PEX19

Summary

PEX19 (peroxisomal biogenesis factor 19, HGNC:9713) is a protein-coding gene on chromosome 1q23.2, encoding Peroxisomal biogenesis factor 19 (P40855). Necessary for early peroxisomal biogenesis.

This gene is necessary for early peroxisomal biogenesis. It acts both as a cytosolic chaperone and as an import receptor for peroxisomal membrane proteins (PMPs). 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. These disorders have at least 14 complementation groups, with more than one phenotype being observed for some 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), as well as peroxisome biogenesis disorder complementation group 14 (PBD-CG14), which is also known as PBD-CGJ. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 5824 — RefSeq curated summary.

At a glance

• Gene–disease (curated): peroxisome biogenesis disorder (Definitive, ClinGen) — +2 more curated relationships
• Clinical variants (ClinVar): 459 total — 11 pathogenic, 13 likely-pathogenic
• Phenotypes (HPO): 117
• MANE Select transcript: NM_002857

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9713
Approved symbol	PEX19
Name	peroxisomal biogenesis factor 19
Location	1q23.2
Locus type	gene with protein product
Status	Approved
Aliases	HK33, D1S2223E, PMP1, PMPI, PXMP1
Ensembl gene	ENSG00000162735
Ensembl biotype	protein_coding
OMIM	600279
Entrez	5824

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 6 protein_coding, 4 protein_coding_CDS_not_defined, 3 nonsense_mediated_decay, 2 retained_intron

ENST00000368072, ENST00000392220, ENST00000462644, ENST00000467711, ENST00000472750, ENST00000495624, ENST00000524939, ENST00000532508, ENST00000532516, ENST00000532643, ENST00000533104, ENST00000533699, ENST00000857246, ENST00000920352, ENST00000920353

RefSeq mRNA: 2 — MANE Select: NM_002857 NM_001193644, NM_002857

CCDS: CCDS1201

Canonical transcript exons

ENST00000368072 — 8 exons

Exon	Start	End
ENSE00001068101	160276807	160279634
ENSE00003534935	160280070	160280246
ENSE00003535307	160282039	160282200
ENSE00003609986	160282417	160282502
ENSE00003612122	160283530	160283639
ENSE00003641736	160282944	160283109
ENSE00003682525	160279801	160279845
ENSE00003899549	160285055	160285133

Expression profiles

Bgee: expression breadth ubiquitous, 282 present calls, max score 94.91.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 41.0726 / max 393.6424, expressed in 1821 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
15490	40.0858	1821
15489	0.8899	64
15488	0.0785	30
15487	0.0183	14

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
hindlimb stylopod muscle	UBERON:0004252	94.91	gold quality
muscle of leg	UBERON:0001383	94.58	gold quality
gastrocnemius	UBERON:0001388	94.54	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	94.47	gold quality
ventricular zone	UBERON:0003053	94.41	gold quality
colonic epithelium	UBERON:0000397	94.31	gold quality
adipose tissue of abdominal region	UBERON:0007808	94.28	gold quality
omental fat pad	UBERON:0010414	94.27	gold quality
adipose tissue	UBERON:0001013	94.23	gold quality
peritoneum	UBERON:0002358	94.21	gold quality
diaphragm	UBERON:0001103	94.14	gold quality
subcutaneous adipose tissue	UBERON:0002190	94.13	gold quality
islet of Langerhans	UBERON:0000006	93.89	gold quality
right lobe of liver	UBERON:0001114	93.87	gold quality
prefrontal cortex	UBERON:0000451	93.66	gold quality
muscle organ	UBERON:0001630	93.66	gold quality
biceps brachii	UBERON:0001507	93.61	gold quality
connective tissue	UBERON:0002384	93.55	gold quality
right atrium auricular region	UBERON:0006631	93.48	gold quality
right adrenal gland cortex	UBERON:0035827	93.47	gold quality
right adrenal gland	UBERON:0001233	93.40	gold quality
rectum	UBERON:0001052	93.28	gold quality
skeletal muscle tissue	UBERON:0001134	93.23	gold quality
cardiac atrium	UBERON:0002081	93.12	gold quality
heart left ventricle	UBERON:0002084	93.03	gold quality
left ovary	UBERON:0002119	93.03	gold quality
muscle tissue	UBERON:0002385	93.01	gold quality
left adrenal gland	UBERON:0001234	92.99	gold quality
gall bladder	UBERON:0002110	92.98	gold quality
popliteal artery	UBERON:0002250	92.98	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

Upstream regulators (CollecTRI, top): MYC

miRNA regulators (miRDB)

127 targeting PEX19, 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-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-7153-5P	99.94	68.89	1006
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-6744-5P	99.93	66.82	748
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-8063	99.91	69.76	3146

Literature-anchored findings (GeneRIF, showing 34)

• LDRP (ABCD2) interacts with both farnesylated wild-type and farnesylation-deficient mutant PEX19. This interaction is mediated by amino acids 1-218 of ALDRP. (PMID:10777694)
• MP70 (ABCD3) interacts with both farnesylated wild-type and farnesylation-deficient mutant PEX19. (PMID:10777694)
• ALDRP interacts with PEX19 splice variants PEX19-delta-E2 and PEX19-delta-E8. (PMID:11883941)
• MP70 interacts with PEX19 splice variants PEX19-delta-E2 and PEX19p-delta-E8. (PMID:11883941)
• a considerable functional diversity of the proteins encoded by two PEX19 splice variants and thereby provide first experimental evidence for specific biological functions of the different predicted domains of the PEX19 protein. (PMID:11883941)
• PEX19 binds and stabilizes newly synthesized PMPs in the cytosol, binds to multiple PMP targeting signals (mPTSs), interacts with the hydrophobic domains of PMP targeting signals, and is essential for PMP targeting and import. (PMID:14709540)
• Interaction of PEX3 and PEX19 visualized by fluorescence resonance energy transfer (FRET). (PMID:14713233)
• Pex19p has a role in assembly of PTS-receptor docking complexes (PMID:14715663)
• Results suggest that PEX3 plays a selective, essential, and direct role in class I peroxisomal membrane protein import as a docking factor for PEX19. (PMID:15007061)
• human Pex19p domain architecture and activity (PMID:15252024)
• analysis of the PEX19-binding site of human adrenoleukodystrophy protein (PMID:15781447)
• Pex19p translocates the membrane peroxins from the cytosol to peroxisomes in an ATP- and Pex3p-dependent manner and then shuttles back to the cytosol (PMID:16280322)
• Pex19p binds to PMP70 co-translationally and keeps PMP70 in a proper conformation for the localization to peroxisome. (PMID:16344115)
• Nonfarnesylated and farnesylated human Pex19p display a similar affinity towards a select set of peroxisomal membrane proteins. (PMID:16791427)
• Data suggest that Pex19p probably functions as a chaperone for membrane proteins and transports them to peroxisomes by anchoring to Pex3p using residues 12-73 and 40-131. (PMID:16895967)
• either one or two tryptophan residues of Pex3p (Trp-104 and Trp-224) are directly involved in binding to Pex19p. (PMID:18174172)
• targeting of hFis1 to peroxisomes and mitochondria are independent events and support a direct, Pex19p-dependent targeting of peroxisomal tail-anchored proteins. (PMID:18782765)
• N-terminal domain of Pex14, Pex14(N), adopts a three-helical fold. Pex5 and Pex19 ligand helices bind competitively to the same surface in Pex14(N) albeit with opposite directionality. (PMID:19197237)
• data indicate a divided N-terminal and C-terminal structural arrangement in Pex19p, which is reminiscent of a similar division in the Pex5p receptor, to allow separation of cargo-targeting signal recognition and additional functions. (PMID:20531392)
• The crystal structure of the cytosolic domain of PEX3 in complex with a PEX19-derived peptide. PEX3 adopts a novel fold that is best described as a large helical bundle. (PMID:20554521)
• The Pex19p peptide contains a characteristic motif, consisting of the leucine triad (Leu18, Leu21, Leu22), and Phe29, which are critical for the Pex3p binding and peroxisome biogenesis. (PMID:21102411)
• PEX3-PEX19 interaction is crucial for de novo formation of peroxisomes in peroxisome-deficient cells. (PMID:22624858)
• 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)
• Thus within the cell, PEX3 is stabilized by PEX19 preventing PEX3 aggregation. (PMID:25062251)
• suggest a novel regulatory mechanism for peroxisome biogenesis through the interaction between Pex19p and PLA/AT-3 (PMID:26018079)
• that newly synthesized UBXD8 is post-translationally inserted into discrete ER subdomains by a mechanism requiring cytosolic PEX19 and membrane-integrated PEX3, proteins hitherto exclusively implicated in peroxisome biogenesis (PMID:27295553)
• The results demonstrate an allosteric mechanism for the modulation of PEX19 function by farnesylation. (PMID:28281558)
• Hnf4-induced lipotoxicity and accumulation of free fatty acids is the cause for mitochondrial damage in consequence of peroxisome loss in Pex19 mutants (PMID:29282281)
• Thus, PEX19 and PEX3 peroxisome biogenesis factors provide an alternative posttranslational route for membrane insertion of the reticulon homology domain-containing proteins, implying that endoplasmic reticulum membrane shaping and peroxisome biogenesis may be coordinated. (PMID:29396426)
• The summarize recent insights into the biogenesis and function of Lipid droplets and peroxisomes with emphasis on the role of PEX19 in these processes. (PMID:29500918)
• studies indicate that Pex3 and Pex19 can also facilitate sorting of certain membrane proteins to other cellular organelles, including the endoplasmic reticulum, lipid droplets, and mitochondria (PMID:30776093)
• Viperin interacts with PEX19 to mediate peroxisomal augmentation of the innate antiviral response. (PMID:34108265)
• Dengue and Zika Virus Capsid Proteins Contain a Common PEX19-Binding Motif. (PMID:35215846)
• The M2 Protein of the Influenza A Virus Interacts with PEX19 to Facilitate Virus Replication by Disrupting the Function of Peroxisome. (PMID:39205283)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	pex19	ENSDARG00000004891
mus_musculus	Pex19	ENSMUSG00000003464
rattus_norvegicus	Pex19	ENSRNOG00000057116
drosophila_melanogaster	Pex19	FBGN0032407
caenorhabditis_elegans		WBGENE00004201

Protein

Protein identifiers

Peroxisomal biogenesis factor 19 — P40855 (reviewed: P40855)

Alternative names: 33 kDa housekeeping protein, Peroxin-19, Peroxisomal farnesylated protein

All UniProt accessions (6): A0A0S2Z497, B7Z8B3, P40855, E9PS71, H0YDY4, Q5QNY5

UniProt curated annotations — full annotation on UniProt →

Function. Necessary for early peroxisomal biogenesis. Acts both as a cytosolic chaperone and as an import receptor for peroxisomal membrane proteins (PMPs). Binds and stabilizes newly synthesized PMPs in the cytoplasm by interacting with their hydrophobic membrane-spanning domains, and targets them to the peroxisome membrane by binding to the integral membrane protein PEX3. Excludes CDKN2A from the nucleus and prevents its interaction with MDM2, which results in active degradation of TP53.

Subunit / interactions. Interacts with a broad range of peroxisomal membrane proteins, including PEX3, PEX10, PEX11A, PEX11B, PEX12, PEX13, PEX14 and PEX16, PXMP2/PMP22, PXMP4/PMP24, SLC25A17/PMP34, ABCD1/ALDP, ABCD2/ALDRP, and ABCD3/PMP70. Also interacts with the tumor suppressor CDKN2A/p19ARF. (Microbial infection) Interacts with human cytomegalovirus protein UL37 isoform vMIA; this interaction inhibits the peroxisomal-dependent antiviral signaling.

Subcellular location. Cytoplasm. Peroxisome membrane.

Tissue specificity. Ubiquitously expressed. Isoform 1 is strongly predominant in all tissues except in utero where isoform 2 is the main form.

Disease relevance. Peroxisome biogenesis disorder complementation group 14 (PBD-CG14) [MIM:614886] 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 12A (PBD12A) [MIM:614886] 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.

Miscellaneous. The two main transcripts are PXF-all and PXF-delta-2. The two main transcripts are PXF-all and PXF-delta-2. May be produced at very low levels due to a premature stop CC codon in the mRNA, leading to nonsense-mediated mRNA decay.

Similarity. Belongs to the peroxin-19 family.

Isoforms (5)

UniProt ID	Names	Canonical?
P40855-1	1, PXF-all	yes
P40855-2	2, PXF-delta-2, PXF lacking exon 2
P40855-3	3, PXF-delta-4, PXF lacking exon 4
P40855-4	4, PXF-delta-8, PXF lacking part of exon 8
P40855-6	6

RefSeq proteins (2): NP_001180573, NP_002848* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006708	Pex19	Family
IPR038322	Pex19_C_sf	Homologous_superfamily

Pfam: PF04614

UniProt features (32 total): helix 11, modified residue 6, mutagenesis site 4, region of interest 3, splice variant 2, initiator methionine 1, chain 1, lipid moiety-binding region 1, sequence variant 1, propeptide 1, compositionally biased region 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
2WL8	X-RAY DIFFRACTION	2.05
3MK4	X-RAY DIFFRACTION	2.42
3AJB	X-RAY DIFFRACTION	2.5
2W85	SOLUTION NMR
5LNF	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P40855-F1	71.95	0.23

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 (7): 66, 236, 296, 296, 2, 35, 54

Mutagenesis-validated functional residues (4):

Position	Phenotype
29	abolishes binding to pex3.
296–299	abolishes binding to pex10, pex11b, pex12 and pex13. does not affect binding to pex3 and pex16.
296	slightly inhibits pex19 function on peroxisome biogenesis.
296	abolishes farnesylation. abolishes pex19 function on peroxisome biogenesis. does not affect binding to abcd1, abcd2 and

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-1369062	ABC transporters in lipid homeostasis
R-HSA-9603798	Class I peroxisomal membrane protein import
R-HSA-9918481	Dengue Virus-Host Interactions

MSigDB gene sets: 410 (showing top): GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_MEMBRANE_BIOGENESIS, GOBP_PROTEIN_TARGETING, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_PROTEIN_MATURATION, GOBP_ORGANELLE_FISSION, GOBP_PROTEIN_STABILIZATION, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_MEMBRANE, GOBP_NEGATIVE_REGULATION_OF_MOLECULAR_FUNCTION, GOBP_PROTEIN_FOLDING, GOBP_REGULATION_OF_PROTEIN_STABILITY, SCHLOSSER_SERUM_RESPONSE_DN, GOCC_APICAL_PLASMA_MEMBRANE, GOBP_PEROXISOMAL_TRANSPORT, GOBP_PROTEIN_LOCALIZATION_TO_ORGANELLE

GO Biological Process (9): protein folding (GO:0006457), protein targeting to peroxisome (GO:0006625), peroxisome organization (GO:0007031), peroxisome membrane biogenesis (GO:0016557), peroxisome fission (GO:0016559), protein import into peroxisome membrane (GO:0045046), protein stabilization (GO:0050821), establishment of protein localization to peroxisome (GO:0072663), negative regulation of lipid binding (GO:1900131)

GO Molecular Function (5): peroxisome membrane targeting sequence binding (GO:0033328), peroxisome membrane class-1 targeting sequence binding (GO:0036105), ATPase binding (GO:0051117), protein carrier activity (GO:0140597), protein binding (GO:0005515)

GO Cellular Component (9): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), peroxisome (GO:0005777), peroxisomal membrane (GO:0005778), cytosol (GO:0005829), membrane (GO:0016020), brush border membrane (GO:0031526), protein-containing complex (GO:0032991)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
ABC-family protein mediated transport	1
Protein localization	1
Dengue Virus Infection	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
establishment of protein localization to peroxisome	2
peroxisome organization	2
cellular process	1
protein maturation	1
protein targeting	1
organelle organization	1
membrane biogenesis	1
organelle fission	1
intracellular protein transport	1
peroxisomal membrane transport	1
protein localization to membrane	1
protein localization to peroxisome	1
establishment of protein localization to membrane	1
regulation of protein stability	1
establishment of protein localization to organelle	1
lipid binding	1
negative regulation of binding	1
peroxisome signal sequence receptor activity	1
peroxisome membrane targeting sequence binding	1
enzyme binding	1
molecular carrier activity	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
microbody	1
peroxisome	1
microbody membrane	1
cytoplasm	1
brush border	1
apical plasma membrane	1
cell projection membrane	1
cellular_component	1

Protein interactions and networks

STRING

1782 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PEX19	PEX3	P56589	989
PEX19	PEX16	Q9Y5Y5	987
PEX19	PEX13	Q92968	983
PEX19	PEX10	O60683	973
PEX19	PEX14	O75381	969
PEX19	PEX12	O00623	965
PEX19	PEX6	Q13608	957
PEX19	PEX7	O00628	957
PEX19	PEX5	P50542	957
PEX19	PEX2	P28328	954
PEX19	PEX26	Q7Z412	944
PEX19	ABCD3	P28288	908
PEX19	PEX5L	Q8IYB4	897
PEX19	PEX11B	O96011	890
PEX19	PEX1	O43933	868

IntAct

347 interactions, top by confidence:

A	B	Type	Score
PEX19	PEX3	psi-mi:“MI:0915”(physical association)	0.980
PEX3	PEX19	psi-mi:“MI:0915”(physical association)	0.980
PEX19	PEX3	psi-mi:“MI:2364”(proximity)	0.980
PEX3	PEX19	psi-mi:“MI:2364”(proximity)	0.980

BioGRID (415): PEX19 (Two-hybrid), PEX3 (Two-hybrid), IL23A (Two-hybrid), FKBP7 (Two-hybrid), PEX19 (Affinity Capture-MS), PEX19 (Affinity Capture-MS), PEX19 (Affinity Capture-MS), PEX19 (Affinity Capture-MS), SLC27A4 (Affinity Capture-MS), ASPM (Affinity Capture-MS), MYO1D (Affinity Capture-MS), MYO5C (Affinity Capture-MS), MYO5B (Affinity Capture-MS), MYO5A (Affinity Capture-MS), PXMP2 (Affinity Capture-MS)

ESM2 similar proteins: A1L5A6, A2VDN6, A4IGK4, O00401, O08816, O12940, O35226, O43395, O48726, O60784, O88746, P40855, P50503, P55036, Q15459, Q16186, Q2KIA6, Q3SZD1, Q4WTC0, Q58DA0, Q5R5F1, Q5R684, Q5R7U2, Q5XHH7, Q5ZLF0, Q60415, Q62698, Q68FJ8, Q6GN67, Q6NRL6, Q6NZ09, Q6P877, Q6PDL0, Q7ZXD6, Q84L30, Q84L31, Q84L33, Q8BUR9, Q8K4Z5, Q8R1Q8

Diamond homologs: P34453, P40855, Q3SZD1, Q5R7U2, Q60415, Q8VCI5, Q9QYU1, Q94EI3, Q9SRQ3, Q10485

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
PEX3	“up-regulates activity”	PEX19	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 94 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
Class I peroxisomal membrane protein import	6	50.2×	5e-07

GO biological processes:

GO term	Partners	Fold	FDR
peroxisome organization	5	55.0×	2e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	11
Likely pathogenic	13
Uncertain significance	217
Likely benign	159
Benign	17

Top pathogenic / likely-pathogenic (24)

Variant ID	HGVS	Classification
1385253	NM_002857.4(PEX19):c.294del (p.Glu98fs)	Pathogenic
1444009	NM_002857.4(PEX19):c.398dup (p.Ser134fs)	Pathogenic
1521989	NM_002857.4(PEX19):c.161C>T (p.Ser54Leu)	Pathogenic
2011554	NM_002857.4(PEX19):c.9del (p.Ala4fs)	Pathogenic
2088255	NM_002857.4(PEX19):c.526C>T (p.Gln176Ter)	Pathogenic
225039	NM_002857.4(PEX19):c.775C>T (p.Gln259Ter)	Pathogenic
2842183	NM_002857.4(PEX19):c.86del (p.Phe29fs)	Pathogenic
30062	NM_002857.4(PEX19):c.320del (p.Lys107fs)	Pathogenic
3680741	NM_002857.4(PEX19):c.262del (p.Glu88fs)	Pathogenic
4715460	NM_002857.4(PEX19):c.326C>G (p.Ser109Ter)	Pathogenic
4774519	NM_002857.4(PEX19):c.430C>T (p.Gln144Ter)	Pathogenic
1066259	NM_002857.4(PEX19):c.346+2T>C	Likely pathogenic
1066362	NM_002857.4(PEX19):c.181-2A>G	Likely pathogenic
1067988	NM_002857.4(PEX19):c.346+1G>A	Likely pathogenic
1324882	NM_002857.4(PEX19):c.180+1G>T	Likely pathogenic
2122971	NM_002857.4(PEX19):c.70+2T>G	Likely pathogenic
2432567	NM_002857.4(PEX19):c.281T>A (p.Leu94Ter)	Likely pathogenic
2806573	NM_002857.4(PEX19):c.594+1G>C	Likely pathogenic
3075992	NM_002857.4(PEX19):c.606del (p.Trp202fs)	Likely pathogenic
3599001	NM_002857.4(PEX19):c.397_400del (p.Leu133fs)	Likely pathogenic
3659074	NM_002857.4(PEX19):c.181-1G>A	Likely pathogenic
3771562	NM_002857.4(PEX19):c.816+5G>A	Likely pathogenic
3911772	NM_002857.4(PEX19):c.496del (p.Asp166fs)	Likely pathogenic
593156	NM_002857.4(PEX19):c.595-2A>G	Likely pathogenic

SpliceAI

1069 predictions. Top by Δscore:

Variant	Effect	Δscore
1:160279843:TAGC:T	acceptor_loss	1.0000
1:160279845:GCTA:G	acceptor_loss	1.0000
1:160279846:C:CC	acceptor_gain	1.0000
1:160280064:CCTTA:C	donor_loss	1.0000
1:160280065:CTTA:C	donor_loss	1.0000
1:160280066:TTAC:T	donor_loss	1.0000
1:160280066:TTACC:T	donor_loss	1.0000
1:160280067:TACCT:T	donor_loss	1.0000
1:160280068:A:AC	donor_gain	1.0000
1:160280068:A:T	donor_loss	1.0000
1:160280069:C:CA	donor_loss	1.0000
1:160280069:C:CC	donor_gain	1.0000
1:160280069:CCTG:C	donor_gain	1.0000
1:160280242:GGATA:G	acceptor_gain	1.0000
1:160280243:GATA:G	acceptor_gain	1.0000
1:160280244:ATA:A	acceptor_gain	1.0000
1:160280245:TA:T	acceptor_gain	1.0000
1:160280247:C:CC	acceptor_gain	1.0000
1:160282036:AACCT:A	donor_loss	1.0000
1:160282037:A:AC	donor_gain	1.0000
1:160282038:C:CC	donor_gain	1.0000
1:160282038:C:CG	donor_loss	1.0000
1:160282196:GAGTT:G	acceptor_gain	1.0000
1:160282197:AGTT:A	acceptor_gain	1.0000
1:160282198:GTT:G	acceptor_gain	1.0000
1:160282199:TT:T	acceptor_gain	1.0000
1:160282201:C:CC	acceptor_gain	1.0000
1:160282499:CTGC:C	acceptor_gain	1.0000
1:160282938:CCTCA:C	donor_loss	1.0000
1:160282939:CTCAC:C	donor_loss	1.0000

AlphaMissense

1988 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:160279844:A:G	L258P	0.999
1:160282058:A:G	L192P	0.999
1:160282070:A:G	L188P	0.999
1:160282085:A:G	L183P	0.999
1:160282088:A:G	L182P	0.999
1:160282442:A:G	L136S	0.999
1:160282451:A:G	L133P	0.999
1:160282463:A:G	L129P	0.999
1:160282475:A:G	F125S	0.999
1:160282967:A:G	L108P	0.999
1:160279823:G:T	P265Q	0.998
1:160280158:A:T	I228K	0.998
1:160280237:A:G	W202R	0.998
1:160280237:A:T	W202R	0.998
1:160280246:A:C	Y199D	0.998
1:160282070:A:T	L188Q	0.998
1:160282083:A:G	S184P	0.998
1:160282474:G:C	F125L	0.998
1:160282474:G:T	F125L	0.998
1:160282475:A:C	F125C	0.998
1:160282476:A:G	F125L	0.998
1:160282976:A:G	F105S	0.998
1:160283022:C:G	A90P	0.998
1:160283030:A:G	F87S	0.998
1:160279824:G:T	P265T	0.997
1:160279832:C:A	G262V	0.997
1:160280178:C:A	Q221H	0.997
1:160280178:C:G	Q221H	0.997
1:160280179:T:G	Q221P	0.997
1:160282085:A:T	L183H	0.997

dbSNP variants (sampled 300 via entrez): RS1000135525 (1:160286016 T>C), RS1001110734 (1:160277973 T>C), RS1001322198 (1:160284916 C>A,T), RS1001362856 (1:160281551 G>A,T), RS1001539791 (1:160281940 C>A,T), RS1001812182 (1:160281928 A>G), RS1001873228 (1:160283324 C>T), RS1002144047 (1:160280412 T>G), RS1002190439 (1:160286513 A>G), RS1002528104 (1:160276326 T>C), RS1003690222 (1:160279879 G>A), RS1003760111 (1:160286705 A>G), RS1004362935 (1:160276470 A>T), RS1004429565 (1:160283868 A>T), RS1004697206 (1:160278102 C>G,T)

Disease associations

OMIM: gene MIM:600279 | disease phenotypes: MIM:614886, MIM:214100

GenCC curated gene-disease

Disease	Classification	Inheritance
peroxisome biogenesis disorder 12A (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 (3): peroxisome biogenesis disorder 12A (Zellweger) (MONDO:0013951), Zellweger spectrum disorders (MONDO:0019609), peroxisome biogenesis disorder (MONDO:0019234)

Orphanet (3): Zellweger syndrome (Orphanet:912), Peroxisome biogenesis disorder (Orphanet:79189), Infantile Refsum disease (Orphanet:772)

HPO phenotypes

117 total (30 of 117 shown, HPO-id order):

HPO	Term
HP:0000003	Multicystic kidney dysplasia
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000047	Hypospadias
HP:0000124	Renal tubular dysfunction
HP:0000126	Hydronephrosis
HP:0000157	Abnormality of the tongue
HP:0000174	Abnormal palate morphology
HP:0000218	High palate
HP:0000238	Hydrocephalus
HP:0000252	Microcephaly
HP:0000256	Macrocephaly
HP:0000260	Wide anterior fontanel
HP:0000267	Cranial asymmetry
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:0000448	Prominent nose
HP:0000463	Anteverted nares
HP:0000474	Thickened nuchal skin fold
HP:0000486	Strabismus
HP:0000501	Glaucoma

GWAS associations

0 associations (top):

MeSH disease descriptors (3)

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
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

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression	4
Decitabine	decreases expression, increases expression, increases reaction, increases response to substance	2
Cyclosporine	decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
pirinixic acid	affects binding, increases activity, increases expression	1
bisphenol A	increases expression	1
sodium arsenate	decreases expression	1
trichostatin A	decreases expression	1
sodium arsenite	increases expression	1
coumarin	decreases phosphorylation	1
diallyl trisulfide	decreases 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
bisphenol B	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
bisphenol S	increases expression	1
bisphenol AF	increases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	affects methylation	1
Ivermectin	decreases expression	1
Quercetin	decreases phosphorylation	1
Thiram	decreases expression	1
Toluene	decreases expression	1
Isotretinoin	decreases expression	1
Okadaic Acid	decreases expression	1
Copper Sulfate	decreases expression	1
Lactic Acid	decreases expression	1
Acrylamide	decreases expression	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_C7Y3	HAP1 PEX19 (-) 1	Cancer cell line	Male
CVCL_C7Y4	HAP1 PEX19 (-) 2	Cancer cell line	Male
CVCL_C7Y5	HAP1 PEX19 (-) 3	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