PEX16

Chr 11

peroxisomal biogenesis factor 16

Also known as: PBD8A, PBD8B

NCBI Gene: 9409 ENSG00000121680 UniProt: Q9Y5Y5

The protein is an integral peroxisomal membrane protein required for peroxisome biogenesis and organization. Mutations cause autosomal recessive peroxisome biogenesis disorders including Zellweger syndrome (type 8A) and the milder type 8B, through loss of protein function that prevents normal peroxisome formation.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

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]

GeneReviews ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.82

Clinical Summary— PEX16

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Gene-Disease Validity (ClinGen)

peroxisome biogenesis disorder · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

42 unique Pathogenic / Likely Pathogenic· 214 VUS of 665 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — PEX16

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.82LOEUF

pLI 0.000

Z-score 2.16

OE 0.49 (0.30–0.82)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.45Z-score

OE missense 0.91 (0.81–1.03)

195 obs / 213.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.49 (0.30–0.82)

0≤0.351.4

Missense OE?0.91 (0.81–1.03)

0≤0.61.4

Synonymous OE?1.02

0≤1.21.6

LoF obs/exp: 10 / 20.6Missense obs/exp: 195 / 213.6Syn Z: -0.12

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitivePEX16-related peroxisome biogenesis disorder 8BLOFAR

definitivePEX16-related peroxisome biogenesis disorder 8A (Zellweger)LOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.7035th %ile

GOF

0.5269th %ile

LOF

0.3259th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

665 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic26

Likely Pathogenic16

VUS214

Likely Benign340

Benign23

Conflicting35

Pathogenic

Likely Pathogenic

214

VUS

340

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	25	1	0	0	26
Likely Pathogenic	11	5	0	0	16
VUS	2	180	27	5	214
Likely Benign	0	6	170	164	340
Benign	0	1	20	2	23
Conflicting	—				35
Total	38	193	217	171	654

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

View in ClinVar →

16 pathogenic / likely-pathogenic (of 21) ClinVar copy-number / structural variants overlap PEX16 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →