TMEM163

Chr 2AD

transmembrane protein 163

Also known as: DC29, HLD25, SLC30A11, SV31

NCBI Gene: 81615 ENSG00000152128 UniProt: Q8TC26 OMIM: 618978

TMEM163 encodes a zinc ion transporter that mediates zinc efflux and is required for oligodendrocyte survival, proliferation, and myelination in the central nervous system. Mutations cause autosomal dominant hypomyelinating leukodystrophy 25. The gene shows moderate constraint to loss-of-function variation (LOEUF 0.851).

OMIM ResearchSummary from RefSeq, OMIM, UniProt

Predicted to enable zinc ion binding activity. Involved in intracellular zinc ion homeostasis; myelination; and zinc export across plasma membrane. Is active in late endosome; lysosome; and plasma membrane. Implicated in hypomyelinating leukodystrophy 25. [provided by Alliance of Genome Resources, Jun 2026]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Leukodystrophy, hypomyelinating, 25MIM #620243

Clinical highlights

Gene–disease validity (ClinGen)

Moderate · leukodystrophy, hypomyelinating, 25 · AD · ClinGen 2026

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.85

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.85LOEUF

pLI 0.040

Z-score 1.91

OE 0.37 (0.18–0.85)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.77Z-score

OE missense 0.59 (0.49–0.70)

85 obs / 144.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.37 (0.18–0.85)

0≤0.351.4

Missense OE?0.59 (0.49–0.70)

0≤0.61.4

Synonymous OE?1.00

0≤1.21.6

LoF obs/exp: 4 / 10.8Missense obs/exp: 85 / 144.8Syn Z: -0.00

Background carrier burden — how many people carry a rare variant somewhere in TMEM163?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 270

333 rare PASS variants

Rare truncating (LoF)

1 in 11,000

32 rare PASS variants

Rare synonymous (reference)

1 in 380

168 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TMEM163. 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 330	1 in 13,000
South Asian	~43k	1 in 120	1 in 5,400
Remaining (unassigned)	~30k	1 in 270	1 in 4,800
European (Finnish)	~27k	1 in 920	none seen
Admixed American	~22k	1 in 210	≈ 1 in 7,500
African / African American	~21k	1 in 150	none seen
East Asian	~20k	1 in 120	1 in 2,300
Ashkenazi Jewish	~13k	1 in 490	none seen
Middle Eastern	~2,884	1 in 360	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.

Exome coverage (gnomAD): 7 of 8 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 8.? see exons ↓