TMEM168

Chr 7

transmembrane protein 168

NCBI Gene: 64418 ENSG00000146802 UniProt: Q9H0V1 OMIM: 621529

Enables sodium channel regulator activity. Predicted to act upstream of or within regulation of ubiquitin-dependent protein catabolic process and regulation of voltage-gated sodium channel activity. Located in nuclear membrane and transport vesicle. [provided by Alliance of Genome Resources, Apr 2025]

OMIM Research

OMIM ResearchGenerating clinical summary…

Clinical highlights

Gene–disease validity (ClinGen)

Disputed · Brugada syndrome · AD · ClinGen 2026

evidence questions this relationship

Active trials

—

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.65

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.65LOEUF

pLI 0.004

Z-score 2.80

OE 0.36 (0.21–0.65)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.89Z-score

OE missense 0.87 (0.79–0.95)

325 obs / 373.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.36 (0.21–0.65)

0≤0.351.4

Missense OE?0.87 (0.79–0.95)

0≤0.61.4

Synonymous OE?1.09

0≤1.21.6

LoF obs/exp: 8 / 22.2Missense obs/exp: 325 / 373.4Syn Z: -0.81

Background carrier burden — how many people carry a rare variant somewhere in TMEM168?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 100

818 rare PASS variants

Rare truncating (LoF)

1 in 1,200

120 rare PASS variants

Rare synonymous (reference)

1 in 160

301 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TMEM168. 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 1,500
South Asian	~43k	1 in 73	1 in 900
Remaining (unassigned)	~30k	1 in 95	1 in 1,800
European (Finnish)	~27k	1 in 320	1 in 5,200
Admixed American	~22k	1 in 85	1 in 1,100
African / African American	~21k	1 in 74	1 in 3,000
East Asian	~20k	1 in 60	1 in 880
Ashkenazi Jewish	~13k	1 in 540	none seen
Middle Eastern	~2,884	1 in 76	≈ 1 in 580

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): All 4 coding exons well covered in gnomAD exomes and genomes.? see exons ↓