METRNL
Chr 17meteorin like, glial cell differentiation regulator
Predicted to enable hormone activity. Predicted to be involved in several processes, including brown fat cell differentiation; positive regulation of brown fat cell differentiation; and response to muscle activity. Located in extracellular exosome. [provided by Alliance of Genome Resources, Jul 2025]
Clinical Summary— METRNL
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Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.75) — some intolerance to loss-of-function variants.
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ClinVar Variants
22 Pathogenic / Likely Pathogenic· 84 VUS of 121 total submissions
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Moderate LoF intolerance
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.
0.54LOEUF
pLI 0.745
Z-score 2.45
OE 0.11 (0.04–0.54)
More LoF-intolerant than ~75% of genes
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.
1.11Z-score
OE missense 0.77 (0.67–0.89)
140 obs / 182.1 exp
Mild missense constraint
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.0.11 (0.04–0.54)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.77 (0.67–0.89)
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.1.05
0≤1.21.6
LoF obs/exp: 1 / 8.9Missense obs/exp: 140 / 182.1Syn Z: -0.36
ClinVar Variant Classifications
121 submitted variants in ClinVar
Classification Summary
Pathogenic17
Likely Pathogenic5
VUS84
Likely Benign10
Benign5
17
Pathogenic
5
Likely Pathogenic
84
VUS
10
Likely Benign
5
Benign
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 17 | 0 | 17 |
Likely Pathogenic | 0 | 0 | 5 | 0 | 5 |
VUS | 0 | 56 | 28 | 0 | 84 |
Likely Benign | 0 | 6 | 2 | 2 | 10 |
Benign | 0 | 2 | 1 | 2 | 5 |
| Total | 0 | 64 | 53 | 4 | 121 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
METRNL · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
Endothelial METRNL determines circulating METRNL level and maintains endothelial function against atherosclerosis
Zheng S et al.·Acta Pharm Sin B
2023
Meteorin-like protein elevation post-exercise improved vascular inflammation among coronary artery disease patients by downregulating NLRP3 inflammasome activity
Liu J et al.·Aging (Albany NY)
2023Cohort
Low Levels of Metrnl are Linked to the Deterioration of Diabetic Kidney Disease
Chen J et al.·Diabetes Metab Syndr Obes
2024
Effects of 12-week exercise on Meteorin-like levels, inflammation, and functional capacity in older adults: Korean national aging project randomized controlled study
Jamrasi P et al.·Eur Geriatr Med
2025Functional
Meteorin-Like Protein (Metrnl) in Obesity, during Weight Loss and in Adipocyte Differentiation
Schmid A et al.·J Clin Med
2021
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
Metrnl as a secreted protein: Discovery and cardiovascular research.
Miao ZW et al.·Pharmacol Ther
2024Review
Meteorin-like protein (Metrnl): A metabolic syndrome biomarker and an exercise mediator.
Alizadeh H·Cytokine
2022Review
Meteorin-like/Metrnl: A pleiotropic cytokine implicated in metabolic, inflammatory and malignant disorders.
Li J et al.·Cytokine Growth Factor Rev
2026Review
Meteorin-like protein (Metrnl): a key exerkine in exercise-mediated cardiovascular health.
Alizadeh H et al.·Arch Physiol Biochem
2025Review
Involvement of the secreted protein Metrnl in human diseases.
Miao ZW et al.·Acta Pharmacol Sin
2020Review
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Evaluation of serum irisin and meteorin-like (METRNL) levels in people with drug-resistant and drug-responsive temporal lobe epilepsy.
Kaya E et al.·Epileptic Disord
2026
Metrnl in health and disease: tissue-specific actions and signaling networks.
Zhao R et al.·Apoptosis
2026
Metrnl as a predictive biomarker for postprandial hypertriglyceridemia in overweight and obese populations.
Wang X et al.·Front Endocrinol (Lausanne)
2026Open Access
Endothelial versus global METRNL reveals importance of endothelial METRNL against atherosclerosis via mitochondrial homeostasis.
Wang DX et al.·Pharmacol Res
2026
Ergosterol Attenuates Palmitate-Induced Tenocyte Apoptosis Through the Suppression of ER Stress and Myocyte-Derived IL-15/METRNL-Mediated Crosstalk.
Pyo MK et al.·Mycobiology
2026Open Access
Top 5 resultsSearch Europe PMC ↗
External Resources
Links to major genomics databases and tools