PEX7

Summary

PEX7 (peroxisomal biogenesis factor 7, HGNC:8860) is a protein-coding gene on chromosome 6q23.3, encoding Peroxisomal targeting signal 2 receptor (O00628). Receptor required for the peroxisomal import of proteins containing a C-terminal PTS2-type peroxisomal targeting signal.

This gene encodes the cytosolic receptor for the set of peroxisomal matrix enzymes targeted to the organelle by the peroxisome targeting signal 2 (PTS2). Defects in this gene cause peroxisome biogenesis disorders (PBDs), which are characterized by multiple defects in peroxisome function. There are at least 14 complementation groups for PBDs, with more than one phenotype being observed in cases falling into particular complementation groups. Although the clinical features of PBD patients vary, cells from all PBD patients exhibit a defect in the import of one or more classes of peroxisomal matrix proteins into the organelle. Defects in this gene have been associated with PBD complementation group 11 (PBD-CG11) disorders, rhizomelic chondrodysplasia punctata type 1 (RCDP1), and Refsum disease (RD).

Source: NCBI Gene 5191 — RefSeq curated summary.

At a glance

• Gene–disease (curated): peroxisome biogenesis disorder (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 6
• Clinical variants (ClinVar): 762 total — 54 pathogenic, 79 likely-pathogenic
• Phenotypes (HPO): 85
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• MANE Select transcript: NM_000288

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8860
Approved symbol	PEX7
Name	peroxisomal biogenesis factor 7
Location	6q23.3
Locus type	gene with protein product
Status	Approved
Aliases	PTS2R, RD
Ensembl gene	ENSG00000112357
Ensembl biotype	protein_coding
OMIM	601757
Entrez	5191

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 7 protein_coding, 3 nonsense_mediated_decay

ENST00000318471, ENST00000367756, ENST00000541292, ENST00000678002, ENST00000678557, ENST00000678593, ENST00000679286, ENST00000865442, ENST00000865443, ENST00000939187

RefSeq mRNA: 2 — MANE Select: NM_000288 NM_000288, NM_001410945

CCDS: CCDS5180, CCDS94011

Canonical transcript exons

ENST00000318471 — 10 exons

Exon	Start	End
ENSE00000764442	136825214	136825271
ENSE00000764457	136826319	136826469
ENSE00000764473	136845615	136845692
ENSE00000764482	136846073	136846181
ENSE00000764483	136866627	136866733
ENSE00000764484	136869890	136870003
ENSE00001277693	136913458	136913934
ENSE00001838365	136822592	136822795
ENSE00003592608	136872198	136872253
ENSE00003683400	136898142	136898241

Expression profiles

Bgee: expression breadth ubiquitous, 276 present calls, max score 91.55.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.3179 / max 74.8246, expressed in 1794 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
69979	9.3179	1794

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pigmented layer of retina	UBERON:0001782	91.55	gold quality
sperm	CL:0000019	90.17	gold quality
esophagus squamous epithelium	UBERON:0006920	87.88	gold quality
male germ cell	CL:0000015	87.83	gold quality
right adrenal gland	UBERON:0001233	87.57	gold quality
right adrenal gland cortex	UBERON:0035827	87.50	gold quality
left adrenal gland	UBERON:0001234	86.95	gold quality
secondary oocyte	CL:0000655	86.89	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.77	gold quality
body of pancreas	UBERON:0001150	86.57	gold quality
adrenal tissue	UBERON:0018303	86.43	gold quality
left adrenal gland cortex	UBERON:0035825	86.42	gold quality
nephron tubule	UBERON:0001231	86.33	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	86.19	gold quality
adrenal cortex	UBERON:0001235	85.81	gold quality
adrenal gland	UBERON:0002369	85.74	gold quality
epithelium of esophagus	UBERON:0001976	85.51	gold quality
pancreas	UBERON:0001264	85.35	gold quality
palpebral conjunctiva	UBERON:0001812	85.19	gold quality
parotid gland	UBERON:0001831	84.89	gold quality
body of stomach	UBERON:0001161	84.84	gold quality
squamous epithelium	UBERON:0006914	84.75	gold quality
heart left ventricle	UBERON:0002084	84.34	gold quality
cardiac ventricle	UBERON:0002082	84.12	gold quality
skin of leg	UBERON:0001511	83.76	gold quality
skin of abdomen	UBERON:0001416	83.74	gold quality
islet of Langerhans	UBERON:0000006	83.69	gold quality
apex of heart	UBERON:0002098	83.59	gold quality
germinal epithelium of ovary	UBERON:0001304	83.37	gold quality
buccal mucosa cell	CL:0002336	83.35	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.09

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

25 targeting PEX7, 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-3646	100.00	73.56	5283
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-4713-5P	99.78	67.80	1794
HSA-MIR-2116-3P	99.74	64.32	889
HSA-MIR-4422	99.72	72.07	2908
HSA-MIR-587	99.64	70.86	2611
HSA-MIR-510-3P	99.54	70.06	2965
HSA-MIR-889-5P	99.41	68.75	1025
HSA-MIR-135A-5P	99.36	71.85	1601
HSA-MIR-135B-5P	99.36	71.63	1613
HSA-MIR-4427	99.34	70.33	1854
HSA-MIR-3978	99.24	68.39	2201
HSA-MIR-374A-3P	98.87	67.82	1531
HSA-MIR-34C-3P	98.11	65.60	858
HSA-MIR-3157-5P	97.41	67.61	998
HSA-MIR-6736-3P	96.98	65.22	1342
HSA-MIR-4256	96.22	67.70	669
HSA-MIR-11181-5P	96.12	67.46	665
HSA-MIR-6826-5P	93.80	67.42	514

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 17)

• mutational spectrum in the PEX7 gene of 78 patients (including five pairs of sibs) clinically and biochemically diagnosed with RCDP type I (PMID:11781871)
• Functional studies on human Pex7p: subcellular localization and interaction with proteins containing a peroxisome-targeting signal type 2 and other peroxins. (PMID:11931631)
• The residual activity of mutant Pex7 protein in rhizomelic chondrodysplasia punctata patients and reduced amounts of normal Pex7 are associated with milder and variant phenotypes. (PMID:12325024)
• This gene codes for the peroxin 7 receptor protein required for peroxisomal import of proteins containing a peroxisomal targeting signal type 2. Mutations may result in a broad clinical spectrum of Refsum disease. (PMID:12522768)
• Identification of PEX7 as the second gene involved in Refsum disease. (PMID:14713215)
• Missense mutations, sequence duplications and deletions in PRX7 in 3 patients with the Refsum disease phenotypes. (PMID:14974078)
• Mutations in PEX7 gene is associated with Rhizomelic chondrodysplasia punctata. (PMID:20145307)
• Structural requirements for interaction of peroxisomal targeting signal 2 and its receptor PEX7. (PMID:22057399)
• This results of this studt revealed the association of 2 single nucleotide polymorphisms and 1 haplotype with autism spectrum disorder (P < .05). (PMID:22378669)
• Export of peroxisomal PEX7 back into the cytosol requires export of PEX5. (PMID:24865970)
• dysfunctional Pex7p, including mutants from RCDP patients, is degraded by a ubiquitin-dependent proteasomal pathway involving the CRL4A (Cullin4A-RING ubiquitin ligase) complex. (PMID:24989250)
• the sequential formation of a highly stable trimeric complex involving cargo protein, PEX7 and PEX5L stabilizes cargo binding and is a prerequisite for PTS2-mediated peroxisomal import. (PMID:25538232)
• Mutation in the PEX7 Gene is associated with Rhizomelic Chondrodysplasia Punctata Type 1. (PMID:25800479)
• our data suggest that insertion of the trimeric PEX5-PEX7-PTS2 protein complex into the DTM is probably accompanied by conformational alterations in PEX5 to allow release of the PTS2 protein into the organelle matrix (PMID:26138649)
• This revealed a marked plasmalogen deficiency and a deficient fatty acid alpha-oxidation in the IHH cells, due to a defect of PEX7, a cytosolic receptor protein required for peroxisomal import of a subset of peroxisomal proteins. (PMID:28013369)
• Data suggest that P7BP2 is localized to peroxisomes by binding to PEX5 via PEX7 in manner dependent on apparent PTS2 (type 2 peroxisomal targeting signal peptide) in N-terminal region of P7BP2; the PTS2 is subsequently cleaved off in peroxisomes. (P7BP2 = PEX7-binding protein-2; PEX5 = peroxisomal biogenesis factor-5; PEX7 = peroxisomal biogenesis factor-7) (PMID:30204880)
• Twins with PEX7 related intellectual disability and cataract: Highlighting phenotypes of peroxisome biogenesis disorder 9B. (PMID:33586206)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	pex7	ENSDARG00000042553
mus_musculus	Pex7	ENSMUSG00000020003
rattus_norvegicus	Pex7	ENSRNOG00000012322
drosophila_melanogaster	Pex7	FBGN0035922

Paralogs (9): ERCC8 (ENSG00000049167), GEMIN5 (ENSG00000082516), RBBP7 (ENSG00000102054), WDR59 (ENSG00000103091), GRWD1 (ENSG00000105447), WDR77 (ENSG00000116455), WDR24 (ENSG00000127580), RBBP4 (ENSG00000162521), WDR73 (ENSG00000177082)

Protein

Protein identifiers

Peroxisomal targeting signal 2 receptor — O00628 (reviewed: O00628)

Alternative names: Peroxin-7

All UniProt accessions (7): O00628, A0A7I2V2J8, A0A7I2V2W7, A0A7I2V3V6, A0A7I2YQJ4, Q5TDQ5, Q6FGN1

UniProt curated annotations — full annotation on UniProt →

Function. Receptor required for the peroxisomal import of proteins containing a C-terminal PTS2-type peroxisomal targeting signal. Specifically binds to cargo proteins containing a PTS2 peroxisomal targeting signal in the cytosol. Cargo protein-binding triggers interaction with PEX5 and formation of a ternary complex composed of PEX5 and PEX7 along with PTS2-containing cargo proteins, which is tranlocated into peroxisomes by passing through the PEX13-PEX14 docking complex.

Subunit / interactions. Interacts with PEX5; interaction only takes place when PEX7 is associated with cargo proteins. Interacts with VWA8.

Subcellular location. Cytoplasm. Cytosol. Peroxisome matrix.

Tissue specificity. Ubiquitous. Highest expression in pancreas, skeletal muscle and heart.

Disease relevance. Peroxisome biogenesis disorder complementation group 11 (PBD-CG11) [MIM:614879] 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. Rhizomelic chondrodysplasia punctata 1 (RCDP1) [MIM:215100] A peroxisome biogenesis disorder. It is characterized by severely disturbed endochondral bone formation, rhizomelic shortening of femur and humerus, vertebral disorders, dwarfism, cataract, cutaneous lesions, facial dysmorphism, and severe intellectual disability with spasticity. The disease is caused by variants affecting the gene represented in this entry. Peroxisome biogenesis disorder 9B (PBD9B) [MIM:614879] A peroxisome biogenesis disorder with unusually mild clinical and biochemical manifestations. Affected individuals manifest a variable phenotype similar to, and in some cases indistinguishable from, classic Refsum disease. Variable features include ocular abnormalities, sensorimotor neuropathy, ichthyosis, deafness, chondrodysplasia punctata without rhizomelia or growth failure. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the WD repeat peroxin-7 family.

Isoforms (2)

UniProt ID	Names	Canonical?
O00628-1	1	yes
O00628-2	2

RefSeq proteins (2): NP_000279, NP_001397874 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001680	WD40_rpt	Repeat
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR019775	WD40_repeat_CS	Conserved_site
IPR020472	WD40_PAC1	Repeat
IPR036322	WD40_repeat_dom_sf	Homologous_superfamily
IPR044536	PEX7	Family

Pfam: PF00400

UniProt features (14 total): repeat 6, sequence variant 3, mutagenesis site 3, chain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O00628-F1	95.54	0.93

Functional residue map

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

Mutagenesis-validated functional residues (3):

Position	Phenotype
113	impaired binding to cargo proteins containing a pts2 peroxisomal targeting signal.
200	impaired binding to cargo proteins containing a pts2 peroxisomal targeting signal.
287	impaired interaction with pex5, leading to decreased peroxisomal import of proteins containing a pts2 peroxisomal target

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9033241	Peroxisomal protein import

MSigDB gene sets: 317 (showing top): GOBP_LIPID_MODIFICATION, GOBP_FATTY_ACID_CATABOLIC_PROCESS, BROWNE_HCMV_INFECTION_6HR_DN, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_PROTEIN_TARGETING, GOBP_NEUROGENESIS, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, CAGCTG_AP4_Q5, GOBP_REPLACEMENT_OSSIFICATION, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, GOBP_BONE_DEVELOPMENT, LI_WILMS_TUMOR_VS_FETAL_KIDNEY_1_UP

GO Biological Process (9): neuron migration (GO:0001764), endochondral ossification (GO:0001958), protein targeting to peroxisome (GO:0006625), fatty acid beta-oxidation (GO:0006635), peroxisome organization (GO:0007031), ether lipid biosynthetic process (GO:0008611), protein import into peroxisome matrix (GO:0016558), protein transport (GO:0015031), establishment of protein localization to peroxisome (GO:0072663)

GO Molecular Function (4): peroxisome matrix targeting signal-2 binding (GO:0005053), enzyme binding (GO:0019899), protein homodimerization activity (GO:0042803), protein binding (GO:0005515)

GO Cellular Component (5): peroxisome (GO:0005777), peroxisomal membrane (GO:0005778), peroxisomal matrix (GO:0005782), cytosol (GO:0005829), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Protein localization	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
establishment of protein localization to peroxisome	2
peroxisome	2
cellular anatomical structure	2
cell migration	1
generation of neurons	1
replacement ossification	1
endochondral bone morphogenesis	1
protein targeting	1
fatty acid catabolic process	1
fatty acid ligase activity	1
fatty acid oxidation	1
organelle organization	1
lipid biosynthetic process	1
ether lipid metabolic process	1
glycerol ether biosynthetic process	1
peroxisomal membrane transport	1
protein transmembrane import into intracellular organelle	1
protein localization to peroxisome	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
establishment of protein localization to organelle	1
peroxisome signal sequence receptor activity	1
protein binding	1
identical protein binding	1
protein dimerization activity	1
binding	1
microbody	1
microbody membrane	1
microbody lumen	1
cytoplasm	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1236 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PEX7	PEX5	P50542	995
PEX7	PEX13	Q92968	992
PEX7	PEX14	O75381	989
PEX7	PEX12	O00623	974
PEX7	PEX10	O60683	972
PEX7	PEX6	Q13608	970
PEX7	PEX5L	Q8IYB4	967
PEX7	PEX19	P40855	957
PEX7	PEX16	Q9Y5Y5	955
PEX7	PEX2	P28328	953
PEX7	PHYH	O14832	945
PEX7	PEX3	P56589	944
PEX7	AGPS	O00116	922
PEX7	PEX1	O43933	877
PEX7	PEX26	Q7Z412	865

IntAct

39 interactions, top by confidence:

A	B	Type	Score
PDCL3	PEX7	psi-mi:“MI:0914”(association)	0.640
CFAP298	PEX7	psi-mi:“MI:0914”(association)	0.620
CFAP298	PEX7	psi-mi:“MI:0915”(physical association)	0.620
PEX7	PIAS1	psi-mi:“MI:0915”(physical association)	0.560
PSG8	PEX7	psi-mi:“MI:0914”(association)	0.530
ACAA1	PEX7	psi-mi:“MI:0914”(association)	0.530
PEX39	PEX7	psi-mi:“MI:0914”(association)	0.530
KLHDC8A	PEX7	psi-mi:“MI:0914”(association)	0.530
PEX7	TCP1	psi-mi:“MI:0914”(association)	0.530
PEX7	TXNDC9	psi-mi:“MI:0914”(association)	0.530
CCT7	PEX7	psi-mi:“MI:0914”(association)	0.530
PEX7	INKA1	psi-mi:“MI:0915”(physical association)	0.400
PEX7	NUDC	psi-mi:“MI:0915”(physical association)	0.400
PEX7	KDM1A	psi-mi:“MI:0915”(physical association)	0.370
PRMT6	PEX7	psi-mi:“MI:0915”(physical association)	0.370
PEX5	AGPS	psi-mi:“MI:0914”(association)	0.350
TFPT	KRBA1	psi-mi:“MI:0914”(association)	0.350
FADS3	PEX7	psi-mi:“MI:0914”(association)	0.350
IFNA7	PEX7	psi-mi:“MI:0914”(association)	0.350
ABHD15	PEX7	psi-mi:“MI:0914”(association)	0.350
RETSAT	PEX7	psi-mi:“MI:0914”(association)	0.350
PHYH	PEX7	psi-mi:“MI:0914”(association)	0.350

BioGRID (81): PEX7 (Affinity Capture-MS), CCT7 (Affinity Capture-MS), CCT4 (Affinity Capture-MS), CCT3 (Affinity Capture-MS), CCT6B (Affinity Capture-MS), CCT6A (Affinity Capture-MS), CCT2 (Affinity Capture-MS), PDCL3 (Affinity Capture-MS), TCP1 (Affinity Capture-MS), CCT5 (Affinity Capture-MS), PDCL (Affinity Capture-MS), TXNDC9 (Affinity Capture-MS), VBP1 (Affinity Capture-MS), PEX13 (Affinity Capture-MS), TLE3 (Affinity Capture-MS)

ESM2 similar proteins: A0A1L8EXB5, A4QNE6, A8WGE3, B7PS00, O00628, O22466, O22467, O43684, O74184, P97865, Q12788, Q1JQB2, Q29RH4, Q29RZ9, Q2KJJ5, Q3KPT3, Q3KQ62, Q4R571, Q53HC9, Q561Y0, Q5BLX8, Q5I0B4, Q5M7F6, Q5M8I4, Q5PPK9, Q5RB58, Q5U2W5, Q5XGI5, Q5XJP1, Q6DH44, Q6DUZ9, Q6PA72, Q8AVT9, Q8BGF3, Q8C4J7, Q8K0G5, Q8NFH4, Q8R537, Q8VE80, Q96J01

Diamond homologs: A1C6X5, A1DHK2, A2QBZ0, A3GFK8, A4RD35, A5DB75, A5DTX3, O00628, P38968, P97865, Q0CYG9, Q1DX43, Q21624, Q2GVT8, Q2UF60, Q4P2B6, Q4X0M4, Q5AAU3, Q5AZM3, Q5S580, Q6BRR2, Q6C414, Q6CL75, Q6NQ88, Q75A30, Q873A1, Q8L611, Q8R537, A4RDD7, A6ZPA6, A7EF03, A7THX0, B3LJT5, B4HSL3, B4QHG6, B8P4B0, B8PD53, B9WD30, C4YPI7, C5DF48

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
PEX14	“up-regulates activity”	PEX7	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 29 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.

GO biological processes:

GO term	Partners	Fold	FDR
protein folding	5	21.5×	5e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	54
Likely pathogenic	79
Uncertain significance	222
Likely benign	307
Benign	33

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1068851	NM_000288.4(PEX7):c.112C>T (p.Gln38Ter)	Pathogenic
1070609	NC_000006.11:g.(?137187755)(137193401_?)del	Pathogenic
1073525	NM_000288.4(PEX7):c.860_861del (p.Glu287fs)	Pathogenic
1074641	NM_000288.4(PEX7):c.364del (p.Thr122fs)	Pathogenic
1338760	NM_000288.4(PEX7):c.294del (p.Ala100fs)	Pathogenic
1384934	NM_000288.4(PEX7):c.57_67dup (p.Glu23fs)	Pathogenic
1453098	NM_000288.4(PEX7):c.130+2T>G	Pathogenic
1454842	NC_000006.11:g.(?137143759)(137143943_?)del	Pathogenic
1455239	NM_000288.4(PEX7):c.546_547del (p.Ile182fs)	Pathogenic
1457391	NC_000006.11:g.(?137143759)(137167329_?)del	Pathogenic
1459604	NC_000006.11:g.(?137167201)(137234674_?)del	Pathogenic
1996134	NM_000288.4(PEX7):c.105_117del (p.Gln38fs)	Pathogenic
2015707	NM_000288.4(PEX7):c.294_313dup (p.Gln105fs)	Pathogenic
2029049	NM_000288.4(PEX7):c.111_112del (p.Gln38fs)	Pathogenic
2033816	NM_000288.4(PEX7):c.52dup (p.His18fs)	Pathogenic
2074726	NM_000288.4(PEX7):c.652del (p.Ala218fs)	Pathogenic
2117483	NM_000288.4(PEX7):c.250dup (p.Ile84fs)	Pathogenic
2136476	NM_000288.4(PEX7):c.45_52del (p.Gly16fs)	Pathogenic
2180404	NM_000288.4(PEX7):c.370_396del (p.Gly124_Ser132del)	Pathogenic
2422816	NC_000006.11:g.(?137143759)(137166840_?)del	Pathogenic
2422817	NC_000006.11:g.(?137166743)(137167329_?)del	Pathogenic
2703133	NM_000288.4(PEX7):c.12del (p.Cys5fs)	Pathogenic
2705515	NM_000288.4(PEX7):c.22_31del (p.Ala8fs)	Pathogenic
2708901	NM_000288.4(PEX7):c.31_56dup (p.Tyr20fs)	Pathogenic
2746764	NM_000288.4(PEX7):c.10del (p.Val4fs)	Pathogenic
2759681	NM_000288.4(PEX7):c.683dup (p.Leu228fs)	Pathogenic
2829116	NM_000288.4(PEX7):c.818C>G (p.Ser273Ter)	Pathogenic
2835308	NM_000288.4(PEX7):c.751dup (p.Ser251fs)	Pathogenic
2848952	NM_000288.4(PEX7):c.289_290del (p.Thr97fs)	Pathogenic
2852234	NM_000288.4(PEX7):c.523_526dup (p.Gly176fs)	Pathogenic

SpliceAI

2435 predictions. Top by Δscore:

Variant	Effect	Δscore
6:136825211:TAGGC:T	acceptor_loss	1.0000
6:136825212:A:AG	acceptor_gain	1.0000
6:136825213:G:GC	acceptor_loss	1.0000
6:136825213:G:GG	acceptor_gain	1.0000
6:136825213:GGCT:G	acceptor_gain	1.0000
6:136826308:TCCTA:T	acceptor_loss	1.0000
6:136826309:CCTAG:C	acceptor_loss	1.0000
6:136826310:CTAGT:C	acceptor_loss	1.0000
6:136826311:TAG:T	acceptor_loss	1.0000
6:136826312:A:AG	acceptor_gain	1.0000
6:136826312:AGT:A	acceptor_gain	1.0000
6:136826313:G:A	acceptor_loss	1.0000
6:136826313:G:GA	acceptor_gain	1.0000
6:136826313:GT:G	acceptor_gain	1.0000
6:136826313:GTG:G	acceptor_gain	1.0000
6:136826313:GTGT:G	acceptor_gain	1.0000
6:136826313:GTGTA:G	acceptor_gain	1.0000
6:136826465:AGGAG:A	donor_loss	1.0000
6:136826466:GGAG:G	donor_gain	1.0000
6:136826467:GAG:G	donor_gain	1.0000
6:136826467:GAGG:G	donor_gain	1.0000
6:136826468:AGGTA:A	donor_loss	1.0000
6:136826470:G:C	donor_loss	1.0000
6:136826471:T:G	donor_loss	1.0000
6:136869999:TGA:T	donor_gain	1.0000
6:136870000:GAA:G	donor_gain	1.0000
6:136870001:AAA:A	donor_gain	1.0000
6:136870004:G:GG	donor_gain	1.0000
6:136898136:TCACA:T	acceptor_loss	1.0000
6:136898137:CACAG:C	acceptor_loss	1.0000

AlphaMissense

2110 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:136866716:T:A	W206R	0.999
6:136866716:T:C	W206R	0.999
6:136898200:T:C	F288L	0.999
6:136898202:T:A	F288L	0.999
6:136898202:T:G	F288L	0.999
6:136826353:T:A	W75R	0.998
6:136826353:T:C	W75R	0.998
6:136845630:T:A	W119R	0.998
6:136845630:T:C	W119R	0.998
6:136846170:C:A	A172D	0.998
6:136869932:T:A	W226R	0.998
6:136869932:T:C	W226R	0.998
6:136872235:C:G	S262W	0.998
6:136913473:T:A	W307R	0.998
6:136913473:T:C	W307R	0.998
6:136913475:G:C	W307C	0.998
6:136913475:G:T	W307C	0.998
6:136913476:G:C	D308H	0.998
6:136825220:G:A	G46E	0.997
6:136826413:T:A	W95R	0.997
6:136826413:T:C	W95R	0.997
6:136872226:C:A	A259D	0.997
6:136872229:C:A	S260Y	0.997
6:136913477:A:T	D308V	0.997
6:136822763:C:A	A33D	0.996
6:136826356:A:C	S76R	0.996
6:136826358:T:A	S76R	0.996
6:136826358:T:G	S76R	0.996
6:136845663:T:C	S130P	0.996
6:136845664:C:A	S130Y	0.996

dbSNP variants (sampled 300 via entrez): RS1000034080 (6:136822412 C>G,T), RS1000102083 (6:136886273 G>A), RS1000147980 (6:136904467 A>C), RS1000175590 (6:136849111 T>C), RS1000209185 (6:136831261 AAGAG>A,AAG), RS1000215639 (6:136859064 A>G), RS1000232173 (6:136873355 T>G), RS1000248919 (6:136854288 C>A), RS1000259637 (6:136892915 C>G), RS1000287761 (6:136879342 T>A), RS1000308624 (6:136897900 G>T), RS1000322781 (6:136854479 G>A,T), RS1000363947 (6:136906214 C>G), RS1000368115 (6:136899485 C>A), RS1000448155 (6:136843506 T>G)

Disease associations

OMIM: gene MIM:601757 | disease phenotypes: MIM:614879, MIM:215100, MIM:266500, MIM:600964, MIM:214100

GenCC curated gene-disease

Disease	Classification	Inheritance
rhizomelic chondrodysplasia punctata type 1	Definitive	Autosomal recessive
peroxisome biogenesis disorder 9B	Definitive	Autosomal recessive
peroxisome biogenesis disorder	Strong	Autosomal recessive
adult Refsum disease	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 (9): peroxisome biogenesis disorder 9B (MONDO:0013945), rhizomelic chondrodysplasia punctata (MONDO:0015776), rhizomelic chondrodysplasia punctata type 1 (MONDO:0008972), adult Refsum disease (MONDO:0009958), inherited retinal dystrophy (MONDO:0019118), connective tissue disorder (MONDO:0003900), peroxisome biogenesis disorder (MONDO:0019234), intellectual disability (MONDO:0001071), retinal disorder (MONDO:0005283)

Orphanet (6): Adult Refsum disease (Orphanet:773), Rhizomelic chondrodysplasia punctata (Orphanet:177), Rhizomelic chondrodysplasia punctata type 1 (Orphanet:309789), OBSOLETE: Inherited retinal disorder (Orphanet:71862), Peroxisome biogenesis disorder (Orphanet:79189), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

85 total (30 of 85 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000083	Renal insufficiency
HP:0000175	Cleft palate
HP:0000252	Microcephaly
HP:0000272	Malar flattening
HP:0000347	Micrognathia
HP:0000407	Sensorineural hearing impairment
HP:0000458	Anosmia
HP:0000478	Abnormality of the eye
HP:0000488	Retinopathy
HP:0000496	Abnormality of eye movement
HP:0000504	Abnormality of vision
HP:0000505	Visual impairment
HP:0000508	Ptosis
HP:0000510	Rod-cone dystrophy
HP:0000518	Cataract
HP:0000519	Developmental cataract
HP:0000529	Progressive visual loss
HP:0000546	Retinal degeneration
HP:0000568	Microphthalmia
HP:0000582	Upslanted palpebral fissure
HP:0000616	Miosis
HP:0000639	Nystagmus
HP:0000662	Nyctalopia
HP:0000958	Dry skin
HP:0001133	Constriction of peripheral visual field
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001252	Hypotonia

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST011124_19	Caffeine consumption from tea	9.000000e-09
GCST011126_13	Caffeine consumption from coffee or tea	4.000000e-15
GCST90002389_337	Lymphocyte percentage of white cells	7.000000e-12
GCST90002396_346	Mean reticulocyte volume	5.000000e-11
GCST90002397_487	Mean spheric corpuscular volume	3.000000e-11
GCST90002399_309	Neutrophil percentage of white cells	5.000000e-09

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0010091	tea consumption measurement
EFO:0006781	coffee consumption measurement
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0010701	mean reticulocyte volume
EFO:0007990	neutrophil percentage of leukocytes

MeSH disease descriptors (9)

Descriptor	Name	Tree numbers
D018902	Chondrodysplasia Punctata, Rhizomelic	C05.116.099.708.195.200; C16.320.565.663.265; C18.452.648.663.265
D003240	Connective Tissue Diseases	C17.300
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D012035	Refsum Disease	C10.228.140.163.100.813; C10.500.300.780; C10.574.500.495.780; C10.668.829.800.300.780; C16.131.666.300.780; C16.320.400.375.780; C16.320.565.189.813; C16.320.565.663.760; C18.452.132.100.813; C18.452.648.189.813; C18.452.648.663.760
D012164	Retinal Diseases	C11.768
D058499	Retinal Dystrophies	C11.768.585.658
C536664	Peroxisome biogenesis disorders (supp.)
C535517	Refsum disease with increased pipecolic acidemia (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

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
cobaltous chloride	decreases expression	2
Valproic Acid	affects expression, decreases expression	2
aristolochic acid I	decreases expression	1
bisphenol A	increases methylation	1
sodium arsenite	increases abundance, decreases expression	1
jinfukang	affects cotreatment, increases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	decreases expression, increases abundance	1
Cisplatin	affects cotreatment, increases expression	1
Hydrogen Peroxide	affects cotreatment, decreases expression	1
Methotrexate	increases expression	1
Phthalic Acids	increases methylation	1
Selenium	affects cotreatment, increases expression	1
Theophylline	affects cotreatment, decreases expression	1
Thiram	decreases expression	1
Tretinoin	increases expression	1
Vitamin E	affects cotreatment, increases expression	1
Isotretinoin	decreases expression	1
Cyclosporine	decreases expression	1
Lactic Acid	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_8278	IHH-A5	Transformed cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01042158	PHASE4	COMPLETED	A Clinical Trial of Ambrisentan and Tadalafil in Pulmonary Arterial Hypertension Associated With Systemic Sclerosis
NCT03688191	PHASE4	UNKNOWN	Study of Sirolimus in CTD-TP in China
NCT04169100	PHASE4	UNKNOWN	Novel Form of Acquired Long QT Syndrome
NCT04197050	PHASE4	UNKNOWN	Effect of Sacubitril/Valsartan on Reduced Right Ventricular Ejection Fraction in Patients With CTD
NCT04928586	PHASE4	UNKNOWN	Immunosuppressant Combined With Pirfenidone in CTD-ILD
NCT05440240	PHASE4	RECRUITING	Percutaneous Needle Fasciotomy +/- Corticosteroid Injection for Dupuytren’s Contracture
NCT05505409	PHASE4	UNKNOWN	Efficacy and Safety of Pirfenidone in CTD-ILD
NCT06499233	PHASE4	RECRUITING	Efficacy and Safety of Prophylactic Treatment for Pneumocystis Jirovecii Pneumonia in Patients With Autoimmune Inflammatory Rheumatic Disease
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT01838941	PHASE3	COMPLETED	Betaine and Peroxisome Biogenesis Disorders
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
NCT00864201	PHASE3	UNKNOWN	A Study to Evaluate the Use of Bosentan in Patients With Exercise Induced Pulmonary Arterial Hypertension Associated With Connective Tissue Disease
NCT01196091	PHASE3	COMPLETED	A Study of LY2127399 in Participants With Systemic Lupus Erythematosus
NCT01205438	PHASE3	COMPLETED	A Study of LY2127399 in Participants With Systemic Lupus Erythematosus
NCT01488708	PHASE3	TERMINATED	On Open-Label Study in Participants With Systemic Lupus Erythematosus
NCT03626688	PHASE3	COMPLETED	A Study Evaluating the Efficacy and Safety of Ralinepag to Improve Treatment Outcomes in PAH Patients
NCT03683186	PHASE3	ENROLLING_BY_INVITATION	A Study Evaluating the Long-Term Efficacy and Safety of Ralinepag in Subjects With PAH Via an Open-Label Extension
NCT04084678	PHASE3	TERMINATED	A Study of Ralinepag to Evaluate Effects on Exercise Capacity by CPET in Subjects With WHO Group 1 PH
NCT06716606	PHASE3	RECRUITING	A Study to Investigate the Long-term Safety and Efficacy of Belimumab in Adults With Interstitial Lung Disease (ILD) Associated With Systemic Sclerosis (SSc) and Other Connective Tissue Diseases (CTD) (BLISSconneCTD-OLE)
NCT06917690	PHASE3	RECRUITING	A Study to Learn About the Safety and Efficacy of the Drug Oleogel-S10 in Japanese Patients With Epidermolysis Bullosa
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT03856866	PHASE2	COMPLETED	Hydroxychloroquine Administration for Reduction of Pexophagy
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]
NCT00004357	PHASE2	COMPLETED	Absorption of Corticosteroids in Children With Juvenile Dermatomyositis
NCT00005675	PHASE2	COMPLETED	Oral Type I Collagen for Relieving Scleroderma
NCT01808196	PHASE2	COMPLETED	Testing Effectiveness of Losartan in Patients With EoE With or Without a CTD
NCT02682511	PHASE2	ACTIVE_NOT_RECRUITING	Oral Ifetroban to Treat Diffuse Cutaneous Systemic Sclerosis (SSc) or SSc-associated Pulmonary Arterial Hypertension
NCT04993885	PHASE2	RECRUITING	Avatrombopag in the Treatment of Adult Immune Thrombocytopenia With Autoantibodies
NCT05516758	PHASE2	TERMINATED	A Study of Peresolimab (LY3462817) in Participants With Moderately-to-Severely Active Rheumatoid Arthritis
NCT05998759	PHASE2	RECRUITING	Telitacicept for the Treatment of Connective Tissue Disease-associated Thrombocytopenia
NCT06104228	PHASE2	RECRUITING	129 Xenon MRI as a Biomarker for Diagnosis and Response to Therapy in Pulmonary Arterial Hypertension (PAH)
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis