PEX11A

Chr 15

peroxisomal biogenesis factor 11 alpha

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

NCBI Gene: 8800 ENSG00000166821 UniProt: O75192

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.

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]

ResearchGenerating clinical summary…

Clinical highlights

Gene–disease validity (ClinGen)

Refuted · peroxisome biogenesis disorder · AR · ClinGen 2020

evidence has disproved this relationship

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.49

LOEUF

Mechanism· predicted

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?

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

Background carrier burden — how many people carry a rare variant somewhere in PEX11A?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 170

319 rare PASS variants

Rare truncating (LoF)

1 in 1,400

46 rare PASS variants

Rare synonymous (reference)

1 in 1,100

106 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PEX11A. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 170	1 in 1,300
South Asian	~43k	1 in 150	1 in 1,700
Remaining (unassigned)	~30k	1 in 210	1 in 1,700
European (Finnish)	~27k	1 in 310	1 in 5,300
Admixed American	~22k	1 in 200	1 in 2,500
African / African American	~21k	1 in 130	1 in 1,500
East Asian	~20k	1 in 200	1 in 1,200
Ashkenazi Jewish	~13k	≈ 1 in 6,500	none seen
Middle Eastern	~2,884	1 in 240	≈ 1 in 2,600

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 2 of 3 coding exons well covered in gnomAD exomes; exon 2 marginal. Genomes: all 3.? see exons ↓