PEX11A

Chr 15

peroxisomal biogenesis factor 11 alpha

Also known as: PEX11-ALPHA, PEX11alpha, PMP28, hsPEX11p

NCBI Gene: 8800 ENSG00000166821 UniProt: O75192 OMIM: 603866

The PEX11A protein is a peroxisomal membrane elongation factor that promotes peroxisome proliferation and division by mediating membrane protrusion and elongation. Mutations cause autosomal recessive peroxisomal biogenesis disorders, which typically present in infancy with developmental delay, hypotonia, seizures, and hepatomegaly. This gene shows low constraint against loss-of-function variants, consistent with recessive inheritance requiring biallelic mutations for disease manifestation.

OMIM ResearchSummary from RefSeq, UniProt

This gene is a member of the PEX11 family, which is composed of membrane elongation factors involved in regulation of peroxisome maintenance and proliferation. This gene product interacts with peroxisomal membrane protein 19 and may respond to outside stimuli to increase peroxisome abundance. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Oct 2012]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.49

Clinical Summary— PEX11A

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Gene-Disease Validity (ClinGen)

peroxisome biogenesis disorder · ARNo Known Disease Relationship

No known disease relationship

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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

46 VUS of 53 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.49LOEUF

pLI 0.000

Z-score 0.37

OE 0.88 (0.54–1.49)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.10Z-score

OE missense 0.98 (0.85–1.13)

132 obs / 135.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.88 (0.54–1.49)

0≤0.351.4

Missense OE?0.98 (0.85–1.13)

0≤0.61.4

Synonymous OE?0.99

0≤1.21.6

LoF obs/exp: 10 / 11.4Missense obs/exp: 132 / 135.3Syn Z: 0.07

This gene — mechanism propensity

0.7034th %ile

GOF

0.5366th %ile

LOF

0.3552th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

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

ClinVar Variant Classifications

53 submitted variants in ClinVar

ClinVar

Classification Summary

VUS46

Likely Benign3

Conflicting1

VUS

Likely Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	0	0	0	0
VUS	0	46	0	0	46
Likely Benign	0	2	0	1	3
Benign	0	0	0	0	0
Conflicting	—				1
Total	0	48	0	1	50

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

View in ClinVar →

37 pathogenic / likely-pathogenic (of 45) ClinVar copy-number / structural variants overlap PEX11A — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →