NXF1

Summary

NXF1 (nuclear RNA export factor 1, HGNC:8071) is a protein-coding gene on chromosome 11q12.3, encoding Nuclear RNA export factor 1 (Q9UBU9). Involved in the nuclear export of mRNA species bearing retroviral constitutive transport elements (CTE) and in the export of mRNA from the nucleus to the cytoplasm (TAP/NFX1 pathway). It is a common-essential gene (DepMap: required in 99.3% of cancer cell lines).

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.

Source: NCBI Gene 10482 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 62 total
• Druggable target: yes
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 1 cancer types
• Cancer dependency (DepMap): dependent in 99.3% of screened cell lines (common-essential)
• MANE Select transcript: NM_006362

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8071
Approved symbol	NXF1
Name	nuclear RNA export factor 1
Location	11q12.3
Locus type	gene with protein product
Status	Approved
Aliases	TAP, Mex67, DKFZp667O0311
Ensembl gene	ENSG00000162231
Ensembl biotype	protein_coding
OMIM	602647
Entrez	10482

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 14 protein_coding, 5 retained_intron, 3 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000294172, ENST00000525576, ENST00000526163, ENST00000527064, ENST00000527497, ENST00000527902, ENST00000530875, ENST00000531131, ENST00000531474, ENST00000531579, ENST00000531709, ENST00000531872, ENST00000532297, ENST00000533048, ENST00000533440, ENST00000533499, ENST00000533671, ENST00000884690, ENST00000884691, ENST00000884692, ENST00000940439, ENST00000940440, ENST00000970778

RefSeq mRNA: 2 — MANE Select: NM_006362 NM_001081491, NM_006362

CCDS: CCDS44629, CCDS8037

Canonical transcript exons

ENST00000294172 — 21 exons

Exon	Start	End
ENSE00001198195	62792130	62792514
ENSE00003471880	62797318	62797386
ENSE00003474199	62797183	62797238
ENSE00003513718	62796287	62796345
ENSE00003522640	62796066	62796181
ENSE00003594703	62795901	62795943
ENSE00003598445	62794258	62794440
ENSE00003605558	62805329	62805440
ENSE00003633788	62800377	62800486
ENSE00003638986	62796460	62796567
ENSE00003654610	62792641	62792701
ENSE00003655676	62802177	62802260
ENSE00003667837	62794935	62795007
ENSE00003705779	62801329	62801417
ENSE00003890207	62803792	62803978
ENSE00003890392	62801094	62801201
ENSE00003890680	62803419	62803572
ENSE00003891006	62801562	62801631
ENSE00003893062	62798539	62798575
ENSE00003893556	62801942	62802046
ENSE00003895300	62801739	62801819

Expression profiles

Bgee: expression breadth ubiquitous, 144 present calls, max score 98.76.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 64.8666 / max 1781.5722, expressed in 1825 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
120238	64.2555	1825
120235	0.2998	132
120237	0.2190	82
120236	0.0807	24
120239	0.0117	4

Top tissues by expression

145 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	98.76	gold quality
adenohypophysis	UBERON:0002196	98.73	gold quality
pituitary gland	UBERON:0000007	98.72	gold quality
spleen	UBERON:0002106	98.30	gold quality
left lobe of thyroid gland	UBERON:0001120	98.28	gold quality
right lobe of thyroid gland	UBERON:0001119	98.20	gold quality
thyroid gland	UBERON:0002046	98.18	gold quality
skin of abdomen	UBERON:0001416	98.08	gold quality
zone of skin	UBERON:0000014	97.96	gold quality
prostate gland	UBERON:0002367	97.93	gold quality
skin of leg	UBERON:0001511	97.90	gold quality
muscle layer of sigmoid colon	UBERON:0035805	97.85	gold quality
right ovary	UBERON:0002118	97.81	gold quality
left uterine tube	UBERON:0001303	97.78	gold quality
monocyte	CL:0000576	97.77	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	97.77	gold quality
bone marrow	UBERON:0002371	97.76	gold quality
bone element	UBERON:0001474	97.75	gold quality
mucosa of stomach	UBERON:0001199	97.72	gold quality
endocervix	UBERON:0000458	97.68	gold quality
lower esophagus mucosa	UBERON:0035834	97.64	gold quality
leukocyte	CL:0000738	97.63	gold quality
body of uterus	UBERON:0009853	97.62	gold quality
left ovary	UBERON:0002119	97.61	gold quality
lower esophagus muscularis layer	UBERON:0035833	97.61	gold quality
lower esophagus	UBERON:0013473	97.60	gold quality
metanephros cortex	UBERON:0010533	97.44	gold quality
ovary	UBERON:0000992	97.42	gold quality
popliteal artery	UBERON:0002250	97.42	gold quality
tibial artery	UBERON:0007610	97.42	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-6058	no	298.60
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

55 targeting NXF1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488
HSA-MIR-548I	99.94	71.25	3481
HSA-MIR-548J-5P	99.94	71.14	3489
HSA-MIR-548O-5P	99.94	71.24	3488
HSA-MIR-548W	99.94	71.24	3488
HSA-MIR-548Y	99.94	71.28	3514
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.3% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 40)

• The structural and mutational data define a novel RNA-binding site on the Tap protein (PMID:11854490)
• Structure of the C-terminal FG-nucleoporin binding domain of Tap/NXF1 (PMID:11875519)
• Karyopherin beta2B is a nuclear export factor and mediates mRNA export in cooperation with TAP (PMID:12384575)
• structural basis for interaction of UBA domain and FG nucleoporins (PMID:12581645)
• nuclear export sequences regulate human TAP function in mRNA export by direct nuclear pore interactions (PMID:14963046)
• hypophosphorylation of ASF in mRNPs coincides with its higher affinity for TAP (PMID:15184380)
• SR proteins 9G8 and ASF/SF2 exhibit higher affinity for TAP/NXF1 when hypophosphorylated (PMID:15210956)
• concluded that herpes simplex virus type 1 ICP27 and the viral RNAs to which it binds are exported via the TAP/NXF1 export receptor. (PMID:15767397)
• results indicate that Tap regulates expression of its own intron-containing RNA through a CTE (constitutive transport element)-mediated mechanism (PMID:16971948)
• RNA transport element RTE evolved as a high affinity RBM15 ligand to provide a splicing-independent link to NXF1, thereby ensuring efficient nuclear export and expression of retrotransposon transcripts (PMID:17001072)
• evidence presented that the export factor TAP/NXF1 binds poorly to XIST RNA in comparison to exported mRNAs, suggesting that reduced TAP/NFX1 binding may contribute to nuclear retention of XIST RNA (PMID:17333237)
• ORF57 interacts with the cellular export factor REF and with RNA, suggesting that it may provide target mRNAs with access to REF, which mediates nuclear RNA export by binding to TAP/NXF1. (PMID:17609285)
• Homotypic Tap complex can interact with both Nxt1 and nucleoporins in vitro. (PMID:17978099)
• oligomerization of Tap affects its interactions with nucleoporins (PMID:17978099)
• The efficiency and stability of the approach are demonstrated by reconstructing the structure of a two domain region of the 31 kDa nuclear export factor TAP (TIP-associated protein). (PMID:18670889)
• ICP27 is the major export adaptor for HSV-1 mRNA and that it links bound transcripts to the TAP/NXF1 export receptor (PMID:19019956)
• TAP/NXF1, but not Aly/REF, is required for RNA export during HSV-1 infection. (PMID:19369354)
• The RNA-binding motif protein 15B (RBM15B/OTT3) acts as cofactor of the nuclear export receptor NXF1. (PMID:19586903)
• Varicella-zoster virus IE4 protein interacts with SR proteins and exports mRNAs through the TAP/NXF1 pathway (PMID:19924249)
• Results describe the subcellular localization of ICP27 and its colocalization with cellular RNA export factors Aly/REF and TAP/NXF1. (PMID:20015986)
• Depletion of NXF1 or 5,6-dichloro-1-beta-d-ribofuranosyl-benzimidazole treatment had similar effects, inhibiting the nuclear export of several of the H5N1 influenza virus mRNAs. (PMID:20071484)
• These results showed that the interaction between herpes simplex virus type 1 ICP27 and human TAP/NXF1 occurred in living cells upon head-to-tail intramolecular association of ICP27. (PMID:21060739)
• these data revealed a redox-regulated chaperone function of PDI in delivering antigenic peptides from TAP to MHC-I. (PMID:21299467)
• Tpr plays an important role in quality control of mRNA trafficked on the Nxf1 pathway. (PMID:21613532)
• The U2AF65 protein served as an adaptor to link expanded CAG RNA to NXF1 for RNA export. (PMID:21725067)
• The crystal structure of the RNA recognition and leucine-rich repeat motifs of TAP bound to one symmetrical half of the CTE RNA is solved. (PMID:21822283)
• the organization of the NXF1 proline-tyrosine nuclear localization signal reveal unexpected redundancy in the nuclear import pathways used by NXF1. (PMID:21965294)
• TREX is the major complex used to recruit Nxf1 to mRNA in human cells. (PMID:22893130)
• a spatial map is produced in living cells of the sites for the interaction of two TREX subunits, Alyref and Chtop, with Nxf1. (PMID:23826332)
• Gag polyprotein synthesis was decreased by NXF1 knockdown. (PMID:25212909)
• Hepatitis B virus core protein associates with the cellular NXF1-p15 complex via the nuclear export signal motif of hepatitis B virus core protein.Nuclear export of human hepatitis B virus core protein and pregenomic RNA depends on the NXF1-p15 machinery. (PMID:25360769)
• Complementary structural, biochemical and cellular techniques indicated that the formation of a symmetric RNA binding platform generated by dimerization of NXF1:NXT1 facilitates the recognition of CTE-RNA and promotes its nuclear export (PMID:25628361)
• small hairpin RNA-mediated down-regulation of TAP or Aly reduced nuclear export of HDAg-L and assembly of HDV virions. Furthermore, a peptide, TAT-HDAg-L(198-210), containing the 10-amino acid TAT peptide and HDAg-L(198-210), inhibited the interaction between HDAg-L and TAP and blocked HDV virion assembly and secretion. (PMID:27807029)
• Gain or loss-of-function experiments revealed NXF1 selectively regulates TLR7-driven IRF5 transcriptional activity, suggesting a new role for NXF1 in the IRF5 signaling pathway. (PMID:28578407)
• repeat RNA-sequestration of SRSF1 triggers the NXF1-dependent nuclear export of C9ORF72 transcripts retaining expanded hexanucleotide repeats (PMID:28677678)
• NXF1 is involved in coordinating transcriptional dynamics, 3’ end processing, and nuclear export of long 3’ UTR transcripts, implicating NXF1 as a nexus of gene regulation. (PMID:30819645)
• Using iCLIP, we show that the export receptor Nxf1 and two TREX subunits, Alyref and Chtop, are recruited to the whole mRNA co-transcriptionally via splicing but before 3’ end processing. (PMID:31104896)
• The Ebola Virus Nucleoprotein Recruits the Nuclear RNA Export Factor NXF1 into Inclusion Bodies to Facilitate Viral Protein Expression. (PMID:31940815)
• Association between TAP gene polymorphisms and tuberculosis susceptibility in a Han Chinese population in Guangdong. (PMID:35325275)
• HnRNPA2B1 ISGylation Regulates m6A-Tagged mRNA Selective Export via ALYREF/NXF1 Complex to Foster Breast Cancer Development. (PMID:38626369)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	nxf1b	ENSDARG00000055076
danio_rerio	nxf1a	ENSDARG00000086017
mus_musculus	Nxf1	ENSMUSG00000010097
rattus_norvegicus	Nxf1	ENSRNOG00000019069
drosophila_melanogaster	nxf4	FBGN0051501
caenorhabditis_elegans		WBGENE00003834
caenorhabditis_elegans		WBGENE00003835

Paralogs (3): NXF3 (ENSG00000147206), NXF2 (ENSG00000269405), NXF2B (ENSG00000269437)

Protein

Protein identifiers

Nuclear RNA export factor 1 — Q9UBU9 (reviewed: Q9UBU9)

Alternative names: Tip-associated protein, Tip-associating protein, mRNA export factor TAP

All UniProt accessions (7): Q9UBU9, B4E227, E9PIN3, E9PLA7, E9PMV7, E9PQA4, H0YDU0

UniProt curated annotations — full annotation on UniProt →

Function. Involved in the nuclear export of mRNA species bearing retroviral constitutive transport elements (CTE) and in the export of mRNA from the nucleus to the cytoplasm (TAP/NFX1 pathway). The NXF1-NXT1 heterodimer is involved in the export of HSP70 mRNA in conjunction with ALYREF/THOC4 and THOC5 components of the TREX complex. ALYREF/THOC4-bound mRNA is thought to be transferred to the NXF1-NXT1 heterodimer for export. Also involved in nuclear export of m6A-containing mRNAs: interaction between SRSF3 and YTHDC1 facilitates m6A-containing mRNA-binding to both SRSF3 and NXF1, promoting mRNA nuclear export.

Subunit / interactions. Heterodimer (via NTF2 domain) with NXT1. The formation of NXF1-NXT1 heterodimers is required for the NXF1-mediated nuclear mRNA export. Forms a complex with RANBP2/NUP358, NXT1 and RANGAP1. Associates with the exon junction complex (EJC) and with the transcription/export (TREX) complex. Found in a mRNA complex with UPF3A and UPF3B. Found in a post-splicing complex with RBM8A, UPF1, UPF2, UPF3A, UPF3B and RNPS1. Interacts (via N-terminus) with DHX9 (via N-terminus); this interaction is direct and negatively regulates NXF1-mediated nuclear export of constitutive transport element (CTE)-containing cellular mRNAs. Interacts with ALYREF/THOC4. Interacts with FYTTD1/UIF. Interacts with EIF4A3. Interacts with NUP42. Interacts with THOC5. Interacts with CHTOP. Interacts with FRG1 (via N-terminus). Interacts with LUZP4. Interacts with FMR1; the interaction occurs in a mRNA-dependent and polyribosomes-independent manner in the nucleus. Interacts with CPSF6 (via N-terminus); this interaction is direct. Interacts with RBM15. Interacts with RBM15B. Interacts with MCM3AP isoform GANP; this interaction is not mediated by RNA. Interacts with DDX3X (via C-terminus); this interaction may be partly involved in DDX3X nuclear export and in NXF1 localization to stress granules. Interacts with PABPC1/PABP1. (Microbial infection) Interacts with Saimiriine herpesvirus 2 TIP protein. (Microbial infection) Interacts with human herpes virus 1 (HHV-1) ICP27 protein; this interaction allows efficient export of HHV-1 early and late transcripts. (Microbial infection) Interacts (via RNA-binding domain) with Ebolavirus nucleoprotein; this interaction recruits NXF1 to the inclusion bodies were viral replication takes place, probably to export viral mRNA-NXF1 complexes from these sites. (Microbial infection) Interacts with Epstein Barr virus (EBV) mRNA export factor ICP27 homolog; this interaction plays a role in mRNA export.

Subcellular location. Nucleus. Nucleoplasm. Nucleus speckle. Nuclear pore complex. Nucleus envelope. Cytoplasm. Stress granule.

Tissue specificity. Expressed ubiquitously.

Domain organisation. The minimal CTE binding domain consists of an RNP-type RNA binding domain (RBD) and leucine-rich repeats. The nucleoporin binding domain consists of a NTF2 domain (also called NTF2-like domain) and a TAP-C domain (also called UBA-like domain). It has 2 nucleoporin-FG-repeats binding sites (one in the NTF2 and the other in the TAP-C domain) which contribute to nucleoporin association and act synergistically to export cellular mRNAs. The NTF2 domain is functional only in the presence of NXT1 and is essential for the export of mRNA from the nucleus. It inhibits RNA binding activity through an intramolecular interaction with the N-terminal RNA binding domain (RBD); the inhibition is removed by an association with the TREX complex, specifically involving ALYREF/THOC4 and THOC5. The TAP-C domain mediates direct interactions with nucleoporin-FG-repeats and is necessary and sufficient for localization of NXF1 to the nuclear rim. The conserved loop 594-NWD-596 of the TAP-C domain has a critical role in the interaction with nucleoporins. The leucine-rich repeats are essential for the export of mRNA from the nucleus. The RNA-binding domain is a non-canonical RNP-type domain.

Similarity. Belongs to the NXF family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9UBU9-1	1	yes
Q9UBU9-2	2

RefSeq proteins (2): NP_001074960, NP_006353* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001611	Leu-rich_rpt	Repeat
IPR002075	NTF2_dom	Domain
IPR005637	TAP_C_dom	Domain
IPR009060	UBA-like_sf	Homologous_superfamily
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR015245	Tap_RNA-bd	Domain
IPR018222	Nuclear_transport_factor_2_euk	Domain
IPR030217	NXF_fam	Family
IPR032675	LRR_dom_sf	Homologous_superfamily
IPR032710	NTF2-like_dom_sf	Homologous_superfamily
IPR035979	RBD_domain_sf	Homologous_superfamily
IPR057125	NXF1/2/3/5-like_LRR	Domain

Pfam: PF03943, PF09162, PF22602, PF24048

UniProt features (99 total): mutagenesis site 25, helix 24, strand 18, region of interest 5, modified residue 5, turn 5, repeat 4, domain 3, short sequence motif 2, compositionally biased region 2, splice variant 2, sequence conflict 2, initiator methionine 1, chain 1

Structure

Experimental structures (PDB)

15 structures.

PDB	Method	Resolution (Å)
1OAI	X-RAY DIFFRACTION	1
9I8A	X-RAY DIFFRACTION	1.5
1JKG	X-RAY DIFFRACTION	1.9
3RW6	X-RAY DIFFRACTION	2.3
2Z5K	X-RAY DIFFRACTION	2.6
1JN5	X-RAY DIFFRACTION	2.8
1FO1	X-RAY DIFFRACTION	2.9
2Z5M	X-RAY DIFFRACTION	3
3RW7	X-RAY DIFFRACTION	3
1FT8	X-RAY DIFFRACTION	3.15
4WYK	X-RAY DIFFRACTION	3.4
1KOH	X-RAY DIFFRACTION	3.8
1KOO	X-RAY DIFFRACTION	3.8
6E5U	X-RAY DIFFRACTION	3.8
1GO5	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UBU9-F1	79.63	0.57

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (5): 2, 9, 42, 42, 126

Mutagenesis-validated functional residues (25):

Position	Phenotype
71	greatly reduces rna binding and no effect on interaction with alyref/thoc4; when associated with a-78, a-81, a-82, a-89,
78	greatly reduces rna binding and no effect on interaction with alyref/thoc4; when associated with a-71, a-81, a-82, a-89,
81	greatly reduces rna binding and no effect on interaction with alyref/thoc4; when associated with a-71, a-78, a-82, a-89,
82	greatly reduces rna binding and no effect on interaction with alyref/thoc4; when associated with a-71, a-78, a-81, a-89,
89	greatly reduces rna binding and no effect on interaction with alyref/thoc4; when associated with a-71, a-78, a-81, a-82,
91	greatly reduces rna binding and no effect on interaction with alyref/thoc4; when associated with a-71, a-78, a-81, a-82,
97	greatly reduces rna binding and no effect on interaction with alyref/thoc4; when associated with a-71, a-78, a-81, a-82,
98	greatly reduces rna binding and no effect on interaction with alyref/thoc4; when associated with a-71, a-78, a-81, a-82,
100	greatly reduces rna binding and no effect on interaction with alyref/thoc4; when associated with a-71, a-78, a-81, a-82,
105	greatly reduces rna binding and no effect on interaction with alyref/thoc4; when associated with a-71, a-78, a-81, a-82,
306–308	decreases the export of mrnas from the nucleus.
383	diminishes nuclear rim staining and 80% reduction in mrna export activity; when associated with r-386. complete loss of
386	diminishes nuclear rim staining and 80% reduction in mrna export activity; when associated with r-383. complete loss of
399	60% reduction in mrna export activity.
450–453	abolishes interaction with thoc5 and chtop.
453	impairs intramolecular interaction between rbd and ntf2.
456–459	abolishes interaction with thoc5 and chtop, no effect on interaction with nxt1; enhances intramolecular interaction betw
456	impairs intramolecular interaction between rbd and ntf2; when associated with d-459.
459	impairs intramolecular interaction between rbd and ntf2; when associated with d-456.
482	90% reduction in mrna export activity.
518	98% reduction in mrna export activity.
521	35% reduction in mrna export activity.
594	suppresses fg-nucleoporin binding. diminishes nuclear rim staining and 88% reduction in mrna export activity. complete l
595	suppresses fg-nucleoporin binding.
617	suppresses fg-nucleoporin binding.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-159227	Transport of the SLBP independent Mature mRNA
R-HSA-159230	Transport of the SLBP Dependant Mature mRNA
R-HSA-159231	Transport of Mature mRNA Derived from an Intronless Transcript
R-HSA-159236	Transport of Mature mRNA derived from an Intron-Containing Transcript

MSigDB gene sets: 274 (showing top): AGGAAGC_MIR5163P, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, TGCGCANK_UNKNOWN, PEREZ_TP63_TARGETS, LFA1_Q6, ENK_UV_RESPONSE_KERATINOCYTE_UP, TTTGTAG_MIR520D, MORF_SNRP70, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, GOBP_NUCLEAR_TRANSPORT, REACTOME_PROCESSING_OF_CAPPED_INTRON_CONTAINING_PRE_MRNA, GOBP_NUCLEOBASE_CONTAINING_COMPOUND_TRANSPORT, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_UP, GARY_CD5_TARGETS_DN, DACOSTA_UV_RESPONSE_VIA_ERCC3_COMMON_UP

GO Biological Process (5): mRNA export from nucleus (GO:0006406), protein transport (GO:0015031), poly(A)+ mRNA export from nucleus (GO:0016973), RNA export from nucleus (GO:0006405), mRNA transport (GO:0051028)

GO Molecular Function (4): RNA binding (GO:0003723), mRNA binding (GO:0003729), nucleic acid binding (GO:0003676), protein binding (GO:0005515)

GO Cellular Component (11): nucleus (GO:0005634), nuclear pore (GO:0005643), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), cytoplasmic stress granule (GO:0010494), nuclear speck (GO:0016607), nuclear RNA export factor complex (GO:0042272), nuclear inclusion body (GO:0042405), transcription export complex (GO:0000346), nuclear envelope (GO:0005635)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Transport of Mature mRNAs Derived from Intronless Transcripts	3
Transport of Mature Transcript to Cytoplasm	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
nuclear protein-containing complex	3
cellular anatomical structure	3
RNA transport	2
binding	2
nucleus	2
RNA export from nucleus	1
gene expression	1
mRNA transport	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
mRNA export from nucleus	1
nuclear export	1
nucleic acid binding	1
RNA binding	1
intracellular membrane-bounded organelle	1
nuclear envelope	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1
cytoplasmic ribonucleoprotein granule	1
nuclear ribonucleoprotein granule	1
inclusion body	1
endomembrane system	1
organelle envelope	1

Protein interactions and networks

STRING

2482 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NXF1	NXT1	Q9UKK6	999
NXF1	SRSF3	P23152	989
NXF1	HNRNPUL1	Q9BUJ2	989
NXF1	ALYREF	Q86V81	988
NXF1	RAE1	P78406	964
NXF1	NUTF2	P13662	963
NXF1	FYTTD1	Q96QD9	960
NXF1	NUP98	P52948	951
NXF1	RBM15	Q96T37	926
NXF1	YTHDC1	Q96MU7	917
NXF1	SRSF1	Q07955	913
NXF1	NUP214	P35658	903
NXF1	DDX39B	Q13838	881
NXF1	SH2D3A	Q9BRG2	878
NXF1	TNPO2	O14787	868

IntAct

419 interactions, top by confidence:

A	B	Type	Score
NXF1	NXT1	psi-mi:“MI:0407”(direct interaction)	0.910
NXF1	NXT1	psi-mi:“MI:0915”(physical association)	0.910
NUP62	NXF1	psi-mi:“MI:0915”(physical association)	0.880
NXF1	NUP62	psi-mi:“MI:0915”(physical association)	0.880
NXF1	GFAP	psi-mi:“MI:0915”(physical association)	0.780
GFAP	NXF1	psi-mi:“MI:0915”(physical association)	0.780
TIFA	NXF1	psi-mi:“MI:0915”(physical association)	0.720
LDOC1	NXF1	psi-mi:“MI:0915”(physical association)	0.670
NXF1	LDOC1	psi-mi:“MI:0915”(physical association)	0.670
TP53BP2	NXF1	psi-mi:“MI:0915”(physical association)	0.560
KRT40	NXF1	psi-mi:“MI:0915”(physical association)	0.560
DVL3	NXF1	psi-mi:“MI:0915”(physical association)	0.560
NXF1	MID2	psi-mi:“MI:0915”(physical association)	0.560
NXF1	TP53BP2	psi-mi:“MI:0915”(physical association)	0.560
NXF1	KRT40	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (1591): NXF1 (Two-hybrid), NXF1 (Two-hybrid), NXF1 (Two-hybrid), MID2 (Two-hybrid), NUP62 (Two-hybrid), LDOC1 (Two-hybrid), TIFA (Two-hybrid), KRT40 (Two-hybrid), NOC2L (Affinity Capture-RNA), AGRN (Affinity Capture-RNA), PARK7 (Affinity Capture-RNA), PGD (Affinity Capture-RNA), DFFA (Affinity Capture-RNA), SRM (Affinity Capture-RNA), EXOSC10 (Affinity Capture-RNA)

ESM2 similar proteins: A6QLK2, A6QNT8, D3ZMY7, D4A055, F1QH17, O00305, O35431, O95486, O95487, P40692, P49902, P54288, P56223, P97679, Q01973, Q0VGM9, Q13330, Q16514, Q1RMS5, Q3SWT1, Q3T174, Q3U2P1, Q3UNW5, Q3V1L4, Q5EBF1, Q5PYH5, Q5RA22, Q5RB16, Q5RE34, Q5RJZ1, Q5ZIZ4, Q61187, Q62599, Q6AY57, Q6DKB0, Q6H1L8, Q6IRE4, Q7ZWU5, Q80W47, Q80YA3

Diamond homologs: O01615, O35381, O43423, O88984, O95626, P39687, P49911, P51122, P97822, Q28XE2, Q3SZC6, Q4P5F9, Q5BGW9, Q5F4A3, Q5XIE0, Q5ZMN0, Q64G17, Q6A1I3, Q6NUW5, Q6P1U7, Q6PAF6, Q6YSF3, Q7Y180, Q7ZUP0, Q7ZY40, Q86QS6, Q8AVC1, Q8HY67, Q8ILI6, Q92688, Q9BTT0, Q9EST5, Q9EST6, Q9SCQ7, Q9UBU9, Q9V4Q8, Q9V895, P58797, Q1RMS5, Q5R752

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
NXF1	“form complex”	RBM15/NXF1	binding
SRSF7	up-regulates	NXF1	binding
SRSF3	up-regulates	NXF1	binding
SUN1	“up-regulates activity”	NXF1	binding
“LINC complex”	“up-regulates activity”	NXF1	binding
NXF1	up-regulates	mRNA_nuclear_export

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 111 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Transport of Ribonucleoproteins into the Host Nucleus	9	52.6×	2e-11
IPs transport between nucleus and cytosol	8	49.9×	1e-10
IP3 and IP4 transport between cytosol and nucleus	8	49.9×	1e-10
IP6 and IP7 transport between cytosol and nucleus	8	49.9×	1e-10
Nuclear import of Rev protein	9	49.6×	2e-11
SUMOylation of SUMOylation proteins	9	48.1×	2e-11
Regulation of Glucokinase by Glucokinase Regulatory Protein	8	46.8×	1e-10
Defective TPR may confer susceptibility towards thyroid papillary carcinoma (TPC)	8	46.8×	1e-10

GO biological processes:

GO term	Partners	Fold	FDR
RNA export from nucleus	6	60.4×	3e-07
nucleocytoplasmic transport	7	29.5×	1e-06
mRNA export from nucleus	7	22.2×	6e-06
mitotic metaphase chromosome alignment	5	20.6×	5e-04
mRNA transport	5	14.2×	2e-03
protein import into nucleus	8	12.4×	4e-05

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 1 cancer types — CLLSLL.

Clinical variants and AI predictions

ClinVar

62 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	43
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2607 predictions. Top by Δscore:

Variant	Effect	Δscore
11:62792635:CCTTA:C	donor_loss	1.0000
11:62792637:TTA:T	donor_loss	1.0000
11:62792638:TA:T	donor_loss	1.0000
11:62792639:A:AC	donor_gain	1.0000
11:62792640:C:CC	donor_gain	1.0000
11:62792640:C:CG	donor_loss	1.0000
11:62792699:CAC:C	acceptor_gain	1.0000
11:62792700:AC:A	acceptor_gain	1.0000
11:62792701:CC:C	acceptor_gain	1.0000
11:62792701:CCT:C	acceptor_loss	1.0000
11:62792702:C:CC	acceptor_gain	1.0000
11:62792702:CTGG:C	acceptor_loss	1.0000
11:62792707:G:C	acceptor_gain	1.0000
11:62792707:G:GC	acceptor_gain	1.0000
11:62794931:TTACC:T	donor_loss	1.0000
11:62794933:A:AC	donor_gain	1.0000
11:62794933:AC:A	donor_gain	1.0000
11:62794933:ACC:A	donor_gain	1.0000
11:62794934:C:CT	donor_gain	1.0000
11:62794934:CC:C	donor_gain	1.0000
11:62794934:CCC:C	donor_gain	1.0000
11:62794934:CCCT:C	donor_gain	1.0000
11:62794934:CCCTG:C	donor_gain	1.0000
11:62795003:GTCCA:G	acceptor_gain	1.0000
11:62795004:TCCA:T	acceptor_gain	1.0000
11:62795005:CCA:C	acceptor_gain	1.0000
11:62795005:CCAC:C	acceptor_gain	1.0000
11:62795006:CA:C	acceptor_gain	1.0000
11:62795006:CAC:C	acceptor_gain	1.0000
11:62795007:ACT:A	acceptor_loss	1.0000

AlphaMissense

4074 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:62794268:A:G	W584R	1.000
11:62794268:A:T	W584R	1.000
11:62794279:A:G	M580T	1.000
11:62794968:C:G	R515P	1.000
11:62795921:A:T	V495D	1.000
11:62796312:T:A	R440S	1.000
11:62796312:T:G	R440S	1.000
11:62796313:C:G	R440T	1.000
11:62796518:A:C	Y410D	1.000
11:62792485:G:C	F617L	0.999
11:62792485:G:T	F617L	0.999
11:62792487:A:G	F617L	0.999
11:62792653:G:C	F603L	0.999
11:62792653:G:T	F603L	0.999
11:62792654:A:G	F603S	0.999
11:62792655:A:G	F603L	0.999
11:62792680:C:A	W594C	0.999
11:62792680:C:G	W594C	0.999
11:62792682:A:G	W594R	0.999
11:62792682:A:T	W594R	0.999
11:62792696:A:G	L589P	0.999
11:62792696:A:T	L589H	0.999
11:62794264:G:A	S585F	0.999
11:62794265:A:G	S585P	0.999
11:62794266:C:A	W584C	0.999
11:62794266:C:G	W584C	0.999
11:62794278:C:A	M580I	0.999
11:62794278:C:G	M580I	0.999
11:62794278:C:T	M580I	0.999
11:62794417:A:G	L534P	0.999

dbSNP variants (sampled 300 via entrez): RS1000180993 (11:62803324 A>T), RS1000409694 (11:62796672 C>G,T), RS1000637750 (11:62803879 C>A,T), RS1000854383 (11:62805418 TC>T), RS1001530986 (11:62797612 G>A), RS1001981734 (11:62797854 G>A,C), RS1002050427 (11:62799760 G>A), RS1002582832 (11:62799253 A>C,G), RS1002665055 (11:62804915 G>A,C,T), RS1002808637 (11:62792751 C>A,G), RS1003005924 (11:62805501 C>A,G,T), RS1003030280 (11:62798833 G>C), RS1003621209 (11:62797614 G>C,T), RS1003667214 (11:62803253 C>A), RS1003812058 (11:62794149 C>A,T)

Disease associations

OMIM: gene MIM:602647 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST005956_2	Waist-to-hip ratio adjusted for BMI	1.000000e-08
GCST005962_51	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	1.000000e-07

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067072 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.74	Kd	18.33	nM	CHEMBL5653589
7.71	ED50	19.74	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148909: Binding affinity to human NXF1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0183	uM

CTD chemical–gene interactions

74 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, increases abundance, increases expression, decreases expression	3
(+)-JQ1 compound	increases expression	2
Air Pollutants	affects cotreatment, decreases expression, increases abundance, affects expression	2
Arsenic	affects cotreatment, increases abundance, increases expression, decreases expression	2
Cisplatin	decreases expression, increases expression	2
Ozone	affects expression, affects cotreatment, decreases expression, increases abundance	2
Tobacco Smoke Pollution	increases expression	2
Valproic Acid	affects expression, increases expression	2
Cadmium Chloride	increases expression	2
aristolochic acid I	increases expression	1
FR900359	decreases phosphorylation	1
bisphenol F	affects cotreatment, decreases expression	1
TAK-243	increases sumoylation	1
dicrotophos	increases expression	1
2,4,6-tribromophenol	decreases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
bisphenol A	affects cotreatment, increases methylation, decreases methylation	1
nobiletin	decreases expression, decreases reaction	1
sodium arsenate	decreases expression, decreases reaction	1
2-methyl-4-isothiazolin-3-one	increases expression	1
trichostatin A	affects expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
potassium chromate(VI)	affects cotreatment, increases expression	1
versicolorin A	increases expression	1
methacrylaldehyde	increases abundance, affects cotreatment, decreases expression	1
epigallocatechin gallate	affects cotreatment, increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651951	Binding	Binding affinity to human NXF1 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.