PEX7

Chr 6AR

peroxisomal biogenesis factor 7

NCBI Gene: 5191ENSG00000112357UniProt: O00628

Receptor required for the peroxisomal import of proteins containing a C-terminal PTS2-type peroxisomal targeting signal (PubMed:11931631, PubMed:22057399, PubMed:25538232, PubMed:9090381). Specifically binds to cargo proteins containing a PTS2 peroxisomal targeting signal in the cytosol (PubMed:11931631, PubMed:22057399, PubMed:25538232). 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 (PubMed:11546814, PubMed:25538232)

Primary Disease Associations & Inheritance

Peroxisome biogenesis disorder 9BMIM #614879
AR
Rhizomelic chondrodysplasia punctata, type 1MIM #215100
AR
565
ClinVar variants
129
Pathogenic / LP
0.00
pLI score
4
Active trials
Clinical Summary— PEX7
🧬
Gene-Disease Validity (ClinGen)
peroxisome biogenesis disorder · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
129 Pathogenic / Likely Pathogenic· 163 VUS of 565 total submissions
💊
Clinical Trials
4 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.42LOEUF
pLI 0.000
Z-score 0.14
OE 0.97 (0.67–1.42)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.50Z-score
OE missense 0.89 (0.78–1.02)
145 obs / 162.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.97 (0.67–1.42)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.89 (0.78–1.02)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.12
0≤1.21.6
LoF obs/exp: 19 / 19.7Missense obs/exp: 145 / 162.9Syn Z: -0.75

ClinVar Variant Classifications

565 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic59
Likely Pathogenic70
VUS163
Likely Benign233
Benign23
Conflicting17
59
Pathogenic
70
Likely Pathogenic
163
VUS
233
Likely Benign
23
Benign
17
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
28
1
30
0
59
Likely Pathogenic
42
8
20
0
70
VUS
2
132
22
7
163
Likely Benign
0
2
127
104
233
Benign
0
0
23
0
23
Conflicting
—17
Total72143222111565

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

PEX7 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

PEX7-related peroxisome biogenesis disorder complementation group 11

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersSkin
G2P ↗

PEX7-related rhizomelic chondrodysplasia punctata

definitive
ARLoss Of FunctionAbsent Gene Product
Eye
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Peroxisome biogenesis disorder 9B

MIM #614879

Molecular basis of disorder known

Autosomal recessive

Rhizomelic chondrodysplasia punctata, type 1

MIM #215100

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — PEX7
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Clinical, biochemical and genetic aspects and neuronal migration in peroxisome biogenesis disorders.
Suzuki Y et al.·J Inherit Metab Dis
2001Review
Twins with PEX7 related intellectual disability and cataract: Highlighting phenotypes of peroxisome biogenesis disorder 9B.
Masih S et al.·Am J Med Genet A
2021Case report
Mutation analysis of PEX7 in 60 probands with rhizomelic chondrodysplasia punctata and functional correlations of genotype with phenotype.
Braverman N et al.·Hum Mutat
2002Functional
Clinical, biochemical, and molecular characterization of mild (nonclassic) rhizomelic chondrodysplasia punctata.
Fallatah W et al.·J Inherit Metab Dis
2021
Human PEX7 encodes the peroxisomal PTS2 receptor and is responsible for rhizomelic chondrodysplasia punctata.
Braverman N et al.·Nat Genet
1997
Genotype-phenotype correlations in disorders of peroxisome biogenesis.
Moser HW·Mol Genet Metab
1999Review
Metabolomic Profiling Reveals Brain Lipid Alterations in PEX7-Deficient Models of Rhizomelic Chondrodysplasia Punctata.
Sankhe R et al.·Biomolecules
2025Functional
Identification of PEX7 as the second gene involved in Refsum disease.
van den Brink DM et al.·Am J Hum Genet
2003
Rhizomelic Chondrodysplasia Punctata Type 1 Caused by a Novel Mutation in the PEX7 Gene.
Çim A et al.·J Clin Res Pediatr Endocrinol
2015Case report
Peroxisomal Localization of a Truncated HMG-CoA Reductase under Low Cholesterol Conditions.
Wang J et al.·Biomolecules
2024
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Eye Diseases HereditaryRetinal DiseaseAchromatopsia

Inherited Retinal Degenerative Disease Registry

RECRUITING
NCT02435940Foundation Fighting BlindnessStarted 2014-06
Rare DisordersUndiagnosed DisordersDisorders of Unknown Prevalence

Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford

RECRUITING
NCT01793168Sanford HealthStarted 2010-07
LeukodystrophyWhite Matter DiseaseLeukoencephalopathies

The Myelin Disorders Biorepository Project

RECRUITING
NCT03047369Children's Hospital of PhiladelphiaStarted 2016-12-08
Peroxisome Biogenesis DisorderZellweger Spectrum DisorderRCDP - Rhizomelic Chondrodysplasia Punctata

Longitudinal Natural History Study of Patients With Peroxisome Biogenesis Disorders (PBD)

RECRUITING
NCT01668186McGill University Health Centre/Research Institute of the McGill University Health CentreStarted 2012-01

External Resources

Links to major genomics databases and tools