NXF1

Chr 11

nuclear RNA export factor 1

Also known as: MEX67, TAP

NCBI Gene: 10482ENSG00000162231UniProt: Q9UBU9

This gene is one member of a family of nuclear RNA export factor genes. Common domain features of this family are a noncanonical RNP-type RNA-binding domain (RBD), 4 leucine-rich repeats (LRRs), a nuclear transport factor 2 (NTF2)-like domain that allows heterodimerization with NTF2-related export protein-1 (NXT1), and a ubiquitin-associated domain that mediates interactions with nucleoporins. The LRRs and NTF2-like domains are required for export activity. Alternative splicing seems to be a common mechanism in this gene family. The encoded protein of this gene shuttles between the nucleus and the cytoplasm and binds in vivo to poly(A)+ RNA. It is the vertebrate homologue of the yeast protein Mex67p. The encoded protein overcomes the mRNA export block caused by the presence of saturating amounts of CTE (constitutive transport element) RNA of type D retroviruses. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2008]

63
ClinVar variants
11
Pathogenic / LP
0.98
pLI score· haploinsufficient
0
Active trials
Clinical Summary— NXF1
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.98). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
11 Pathogenic / Likely Pathogenic· 47 VUS of 63 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.
0.31LOEUF
pLI 0.976
Z-score 5.03
OE 0.17 (0.09–0.31)
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.
2.66Z-score
OE missense 0.61 (0.55–0.69)
231 obs / 376.0 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.0.17 (0.09–0.31)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.61 (0.55–0.69)
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.0.93
0≤1.21.6
LoF obs/exp: 7 / 42.4Missense obs/exp: 231 / 376.0Syn Z: 0.66

ClinVar Variant Classifications

63 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic8
Likely Pathogenic3
VUS47
Likely Benign5
8
Pathogenic
3
Likely Pathogenic
47
VUS
5
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
8
0
8
Likely Pathogenic
0
0
3
0
3
VUS
0
42
5
0
47
Likely Benign
0
3
1
1
5
Benign
0
0
0
0
0
Total04517163

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

View in ClinVar →

Protein Context — Lollipop Plot

NXF1 · 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
The FANCI/FANCD2 complex links DNA damage response to R-loop regulation through SRSF1-mediated mRNA export.
Olazabal-Herrero A et al.·Cell Rep
2024
mRNA export factors store nascent transcripts within nuclear speckles as an adaptive response to transient global inhibition of transcription.
Williams TD et al.·Mol Cell
2025
mRNA export and cancer.
Siddiqui N et al.·Wiley Interdiscip Rev RNA
2012Review
Evidence for Viral mRNA Export from Ebola Virus Inclusion Bodies by the Nuclear RNA Export Factor NXF1.
Wendt L et al.·J Virol
2022
Multipotent genetic suppression of retrotransposon-induced mutations by Nxf1 through fine-tuning of alternative splicing.
Concepcion D et al.·PLoS Genet
2009
Nuclear RNA transcript levels modulate nucleocytoplasmic distribution of ALS/FTD-associated protein FUS.
Tsai YL et al.·Sci Rep
2022
Drug repositioning for pan-cancers of the digestive system: Identification of amonafide and BX795 as potential therapeutics via integrative Omics analysis.
Liu W et al.·PLoS One
2025
Network centrality-driven TOPSIS approach for prioritizing cancer therapeutic targets.
Nithya C et al.·Comput Biol Chem
2026
A Quantitative Analysis of Subclonal and Clonal Gene Mutations before and after Therapy in Chronic Lymphocytic Leukemia.
Amin NA et al.·Clin Cancer Res
2016
NTF2-like domain of Tap plays a critical role in cargo mRNA recognition and export.
Katahira J et al.·Nucleic Acids Res
2015
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