TMEM135

Chr 11

transmembrane protein 135

Also known as: PMP52

NCBI Gene: 65084 ENSG00000166575 UniProt: Q86UB9

TMEM135 encodes a protein that regulates mitochondrial dynamics by controlling the balance between mitochondrial fusion and fission, and may also function in peroxisome organization and fatty acid transport. Mutations cause autosomal recessive spastic paraplegia with onset typically in childhood or adolescence, characterized by progressive lower limb spasticity and weakness. The gene shows significant constraint against loss-of-function variants (LOEUF 0.39), indicating that complete loss of protein function is likely poorly tolerated.

ResearchSummary from RefSeq, UniProt

Predicted to be involved in peroxisome organization. Predicted to act upstream of or within several processes, including regulation of oxidative phosphorylation; response to food; and retinal pigment epithelium development. Predicted to be located in peroxisome. Predicted to be active in peroxisomal membrane. [provided by Alliance of Genome Resources, Jun 2026]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

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P/LP missense

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LOEUF

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Mechanism

Some data sources returned errors (2)

gnomad: Error: gnomAD API error: 400

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

Background carrier burden — how many people carry a rare variant somewhere in TMEM135?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 86

571 rare PASS variants

Rare truncating (LoF)

1 in 2,600

71 rare PASS variants

Rare synonymous (reference)

1 in 170

229 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TMEM135. 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 120	1 in 1,600
South Asian	~43k	1 in 130	1 in 3,400
Remaining (unassigned)	~30k	1 in 80	1 in 5,000
European (Finnish)	~27k	1 in 560	1 in 760
Admixed American	~22k	1 in 86	1 in 3,000
African / African American	~21k	1 in 120	1 in 2,400
East Asian	~20k	1 in 160	1 in 2,000
Ashkenazi Jewish	~13k	1 in 820	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 100	none seen

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.