TMEM106B

Chr 7AD

transmembrane protein 106B

Also known as: HLD16

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.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismADLOEUF 0.601 OMIM phenotype
Clinical SummaryTMEM106B
🧬
Gene-Disease Validity (ClinGen)
leukodystrophy, hypomyelinating, 16 · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.23) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.60LOEUF
pLI 0.326
Z-score 2.55
OE 0.23 (0.100.60)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.92Z-score
OE missense 0.79 (0.680.92)
115 obs / 146.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.23 (0.100.60)
00.351.4
Missense OE0.79 (0.680.92)
00.61.4
Synonymous OE1.11
01.21.6
LoF obs/exp: 3 / 12.8Missense obs/exp: 115 / 146.2Syn Z: -0.62
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongTMEM106B related hypomyelinating leukodystrophyOTHERAD
DN
0.5378th %ile
GOF
0.5661th %ile
LOF
0.4233th %ile

The Badonyi & Marsh model scores gain-of-function highest, but genomic evidence most strongly supports loss-of-function (haploinsufficiency) as the primary mechanism.

LOF1 literature citation

Literature Evidence

LOFTogether, these data raise the possibility that reduction of TMEM106B levels may protect against the pathogenic effects of progranulin haploinsufficiency.PMID:29929528

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

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

TMEM106B · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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