PEX16

Chr 11AR

peroxisomal biogenesis factor 16

Also known as: PBD8A, PBD8B

NCBI Gene: 9409ENSG00000121680UniProt: Q9Y5Y5

The protein encoded by this gene is an integral peroxisomal membrane protein. An inactivating nonsense mutation localized to this gene was observed in a patient with Zellweger syndrome of the complementation group CGD/CG9. Expression of this gene product morphologically and biochemically restores the formation of new peroxisomes, suggesting a role in peroxisome organization and biogenesis. Alternative splicing has been observed for this gene and two variants have been described. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Peroxisome biogenesis disorder 8A (Zellweger)MIM #614876
AR
Peroxisome biogenesis disorder 8BMIM #614877
AR
572
ClinVar variants
53
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— PEX16
🧬
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
53 Pathogenic / Likely Pathogenic· 166 VUS of 572 total submissions

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.
0.82LOEUF
pLI 0.000
Z-score 2.16
OE 0.49 (0.30–0.82)
Tolerant

Typical tolerance to LoF variation

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.
0.45Z-score
OE missense 0.91 (0.81–1.03)
195 obs / 213.6 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.0.49 (0.30–0.82)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.91 (0.81–1.03)
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.1.02
0≤1.21.6
LoF obs/exp: 10 / 20.6Missense obs/exp: 195 / 213.6Syn Z: -0.12

ClinVar Variant Classifications

572 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic37
Likely Pathogenic16
VUS166
Likely Benign312
Benign13
Conflicting28
37
Pathogenic
16
Likely Pathogenic
166
VUS
312
Likely Benign
13
Benign
28
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
9
1
27
0
37
Likely Pathogenic
10
4
2
0
16
VUS
2
134
27
3
166
Likely Benign
0
5
161
146
312
Benign
0
0
11
2
13
Conflicting
—28
Total21144228151572

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

View in ClinVar →

Protein Context — Lollipop Plot

PEX16 · protein map & ClinVar variants

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

Gene2Phenotype Curations

PEX16-related peroxisome biogenesis disorder 8B

definitive
ARLoss Of FunctionAbsent Gene Product
Eye
G2P ↗

PEX16-related peroxisome biogenesis disorder 8A (Zellweger)

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Peroxisome biogenesis disorder 8A (Zellweger)

MIM #614876

Molecular basis of disorder known

Autosomal recessive

Peroxisome biogenesis disorder 8B

MIM #614877

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — PEX16
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Distinguishing PEX2 and PEX16 gene variant severity for mild, severe and atypical peroxisome biogenesis disorders.
Gomez VA et al.·Dis Model Mech
2025
Clinical, neuroradiological, and molecular characterization of patients with atypical Zellweger spectrum disorder caused by PEX16 mutations: a case series.
Cheung A et al.·Neurogenetics
2022Cohort
Atypical PEX16 peroxisome biogenesis disorder with mild biochemical disruptions and long survival.
Zaabi NA et al.·Brain Dev
2019Review
Clinical, biochemical and genetic aspects and neuronal migration in peroxisome biogenesis disorders.
Suzuki Y et al.·J Inherit Metab Dis
2001Review
Zellweger syndrome and secondary mitochondrial myopathy.
Salpietro V et al.·Eur J Pediatr
2015Review
Peroxisome Membrane Protein PEX16 Inhibits Melanogenesis by Inhibiting the Wnt/β-Catenin Signalling Pathway.
Duan X et al.·Exp Dermatol
2026
Mitochondria and Peroxisome Crosstalk in Peroxisome Biogenesis Disorder 8A Caused by a Rare Variant in PEX16 Gene.
Wehbe M et al.·Clin Genet
2025Case report
Identification of an unusual variant peroxisome biogenesis disorder caused by mutations in the PEX16 gene.
Ebberink MS et al.·J Med Genet
2010Case report
Drosophila models uncover substrate channeling effects on phospholipids and sphingolipids in peroxisomal biogenesis disorders.
Wangler MF et al.·PLoS One
2025Functional
Peroxisome synthesis in the absence of preexisting peroxisomes.
South ST et al.·J Cell Biol
1999Case report
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

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools