MKRN1

Chr 7

makorin ring finger protein 1

Also known as: RNF61

NCBI Gene: 23608ENSG00000133606UniProt: Q9UHC7

This gene encodes a protein that belongs to a novel class of zinc finger proteins. The encoded protein functions as a transcriptional co-regulator, and as an E3 ubiquitin ligase that promotes the ubiquitination and proteasomal degradation of target proteins. The protein encoded by this gene is thought to regulate RNA polymerase II-catalyzed transcription. Substrates for this protein's E3 ubiquitin ligase activity include the capsid protein of the West Nile virus and the catalytic subunit of the telomerase ribonucleoprotein. This protein controls cell cycle arrest and apoptosis by regulating p21, a cell cycle regulator, and the tumor suppressor protein p53. Pseudogenes of this gene are present on chromosomes 1, 3, 9, 12 and 20, and on the X chromosome. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Apr 2014]

124
ClinVar variants
42
Pathogenic / LP
0.99
pLI score· haploinsufficient
0
Active trials
Clinical Summary— MKRN1
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
42 Pathogenic / Likely Pathogenic· 78 VUS of 124 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
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.
0.26LOEUF
pLI 0.994
Z-score 4.17
OE 0.08 (0.03–0.26)
Highly constrained

Highly LoF-intolerant (top ~10% 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.
1.33Z-score
OE missense 0.77 (0.68–0.86)
198 obs / 258.2 exp
Tolerant

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.0.08 (0.03–0.26)
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 (0.68–0.86)
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.1.16
0≤1.21.6
LoF obs/exp: 2 / 24.1Missense obs/exp: 198 / 258.2Syn Z: -1.21

ClinVar Variant Classifications

124 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic40
Likely Pathogenic2
VUS78
Likely Benign4
40
Pathogenic
2
Likely Pathogenic
78
VUS
4
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
40
0
40
Likely Pathogenic
0
0
2
0
2
VUS
0
70
8
0
78
Likely Benign
0
3
0
1
4
Benign
0
0
0
0
0
Total073501124

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

View in ClinVar →

Protein Context — Lollipop Plot

MKRN1 · 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
MAKORIN 1; MKRN1
MIM #607754 · *
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
MKRN1 promotes colorectal cancer metastasis by activating the TGF-β signalling pathway through SNIP1 protein degradation.
Zhang Y et al.·J Exp Clin Cancer Res
2023
CircVPS8 promotes the malignant phenotype and inhibits ferroptosis of glioma stem cells by acting as a scaffold for MKRN1, SOX15 and HNF4A.
Hu J et al.·Oncogene
2024
MKRN1 induces degradation of West Nile virus capsid protein by functioning as an E3 ligase.
Ko A et al.·J Virol
2010
Low expression of MKRN1 promotes leukemia cell proliferation.
Song L et al.·Eur J Med Res
2025
Identification and validation of the nicotine metabolism-related signature of bladder cancer by bioinformatics and machine learning.
Zhan Y et al.·Front Immunol
2024
Makorin Ring Finger Protein 1 as Adjunctive Marker in Liquid-based Cervical Cytology.
Lee M et al.·Medicine (Baltimore)
2016
Endothelial senescence-associated secretory phenotype (SASP) is regulated by Makorin-1 ubiquitin E3 ligase.
Kotla S et al.·Metabolism
2019
Porcine MKRN1 Modulates the Replication and Pathogenesis of Porcine Circovirus Type 2 by Inducing Capsid Protein Ubiquitination and Degradation.
Wang T et al.·J Virol
2018
Spectrum of BRAF Mutations and Gene Rearrangements in Ovarian Serous Carcinoma.
Chui MH et al.·JCO Precis Oncol
2021
Clinicopathologic features of kinase fusion-related thyroid carcinomas: an integrative analysis with molecular characterization.
Chu YH et al.·Mod Pathol
2020
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