MKRN2
Chr 3makorin ring finger protein 2
Also known as: HSPC070, RNF62
This gene encodes an E3 ubiquitin ligase that catalyzes ubiquitin attachment to target proteins for degradation and suppresses inflammatory responses by promoting degradation of the NF-kappaB component RELA/p65. The gene is highly constrained against loss-of-function variants (LOEUF 0.664), but no definitive human disease associations have been established in the provided data. Additional clinical and genetic studies would be needed to determine specific phenotypes and inheritance patterns associated with MKRN2 variants.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
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.
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
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
MKRN2 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
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 →External Resources
Links to major genomics databases and tools