TMEM164

Chr X

transmembrane protein 164

Also known as: bB360B22.3

NCBI Gene: 84187 ENSG00000157600 UniProt: Q5U3C3

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.

ResearchSummary from RefSeq, UniProt

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

ResearchGenerating clinical summary…

LOEUF 0.33

Clinical Summary— TMEM164

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.94). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

21 VUS of 99 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

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

ClinVar Variant Classifications

99 submitted variants in ClinVar

ClinVar

Classification Summary

VUS21

Likely Benign4

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	0	0	0	0
VUS	1	19	1	0	21
Likely Benign	0	3	0	1	4
Benign	0	0	0	0	0
Total	1	22	1	1	25

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

93 pathogenic / likely-pathogenic (of 101) ClinVar copy-number / structural variants overlap TMEM164 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →