METRNL
protein-codingmeteorin like, glial cell differentiation regulator
Gene summary
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]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~15.5 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to METRNL variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001004431.3. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 2 | 2 | 5 | ||
| missense | 56 | 6 | 2 | 64 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 58 | 8 | 4 | 70 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001004431.1 | 4 | MANE Select | |
| Ensembl | ENSP00000315731.6 | 4 | MANE Select | |
| RefSeq | NP_001350782.1 | 3 | Standard | |
| Ensembl | ENSP00000458566.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- response to cold
- regulation of signaling receptor activity
- response to muscle activity
- fat cell differentiation
- negative regulation of inflammatory response
Molecular Function
- molecular_function
- hormone activity
Cellular Component
- extracellular space
- extracellular exosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000320095
- Coding exons
- 4
- Length
- 15298
- Individuals with no LoFs
- 125344
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 5
- Defined
- 125349
- p
- 0.0000199
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.11 | 140 | 182 | 0.769 | 0.0000135 | 1962 |
| Missense (PolyPhen) | 44 | 68.485 | 0.64247 | 750 | ||
| Synonymous | -0.362 | 89 | 84.8 | 1.05 | 0.00000685 | 675 |
| Loss of Function | 2.45 | 1 | 8.85 | 0.113 | 4.39e-7 | 111 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000018 | 0.000018 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0.00018 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Hormone induced following exercise or cold exposure that promotes energy expenditure. Induced either in the skeletal muscle after exercise or in adipose tissue following cold exposure and is present in the circulation. Able to stimulate energy expenditure associated with the browning of the white fat depots and improves glucose tolerance. Does not promote an increase in a thermogenic gene program via direct action on adipocytes, but acts by stimulating several immune cell subtypes to enter the adipose tissue and activate their prothermogenic actions. Stimulates an eosinophil-dependent increase in IL4 expression and promotes alternative activation of adipose tissue macrophages, which are required for the increased expression of the thermogenic and anti- inflammatory gene programs in fat. Required for some cold-induced thermogenic responses, suggesting a role in metabolic adaptations to cold temperatures (By similarity). {ECO:0000250}.;
Recessive Scores
- pRec
- 0.108
Intolerance Scores
- LoFtool
- 0.130
- RVIS EVS
- -0.09
- RVIS percentile EVS
- 46.99
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.0902
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |