PEX12

Summary

PEX12 (peroxisomal biogenesis factor 12, HGNC:8854) is a protein-coding gene on chromosome 17q12, encoding Peroxisome assembly protein 12 (O00623). 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 belongs to the peroxin-12 family. Peroxins (PEXs) are proteins that are essential for the assembly of functional peroxisomes. The peroxisome biogenesis disorders (PBDs) are a group of genetically heterogeneous autosomal recessive, lethal diseases characterized by multiple defects in peroxisome function. The peroxisomal biogenesis disorders are a heterogeneous group with at least 14 complementation groups and with more than 1 phenotype being observed in cases falling into particular complementation groups. Although the clinical features of PBD patients vary, cells from all PBD patients exhibit a defect in the import of one or more classes of peroxisomal matrix proteins into the organelle. Defects in this gene are a cause of Zellweger syndrome (ZWS).

Source: NCBI Gene 5193 — RefSeq curated summary.

At a glance

• Gene–disease (curated): peroxisome biogenesis disorder (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 7
• Clinical variants (ClinVar): 552 total — 62 pathogenic, 24 likely-pathogenic
• Phenotypes (HPO): 115
• MANE Select transcript: NM_000286

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8854
Approved symbol	PEX12
Name	peroxisomal biogenesis factor 12
Location	17q12
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000108733
Ensembl biotype	protein_coding
OMIM	601758
Entrez	5193

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 non_stop_decay

ENST00000225873, ENST00000585380, ENST00000586663

RefSeq mRNA: 1 — MANE Select: NM_000286 NM_000286

CCDS: CCDS11296

Canonical transcript exons

ENST00000225873 — 3 exons

Exon	Start	End
ENSE00003994401	35577038	35577591
ENSE00003994402	35577896	35578571
ENSE00003994406	35574795	35576181

Expression profiles

Bgee: expression breadth ubiquitous, 270 present calls, max score 92.57.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 4.8451 / max 48.3036, expressed in 1674 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
165384	4.8451	1674

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	92.57	gold quality
choroid plexus epithelium	UBERON:0003911	89.17	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.57	gold quality
germinal epithelium of ovary	UBERON:0001304	83.18	gold quality
oocyte	CL:0000023	82.27	gold quality
islet of Langerhans	UBERON:0000006	81.44	gold quality
tibialis anterior	UBERON:0001385	81.38	gold quality
biceps brachii	UBERON:0001507	80.71	gold quality
ventricular zone	UBERON:0003053	80.57	gold quality
deltoid	UBERON:0001476	80.53	gold quality
corpus epididymis	UBERON:0004359	79.78	gold quality
hindlimb stylopod muscle	UBERON:0004252	79.61	gold quality
right adrenal gland	UBERON:0001233	79.49	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	79.32	gold quality
muscle of leg	UBERON:0001383	78.99	gold quality
skeletal muscle tissue	UBERON:0001134	78.97	gold quality
diaphragm	UBERON:0001103	78.90	silver quality
skeletal muscle organ	UBERON:0014892	78.65	gold quality
muscle organ	UBERON:0001630	78.64	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.57	gold quality
gastrocnemius	UBERON:0001388	78.52	gold quality
upper leg skin	UBERON:0004262	78.52	gold quality
right adrenal gland cortex	UBERON:0035827	78.51	gold quality
nephron tubule	UBERON:0001231	78.20	gold quality
pigmented layer of retina	UBERON:0001782	78.17	gold quality
muscle tissue	UBERON:0002385	78.08	gold quality
left adrenal gland	UBERON:0001234	77.81	gold quality
hair follicle	UBERON:0002073	77.64	silver quality
renal glomerulus	UBERON:0000074	77.27	gold quality
palpebral conjunctiva	UBERON:0001812	77.19	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.81

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

58 targeting PEX12, 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-4282	99.99	75.36	6408
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-8076	99.78	68.52	1170
HSA-MIR-320A-3P	99.77	69.73	2107
HSA-MIR-320B	99.77	69.73	2107
HSA-MIR-320C	99.77	69.73	2107
HSA-MIR-320D	99.77	69.73	2107
HSA-MIR-4429	99.77	69.62	2111
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-1283	99.69	72.42	3009
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-466	99.67	70.85	2863
HSA-MIR-3679-3P	99.64	69.88	1599

Literature-anchored findings (GeneRIF, showing 5)

• examination of role in PEX5 binding of PTS1 (PMID:12456682)
• A single missense mutation was found in PEX12 in eight neonatal adrenoleukodystrophy, and infantile Refsum disease patients With Peroxisomal Mosaicism. (PMID:15241794)
• Highly probable candidate gene for direct sequencing in the context of a peroxisomal biogenesis disorder with a mild clinical phenotype, mosaicism and minimally abnormal peroxisomal parameters in fibroblasts. (PMID:17534573)
• the relative fraction of disease-causing alleles that occur in the coding and splice junction sequences of PEX12 gene. (PMID:19105186)
• A founder mutation in PEX12 among Egyptian patients in peroxisomal biogenesis disorder. (PMID:33123925)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	pex12	ENSDARG00000035149
mus_musculus	Pex12	ENSMUSG00000018733
rattus_norvegicus	Pex12	ENSRNOG00000009718
drosophila_melanogaster	Pex12	FBGN0031282
caenorhabditis_elegans		WBGENE00004197

Protein

Protein identifiers

Peroxisome assembly protein 12 — O00623 (reviewed: O00623)

Alternative names: Peroxin-12, Peroxisome assembly factor 3

All UniProt accessions (3): O00623, A0A075B773, K7ELY8

UniProt curated annotations — full annotation on UniProt →

Function. 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. PEX12 also regulates PEX5 recycling by activating the E3 ubiquitin-protein ligase activity of PEX10. When PEX5 recycling is compromised, PEX12 stimulates PEX10-mediated polyubiquitination of PEX5, leading to its subsequent degradation.

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

Subcellular location. Peroxisome membrane.

Disease relevance. Peroxisome biogenesis disorder complementation group 3 (PBD-CG3) [MIM:614859] 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 3A (PBD3A) [MIM:614859] 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 3B (PBD3B) [MIM:266510] 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.

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. The RING-type zinc-finger is degenerated and only coordinates one zinc ions, preventing E3 ubiquitin-protein ligase activity.

Pathway. Protein modification; protein ubiquitination.

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

RefSeq proteins (1): NP_000277* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006845	Pex_N	Domain
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR017375	PEX12	Family

Pfam: PF04757

UniProt features (26 total): sequence variant 7, topological domain 6, transmembrane region 5, binding site 4, mutagenesis site 2, chain 1, zinc finger region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O00623-F1	81.58	0.34

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 (4): 304; 307; 325; 328

Mutagenesis-validated functional residues (2):

Position	Phenotype
304	abolishes ability to activate the e3 ubiquitin-protein ligase activity of pex10. abolishes interaction with pex19; when
307	abolishes interaction with pex19; when associated with w-304.

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: 381 (showing top): BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_PROTEIN_TARGETING, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_PROTEIN_MONOUBIQUITINATION, GOBP_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_RECEPTOR_METABOLIC_PROCESS, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, GOBP_PROTEIN_POLYUBIQUITINATION, MORF_EPHA7, ATF4_Q2, GOBP_PEROXISOMAL_TRANSPORT, GOBP_PROTEIN_LOCALIZATION_TO_ORGANELLE

GO Biological Process (14): protein polyubiquitination (GO:0000209), protein monoubiquitination (GO:0006513), protein quality control for misfolded or incompletely synthesized proteins (GO:0006515), protein targeting to peroxisome (GO:0006625), 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 transport (GO:0015031), protein ubiquitination (GO:0016567), protein unfolding (GO:0043335)

GO Molecular Function (6): ubiquitin-protein transferase activity (GO:0004842), zinc ion binding (GO:0008270), transmembrane protein transporter activity (GO:0008320), ubiquitin ligase activator activity (GO:1990757), protein binding (GO:0005515), metal ion binding (GO:0046872)

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

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 ubiquitination	2
establishment of protein localization to peroxisome	2
protein import into peroxisome matrix	2
cellular anatomical structure	2
protein catabolic process	1
protein targeting	1
organelle organization	1
peroxisomal membrane transport	1
protein transmembrane import into intracellular organelle	1
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
ubiquitin-like protein transferase activity	1
transition metal ion binding	1
macromolecule transmembrane transporter activity	1
protein transmembrane transport	1
protein transporter activity	1
ubiquitin-protein transferase activator activity	1
positive regulation of ubiquitin protein ligase activity	1
binding	1
cation binding	1
microbody	1
peroxisome	1
microbody membrane	1
cytoplasm	1
transporter complex	1

Protein interactions and networks

STRING

759 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PEX12	PEX10	O60683	999
PEX12	PEX2	P28328	999
PEX12	PEX13	Q92968	997
PEX12	PEX14	O75381	983
PEX12	PEX6	Q13608	975
PEX12	PEX7	O00628	974
PEX12	PEX5	P50542	968
PEX12	PEX19	P40855	965
PEX12	PEX16	Q9Y5Y5	962
PEX12	PEX3	P56589	962
PEX12	PEX26	Q7Z412	930
PEX12	PEX5L	Q8IYB4	906
PEX12	PEX1	O43933	876
PEX12	AGPS	O00116	866
PEX12	PEX11A	O75192	860

IntAct

108 interactions, top by confidence:

A	B	Type	Score
PEX12	PEX5	psi-mi:“MI:0915”(physical association)	0.680
PEX5	PEX12	psi-mi:“MI:0915”(physical association)	0.680
CXCL16	PEX12	psi-mi:“MI:0915”(physical association)	0.560
PEX12	SEC22A	psi-mi:“MI:0915”(physical association)	0.560
PEX12	COL8A2	psi-mi:“MI:0915”(physical association)	0.560
PEX12	TMEM11	psi-mi:“MI:0915”(physical association)	0.560
PEX12	DNAJC30	psi-mi:“MI:0915”(physical association)	0.560
PEX12	TTPA	psi-mi:“MI:0915”(physical association)	0.560
PEX12	TREX1	psi-mi:“MI:0915”(physical association)	0.560
PEX12	ADIPOQ	psi-mi:“MI:0915”(physical association)	0.560
PEX12	GJB2	psi-mi:“MI:0915”(physical association)	0.560
PEX12	IER3IP1	psi-mi:“MI:0915”(physical association)	0.560
PEX12	PNLIPRP1	psi-mi:“MI:0915”(physical association)	0.560
PEX12	C5orf46	psi-mi:“MI:0915”(physical association)	0.560
PEX12	FXYD6	psi-mi:“MI:0915”(physical association)	0.560
PEX12	NRM	psi-mi:“MI:0915”(physical association)	0.560
PEX12	FKBP8	psi-mi:“MI:0915”(physical association)	0.560
PEX12	SEC61G	psi-mi:“MI:0915”(physical association)	0.560
PEX12	MARCHF2	psi-mi:“MI:0915”(physical association)	0.560
PEX12	RBFA	psi-mi:“MI:0915”(physical association)	0.560
PEX12	CLDN10	psi-mi:“MI:0915”(physical association)	0.560
PEX12	BNIP2	psi-mi:“MI:0915”(physical association)	0.560
PEX12	FA2H	psi-mi:“MI:0915”(physical association)	0.560
PEX12	PTPN9	psi-mi:“MI:0915”(physical association)	0.560
PEX12	ERMP1	psi-mi:“MI:0915”(physical association)	0.560
PEX12	ACSL5	psi-mi:“MI:0915”(physical association)	0.560
PEX12	NKG7	psi-mi:“MI:0915”(physical association)	0.560
MGLL	PEX12	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (60): PEX5 (Two-hybrid), PEX5 (Two-hybrid), PEX10 (Two-hybrid), PEX10 (Two-hybrid), PEX12 (Affinity Capture-MS), PEX12 (Affinity Capture-MS), PEX12 (Affinity Capture-RNA), PEX12 (Two-hybrid), PEX12 (Two-hybrid), PEX12 (Two-hybrid), PEX12 (Two-hybrid), PEX12 (Two-hybrid), PEX12 (Two-hybrid), PEX12 (Two-hybrid), SEC22A (Two-hybrid)

ESM2 similar proteins: A0A1L8FG46, A0A1L8FM16, A0A1L8FZ98, A0A1L8H814, A0JMW6, A1L2I9, A1L3G9, A4FUD4, A7S641, B0JYZ2, B9X187, E7F4V8, E7FE40, F1QB30, O00623, O70481, O88177, P24392, P28328, P55098, Q00940, Q05568, Q06438, Q0IJ33, Q19189, Q28EH9, Q3UUQ7, Q5RAW5, Q5ZI25, Q68F70, Q6AX31, Q6DFK1, Q6INN0, Q6IR55, Q6NPT7, Q6PD82, Q75T13, Q765A7, Q8BWZ3, Q8CHY3

Diamond homologs: A0A1L8H814, A4FUD4, O00623, O88177, Q19189, Q6DFK1, Q8VC48, Q9ET67, C8VCP8, G2Q5N0, Q54S31, Q9SYU4, Q9VPT5

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
Ub:E2	“up-regulates activity”	PEX12	ubiquitination
PEX12	“up-regulates activity”	PEX5	ubiquitination
PEX12	“up-regulates activity”	UBE2D1	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	62
Likely pathogenic	24
Uncertain significance	234
Likely benign	170
Benign	14

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1066716	NM_000286.3(PEX12):c.1039_1040del (p.Glu347fs)	Pathogenic
1069956	NM_000286.3(PEX12):c.174del (p.Trp58fs)	Pathogenic
1070935	NM_000286.3(PEX12):c.895A>T (p.Lys299Ter)	Pathogenic
1076434	NC_000017.11:g.35577561_35577592del	Pathogenic
1252073	NM_000286.3(PEX12):c.308dup (p.Leu103fs)	Pathogenic
1367479	NM_000286.3(PEX12):c.795C>G (p.Tyr265Ter)	Pathogenic
1374439	NM_000286.3(PEX12):c.305_306del (p.Arg102fs)	Pathogenic
1407609	NM_000286.3(PEX12):c.342G>A (p.Trp114Ter)	Pathogenic
1416654	NM_000286.3(PEX12):c.151_154del (p.His51fs)	Pathogenic
1430060	NM_000286.3(PEX12):c.222dup (p.Leu75fs)	Pathogenic
1435818	NM_000286.3(PEX12):c.471del (p.Ala158fs)	Pathogenic
1438584	NM_000286.3(PEX12):c.116del (p.His39fs)	Pathogenic
1439442	NM_000286.3(PEX12):c.126+1G>A	Pathogenic
1453031	NM_000286.3(PEX12):c.680_680+1delinsCA	Pathogenic
1939812	NM_000286.3(PEX12):c.348dup (p.Ile117fs)	Pathogenic
1994220	NM_000286.3(PEX12):c.725del (p.Gly242fs)	Pathogenic
2000167	NM_000286.3(PEX12):c.669del (p.Gln223fs)	Pathogenic
2009633	NM_000286.3(PEX12):c.86del (p.Ser28_Leu29insTer)	Pathogenic
2011680	NM_000286.3(PEX12):c.379A>T (p.Lys127Ter)	Pathogenic
2064933	NM_000286.3(PEX12):c.20_21dup (p.Phe8fs)	Pathogenic
2092385	NM_000286.3(PEX12):c.286del (p.Asp96fs)	Pathogenic
2096103	NM_000286.3(PEX12):c.268_269del (p.Lys90fs)	Pathogenic
2116235	NM_000286.3(PEX12):c.680_680+12del	Pathogenic
2118321	NM_000286.3(PEX12):c.459del (p.Lys153fs)	Pathogenic
2138007	NM_000286.3(PEX12):c.887del (p.Leu296fs)	Pathogenic
2138008	NM_000286.3(PEX12):c.875_876del (p.Asn291_Ser292insTer)	Pathogenic
2201009	NM_000286.3(PEX12):c.541dup (p.Tyr181fs)	Pathogenic
2736583	NM_000286.3(PEX12):c.775C>T (p.Gln259Ter)	Pathogenic
2753705	NM_000286.3(PEX12):c.4del (p.Ala2fs)	Pathogenic
280211	NM_000286.3(PEX12):c.51_54dup (p.Ser19fs)	Pathogenic

SpliceAI

300 predictions. Top by Δscore:

Variant	Effect	Δscore
17:35576177:TAACA:T	acceptor_gain	1.0000
17:35576180:CA:C	acceptor_gain	1.0000
17:35576182:C:CC	acceptor_gain	1.0000
17:35577033:CTTA:C	donor_loss	1.0000
17:35577034:TTAC:T	donor_loss	1.0000
17:35577035:TAC:T	donor_loss	1.0000
17:35577036:ACCT:A	donor_gain	1.0000
17:35577037:C:CG	donor_loss	1.0000
17:35577037:CCTC:C	donor_gain	1.0000
17:35577039:T:TA	donor_gain	1.0000
17:35577071:G:C	donor_gain	1.0000
17:35576178:AACA:A	acceptor_gain	0.9900
17:35577036:A:AC	donor_gain	0.9900
17:35577037:C:CC	donor_gain	0.9900
17:35577037:CCT:C	donor_gain	0.9900
17:35577591:CCTAA:C	acceptor_loss	0.9900
17:35577890:CCTTA:C	donor_loss	0.9900
17:35577891:CTTA:C	donor_loss	0.9900
17:35577892:TTA:T	donor_loss	0.9900
17:35577894:A:C	donor_loss	0.9900
17:35577895:C:CG	donor_loss	0.9900
17:35576179:ACA:A	acceptor_gain	0.9800
17:35576180:CAC:C	acceptor_gain	0.9800
17:35576181:AC:A	acceptor_loss	0.9800
17:35576182:C:CA	acceptor_loss	0.9800
17:35577587:AGAAC:A	acceptor_gain	0.9700
17:35577589:AACC:A	acceptor_gain	0.9700
17:35577590:ACCT:A	acceptor_gain	0.9700
17:35577591:CCTA:C	acceptor_gain	0.9700
17:35577592:C:A	acceptor_gain	0.9700

AlphaMissense

2322 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:35575847:A:G	C339R	0.997
17:35575887:A:C	C325W	0.997
17:35575952:A:G	C304R	0.997
17:35575889:A:G	C325R	0.996
17:35577445:T:A	R91S	0.996
17:35577445:T:G	R91S	0.996
17:35577467:T:A	E84V	0.996
17:35575810:A:G	L351P	0.995
17:35575845:A:C	C339W	0.995
17:35575888:C:T	C325Y	0.995
17:35575900:C:T	G321D	0.995
17:35577915:G:T	A36D	0.995
17:35575903:G:A	S320F	0.994
17:35575951:C:G	C304S	0.994
17:35575952:A:T	C304S	0.994
17:35577446:C:G	R91T	0.994
17:35575888:C:A	C325F	0.993
17:35575950:G:C	C304W	0.993
17:35575846:C:T	C339Y	0.992
17:35575900:C:A	G321V	0.992
17:35575903:G:T	S320Y	0.992
17:35575942:C:G	C307S	0.992
17:35575943:A:T	C307S	0.992
17:35575803:T:A	K353N	0.991
17:35575803:T:G	K353N	0.991
17:35575878:A:C	C328W	0.991
17:35575901:C:G	G321R	0.991
17:35575912:A:T	L317H	0.991
17:35575880:A:G	C328R	0.990
17:35575943:A:G	C307R	0.990

dbSNP variants (sampled 300 via entrez): RS1000187216 (17:35578665 CTAGA>C), RS1001031184 (17:35576889 T>C), RS1001533705 (17:35578484 C>T), RS1001563469 (17:35578167 G>A), RS1003258614 (17:35578738 T>A,C), RS1003538955 (17:35575270 C>G,T), RS1003905752 (17:35577423 T>C), RS1004771102 (17:35575283 T>C), RS1005106870 (17:35574496 G>C,T), RS1005318437 (17:35579029 T>A,G), RS1005673797 (17:35579215 T>C), RS1005986145 (17:35575608 G>A), RS1006374229 (17:35580567 G>C,T), RS10068 (17:35574946 C>G), RS1007698011 (17:35576305 T>C)

Disease associations

OMIM: gene MIM:601758 | disease phenotypes: MIM:614859, MIM:214100, MIM:266510

GenCC curated gene-disease

Disease	Classification	Inheritance
peroxisome biogenesis disorder	Definitive	Autosomal recessive
peroxisome biogenesis disorder 3A (Zellweger)	Definitive	Autosomal recessive
peroxisome biogenesis disorder type 3B	Definitive	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 (4): peroxisome biogenesis disorder 3A (Zellweger) (MONDO:0013927), peroxisome biogenesis disorder (MONDO:0019234), peroxisome biogenesis disorder type 3B (MONDO:0009959), Zellweger spectrum disorders (MONDO:0019609)

Orphanet (4): Zellweger syndrome (Orphanet:912), Peroxisome biogenesis disorder (Orphanet:79189), Neonatal adrenoleukodystrophy (Orphanet:44), Infantile Refsum disease (Orphanet:772)

HPO phenotypes

115 total (30 of 115 shown, HPO-id order):

HPO	Term
HP:0000003	Multicystic kidney dysplasia
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000047	Hypospadias
HP:0000113	Polycystic kidney dysplasia
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:0000272	Malar flattening
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:0000457	Depressed nasal ridge
HP:0000463	Anteverted nares
HP:0000474	Thickened nuchal skin fold
HP:0000486	Strabismus
HP:0000501	Glaucoma
HP:0000505	Visual impairment

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST004621_190	Red cell distribution width	5.000000e-13
GCST006804_57	Red cell distribution width	4.000000e-12
GCST90002385_411	High light scatter reticulocyte count	4.000000e-90
GCST90002386_183	High light scatter reticulocyte percentage of red cells	2.000000e-95
GCST90002397_566	Mean spheric corpuscular volume	1.000000e-11
GCST90002405_402	Reticulocyte count	1.000000e-55
GCST90002406_457	Reticulocyte fraction of red cells	1.000000e-62

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0009188	Red cell distribution width
EFO:0007986	reticulocyte count

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
C566633	Peroxisome Biogenesis Disorder, Complementation Group 3 (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

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
GSK-J4	decreases expression	1
urushiol	decreases expression	1
ferrous chloride	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Doxorubicin	decreases expression	1
Formaldehyde	increases expression	1
Methyl Methanesulfonate	increases expression	1
Smoke	decreases expression	1
Thiram	decreases expression	1
Cadmium Chloride	decreases expression	1
Lactic Acid	decreases expression	1
Particulate Matter	increases abundance, decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 finite cell line

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

Cellosaurus	Name	Category	Sex
CVCL_VQ74	PBD097	Finite cell line

Clinical trials (associated diseases)

10 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
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