MGRN1

Chr 16

mahogunin ring finger 1

Also known as: RNF156

NCBI Gene: 23295ENSG00000102858UniProt: O60291

Enables ubiquitin-protein transferase activity. Involved in endosome to lysosome transport; negative regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway; and protein monoubiquitination. Located in several cellular components, including early endosome; endoplasmic reticulum; and nucleus. [provided by Alliance of Genome Resources, Jul 2025]

171
ClinVar variants
30
Pathogenic / LP
0.10
pLI score
0
Active trials
Clinical Summary— MGRN1
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.26) despite low pLI — interpret in context.
📋
ClinVar Variants
30 Pathogenic / Likely Pathogenic· 128 VUS of 171 total submissions
Some data sources returned errors (1)

clinvarCount: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
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.
0.47LOEUF
pLI 0.104
Z-score 3.83
OE 0.26 (0.15–0.47)
Moderately constrained

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.
-1.55Z-score
OE missense 1.23 (1.14–1.32)
457 obs / 372.8 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.0.26 (0.15–0.47)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.23 (1.14–1.32)
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.1.44
0≤1.21.6
LoF obs/exp: 8 / 31.1Missense obs/exp: 457 / 372.8Syn Z: -4.63

ClinVar Variant Classifications

171 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic30
VUS128
Likely Benign12
Benign1
30
Pathogenic
128
VUS
12
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
30
0
30
Likely Pathogenic
0
0
0
0
0
VUS
0
115
13
0
128
Likely Benign
0
6
2
4
12
Benign
0
0
0
1
1
Total0121455171

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

View in ClinVar →

Protein Context — Lollipop Plot

MGRN1 · 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
Endoplasmic reticulum stress related super-enhancers suppress cuproptosis via glycolysis reprogramming in lung adenocarcinoma.
Gu Y et al.·Cell Death Dis
2025
An MGRN1-Based Biomarker Combination Accurately Predicts Melanoma Patient Survival.
Sánchez-Beltrán J et al.·Int J Mol Sci
2025
Spatially Informed Gene Signatures for Response to Immunotherapy in Melanoma.
Aung TN et al.·Clin Cancer Res
2024
The E3 ubiquitin ligase Mahogunin ubiquitinates the melanocortin 2 receptor.
Cooray SN et al.·Endocrinology
2011
Molecular Pathways and Animal Models of Atrial Septal Defect.
Magnan RA et al.·Adv Exp Med Biol
2024Review
MGRN1-dependent pigment-type switching requires its ubiquitination activity but not its interaction with TSG101 or NEDD4.
Gunn TM et al.·Pigment Cell Melanoma Res
2013
Mahogunin ring finger-1 (MGRN1) E3 ubiquitin ligase inhibits signaling from melanocortin receptor by competition with Galphas.
Pérez-Oliva AB et al.·J Biol Chem
2009
Abnormal regulation of TSG101 in mice with spongiform neurodegeneration.
Jiao J et al.·Biochim Biophys Acta
2009
Levels of the Mahogunin Ring Finger 1 E3 ubiquitin ligase do not influence prion disease.
Silvius D et al.·PLoS One
2013
The ubiquitin-proteasome system in spongiform degenerative disorders.
Whatley BR et al.·Biochim Biophys Acta
2008Review
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