TMEM213

Chr 7

transmembrane protein 213

NCBI Gene: 155006 ENSG00000214128 UniProt: A2RRL7

TMEM213 encodes a protein predicted to be located in cellular membranes, though its specific function remains unclear. The gene shows low constraint against loss-of-function variants (pLI 0.09, LOEUF 1.36), suggesting tolerance to functional disruption. No established disease associations have been reported for TMEM213 mutations.

ResearchSummary from RefSeq

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

ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.36

Clinical Summary— TMEM213

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Population Constraint (gnomAD)

Low constraint (pLI 0.09) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

25 VUS of 34 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.36LOEUF

pLI 0.087

Z-score 1.10

OE 0.44 (0.18–1.36)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.24Z-score

OE missense 0.91 (0.74–1.14)

57 obs / 62.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.44 (0.18–1.36)

0≤0.351.4

Missense OE?0.91 (0.74–1.14)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 2 / 4.5Missense obs/exp: 57 / 62.4Syn Z: -0.03

This gene — mechanism propensity

0.6937th %ile

GOF

0.83top 10%

LOF

0.2582th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

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

ClinVar Variant Classifications

34 submitted variants in ClinVar

ClinVar

Classification Summary

VUS25

Likely Benign5

Benign3

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	20	3	2	25
Likely Benign	5	0	0	5
Benign	1	2	0	3
Total	26	5	2	33

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

View in ClinVar →

44 pathogenic / likely-pathogenic (of 51) ClinVar copy-number / structural variants overlap TMEM213 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →