PEX26

Summary

PEX26 (peroxisomal biogenesis factor 26, HGNC:22965) is a protein-coding gene on chromosome 22q11.21, encoding Peroxisome assembly protein 26 (Q7Z412). Peroxisomal docking factor that anchors PEX1 and PEX6 to peroxisome membranes.

This gene belongs to the peroxin-26 gene family. It is probably required for protein import into peroxisomes. It anchors PEX1 and PEX6 to peroxisome membranes, possibly to form heteromeric AAA ATPase complexes required for the import of proteins into peroxisomes. Defects in this gene are the cause of peroxisome biogenesis disorder complementation group 8 (PBD-CG8). PBD refers to a group of peroxisomal disorders arising from a failure of protein import into the peroxisomal membrane or matrix. The PBD group is comprised of four disorders: Zellweger syndrome (ZWS), neonatal adrenoleukodystrophy (NALD), infantile Refsum disease (IRD), and classical rhizomelic chondrodysplasia punctata (RCDP). Alternatively spliced transcript variants have been identified for this gene.

Source: NCBI Gene 55670 — RefSeq curated summary.

At a glance

• Gene–disease (curated): peroxisome biogenesis disorder (Definitive, ClinGen) — +3 more curated relationships
• Clinical variants (ClinVar): 600 total — 32 pathogenic, 24 likely-pathogenic
• Phenotypes (HPO): 100
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_001127649

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:22965
Approved symbol	PEX26
Name	peroxisomal biogenesis factor 26
Location	22q11.21
Locus type	gene with protein product
Status	Approved
Aliases	FLJ20695
Ensembl gene	ENSG00000215193
Ensembl biotype	protein_coding
OMIM	608666
Entrez	55670

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 5 protein_coding

ENST00000329627, ENST00000399744, ENST00000428061, ENST00000851847, ENST00000936123

RefSeq mRNA: 3 — MANE Select: NM_001127649 NM_001127649, NM_001199319, NM_017929

CCDS: CCDS13750, CCDS56221

Canonical transcript exons

ENST00000399744 — 5 exons

Exon	Start	End
ENSE00001813110	18077990	18078606
ENSE00003902546	18087972	18105396
ENSE00004472491	18085112	18085258
ENSE00004475258	18083437	18083732
ENSE00004475413	18079874	18080014

Expression profiles

Bgee: expression breadth ubiquitous, 253 present calls, max score 89.31.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.4426 / max 96.2539, expressed in 1809 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
191006	16.4543	1805
191005	0.9883	560

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	89.31	gold quality
tendon of biceps brachii	UBERON:0008188	88.22	silver quality
cortical plate	UBERON:0005343	86.87	gold quality
islet of Langerhans	UBERON:0000006	86.19	gold quality
prefrontal cortex	UBERON:0000451	85.89	gold quality
rectum	UBERON:0001052	85.37	gold quality
ganglionic eminence	UBERON:0004023	85.21	gold quality
stromal cell of endometrium	CL:0002255	84.78	gold quality
anterior cingulate cortex	UBERON:0009835	84.14	gold quality
cingulate cortex	UBERON:0003027	84.13	gold quality
transverse colon	UBERON:0001157	83.97	gold quality
duodenum	UBERON:0002114	83.65	gold quality
ventricular zone	UBERON:0003053	82.70	gold quality
cervix squamous epithelium	UBERON:0006922	82.24	gold quality
medial globus pallidus	UBERON:0002477	82.15	silver quality
neocortex	UBERON:0001950	81.96	gold quality
small intestine	UBERON:0002108	81.96	gold quality
frontal cortex	UBERON:0001870	81.69	gold quality
cerebellar vermis	UBERON:0004720	81.63	gold quality
right frontal lobe	UBERON:0002810	81.35	gold quality
left adrenal gland	UBERON:0001234	81.22	gold quality
monocyte	CL:0000576	81.08	gold quality
amygdala	UBERON:0001876	81.08	gold quality
small intestine Peyer’s patch	UBERON:0003454	81.06	gold quality
leukocyte	CL:0000738	81.01	gold quality
mononuclear cell	CL:0000842	80.97	gold quality
right adrenal gland cortex	UBERON:0035827	80.89	gold quality
left adrenal gland cortex	UBERON:0035825	80.83	gold quality
right adrenal gland	UBERON:0001233	80.79	gold quality
nucleus accumbens	UBERON:0001882	80.69	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-6678	yes	484.06
E-ANND-3	yes	5.79
E-MTAB-4850	no	116.70
E-MTAB-6379	no	67.07

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

61 targeting PEX26, 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-4673	100.00	66.64	1490
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-6755-5P	99.95	65.59	464
HSA-MIR-3151-5P	99.86	63.83	1069
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-2052	99.79	69.37	2031
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-3059-5P	99.70	69.93	2491
HSA-MIR-494-3P	99.70	71.45	2795
HSA-MIR-6892-3P	99.68	66.40	1178
HSA-MIR-1260A	99.61	66.67	1098
HSA-MIR-1260B	99.61	66.67	1098
HSA-MIR-105-5P	99.54	69.24	2060
HSA-MIR-7853-5P	99.54	69.30	2055
HSA-MIR-4753-5P	99.54	68.51	1356
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-513C-5P	99.50	68.42	1730
HSA-MIR-514B-5P	99.50	68.19	1766
HSA-MIR-4696	99.48	67.48	1040
HSA-MIR-4284	99.36	65.25	1293
HSA-MIR-10522-5P	99.26	68.50	2087
HSA-MIR-4426	99.17	66.74	1949
HSA-MIR-4744	99.01	69.91	1581

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 13)

• degree of temperature sensitivity in pex26 cell lines is predictive of the clinical phenotype in patients with PEX26 deficiency (PMID:12851857)
• PEX26 deficiency impairs peroxisomal import of both PTS1- and PTS2-targeted matrix proteins. It undergoes alternative splicing to produce several splice forms, including PEX26-delta, which rescues peroxisome biogenesis in PEX26-deficient cells. (PMID:15858711)
• Pex26p functions in recruiting to peroxisomes the complexes of the AAA ATPase peroxins. (PMID:16257970)
• We analyzed targeting of human PEX26. Its C-terminal-targeting signal contains two binding sites for PEX19 and we conclude C-terminal PEX19-binding sites mark tail-anchored proteins for delivery to peroxisomes. (PMID:16763195)
• the relative fraction of disease-causing alleles that occur in the coding and splice junction sequences of PEX26 gene. (PMID:19105186)
• PEX19 formed a complex with the peroxisomal tail anchored protein PEX26 in the cytosol and translocated it directly to peroxisomes by a TRC40-independent class I pathway. (PMID:23460677)
• results suggested that peroxisome biogenesis requires Pex1p- and Pex6p-regulated dissociation of Pex14p from Pex26p (PMID:25016021)
• In yeast, PEX26 follows the pathway that also ensures correct targeting of Pex15: PEX26 enters the endoplasmic reticulum (ER) in a GET-dependent and Pex19-independent manner. (PMID:26627908)
• Data support an alternative PEX14-dependent mechanism of peroxisomal membrane association for the splice variant, which lacks a transmembrane domain. Structure-function relationships of PEX26 isoforms explain an extended function in peroxisomal homeostasis and these findings may improve our understanding of the broad phenotype of PEX26-associated human disorders. (PMID:30366024)
• An autosomal recessive missense variant, c.153C>A (p.F51L) in PEX26 was identified in Ashkenazi Jewish individual with a milder form of Zellweger spectrum and hearing loss. Binding of Pex26-F51L to Pex1 and Pex6 is severely impaired and affects peroxisome assembly. Pex26 in the patient’s fibroblasts is reduced to approximately 30% of control, suggesting that Pex26-F51L is unstable in cells. There are also other changes… (PMID:30446579)
• There are no significant differences between PEX1-, PEX6-, and PEX26-associated phenotypes inclinical and genetic spectrum of Heimler syndrome. (PMID:31831025)
• Silencing PEX26 as an unconventional mode to kill drug-resistant cancer cells and forestall drug resistance. (PMID:34074205)
• PEX26 Functions as a Metastasis Suppressor in Colorectal Cancer. (PMID:37957408)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	pex26	ENSDARG00000073858
mus_musculus	Pex26	ENSMUSG00000067825
rattus_norvegicus	Pex26	ENSRNOG00000049982

Protein

Protein identifiers

Peroxisome assembly protein 26 — Q7Z412 (reviewed: Q7Z412)

Alternative names: Peroxin-26

All UniProt accessions (3): A0A024R100, A0A0S2Z5M7, Q7Z412

UniProt curated annotations — full annotation on UniProt →

Function. Peroxisomal docking factor that anchors PEX1 and PEX6 to peroxisome membranes. PEX26 is therefore required for the formation of the PEX1-PEX6 AAA ATPase complex, a complex that mediates the extraction of the PEX5 receptor from peroxisomal membrane.

Subunit / interactions. Interacts (via its cytoplasmic domain) with PEX6; interaction is direct and is ATP-dependent. Interacts with PEX1; interaction is indirect and is mediated via interaction with PEX6.

Subcellular location. Peroxisome membrane.

Tissue specificity. Widely expressed. Highly expressed in kidney, liver, brain and skeletal muscles. Expressed at intermediate level in pancreas, placenta and heart. Weakly expressed in lung.

Disease relevance. Peroxisome biogenesis disorder complementation group 8 (PBD-CG8) [MIM:614872] 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 7A (PBD7A) [MIM:614872] 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 7B (PBD7B) [MIM:614873] 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-26 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q7Z412-1	1	yes
Q7Z412-2	2

RefSeq proteins (3): NP_001121121, NP_001186248, NP_060399 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR010797	Pex26	Family

Pfam: PF07163

UniProt features (14 total): sequence variant 7, topological domain 2, chain 1, sequence conflict 1, transmembrane region 1, region of interest 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7Z412-F1	79.87	0.48

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-9033241	Peroxisomal protein import
R-HSA-9603798	Class I peroxisomal membrane protein import

MSigDB gene sets: 302 (showing top): GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_DN, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, TGACCTY_ERR1_Q2, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_MEMBRANE_DOCKING, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_MEMBRANE, GOBP_RECEPTOR_METABOLIC_PROCESS, GOBP_PEROXISOMAL_TRANSPORT, GOBP_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOCC_MICROBODY_MEMBRANE, GOBP_PROTEIN_TRANSMEMBRANE_TRANSPORT, GOBP_LOCALIZATION_WITHIN_MEMBRANE, GOBP_TRANSMEMBRANE_TRANSPORT, GOCC_MICROBODY

GO Biological Process (6): protein import into peroxisome matrix (GO:0016558), protein to membrane docking (GO:0022615), protein import into peroxisome membrane (GO:0045046), protein transport (GO:0015031), protein import into peroxisome matrix, receptor recycling (GO:0016562), protein unfolding (GO:0043335)

GO Molecular Function (4): protein-membrane adaptor activity (GO:0043495), protein-containing complex binding (GO:0044877), ATPase binding (GO:0051117), protein binding (GO:0005515)

GO Cellular Component (4): peroxisome (GO:0005777), peroxisomal membrane (GO:0005778), cytosol (GO:0005829), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Protein localization	2

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
peroxisomal membrane transport	2
protein localization to peroxisome	2
establishment of protein localization to peroxisome	2
binding	2
cellular anatomical structure	2
protein transmembrane import into intracellular organelle	1
membrane docking	1
intracellular protein transport	1
protein localization to membrane	1
establishment of protein localization to membrane	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
receptor recycling	1
protein import into peroxisome matrix	1
cellular process	1
protein-macromolecule adaptor activity	1
enzyme binding	1
microbody	1
peroxisome	1
microbody membrane	1
cytoplasm	1

Protein interactions and networks

STRING

627 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PEX26	PEX6	Q13608	998
PEX26	PEX19	P40855	944
PEX26	PEX10	O60683	943
PEX26	PEX5	P50542	943
PEX26	PEX13	Q92968	931
PEX26	PEX12	O00623	930
PEX26	PEX3	P56589	926
PEX26	PEX2	P28328	920
PEX26	PEX16	Q9Y5Y5	918
PEX26	PEX1	O43933	903
PEX26	ABITRAM	Q9NX38	879
PEX26	PEX7	O00628	865
PEX26	PEX14	O75381	854
PEX26	PEX5L	Q8IYB4	813
PEX26	AGPS	O00116	779

IntAct

124 interactions, top by confidence:

A	B	Type	Score
PEX3	PEX19	psi-mi:“MI:0407”(direct interaction)	0.980
PEX19	PEX26	psi-mi:“MI:0915”(physical association)	0.680
PEX19	PEX26	psi-mi:“MI:0407”(direct interaction)	0.680
PEX26	PEX19	psi-mi:“MI:0407”(direct interaction)	0.680
PEX26	AP2B1	psi-mi:“MI:0915”(physical association)	0.560
PEX26	BIRC5	psi-mi:“MI:0915”(physical association)	0.560
PEX26	DAXX	psi-mi:“MI:0915”(physical association)	0.560
PEX26	MEOX1	psi-mi:“MI:0915”(physical association)	0.560
PEX26		psi-mi:“MI:0915”(physical association)	0.560
PEX26	PFDN5	psi-mi:“MI:0915”(physical association)	0.560
PEX26	TP53	psi-mi:“MI:0915”(physical association)	0.560
PEX26	MKRN3	psi-mi:“MI:0915”(physical association)	0.560
PEX26	RNF112	psi-mi:“MI:0915”(physical association)	0.560
PEX26	COPS3	psi-mi:“MI:0915”(physical association)	0.560
PEX26	IQSEC1	psi-mi:“MI:0915”(physical association)	0.560
BAIAP2	PEX26	psi-mi:“MI:0915”(physical association)	0.560
PEX26	NEBL	psi-mi:“MI:0915”(physical association)	0.560
PEX26	MSRB2	psi-mi:“MI:0915”(physical association)	0.560
PEX26	MKL1	psi-mi:“MI:0915”(physical association)	0.560
PEX26	ABHD17C	psi-mi:“MI:0915”(physical association)	0.560
PEX26	LHX5	psi-mi:“MI:0915”(physical association)	0.560
PEX26	KCTD15	psi-mi:“MI:0915”(physical association)	0.560
PEX26	BBLN	psi-mi:“MI:0915”(physical association)	0.560
PEX26	E2F8	psi-mi:“MI:0915”(physical association)	0.560
PEX26	SKIC8	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (24): PEX26 (Two-hybrid), PEX26 (Affinity Capture-Western), PEX26 (Affinity Capture-MS), PEX1 (Affinity Capture-Western), PEX6 (Affinity Capture-Western), PEX1 (Reconstituted Complex), PEX6 (Reconstituted Complex), PEX26 (Reconstituted Complex), PEX14 (Reconstituted Complex), PEX26 (Affinity Capture-Western), PEX26 (FRET), PEX26 (PCA), PEX6 (FRET), PEX19 (FRET), PEX14 (FRET)

ESM2 similar proteins: A0JN53, A0PJX8, A1L1L2, A1L3T7, A4FV45, B0BMG8, E2JF22, G3HQ82, O15360, O43299, O70491, P60330, Q0KL00, Q0V8E7, Q17Q97, Q24JP3, Q3U829, Q49LS3, Q4QR83, Q562E7, Q5ND34, Q5R7B4, Q5T1A1, Q5XG04, Q6NUQ4, Q6PH58, Q6UX68, Q7L4E1, Q7Z412, Q8BGI5, Q8BM55, Q8BSD4, Q8BXV2, Q8C3R1, Q8C7B8, Q8IXR5, Q8K0R6, Q8N6S5, Q8R115, Q8VCA6

Diamond homologs: G3HQ82, Q7Z412, Q8BGI5, Q9BE65

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
PEX26	“up-regulates activity”	PEX6	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	32
Likely pathogenic	24
Uncertain significance	257
Likely benign	199
Benign	34

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1323438	NM_001127649.3(PEX26):c.613del (p.Gln205fs)	Pathogenic
1331348	NM_001127649.3(PEX26):c.34del (p.Leu12fs)	Pathogenic
1450403	NC_000022.10:g.(?18561143)(18613903_?)del	Pathogenic
1456609	NC_000022.10:g.(?18561143)(18568044_?)del	Pathogenic
1995469	NM_001127649.3(PEX26):c.154del (p.Arg52fs)	Pathogenic
2006097	NM_001127649.3(PEX26):c.443del (p.Pro148fs)	Pathogenic
2118941	NM_001127649.3(PEX26):c.757A>T (p.Lys253Ter)	Pathogenic
2122801	NM_001127649.3(PEX26):c.725_726del (p.Ser242fs)	Pathogenic
2152	NM_001127649.3(PEX26):c.292C>T (p.Arg98Trp)	Pathogenic
2154	NM_001127649.3(PEX26):c.34dup (p.Leu12fs)	Pathogenic
2158	NM_001127649.3(PEX26):c.254dup (p.Cys86fs)	Pathogenic
2159	NM_001127649.3(PEX26):c.230+1G>T	Pathogenic
2677685	NM_001127649.3(PEX26):c.192_216del (p.Ser64fs)	Pathogenic
2677687	NM_001127649.3(PEX26):c.436C>T (p.Gln146Ter)	Pathogenic
2677688	NM_001127649.3(PEX26):c.230+1G>A	Pathogenic
2921344	NM_001127649.3(PEX26):c.28del (p.Ala10fs)	Pathogenic
2925654	NM_001127649.3(PEX26):c.37_38del (p.Arg13fs)	Pathogenic
2925655	NM_001127649.3(PEX26):c.73_79del (p.Val25fs)	Pathogenic
2927899	NM_001127649.3(PEX26):c.354dup (p.Lys119fs)	Pathogenic
2928098	NM_001127649.3(PEX26):c.190_191del (p.Leu65fs)	Pathogenic
2940082	NM_001127649.3(PEX26):c.298C>T (p.Gln100Ter)	Pathogenic
2942557	NM_001127649.3(PEX26):c.297G>A (p.Trp99Ter)	Pathogenic
2942734	NM_001127649.3(PEX26):c.396del (p.Glu133fs)	Pathogenic
2943328	NM_001127649.3(PEX26):c.468T>G (p.Tyr156Ter)	Pathogenic
2954498	NM_001127649.3(PEX26):c.344del (p.Lys115fs)	Pathogenic
3750992	NM_001127649.3(PEX26):c.297dup (p.Gln100fs)	Pathogenic
3754409	NM_001127649.3(PEX26):c.575dup (p.Leu193fs)	Pathogenic
375504	NM_001127649.3(PEX26):c.296G>A (p.Trp99Ter)	Pathogenic
3755800	NM_001127649.3(PEX26):c.214G>T (p.Glu72Ter)	Pathogenic
3759593	NM_001127649.3(PEX26):c.539_540dup (p.Val181Ter)	Pathogenic

SpliceAI

986 predictions. Top by Δscore:

Variant	Effect	Δscore
22:18078607:G:GG	donor_gain	1.0000
22:18079865:T:A	acceptor_gain	1.0000
22:18079868:T:A	acceptor_gain	1.0000
22:18079872:A:AG	acceptor_gain	1.0000
22:18079872:AGCT:A	acceptor_loss	1.0000
22:18079873:G:GG	acceptor_gain	1.0000
22:18079873:GC:G	acceptor_gain	1.0000
22:18079873:GCT:G	acceptor_gain	1.0000
22:18079873:GCTC:G	acceptor_gain	1.0000
22:18079873:GCTCA:G	acceptor_gain	1.0000
22:18080012:GTG:G	donor_gain	1.0000
22:18080013:TG:T	donor_gain	1.0000
22:18080013:TGG:T	donor_loss	1.0000
22:18080014:GG:G	donor_gain	1.0000
22:18080015:G:A	donor_loss	1.0000
22:18080015:G:GG	donor_gain	1.0000
22:18080016:T:A	donor_loss	1.0000
22:18078044:CGAGG:C	donor_loss	0.9900
22:18078045:GAGG:G	donor_loss	0.9900
22:18078046:AGGT:A	donor_loss	0.9900
22:18078048:GTGA:G	donor_loss	0.9900
22:18078049:T:A	donor_loss	0.9900
22:18078593:G:GT	donor_gain	0.9900
22:18078602:GGCAC:G	donor_gain	0.9900
22:18078603:GCAC:G	donor_gain	0.9900
22:18078603:GCACG:G	donor_gain	0.9900
22:18078604:C:T	donor_gain	0.9900
22:18078781:G:T	donor_gain	0.9900
22:18080010:CTGTG:C	donor_gain	0.9900
22:18083417:G:A	acceptor_gain	0.9900

AlphaMissense

1942 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:18083495:T:A	W144R	0.988
22:18083495:T:C	W144R	0.988
22:18079908:G:T	G89W	0.983
22:18079908:G:A	G89R	0.981
22:18079908:G:C	G89R	0.981
22:18078527:T:C	F51L	0.980
22:18078529:C:A	F51L	0.980
22:18078529:C:G	F51L	0.980
22:18079909:G:A	G89E	0.978
22:18079956:T:A	W105R	0.978
22:18079956:T:C	W105R	0.978
22:18080011:T:C	L123P	0.976
22:18083497:G:C	W144C	0.976
22:18083497:G:T	W144C	0.976
22:18079917:G:C	A92P	0.975
22:18079958:G:C	W105C	0.973
22:18079958:G:T	W105C	0.973
22:18080013:T:C	C124R	0.973
22:18083445:T:C	L127S	0.973
22:18079936:G:C	R98P	0.972
22:18079938:T:A	W99R	0.970
22:18079938:T:C	W99R	0.970
22:18079916:G:C	Q91H	0.969
22:18079916:G:T	Q91H	0.969
22:18079921:T:C	L93P	0.966
22:18079928:A:C	E95D	0.966
22:18079928:A:T	E95D	0.966
22:18078549:G:A	C58Y	0.965
22:18079912:T:A	I90N	0.965
22:18079918:C:A	A92D	0.965

dbSNP variants (sampled 300 via entrez): RS1000155327 (22:18094644 G>A), RS1000194551 (22:18097911 T>C), RS1000224239 (22:18097515 G>A), RS1000297942 (22:18097403 A>G), RS1000458949 (22:18092001 C>G,T), RS1000563323 (22:18098705 G>A), RS1000635373 (22:18098416 T>C), RS1000741041 (22:18093397 TAA>T,TA,TAAA), RS1000768750 (22:18093344 G>A), RS1000799809 (22:18099474 A>G,T), RS1000829619 (22:18092172 G>C), RS1000998025 (22:18076982 C>G), RS1001257793 (22:18096546 A>G), RS1001289435 (22:18081927 G>A,C,T), RS1001290345 (22:18096071 C>T)

Disease associations

OMIM: gene MIM:608666 | disease phenotypes: MIM:614872, MIM:614873, MIM:214100

GenCC curated gene-disease

Disease	Classification	Inheritance
peroxisome biogenesis disorder 7B	Definitive	Autosomal recessive
peroxisome biogenesis disorder	Definitive	Autosomal recessive
peroxisome biogenesis disorder 7A (Zellweger)	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 (7): peroxisome biogenesis disorder 7A (Zellweger) (MONDO:0013938), peroxisome biogenesis disorder 7B (MONDO:0013939), peroxisome biogenesis disorder (MONDO:0019234), inherited retinal dystrophy (MONDO:0019118), peroxisome biogenesis disorder 1A (Zellweger) (MONDO:0008953), optic atrophy (MONDO:0003608), Zellweger spectrum disorders (MONDO:0019609)

Orphanet (5): Neonatal adrenoleukodystrophy (Orphanet:44), Zellweger syndrome (Orphanet:912), Peroxisome biogenesis disorder (Orphanet:79189), OBSOLETE: Inherited retinal disorder (Orphanet:71862), Deafness-enamel hypoplasia-nail defects syndrome (Orphanet:3220)

HPO phenotypes

100 total (30 of 100 shown, HPO-id order):

HPO	Term
HP:0000003	Multicystic kidney dysplasia
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000047	Hypospadias
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:0000343	Long philtrum
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

0 associations (top):

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D009896	Optic Atrophy	C10.292.700.225; C11.640.451
D058499	Retinal Dystrophies	C11.768.585.658
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
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

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	affects cotreatment, decreases expression, increases abundance, affects expression	2
Ozone	affects expression, affects cotreatment, decreases expression, increases abundance	2
aristolochic acid I	increases expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
trichostatin A	affects expression	1
cobaltous chloride	decreases expression	1
butyraldehyde	decreases expression	1
methacrylaldehyde	affects cotreatment, decreases expression, increases abundance	1
(+)-JQ1 compound	decreases expression	1
Glyphosate	affects methylation	1
Acrolein	affects cotreatment, decreases expression, increases abundance	1
Benzo(a)pyrene	decreases methylation	1
Doxorubicin	decreases expression	1
Smoke	decreases expression	1
Valproic Acid	increases expression	1
Lactic Acid	increases expression	1
Acrylamide	decreases expression	1
Volatile Organic Compounds	decreases expression, affects cotreatment	1

Cellosaurus cell lines

13 cell lines: 8 finite cell line, 3 transformed cell line, 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_4F76	GM17398	Finite cell line	Female
CVCL_9R30	GM11335	Finite cell line	Female
CVCL_9Z45	GM08771	Finite cell line	Female
CVCL_9Z52	GM16865	Finite cell line	Female
CVCL_9Z53	GM17397	Finite cell line	Female
CVCL_9Z55	GM17399	Finite cell line	Female
CVCL_9Z56	GM17400	Finite cell line	Male
CVCL_W726	GM07370	Transformed cell line	Female
CVCL_W727	GM07371	Finite cell line	Female
CVCL_ZM06	HEK293T Control-PEROXO	Transformed cell line	Female

Clinical trials (associated diseases)

59 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
NCT04224207	PHASE3	COMPLETED	Management of Retinitis Pigmentosa by Mesenchymal Stem Cells by Wharton’s Jelly Derived Mesenchymal Stem Cells
NCT07082855	PHASE3	NOT_YET_RECRUITING	A Multicenter, Randomized, Double-Blind, Controlled Clinical Study of Minocycline for the Treatment of Retinitis Pigmentosa
NCT03856866	PHASE2	COMPLETED	Hydroxychloroquine Administration for Reduction of Pexophagy
NCT02171104	PHASE2	ACTIVE_NOT_RECRUITING	MT2013-31: Allo HCT for Metabolic Disorders and Severe Osteopetrosis
NCT03763227	PHASE2	COMPLETED	Intravitreal Ranibizumab (Lucentis®) in the Treatment of Non-leaking Macular Cysts in Retinal Dystrophy
NCT04068207	PHASE2	COMPLETED	Minocycline Treatment in Retinitis Pigmentosa
NCT04945772	PHASE2	COMPLETED	Efficacy and Safety of MCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE]
NCT05902962	PHASE1	COMPLETED	SAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects
NCT06319872	PHASE1	RECRUITING	The Effects of Disulfiram (Antabuse®) on Visual Acuity in Patients With Retinal Degeneration
NCT06455826	PHASE1	COMPLETED	MAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects (Wallaby)
NCT01064505	PHASE1	COMPLETED	Safety Study of a Single IVT Injection of QPI-1007 in Chronic Optic Nerve Atrophy and Recent Onset NAION Patients
NCT05147701	PHASE1	RECRUITING	Safety of Cultured Allogeneic Adult Umbilical Cord Derived Mesenchymal Stem Cells for NAION
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
NCT04855045	PHASE2/PHASE3	UNKNOWN	An Open-label, Dose Escalation and Double-masked, Randomized, Controlled Trial Evaluating Safety and Tolerability of Sepofarsen in Children (<8 Years of Age) With LCA10 Caused by Mutations in the CEP290 Gene.
NCT03872479	PHASE1/PHASE2	UNKNOWN	Single Ascending Dose Study in Participants With LCA10
NCT04123626	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Study to Evaluate the Safety and Tolerability of QR-1123 in Subjects With Autosomal Dominant Retinitis Pigmentosa Due to the P23H Mutation in the RHO Gene
NCT04545736	PHASE1/PHASE2	RECRUITING	Oral Metformin for Treatment of ABCA4 Retinopathy
NCT06212297	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Fellow-eye Study (FE) of LX101 in Subjects With Inherited Retinal Dystrophy
NCT06852963	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Repeat-Dose, Open-Label, Two Arm Safety and Efficacy Study of Two Doses of VP-001 Administered Intravitreally in Participants With Confirmed PRPF31 Mutation-Associated Retinal Dystrophy, Including Participants Previously Treated With VP001
NCT07177196	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Personalized Antisense Oligonucleotide Therapy for a Single Participant With PRPH2 Mutation Associated With Retinal Dystrophy
NCT07063030	EARLY_PHASE1	RECRUITING	A Study of LX107 Gene Therapy in AIPL1-IRD Patients
NCT01546181	Not specified	COMPLETED	Retinal Imaging by Adaptive Optics in Healthy Eyes and During Retinal and General Diseases
NCT01876147	Not specified	COMPLETED	Visual and Functional Assessment in Low Vision Patients
NCT01920867	Not specified	UNKNOWN	Stem Cell Ophthalmology Treatment Study
NCT02014389	Not specified	RECRUITING	Evaluation of Objective Perimetry Using Chromatic Multifocal Pupillometer
NCT02983305	Not specified	COMPLETED	Optical Head-Mounted Display Technology for Low Vision Rehabilitation
NCT03592017	Not specified	COMPLETED	Performance of Long-wavelength Autofluorescence Imaging
NCT03662386	Not specified	TERMINATED	Prospective Analysis of Genotype-phenotype Correlations Observed in a Large Cohort of Patients With Hereditary Retinal Dystrophies - GEPHIRD
NCT03691168	Not specified	UNKNOWN	Multi-center Observation of the Natural Course of Inherited Retinal Dystrophies
NCT03843840	Not specified	COMPLETED	Dual Wavelength OCT
NCT03853252	Not specified	COMPLETED	iPS Cells of Patients for Models of Retinal Dystrophies
NCT05130385	Not specified	UNKNOWN	High Resolution Optical Coherence Tomography
NCT05294978	Not specified	RECRUITING	EyeConic: Qualification for Cone-Optogenetics