RFPL3

Chr 22

ret finger protein like 3

Also known as: RNF120

NCBI Gene: 10738ENSG00000128276UniProt: O75679

Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in innate immune response and regulation of gene expression. Predicted to be located in nucleus. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Jul 2025]

94
ClinVar variants
16
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— RFPL3
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
16 Pathogenic / Likely Pathogenic· 67 VUS of 94 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
1.94LOEUF
pLI 0.000
Z-score -1.07
OE 1.60 (0.79–1.94)
Tolerant

Highly tolerant — LoF variants common in population

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.
-0.43Z-score
OE missense 1.09 (0.97–1.23)
198 obs / 181.5 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.1.60 (0.79–1.94)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.09 (0.97–1.23)
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.1.20
0≤1.21.6
LoF obs/exp: 6 / 3.8Missense obs/exp: 198 / 181.5Syn Z: -1.37

ClinVar Variant Classifications

94 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic15
Likely Pathogenic1
VUS67
Likely Benign6
15
Pathogenic
1
Likely Pathogenic
67
VUS
6
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
15
0
15
Likely Pathogenic
0
0
1
0
1
VUS
0
62
5
0
67
Likely Benign
0
6
0
0
6
Benign
0
0
0
0
0
Total06821089

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

View in ClinVar →

Protein Context — Lollipop Plot

RFPL3 · 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
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Exploring targeted therapies against RFPL3 for non-small cell lung cancer with lymph node metastasis.
Lin C et al.·Discov Oncol
2025🔓 Open Access
Importin 13 promotes NSCLC progression by mediating RFPL3 nuclear translocation and hTERT expression upregulation.
Zohud BA et al.·Cell Death Dis
2020🔓 Open Access
EGF upregulates RFPL3 and hTERT via the MEK signaling pathway in non‑small cell lung cancer cells.
Lin C et al.·Oncol Rep
2018🔓 Open Access
RFPL3 and CBP synergistically upregulate hTERT activity and promote lung cancer growth.
Qin Y et al.·Oncotarget
2015🔓 Open Access
Identification of RFPL3 protein as a novel E3 ubiquitin ligase modulating the integration activity of human immunodeficiency virus, type 1 preintegration complex using a microtiter plate-based assay.
Tan BH et al.·J Biol Chem
2014
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