TMEM176B

Chr 7

transmembrane protein 176B

Also known as: LR8, MS4B2

NCBI Gene: 28959ENSG00000106565UniProt: Q3YBM2

Predicted to be involved in negative regulation of dendritic cell differentiation. Predicted to be located in nuclear membrane. [provided by Alliance of Genome Resources, Jul 2025]

118
ClinVar variants
68
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— TMEM176B
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
68 Pathogenic / Likely Pathogenic· 45 VUS of 118 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.75LOEUF
pLI 0.000
Z-score -0.52
OE 1.16 (0.76–1.75)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.23Z-score
OE missense 1.05 (0.92–1.20)
155 obs / 147.1 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.1.16 (0.76–1.75)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.05 (0.92–1.20)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.14
0≤1.21.6
LoF obs/exp: 14 / 12.0Missense obs/exp: 155 / 147.1Syn Z: -0.87

ClinVar Variant Classifications

118 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic65
Likely Pathogenic3
VUS45
Likely Benign5
65
Pathogenic
3
Likely Pathogenic
45
VUS
5
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
65
0
65
Likely Pathogenic
0
0
3
0
3
VUS
0
36
9
0
45
Likely Benign
0
5
0
0
5
Benign
0
0
0
0
0
Total041770118

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

View in ClinVar →

Protein Context — Lollipop Plot

TMEM176B · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Single-cell RNA-seq reveals alterations in peripheral CX3CR1 and nonclassical monocytes in familial tauopathy.
Sirkis DW et al.·Genome Med
2023
Identification of genetic profile and biomarkers involved in acute respiratory distress syndrome.
Cao S et al.·Intensive Care Med
2024
The Ala134Thr variant in TMEM176B exerts a beneficial role in colorectal cancer prognosis by increasing NLRP3 inflammasome activation.
Cambui RAG et al.·J Cancer Res Clin Oncol
2023
Functional evaluation of TMEM176B and its predictive role for severe respiratory viral infection through integrated analysis of single-cell and bulk RNA-sequencing.
Shang C et al.·J Med Virol
2024Functional
Lipid metabolism-related gene signature predicts prognosis and unveils novel anti-tumor drugs in specific type of diffuse large B cell lymphoma.
Wang C et al.·Mol Med
2024
Role of inflammasome activation in tumor immunity triggered by immune checkpoint blockers.
Segovia M et al.·Clin Exp Immunol
2020Review
Targeting TMEM176B Enhances Antitumor Immunity and Augments the Efficacy of Immune Checkpoint Blockers by Unleashing Inflammasome Activation.
Segovia M et al.·Cancer Cell
2019
A Systematic Review on the Role of the Stria Vascularis in Menière's Disease Pathogenesis.
Cruz-Granados P et al.·J Assoc Res Otolaryngol
2025Review
Early prediction of renal graft function: Analysis of a multi-center, multi-level data set.
Blazquez-Navarro A et al.·Curr Res Transl Med
2022
Hub Gene and Its Key Effects on Diffuse Large B-Cell Lymphoma by Weighted Gene Coexpression Network Analysis.
Ma C et al.·Biomed Res Int
2021
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools