TMEM106B

Chr 7

transmembrane protein 106B

Also known as: HLD16

NCBI Gene: 54664 ENSG00000106460 UniProt: Q9NUM4

The protein regulates lysosomal transport and acidification in neurons, particularly affecting the movement of late endosomes/lysosomes and dendrite morphogenesis. Mutations cause hypomyelinating leukodystrophy 16, inherited in an autosomal dominant pattern. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.604), suggesting some tolerance to haploinsufficiency while still being associated with neurological disease.

ResearchSummary from RefSeq, OMIM, UniProt

Enables ATPase binding activity. Involved in dendrite morphogenesis and lysosome localization. Located in endosome and lysosomal membrane. Implicated in hypomyelinating leukodystrophy 16. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtFrontotemporal dementia 2

UniProtFrontotemporal dementia and/or amyotrophic lateral sclerosis 1

UniProtLeukodystrophy, hypomyelinating, 16

Clinical highlights

Gene-disease validity (ClinGen)

leukodystrophy, hypomyelinating, 16 · ADDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.60

LOEUF

LOF

Mechanism· predicted

Some data sources returned errors (1)

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