RBFOX1

Chr 16

RNA binding fox-1 homolog 1

NCBI Gene: 54715ENSG00000078328UniProt: Q9NWB1

RNA-binding protein that regulates alternative splicing events by binding to 5'-UGCAUGU-3' elements. Regulates alternative splicing of tissue-specific exons and of differentially spliced exons during erythropoiesis

574
ClinVar variants
25
Pathogenic / LP
0.95
pLI score· haploinsufficient
0
Active trials
Clinical Summary— RBFOX1
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.95). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
25 Pathogenic / Likely Pathogenic· 328 VUS of 574 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
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.
0.34LOEUF
pLI 0.953
Z-score 4.12
OE 0.15 (0.07–0.34)
Highly constrained

Highly LoF-intolerant (top ~10% 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.
0.20Z-score
OE missense 0.97 (0.88–1.07)
271 obs / 280.2 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.0.15 (0.07–0.34)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.97 (0.88–1.07)
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.1.39
0≤1.21.6
LoF obs/exp: 4 / 27.2Missense obs/exp: 271 / 280.2Syn Z: -3.41

ClinVar Variant Classifications

574 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic19
Likely Pathogenic6
VUS328
Likely Benign210
Benign7
Conflicting4
19
Pathogenic
6
Likely Pathogenic
328
VUS
210
Likely Benign
7
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
0
18
0
19
Likely Pathogenic
0
2
4
0
6
VUS
12
190
124
2
328
Likely Benign
0
10
113
87
210
Benign
0
1
6
0
7
Conflicting
—4
Total1320326589574

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

View in ClinVar →

Protein Context — Lollipop Plot

RBFOX1 · protein map & ClinVar variants

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

Gene2Phenotype Curations

RBFOX1-related neurodevelopmental disorder

limited
ADLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
📖
GeneReview available — RBFOX1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Spliceosome malfunction causes neurodevelopmental disorders with overlapping features.
Li D et al.·J Clin Invest
2024
RBFOX1, encoding a splicing regulator, is a candidate gene for aggressive behavior.
Fernàndez-Castillo N et al.·Eur Neuropsychopharmacol
2020Review
Behavioural and functional evidence revealing the role of RBFOX1 variation in multiple psychiatric disorders and traits.
O'Leary A et al.·Mol Psychiatry
2022Functional
Patient Brain Organoids Identify a Link between the 16p11.2 Copy Number Variant and the RBFOX1 Gene.
Kostic M et al.·ACS Chem Neurosci
2023
Variants in CALD1, ESRP1, and RBFOX1 are associated with orofacial cleft risk.
Carlson JC et al.·PLoS Genet
2025Meta-analysis
Association Between Common Variants in RBFOX1, an RNA-Binding Protein, and Brain Amyloidosis in Early and Preclinical Alzheimer Disease.
Raghavan NS et al.·JAMA Neurol
2020Meta-analysis
Orchestration of neurodevelopmental programs by RBFOX1: implications for autism spectrum disorder.
Bill BR et al.·Int Rev Neurobiol
2013Review
The Expression Characteristics of the RBFOX1 Gene in Colorectal Cancer.
Li J et al.·Technol Cancer Res Treat
2025
Genetic Alterations in a Large Population of Italian Patients Affected by Neurodevelopmental Disorders.
Ranieri A et al.·Genes (Basel)
2024Cohort
TCF4 and RBFOX1 as peripheral biomarkers for the differential diagnosis and treatment of major depressive disorder.
Xu K et al.·J Affect Disord
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