RNF39

Chr 6

ring finger protein 39

Also known as: FAP216, HZF, HZFW, LIRF

NCBI Gene: 80352ENSG00000204618UniProt: Q9H2S5

This gene lies within the major histocompatibility complex class I region on chromosome 6. Studies of a similar rat protein suggest that this gene encodes a protein that plays a role in an early phase of synaptic plasticity. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

65
ClinVar variants
6
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— RNF39
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
6 Pathogenic / Likely Pathogenic· 56 VUS of 65 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.
1.19LOEUF
pLI 0.000
Z-score 1.07
OE 0.68 (0.41–1.19)
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.
1.34Z-score
OE missense 0.75 (0.66–0.85)
163 obs / 218.6 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.0.68 (0.41–1.19)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.75 (0.66–0.85)
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.0.69
0≤1.21.6
LoF obs/exp: 9 / 13.2Missense obs/exp: 163 / 218.6Syn Z: 2.42

ClinVar Variant Classifications

65 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic5
Likely Pathogenic1
VUS56
Likely Benign3
5
Pathogenic
1
Likely Pathogenic
56
VUS
3
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
5
0
5
Likely Pathogenic
0
0
1
0
1
VUS
0
43
13
0
56
Likely Benign
0
2
0
1
3
Benign
0
0
0
0
0
Total04519165

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

View in ClinVar →

Protein Context — Lollipop Plot

RNF39 · 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
RNF39 facilitates antiviral immune responses by promoting K63-linked ubiquitination of STING.
Wang W et al.·Int Immunopharmacol
2024
RNF39 promotes colorectal cancer progression by driving RINT1 degradation and suppressing ER stress-induced apoptosis.
Chen L et al.·Clin Transl Med
2026
Smoking-informed methylation and expression QTLs in human brain and colocalization with smoking-associated genetic loci.
Carnes MU et al.·Neuropsychopharmacology
2024
The HLA-B/-C haplotype block contains major determinants for host control of HIV.
Trachtenberg E et al.·Genes Immun
2009
Epigenetic association analysis of clinical sub-phenotypes in patients with polycystic ovary syndrome (PCOS).
Jacobsen VM et al.·Gynecol Endocrinol
2019Cohort
Variants in ZNRD1 gene predict HIV-1/AIDS disease progression in a Han Chinese population in Taiwan.
Lin YJ et al.·PLoS One
2013
[DNA Methylation Profile of CD14+ Monocytes Changes in Primary Progressive Multiple Sclerosis].
Kiselev IS et al.·Mol Biol (Mosk)
2023
Induced pluripotent stem cells from subjects with Lesch-Nyhan disease.
Sutcliffe DJ et al.·Sci Rep
2021
Association of HLA-C and HCP5 gene regions with the clinical course of HIV-1 infection.
van Manen D et al.·AIDS
2009
Genome-wide DNA methylation analysis reveals a unique methylation pattern for pleural mesothelioma compared to healthy pleura and other lung diseases.
Vandenhoeck J et al.·Clin Epigenetics
2024
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