PEX19

Chr 1AR

peroxisomal biogenesis factor 19

Also known as: D1S2223E, HK33, PBD12A, PMP1, PMPI, PXF, PXMP1

NCBI Gene: 5824 ENSG00000162735 UniProt: P40855 OMIM: 600279

PEX19 encodes a cytosolic chaperone and import receptor that is essential for importing peroxisomal membrane proteins and early peroxisomal biogenesis. Mutations cause Zellweger syndrome and other peroxisome biogenesis disorders through an autosomal recessive inheritance pattern, resulting in defective import of peroxisomal matrix proteins and multiple peroxisomal dysfunction. These disorders are characterized as lethal conditions with multiple organ system involvement due to the failure of peroxisome assembly and function.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

This gene is necessary for early peroxisomal biogenesis. It acts both as a cytosolic chaperone and as an import receptor for peroxisomal membrane proteins (PMPs). Peroxins (PEXs) are proteins that are essential for the assembly of functional peroxisomes. The peroxisome biogenesis disorders (PBDs) are a group of genetically heterogeneous autosomal recessive, lethal diseases characterized by multiple defects in peroxisome function. These disorders have at least 14 complementation groups, with more than one phenotype being observed for some 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 are a cause of Zellweger syndrome (ZWS), as well as peroxisome biogenesis disorder complementation group 14 (PBD-CG14), which is also known as PBD-CGJ. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2010]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.941 OMIM phenotype

Clinical Summary— PEX19

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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

25 unique Pathogenic / Likely Pathogenic· 217 VUS of 459 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — PEX19

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.94LOEUF

pLI 0.000

Z-score 1.75

OE 0.52 (0.30–0.94)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.78Z-score

OE missense 1.17 (1.04–1.32)

190 obs / 162.2 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.52 (0.30–0.94)

0≤0.351.4

Missense OE?1.17 (1.04–1.32)

0≤0.61.4

Synonymous OE?1.11

0≤1.21.6

LoF obs/exp: 8 / 15.4Missense obs/exp: 190 / 162.2Syn Z: -0.67

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitivePEX19-related peroxisome biogenesis disorderLOFAR

This gene — mechanism propensity

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

0.6745th %ile

GOF

0.6443th %ile

LOF

0.1698th %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

459 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic11

Likely Pathogenic14

VUS217

Likely Benign167

Benign17

Conflicting25

Pathogenic

Likely Pathogenic

217

VUS

167

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	10	1	0	0	11
Likely Pathogenic	13	0	1	0	14
VUS	2	171	43	1	217
Likely Benign	1	2	84	80	167
Benign	0	0	17	0	17
Conflicting	—				25
Total	26	174	145	81	451

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

View in ClinVar →

9 pathogenic / likely-pathogenic (of 14) ClinVar copy-number / structural variants overlap PEX19 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →