UPF3A

Chr 13

UPF3A regulator of nonsense mediated mRNA decay

Also known as: HUPF3A, RENT3A, UPF3

NCBI Gene: 65110ENSG00000169062UniProt: Q9H1J1OMIM: 605530

UPF3A encodes a protein involved in nonsense-mediated mRNA decay, a cellular quality control mechanism that degrades mRNAs containing premature stop codons by linking the exon junction complex to the NMD surveillance machinery. The gene shows very low constraint against loss-of-function variants (pLI <0.001, LOEUF 0.944), and no established Mendelian disease associations have been reported. Clinical significance of UPF3A variants remains unclear given the lack of constraint and absence of well-characterized disease phenotypes.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 0.94
Clinical Summary— UPF3A
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
118 unique Pathogenic / Likely Pathogenic· 114 VUS of 255 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.94LOEUF
pLI 0.000
Z-score 1.76
OE 0.59 (0.39–0.94)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.60Z-score
OE missense 1.11 (1.00–1.22)
275 obs / 248.2 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.59 (0.39–0.94)
0≤0.351.4
Missense OE1.11 (1.00–1.22)
0≤0.61.4
Synonymous OE1.39
0≤1.21.6
LoF obs/exp: 13 / 21.9Missense obs/exp: 275 / 248.2Syn Z: -2.99
DN
0.6842th %ile
GOF
0.5857th %ile
LOF
0.4825th %ile

The highest-scoring mechanism for this gene is dominant-negative.

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

255 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic115
Likely Pathogenic3
VUS114
Likely Benign6
Benign2
115
Pathogenic
3
Likely Pathogenic
114
VUS
6
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
115
0
115
Likely Pathogenic
0
0
3
0
3
VUS
0
97
17
0
114
Likely Benign
0
2
4
0
6
Benign
0
0
2
0
2
Total0991410240

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

View in ClinVar →

Protein Context — Lollipop Plot

UPF3A · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 4 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Serum methylation of GALNT9, UPF3A, WARS, and LDB2 as noninvasive biomarkers for the early detection of colorectal cancer and advanced adenomas.
Gallardo-Gómez M et al.·Clin Epigenetics
2023Open Access
Upf3a but not Upf1 mediates the genetic compensation response induced by leg1 deleterious mutations in an H3K4me3-independent manner.
Xie A et al.·Cell Discov
2023Open Access
UPF3A is dispensable for nonsense-mediated mRNA decay in mouse pluripotent and somatic cells.
Chen C et al.·Life Sci Alliance
2023Open AccessFunctional
Genetic compensation response could exist in colorectal cancer: UPF3A upregulates the oncogenic homologue gene SRSF3 expression corresponding to SRSF6 to promote colorectal cancer metastasis.
Xu W et al.·J Gastroenterol Hepatol
2023
Structures of nonsense-mediated mRNA decay factors UPF3B and UPF3A in complex with UPF2 reveal molecular basis for competitive binding and for neurodevelopmental disorder-causing mutation.
Bufton JC et al.·Nucleic Acids Res
2022Open 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