RFX3

Chr 9

regulatory factor X3

NCBI Gene: 5991ENSG00000080298UniProt: P48380OMIM: 601337

The protein encoded by RFX3 is a transcription factor essential for ciliogenesis, regulating genes involved in ciliary assembly and motility, and also required for islet cell differentiation during pancreatic development. Mutations cause autosomal recessive primary ciliary dyskinesia with situs inversus and pancreatic islet cell dysfunction. The disorder affects respiratory function due to impaired ciliary motility and can involve laterality defects and endocrine pancreatic abnormalities.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.10
Clinical Summary— RFX3
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Gene-Disease Validity (ClinGen)
complex neurodevelopmental disorder · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint
0.10LOEUF
pLI 1.000
Z-score 6.14
OE 0.02 (0.01–0.10)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint
3.47Z-score
OE missense 0.53 (0.47–0.59)
223 obs / 424.3 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.02 (0.01–0.10)
0≤0.351.4
Missense OE0.53 (0.47–0.59)
0≤0.61.4
Synonymous OE1.21
0≤1.21.6
LoF obs/exp: 1 / 45.8Missense obs/exp: 223 / 424.3Syn Z: -2.11
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveRFX3-related neurodevelopmental disorder with autism and other behavioural abnormalitiesLOFAD
DN
0.3196th %ile
GOF
0.3392th %ile
LOF
0.77top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.10

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

RFX3 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Long noncoding RNA regulatory factor X3- antisense RNA 1 promotes non-small cell lung cancer via the microRNA-577/signal transducer and activator of transcription 3 axis
Hu Y et al.·Bioengineered
2022
Novel Functional Genes Involved in Transdifferentiation of Canine ADMSCs Into Insulin-Producing Cells, as Determined by Absolute Quantitative Transcriptome Sequencing Analysis
Dai P et al.·Front Cell Dev Biol
2021Functional
RFX3 loss disrupts non-coding RNA networks in iPSC-derived pancreatic progenitors.
Aldous N et al.·Genes Dis
2025
Reprogramming adipose mesenchymal stem cells into islet beta-cells for the treatment of canine diabetes mellitus
Dai P et al.·Stem Cell Res Ther
2022
A case of infantile epileptic spasms syndrome and autism spectrum disorder with an RFX3 mutation.
Torio M et al.·Seizure
2023
Top 5 full-text resultsSearch PubTator3 ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Whole Genome Sequence Analysis of Weight Loss in 16 972 Participants With COPD Reveals Novel Risk Loci in DRAIC and RFX3.
Chiles JW et al.·J Cachexia Sarcopenia Muscle
2026
RFX3 is essential for the generation of functional human pancreatic islets from stem cells.
Memon B et al.·Diabetologia
2025Open AccessFunctional
CircRFX3 Up-regulates Its Host Gene RFX3 to Facilitate Tumorigenesis and Progression of Glioma.
Qian Y et al.·J Mol Neurosci
2022
Downregulation of microRNA-342-3p Eases Insulin Resistance and Liver Gluconeogenesis via Regulating Rfx3 in Gestational Diabetes Mellitus.
Sun Y et al.·Crit Rev Eukaryot Gene Expr
2022
Ginsenoside Rg3 and Korean Red Ginseng extract epigenetically regulate the tumor-related long noncoding RNAs RFX3-AS1 and STXBP5-AS1.
Ham J et al.·J Ginseng Res
2019Open 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