TMEM164

Chr X

transmembrane protein 164

Also known as: bB360B22.3

NCBI Gene: 84187 ENSG00000157600 UniProt: Q5U3C3 OMIM: 301169

The TMEM164 protein regulates ferroptosis by mediating the acylation of ether lysophospholipids and controlling autophagosome formation to promote iron accumulation and lipid peroxidation. This gene is highly constrained against loss-of-function variants (pLI 0.94, LOEUF 0.33), but no human diseases have been definitively associated with TMEM164 mutations to date.

OMIM ResearchSummary from RefSeq, UniProt

Involved in positive regulation of ferroptosis. Predicted to be located in membrane. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

Clinical highlights

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.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.33

LOEUF· LoF intol.

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — X-linked: males carry a single copy

LoF Constraint?

0.33LOEUF

pLI 0.944

Z-score 2.80

OE 0.00 (0.00–0.33)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

2.36Z-score

OE missense 0.41 (0.32–0.51)

51 obs / 125.5 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.33)

0≤0.351.4

Missense OE?0.41 (0.32–0.51)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

LoF obs/exp: 0 / 9.1Missense obs/exp: 51 / 125.5Syn Z: 0.18

Background carrier burden — how many people carry a rare variant somewhere in TMEM164?

gnomAD v4 · ~732k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 460

125 rare PASS variants

Rare truncating (LoF)

1 in 28,000

8 rare PASS variants

Rare synonymous (reference)

1 in 290

94 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TMEM164. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 8 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~561k	1 in 970	1 in 15,000
South Asian	~36k	1 in 730	none seen
Remaining (unassigned)	~31k	1 in 520	none seen
European (Finnish)	~27k	1 in 3,400	≈ 1 in 23,000
Admixed American	~23k	1 in 700	none seen
African / African American	~21k	1 in 480	none seen
East Asian	~20k	1 in 920	none seen
Ashkenazi Jewish	~13k	1 in 2,600	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): All 6 coding exons well covered in gnomAD exomes and genomes.? see exons ↓