RUNDC3A

Chr 17

RUN domain containing 3A

Also known as: RAP2IP, RPIP-8, RPIP8

NCBI Gene: 10900ENSG00000108309UniProt: Q59EK9

Predicted to enable GTPase regulator activity. Predicted to be involved in positive regulation of cGMP-mediated signaling. Located in intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2025]

0
Active trials
10
Pathogenic / LP
50
ClinVar variants
3
Pubs (1 yr)
2.7
Missense Z
0.44
LOEUF
Clinical Summary— RUNDC3A
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.64) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
10 Pathogenic / Likely Pathogenic· 38 VUS of 50 total submissions

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.
0.44LOEUF
pLI 0.636
Z-score 3.40
OE 0.19 (0.09–0.44)
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.
2.69Z-score
OE missense 0.52 (0.45–0.60)
127 obs / 245.7 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

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.0.19 (0.09–0.44)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.52 (0.45–0.60)
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.0.89
0≤1.21.6
LoF obs/exp: 4 / 20.7Missense obs/exp: 127 / 245.7Syn Z: 0.92
DN
0.6259th %ile
GOF
0.6637th %ile
LOF
0.48top 25%

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.

GOFprediction above median
DNprediction above median

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

50 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic10
VUS38
Likely Benign1
Benign1
10
Pathogenic
38
VUS
1
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
10
0
10
Likely Pathogenic
0
0
0
0
0
VUS
0
37
1
0
38
Likely Benign
0
0
0
1
1
Benign
0
1
0
0
1
Total03811150

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

View in ClinVar →

Protein Context — Lollipop Plot

RUNDC3A · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 3 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 3 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
RUNDC3A-AS1 is an adverse prognostic factor for triple-negative breast cancer which mediates the Warburg effect and Adriamycin resistance by targeting miR-224-3p/COL5A2.
Kong L et al.·Toxicol Appl Pharmacol
2026
RUNDC3A/SNAP25/Akt signaling mediates tumor progression and chemoresistance in gastric neuroendocrine carcinoma.
Lin Z et al.·Cell Death Dis
2022Open Access
RUNDC3A regulates SNAP25-mediated chemotherapy resistance by binding AKT in gastric neuroendocrine carcinoma (GNEC).
Chen P et al.·Cell Death Discov
2022Open Access
lncRNA RUNDC3A-AS1 Regulates Proliferation and Apoptosis of Thyroid Cancer Cells via the miR-151b/SNRPB Axis.
Deng Y et al.·Int J Endocrinol
2022Open Access
Long Non-coding RNA RUNDC3A-AS1 Promotes Lung Metastasis of Thyroid Cancer via Targeting the miR-182-5p/ADAM9.
Ma D et al.·Front Cell Dev Biol
2021Open Access
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients