002617.4(PEX10):c.867_868insG (p.His290fs)	Pathogenic
2010527	NM_002617.4(PEX10):c.708_709dup (p.Tyr237fs)	Pathogenic
2030695	NM_002617.4(PEX10):c.664del (p.Val222fs)	Pathogenic
2036706	NM_002617.4(PEX10):c.735_738del (p.Lys247fs)	Pathogenic
2050570	NM_002617.4(PEX10):c.907_908insCTTA (p.Ser303delinsThrTer)	Pathogenic
2054831	NM_002617.4(PEX10):c.640del (p.Arg214fs)	Pathogenic
2113202	NM_002617.4(PEX10):c.509del (p.Gly170fs)	Pathogenic
2131746	NM_002617.4(PEX10):c.458_461del (p.Thr153fs)	Pathogenic
2427449	NC_000001.10:g.(?2339881)(2340307_?)del	Pathogenic
2427450	NC_000001.10:g.(?2341800)(2343951_?)del	Pathogenic
2427451	NC_000001.10:g.(?2337195)(2340307_?)del	Pathogenic
2677649	NM_002617.4(PEX10):c.881G>A (p.Trp294Ter)	Pathogenic

SpliceAI

1465 predictions. Top by Δscore:

Variant	Effect	Δscore
1:2405832:CGC:C	acceptor_gain	1.0000
1:2405835:C:CA	acceptor_loss	1.0000
1:2405835:C:CC	acceptor_gain	1.0000
1:2405836:T:A	acceptor_loss	1.0000
1:2406479:CTCA:C	donor_loss	1.0000
1:2406480:TCAC:T	donor_loss	1.0000
1:2406481:CA:C	donor_loss	1.0000
1:2406482:A:AT	donor_loss	1.0000
1:2406483:C:CG	donor_loss	1.0000
1:2406615:AGGCC:A	acceptor_gain	1.0000
1:2406616:GGCC:G	acceptor_gain	1.0000
1:2406617:GCC:G	acceptor_gain	1.0000
1:2406618:CC:C	acceptor_gain	1.0000
1:2406618:CCC:C	acceptor_gain	1.0000
1:2406619:CC:C	acceptor_gain	1.0000
1:2406619:CCTG:C	acceptor_loss	1.0000
1:2406620:C:CA	acceptor_loss	1.0000
1:2406620:C:CC	acceptor_gain	1.0000
1:2406620:C:T	acceptor_gain	1.0000
1:2406621:T:A	acceptor_loss	1.0000
1:2406629:G:C	acceptor_gain	1.0000
1:2406717:CACCT:C	donor_loss	1.0000
1:2406719:C:CA	donor_loss	1.0000
1:2406719:CCTG:C	donor_gain	1.0000
1:2406757:T:TA	donor_gain	1.0000
1:2406891:CGGAG:C	acceptor_gain	1.0000
1:2408450:A:AC	donor_gain	1.0000
1:2408451:C:CA	donor_gain	1.0000
1:2408451:CGT:C	donor_gain	1.0000
1:2408451:CGTA:C	donor_gain	1.0000

AlphaMissense

2056 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:2406514:C:A	W294C	0.994
1:2406514:C:G	W294C	0.994
1:2406520:G:C	F292L	0.993
1:2406520:G:T	F292L	0.993
1:2406522:A:G	F292L	0.993
1:2405828:A:G	C307R	0.991
1:2408506:A:C	F182L	0.990
1:2408506:A:T	F182L	0.990
1:2408508:A:G	F182L	0.990
1:2405827:C:G	C307S	0.985
1:2405828:A:T	C307S	0.985
1:2406517:G:C	C293W	0.985
1:2405818:C:G	C310S	0.984
1:2405819:A:T	C310S	0.984
1:2406526:G:C	H290Q	0.984
1:2406526:G:T	H290Q	0.984
1:2406528:G:C	H290D	0.984
1:2412451:C:G	D18H	0.983
1:2405826:A:C	C307W	0.982
1:2406509:C:G	C296S	0.982
1:2406510:A:T	C296S	0.982
1:2406577:G:C	C273W	0.982
1:2405819:A:G	C310R	0.981
1:2406508:G:C	C296W	0.980
1:2406510:A:G	C296R	0.980
1:2406518:C:T	C293Y	0.980
1:2406519:A:G	C293R	0.980
1:2406533:C:T	C288Y	0.980
1:2406579:A:G	C273R	0.980
1:2406569:C:G	C276S	0.979

dbSNP variants (sampled 300 via entrez): RS1000174643 (1:2415062 C>T), RS1000245344 (1:2413009 C>G,T), RS1000427748 (1:2408073 C>G), RS1000584532 (1:2412107 C>A), RS1000659748 (1:2409302 C>G), RS1000865154 (1:2405093 T>TGA), RS1000908141 (1:2413986 C>T), RS1001891722 (1:2415136 G>A,C), RS1002075173 (1:2408233 T>C), RS1002197065 (1:2415209 T>C), RS1002216261 (1:2410669 C>A,T), RS1002256943 (1:2410862 A>G,T), RS1002429251 (1:2406125 G>A), RS1002467076 (1:2412049 C>T), RS1002552958 (1:2409184 C>T)

Disease associations

OMIM: gene MIM:602859 | disease phenotypes: MIM:614870, MIM:108600, MIM:614871, MIM:214100

GenCC curated gene-disease

Disease	Classification	Inheritance
peroxisome biogenesis disorder 6A (Zellweger)	Definitive	Autosomal recessive
peroxisome biogenesis disorder 6B	Definitive	Autosomal recessive
peroxisome biogenesis disorder	Definitive	Autosomal recessive
autosomal recessive ataxia due to PEX10 deficiency	Supportive	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 (6): Zellweger spectrum disorders (MONDO:0019609), peroxisome biogenesis disorder 6A (Zellweger) (MONDO:0013936), spastic ataxia (MONDO:0017845), peroxisome biogenesis disorder 6B (MONDO:0013937), peroxisome biogenesis disorder (MONDO:0019234), autosomal recessive ataxia due to PEX10 deficiency (MONDO:0016614)

Orphanet (5): Zellweger syndrome (Orphanet:912), Spastic ataxia (Orphanet:316226), Neonatal adrenoleukodystrophy (Orphanet:44), Peroxisome biogenesis disorder (Orphanet:79189), Infantile Refsum disease (Orphanet:772)

HPO phenotypes

134 total (30 of 134 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:0000252	Microcephaly
HP:0000256	Macrocephaly
HP:0000260	Wide anterior fontanel
HP:0000268	Dolichocephaly
HP:0000271	Abnormality of the face
HP:0000286	Epicanthus
HP:0000347	Micrognathia
HP:0000348	High forehead
HP:0000358	Posteriorly rotated ears
HP:0000365	Hearing impairment
HP:0000369	Low-set ears
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
HP:0000510	Rod-cone dystrophy

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001362_2	Non-obstructive azoospermia	6.000000e-12
GCST005951_34	Body mass index	3.000000e-08
GCST005951_35	Body mass index	4.000000e-08
GCST90013406_181	Liver enzyme levels (alkaline phosphatase)	3.000000e-21

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004533	alkaline phosphatase measurement

MeSH disease descriptors (5)

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
C566422	Peroxisome Biogenesis Disorder, Complementation Group 7 (supp.)
C536664	Peroxisome biogenesis disorders (supp.)
C564815	Spastic Ataxia (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

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	decreases expression	1
GSK-J4	decreases expression	1
FR900359	decreases phosphorylation	1
bisphenol F	affects cotreatment, increases methylation	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	affects cotreatment, decreases expression	1
N-benzyloxycarbonylprolylprolinal	increases expression	1
K 7174	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Fulvestrant	increases methylation, affects cotreatment	1
Benzo(a)pyrene	affects methylation	1
Cadmium	increases abundance, increases expression	1
Cisplatin	increases expression, affects cotreatment	1
Doxorubicin	decreases expression	1
Smoke	decreases expression	1
Dihydrotestosterone	increases expression	1
Tretinoin	decreases expression, affects cotreatment	1
Urethane	decreases expression	1
Valproic Acid	increases methylation	1
Cyclosporine	decreases expression	1
Cadmium Chloride	increases abundance, increases expression	1
Acrylamide	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01838941	PHASE3	COMPLETED	Betaine and Peroxisome Biogenesis Disorders
NCT00007020	PHASE3	COMPLETED	Compassionate Treatment of Patients With Inborn Errors of Bile Acid Metabolism With Cholic Acid
NCT03856866	PHASE2	COMPLETED	Hydroxychloroquine Administration for Reduction of Pexophagy
NCT02171104	PHASE2	ACTIVE_NOT_RECRUITING	MT2013-31: Allo HCT for Metabolic Disorders and Severe Osteopetrosis
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
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
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
NCT04297891	Not specified	UNKNOWN	Phenotypes, Biomarkers and Pathophysiology in Spastic Ataxias