PEX13

Summary

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

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

Source: NCBI Gene 5194 — RefSeq curated summary.

At a glance

• Gene–disease (curated): peroxisome biogenesis disorder (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 2
• Clinical variants (ClinVar): 625 total — 30 pathogenic, 11 likely-pathogenic (top 5% of genes corpus-wide)
• GTEx eGene: eQTL in 14 tissues, sQTL in 4 (q < 0.05)
• Phenotypes (HPO): 105
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.16 (unconstrained)
• MANE Select transcript: NM_002618

Identifiers

Gene identifiers

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

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 17 protein_coding, 5 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000295030

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 4, TSL 2: 1

ENST00000295030, ENST00000401576, ENST00000414712, ENST00000444100, ENST00000472678, ENST00000902277, ENST00000902278, ENST00000920043, ENST00000920044, ENST00000971318, ENST00001003036, ENST00001003037, ENST00001003038, ENST00001003039, ENST00001003040, ENST00001014406, ENST00001076060, ENST00001091008, ENST00001091009, ENST00001091010, ENST00001091011, ENST00001121655, ENST00001145200

RefSeq mRNA: 1 — MANE Select: NM_002618 NM_002618

CCDS: CCDS1866

Canonical transcript exons

ENST00000295030 — 4 exons

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

Expression profiles

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

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

Highest expression (Bgee): secondary oocyte, sperm, oocyte, buccal mucosa cell, male germ cell.

Genetic regulation across tissues (GTEx eQTL / sQTL)

PEX13 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 14 tissues and its splicing (sQTL) in 4 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

18 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Brain Spinal cord cervical c-1	eqtl	9.0e-05	+0.37	2:61019010:G:A
Brain Nucleus accumbens basal ganglia	eqtl	2.0e-04	+0.29	2:61038835:A:G
Brain Hypothalamus	eqtl	2.0e-04	+0.36	2:61080847:T:C
Brain Cerebellum	eqtl	4.3e-04	+0.24	2:61054021:C:G
Brain Cortex	eqtl	5.4e-04	+0.27	2:61038835:A:G
Brain Frontal Cortex BA9	eqtl	9.2e-04	+0.25	2:61022966:A:C
Breast Mammary Tissue	sqtl	1.1e-03	+0.42	2:60640841:C:T
Nerve Tibial	sqtl	8.7e-03	+0.27	2:61026581:T:C
Thyroid	eqtl	9.1e-03	-0.13	2:62003835:A:G
Brain Cerebellar Hemisphere	eqtl	1.3e-02	-0.21	2:60614656:T:A
Cells Cultured fibroblasts	eqtl	1.3e-02	-0.12	2:60829754:GA:G
Cells Cultured fibroblasts	sqtl	1.8e-02	+0.30	2:61077242:A:T
Brain Putamen basal ganglia	eqtl	1.9e-02	+0.24	2:61013401:A:T
Artery Tibial	eqtl	2.3e-02	+0.21	2:61424393:G:A
Esophagus Mucosa	eqtl	2.7e-02	+0.13	2:60591549:T:C
Minor Salivary Gland	sqtl	3.0e-02	+0.63	2:60741887:G:C
Skin Sun Exposed Lower leg	eqtl	3.1e-02	+0.10	2:60228129:C:T
Pituitary	eqtl	4.7e-02	+0.14	2:61020099:A:G

FANTOM5 promoters

1 alternative TSS:

Promoter ID	TPM avg	Samples expressed
20468	14.5738	1794

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	95.59	gold quality
sperm	CL:0000019	94.66	gold quality
oocyte	CL:0000023	93.67	gold quality
buccal mucosa cell	CL:0002336	92.76	gold quality
male germ cell	CL:0000015	91.81	gold quality
esophagus squamous epithelium	UBERON:0006920	91.75	gold quality
epithelium of nasopharynx	UBERON:0001951	90.11	gold quality
germinal epithelium of ovary	UBERON:0001304	89.44	gold quality
epithelium of esophagus	UBERON:0001976	88.42	gold quality
visceral pleura	UBERON:0002401	87.99	gold quality
calcaneal tendon	UBERON:0003701	86.97	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.96	gold quality
cortical plate	UBERON:0005343	86.89	gold quality
mucosa of paranasal sinus	UBERON:0005030	86.87	gold quality
ventricular zone	UBERON:0003053	86.85	gold quality
gingival epithelium	UBERON:0001949	86.77	gold quality
parietal pleura	UBERON:0002400	86.62	gold quality
palpebral conjunctiva	UBERON:0001812	86.37	gold quality
adrenal tissue	UBERON:0018303	86.17	gold quality
ganglionic eminence	UBERON:0004023	86.15	gold quality
amniotic fluid	UBERON:0000173	85.94	gold quality
eye	UBERON:0000970	85.90	gold quality
jejunal mucosa	UBERON:0000399	85.81	gold quality
pleura	UBERON:0000977	85.50	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.31	gold quality
hindlimb stylopod muscle	UBERON:0004252	85.00	gold quality
liver	UBERON:0002107	84.85	gold quality
gastrocnemius	UBERON:0001388	84.82	gold quality
squamous epithelium	UBERON:0006914	84.80	gold quality
muscle of leg	UBERON:0001383	84.76	gold quality
gingiva	UBERON:0001828	84.62	gold quality
tibia	UBERON:0000979	84.24	gold quality
pigmented layer of retina	UBERON:0001782	84.20	gold quality
bronchial epithelial cell	CL:0002328	83.89	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	83.89	gold quality
upper leg skin	UBERON:0004262	83.88	gold quality
islet of Langerhans	UBERON:0000006	83.78	gold quality
endothelial cell	CL:0000115	83.76	gold quality
right lobe of liver	UBERON:0001114	83.69	gold quality
endometrium	UBERON:0001295	83.63	gold quality
biceps brachii	UBERON:0001507	83.63	gold quality
jejunum	UBERON:0002115	83.56	gold quality
lower lobe of lung	UBERON:0008949	83.13	gold quality
rectum	UBERON:0001052	82.83	gold quality
stromal cell of endometrium	CL:0002255	82.69	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	82.65	gold quality
mucosa of sigmoid colon	UBERON:0004993	82.60	gold quality
colonic mucosa	UBERON:0000317	82.57	gold quality
gall bladder	UBERON:0002110	82.34	gold quality
oral cavity	UBERON:0000167	82.18	gold quality
mucosa of transverse colon	UBERON:0004991	82.11	gold quality
mammary duct	UBERON:0001765	82.04	gold quality
esophagus mucosa	UBERON:0002469	82.01	gold quality
testis	UBERON:0000473	81.89	gold quality
tendon	UBERON:0000043	81.71	gold quality
ovary	UBERON:0000992	81.64	gold quality
skeletal muscle organ	UBERON:0014892	81.57	gold quality
muscle organ	UBERON:0001630	81.56	gold quality
heart left ventricle	UBERON:0002084	81.38	gold quality
tonsil	UBERON:0002372	81.35	gold quality
skin of hip	UBERON:0001554	81.28	gold quality
cardiac ventricle	UBERON:0002082	81.22	gold quality
lower esophagus mucosa	UBERON:0035834	81.18	gold quality
right testis	UBERON:0004534	81.14	gold quality
vagina	UBERON:0000996	81.08	gold quality
left ovary	UBERON:0002119	81.03	gold quality
left testis	UBERON:0004533	81.02	gold quality
colonic epithelium	UBERON:0000397	80.80	gold quality
seminal vesicle	UBERON:0000998	80.80	gold quality
prostate gland	UBERON:0002367	80.65	gold quality
pancreas	UBERON:0001264	80.61	gold quality
esophagus	UBERON:0001043	80.55	gold quality
epithelium of mammary gland	UBERON:0003244	80.55	gold quality
left lobe of thyroid gland	UBERON:0001120	80.54	gold quality
mammary gland	UBERON:0001911	80.37	gold quality
thyroid gland	UBERON:0002046	80.34	gold quality
thoracic mammary gland	UBERON:0005200	80.30	gold quality
heart	UBERON:0000948	80.25	gold quality
descending thoracic aorta	UBERON:0002345	80.20	gold quality
duodenum	UBERON:0002114	80.06	gold quality
female reproductive system	UBERON:0000474	79.98	gold quality
mouth mucosa	UBERON:0003729	79.93	gold quality
popliteal artery	UBERON:0002250	79.80	gold quality
tibial artery	UBERON:0007610	79.80	gold quality
body of pancreas	UBERON:0001150	79.76	gold quality
adrenal gland	UBERON:0002369	79.71	gold quality
monocyte	CL:0000576	79.66	gold quality
minor salivary gland	UBERON:0001830	79.66	gold quality
right lobe of thyroid gland	UBERON:0001119	79.64	gold quality
uterus	UBERON:0000995	79.59	gold quality
urinary bladder	UBERON:0001255	79.57	gold quality
ectocervix	UBERON:0012249	79.53	gold quality
aorta	UBERON:0000947	79.48	gold quality
left adrenal gland	UBERON:0001234	79.41	gold quality
leukocyte	CL:0000738	79.40	gold quality
large intestine	UBERON:0000059	79.37	gold quality
right atrium auricular region	UBERON:0006631	79.35	gold quality
mononuclear cell	CL:0000842	79.25	gold quality
colon	UBERON:0001155	79.23	gold quality
right ovary	UBERON:0002118	79.23	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

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 74 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Cerebellum	tissue	29.0	high
Liver	tissue	23.4	medium
Pons	tissue	22.8
Midbrain	tissue	21.9
Choroid plexus	tissue	21.2
Thalamus	tissue	20.5
Basal ganglia	tissue	18.6	high
Hypothalamus	tissue	18.6
Septum	tissue	18.6
Cerebral cortex	tissue	18.0	high
Somatosensory cortex	tissue	18.0
Occipital cortex	tissue	17.5
Corpus callosum	tissue	17.3
Hippocampal formation	tissue	16.4
Entorhinal cortex	tissue	16.3
Olfactory bulb	tissue	16.2
Frontal cortex	tissue	16.0
Caudate putamen	tissue	15.7
Amygdala	tissue	15.6
Ventral forebrain	tissue	15.5
Retrosplenial and cingulate cortex	tissue	15.5
Nucleus accumbens	tissue	14.3
Putamen	tissue	14.1
Testis	tissue	13.9	high
Medulla oblongata	tissue	13.7
Spinal cord	tissue	13.7
Prostate	tissue	13.7	medium
Retrosplenial cortex	tissue	13.1
Urinary bladder	tissue	12.9	high
Substantia nigra	tissue	12.8
Thyroid gland	tissue	12.8	high
Postcentral gyrus	tissue	12.8
Tongue	tissue	12.7
Kidney	tissue	12.7	high
Hippocampus	tissue	12.5	medium
Skeletal muscle	tissue	12.4	medium
Locus coeruleus	tissue	12.2
Heart muscle	tissue	11.1	medium
Pancreas	tissue	11.1	medium
Breast	tissue	10.4	high
Ovary	tissue	10.1	high
Rectum	tissue	10.0	medium
Cervix	tissue	9.6	high
Colon	tissue	9.6	high
Duodenum	tissue	9.6	high
Stomach 1	tissue	9.5	medium
Esophagus	tissue	9.2	medium
Small intestine	tissue	9.2	medium
Parathyroid gland	tissue	9.0	high
Vagina	tissue	8.9	medium
Adipose tissue	tissue	8.9	low
Placenta	tissue	8.7	high
Lung	tissue	8.7	high
Endometrium 1	tissue	8.6	medium
Gallbladder	tissue	8.3	high
Retina	tissue	8.1
Salivary gland	tissue	7.6	high
Adrenal gland	tissue	7.6	high
Smooth muscle	tissue	7.5	low
Pituitary gland	tissue	7.1

Brain sub-regions (HPA Brain Atlas): detected in 188; highest nTPM — Cerebellar cortex (19.5), Flocculonodular lobe (19.4), Vermis (18.6), White matter (17.3), Corpus callosum, genu (white matter) (15.1).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting PEX13 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 168 miRNAs:

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

Functional genomics

gnomAD constraint: pLI 2.88e-07, LOEUF 1.16, missense Z -0.753 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000295030 — one region, missense o/e 1.12.

Literature-anchored findings (GeneRIF, showing 9)

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

Cross-species orthologs

5 orthologs

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

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1919379) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 43 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased body weight	2
kyphosis	1
abnormal cerebral cortex morphology	1
abnormal cerebellum development	1
abnormal cerebellum external granule cell layer morphology	1
abnormal cerebellar Purkinje cell layer	1
abnormal Purkinje cell morphology	1
thin cerebellar molecular layer	1
weight loss	1
impaired coordination	1
aphagia	1
limb grasping	1
postnatal growth retardation	1
respiratory distress	1
abnormal reflex	1
premature death	1
gliosis	1
neuron degeneration	1
astrocytosis	1
oxidative stress	1
hypotonia	1
bradykinesia	1
abnormal fatty acids level	1
abnormal renal glomerulus morphology	1
abnormal mitochondrial morphology	1

+18 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Bos taurus	Q0P5B1	92.6%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
PUS10	protein-coding	150962
SANBR	protein-coding	84542
C2orf74-AS1	ncRNA	105374758
C2orf74-DT	ncRNA	339803
DEMA1	protein-coding	339804
USP34	protein-coding	9736
REL	protein-coding	5966

Protein

Protein identifiers

Peroxisomal membrane protein PEX13 — Q92968 (reviewed: Q92968)

Alternative names: Peroxin-13

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

UniProt curated annotations — full annotation on UniProt →

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

Subunit / interactions. Component of the PEX13-PEX14 docking complex, composed of PEX13 and PEX14. Interacts (via SH3 domain) with PEX14 (via SH3-binding motif); forming the PEX13-PEX14 docking complex. Interacts with PEX19. Interacts (via KPWE motif) with PEX7; this interaction is essential for the import of PTS2-containing proteins.

Subcellular location. Peroxisome membrane.

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

Similarity. Belongs to the peroxin-13 family.

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

Domains & families (InterPro)

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

Pfam: PF04088, PF14604

UniProt features (28 total): strand 5, topological domain 4, region of interest 3, transmembrane region 3, helix 3, compositionally biased region 2, sequence variant 2, chain 1, short sequence motif 1, modified residue 1, mutagenesis site 1, turn 1, domain 1

Structure

Experimental structures (PDB)

3 structures by resolution:

PDB	Title	Method	Resolution (Å)
7Z0I	human PEX13 SH3 domain	X-RAY DIFFRACTION	1.8
7Z0J	human PEX13 SH3 domain in complex with internal FxxxF motif	X-RAY DIFFRACTION	2.3
7Z0K	human PEX13 SH3 in complex with PEX5 W4 (WxxxF/Y) motif	X-RAY DIFFRACTION	2.3

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Transporters, Primary Active Transporters, Predicted membrane proteins, Predicted intracellular proteins, Disease related genes, Potential drug targets, Human disease related genes, Congenital disorders of metabolism

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): peroxisomes

Antibody reliability (HPA): IH enhanced · IF supported

Functional residue map

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

Post-translational modifications (1)

Type	Positions
Phosphoserine	354

Mutagenesis-validated functional residues (1)

Position	Phenotype
10–13	abolishes interaction with pex7.

Function

Pathways and Gene Ontology

Reactome pathways

2 curated (TAS) of 7; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

7 pathways:

ID	Pathway	Evidence
R-HSA-9603798	Class I peroxisomal membrane protein import	curated
R-HSA-8866654	E3 ubiquitin ligases ubiquitinate target proteins	curated
R-HSA-392499	Metabolism of proteins	—
R-HSA-9033241	Peroxisomal protein import	electronic
R-HSA-597592	Post-translational protein modification	—
R-HSA-9609507	Protein localization	—
R-HSA-8852135	Protein ubiquitination	—

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

GO Biological Process (10): fatty acid alpha-oxidation (GO:0001561), neuron migration (GO:0001764), suckling behavior (GO:0001967), locomotory behavior (GO:0007626), protein import into peroxisome matrix, docking (GO:0016560), protein import into peroxisome matrix, translocation (GO:0016561), cerebral cortex cell migration (GO:0021795), cellular response to reactive oxygen species (GO:0034614), microtubule-based peroxisome localization (GO:0060152), protein transport (GO:0015031)

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

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

Reactome top-level categories

4 top-level categories:

Category	Pathways
Protein localization	2
Protein ubiquitination	1
Metabolism of proteins	1
Post-translational protein modification	1

GO top-level categories

28 GO namespaces:

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

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 7 of 17 annotations. The rest are phylogenetic / computational / electronic (IEA).

7 experimentally-supported GO terms:

GO term	NS	Evidence
cellular response to reactive oxygen species	BP	direct assay
protein import into peroxisome matrix, docking	BP	direct assay
protein import into peroxisome matrix, translocation	BP	direct assay
membrane	CC	high-throughput assay
peroxisomal membrane	CC	direct assay
peroxisome	CC	direct assay
transmembrane protein transporter activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 754 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PEX13	PEX5	P50542	995
PEX13	PEX10	O60683	994
PEX13	PEX12	O00623	994
PEX13	PEX14	O75381	994
PEX13	PEX7	O00628	992
PEX13	PEX2	P28328	989
PEX13	PEX19	P40855	971
PEX13	PEX6	Q13608	966
PEX13	PEX16	Q9Y5Y5	955
PEX13	PEX3	P56589	955
PEX13	PEX26	Q7Z412	929
PEX13	PEX5L	Q8IYB4	870
PEX13	PEX11B	O96011	848
PEX13	PEX1	O43933	839
PEX13	PEX11A	O75192	822

IntAct

Human interaction partners of PEX13 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

6 partners by confidence:

Partner	Interaction type	MIscore	Records
PEX19	physical association	0.710	12
CEP19	physical association	0.560	3
PEX14	physical association	0.550	1
ADAM10	direct interaction	0.440	1
PRRG4	direct interaction	0.440	1
GRB2	physical association	0.400	1

BioGRID (74 interactions; top human partners by supporting records): PEX5 (Two-hybrid; 8 records), PEX19 (Two-hybrid; 6 records), PEX14 (Reconstituted Complex; 5 records), PEX7 (Affinity Capture-MS; 5 records), BTN3A2 (Affinity Capture-MS; 3 records), C3AR1 (Affinity Capture-MS; 2 records), LPAR1 (Affinity Capture-MS; 2 records), TRAF1 (Affinity Capture-MS; 2 records), ABCD1 (FRET), ACAA1 (FRET), ACBD5 (Proximity Label-MS), AGO2 (Affinity Capture-RNA), AGPS (Proximity Label-MS), AKAP1 (Proximity Label-MS), ALDH3A2 (FRET)

SIGNOR signaling

1 signaling interactions:

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

Disease & clinical

Genetic variants

Variant evidence for PEX13: 625 ClinVar records (41 pathogenic / likely pathogenic); 2 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	30
Likely pathogenic	11
Uncertain significance	328
Likely benign	193
Benign	12

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 41 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
2727059	NM_002618.4(PEX13):c.676C>T (p.Arg226Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
1411346	NM_002618.4(PEX13):c.367G>T (p.Glu123Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
1705035	NM_002618.4(PEX13):c.391C>T (p.Gln131Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
2584448	NM_002618.4(PEX13):c.573_582del (p.Arg193fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
573201	NM_002618.4(PEX13):c.586C>T (p.Gln196Ter)	Pathogenic	criteria provided, single submitter	1
963417	NM_002618.4(PEX13):c.939G>A (p.Trp313Ter)	Pathogenic	criteria provided, single submitter	1
1387888	NM_002618.4(PEX13):c.499del (p.His167fs)	Pathogenic	criteria provided, single submitter	1
1426245	NM_002618.4(PEX13):c.201dup (p.Val68fs)	Pathogenic	criteria provided, single submitter	1
1428939	NM_002618.4(PEX13):c.829dup (p.Ala277fs)	Pathogenic	criteria provided, single submitter	1
1453426	NM_002618.4(PEX13):c.159_160del (p.Pro54fs)	Pathogenic	criteria provided, single submitter	1
1993651	NM_002618.4(PEX13):c.148del (p.Arg50fs)	Pathogenic	criteria provided, single submitter	1
2031148	NM_002618.4(PEX13):c.633G>A (p.Trp211Ter)	Pathogenic	criteria provided, single submitter	1
2109668	NM_002618.4(PEX13):c.759_760del (p.Leu254fs)	Pathogenic	criteria provided, single submitter	1
2722852	NM_002618.4(PEX13):c.744C>G (p.Tyr248Ter)	Pathogenic	criteria provided, single submitter	1
2742993	NM_002618.4(PEX13):c.855del (p.Val286fs)	Pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore PEX13’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 27 predictions of 466):

Position(s)	Effect	Δscore	Sites
2:61045724–61045725	acceptor_loss	1.0000	6
2:61048468	acceptor_gain	1.0000
2:61048470–61048471	acceptor_loss	1.0000	6
2:61017852–61017853	donor_loss	0.9900	6
2:61017856	donor_loss	0.9900
2:61031517	donor_gain	0.9900
2:61045717	acceptor_gain	0.9900
2:61045723	acceptor_gain	0.9900
2:61045852–61045853	donor_loss	0.9900	3
2:61046061	donor_gain	0.9900

AlphaMissense

832 missense substitutions predicted likely pathogenic (of 2,614 scored), across 199 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M146	9	0.929	0.999
F130	8	0.995	0.999
F158	8	0.987	0.999
F239	8	0.936	0.989
F118	8	0.932	0.997
F140	8	0.926	0.997
D163	8	0.910	0.972
S157	8	0.906	1.000
H274	8	0.897	0.986
D148	8	0.878	0.984
S144	8	0.867	0.999
W313	7	0.996	0.999
F283	7	0.993	0.999
W267	7	0.982	0.998
F151	7	0.976	0.995
W12	7	0.969	0.997
E290	7	0.963	0.992
S126	7	0.935	0.999
W211	7	0.934	0.992
H167	7	0.930	0.989

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

1 prognostic cancer types:

Cancer	Prognostic	p-value
Pancreatic Adenocarcinoma (TCGA)	unfavorable	0.000509

Disease associations

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

GenCC curated gene-disease

4 curated gene-disease records:

Disease	Classification	Inheritance	Records
peroxisome biogenesis disorder 11A (Zellweger)	Definitive	Autosomal recessive	2
peroxisome biogenesis disorder 11B	Definitive	Autosomal recessive
peroxisome biogenesis disorder	Strong	Autosomal recessive
Zellweger spectrum disorders	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity

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

1 validity classifications:

Disease	Classification	Inheritance
peroxisome biogenesis disorder	Definitive	AR

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (20 panels, 17 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

20 panels:

Panel	Rating
Arthrogryposis	green
Bilateral congenital or childhood onset cataracts	green
Cerebral malformation	green
DDG2P	green
Fetal anomalies	green
Fetal hydrops	green
Hypotonic infant	green
Inherited white matter disorders	green
Intellectual disability	green
Leukodystrophy, adult onset	green
Leukodystrophy, childhood onset	green
Likely inborn error of metabolism	green
Malformations of cortical development	green
Neonatal cholestasis	green
Peroxisomal disorders	green
Undiagnosed metabolic disorders	green
White matter disorders and cerebral calcification - childhood onset	green
Early onset or syndromic epilepsy	amber
Paediatric disorders	amber
Unexplained death in infancy and sudden unexplained death in childhood	amber

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

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

HPO phenotypes

showing 60 of 105 phenotypes (HPO-id order):

HPO	Term
HP:0000003	Multicystic kidney dysplasia
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000047	Hypospadias
HP:0000107	Renal cyst
HP:0000126	Hydronephrosis
HP:0000157	Abnormality of the tongue
HP:0000174	Abnormal palate morphology
HP:0000218	High palate
HP:0000239	Large fontanelles
HP:0000252	Microcephaly
HP:0000256	Macrocephaly
HP:0000260	Wide anterior fontanel
HP:0000268	Dolichocephaly
HP:0000271	Abnormality of the face
HP:0000286	Epicanthus
HP:0000325	Triangular face
HP:0000347	Micrognathia
HP:0000348	High forehead
HP:0000358	Posteriorly rotated ears
HP:0000365	Hearing impairment
HP:0000377	Abnormal pinna morphology
HP:0000407	Sensorineural hearing impairment
HP:0000431	Wide nasal bridge
HP:0000463	Anteverted nares
HP:0000474	Thickened nuchal skin fold
HP:0000486	Strabismus
HP:0000501	Glaucoma
HP:0000505	Visual impairment
HP:0000508	Ptosis
HP:0000510	Rod-cone dystrophy
HP:0000518	Cataract
HP:0000532	Abnormal chorioretinal morphology
HP:0000572	Visual loss
HP:0000582	Upslanted palpebral fissure
HP:0000627	Posterior embryotoxon
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000662	Nyctalopia
HP:0000708	Atypical behavior
HP:0000952	Jaundice
HP:0001088	Brushfield spots
HP:0001133	Constriction of peripheral visual field
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001257	Spasticity
HP:0001263	Global developmental delay
HP:0001315	Diminished deep tendon reflex
HP:0001324	Muscle weakness
HP:0001339	Lissencephaly
HP:0001347	Hyperreflexia
HP:0001392	Abnormality of the liver
HP:0001399	Hepatic failure
HP:0001410	Decreased liver function
HP:0001433	Hepatosplenomegaly
HP:0001508	Failure to thrive
HP:0001522	Death in infancy
HP:0001622	Premature birth
HP:0001629	Ventricular septal defect

GWAS associations

2 associations:

Study	Trait	p-value
GCST001438_15	Crohn’s disease	5e-9
GCST006956_8	Erectile dysfunction	8e-6

MeSH disease descriptors

4 disease descriptors:

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

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

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

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

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

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

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

10 trials:

NCT	Phase	Status	Title
NCT00007020	Phase 3	COMPLETED	Compassionate Treatment of Patients With Inborn Errors of Bile Acid Metabolism With Cholic Acid
NCT01838941	Phase 3	COMPLETED	Betaine and Peroxisome Biogenesis Disorders
NCT02171104	Phase 2	ACTIVE_NOT_RECRUITING	MT2013-31: Allo HCT for Metabolic Disorders and Severe Osteopetrosis
NCT03856866	Phase 2	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