NXT1

Summary

NXT1 (nuclear transport factor 2 like export factor 1, HGNC:15913) is a protein-coding gene on chromosome 20p11.21, encoding NTF2-related export protein 1 (Q9UKK6). Stimulator of protein export for NES-containing proteins. It is a selective cancer dependency (DepMap: 43.7% of cell lines).

The protein encoded by this gene is located in the nuclear envelope. It has protein similarity to nuclear transport factor 2. This protein functions as a nuclear export factor in both RAN (Ras-related nuclear protein)- and CRM1 (required for chromosome region maintenance)-dependent pathways. It is found to stimulate the export of U1 snRNA in RAN- and CRM1-dependent pathways and the export of tRNA and mRNA in a CRM1-independent pathway. The encoded protein heterodimerizes with Tap protein and may regulate the ability of Tap protein to mediate nuclear mRNA export. The use of alternate polyadenylation sites has been found for this gene.

Source: NCBI Gene 29107 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 14 total — 1 pathogenic
• Cancer dependency (DepMap): dependent in 43.7% of screened cell lines
• MANE Select transcript: NM_013248

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15913
Approved symbol	NXT1
Name	nuclear transport factor 2 like export factor 1
Location	20p11.21
Locus type	gene with protein product
Status	Approved
Aliases	P15, MTR2
Ensembl gene	ENSG00000132661
Ensembl biotype	protein_coding
OMIM	605811
Entrez	29107

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000254998, ENST00000927872, ENST00000961861

RefSeq mRNA: 1 — MANE Select: NM_013248 NM_013248

CCDS: CCDS13150

Canonical transcript exons

ENST00000254998 — 2 exons

Exon	Start	End
ENSE00000906836	23353981	23354771
ENSE00001025742	23350791	23351061

Expression profiles

Bgee: expression breadth ubiquitous, 249 present calls, max score 90.47.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 22.7011 / max 270.9068, expressed in 1805 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
183856	19.9047	1795
183857	2.5791	849
183858	0.2174	79

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left uterine tube	UBERON:0001303	90.47	gold quality
popliteal artery	UBERON:0002250	88.58	gold quality
tibial artery	UBERON:0007610	88.57	gold quality
aorta	UBERON:0000947	87.82	gold quality
mucosa of urinary bladder	UBERON:0001259	87.77	silver quality
omental fat pad	UBERON:0010414	87.75	gold quality
peritoneum	UBERON:0002358	87.73	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	87.47	gold quality
ascending aorta	UBERON:0001496	87.06	gold quality
adipose tissue of abdominal region	UBERON:0007808	86.96	gold quality
thoracic aorta	UBERON:0001515	86.91	gold quality
left ovary	UBERON:0002119	86.83	gold quality
granulocyte	CL:0000094	86.66	gold quality
cartilage tissue	UBERON:0002418	86.57	gold quality
skin of abdomen	UBERON:0001416	86.33	gold quality
ectocervix	UBERON:0012249	86.24	gold quality
right ovary	UBERON:0002118	86.17	gold quality
left coronary artery	UBERON:0001626	86.07	gold quality
endocervix	UBERON:0000458	85.98	gold quality
lower esophagus mucosa	UBERON:0035834	85.97	gold quality
ovary	UBERON:0000992	85.83	gold quality
periodontal ligament	UBERON:0008266	85.80	gold quality
islet of Langerhans	UBERON:0000006	85.76	gold quality
coronary artery	UBERON:0001621	85.73	gold quality
vena cava	UBERON:0004087	85.70	gold quality
gingival epithelium	UBERON:0001949	85.67	gold quality
embryo	UBERON:0000922	85.66	gold quality
ventricular zone	UBERON:0003053	85.62	gold quality
esophagus mucosa	UBERON:0002469	85.45	gold quality
ganglionic eminence	UBERON:0004023	85.37	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.83
E-CURD-112	yes	4.47
E-CURD-97	no	432.37

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F4, MYC

miRNA regulators (miRDB)

22 targeting NXT1, 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-126-5P	100.00	72.71	3180
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-425-5P	99.59	67.67	900
HSA-MIR-5697	99.39	67.74	1249
HSA-MIR-223-5P	99.24	68.82	1206
HSA-MIR-4326	98.97	67.63	962
HSA-MIR-4656	98.79	66.22	1306
HSA-MIR-519A-2-5P	98.78	71.74	1401
HSA-MIR-520B-5P	98.78	71.74	1401
HSA-MIR-3187-5P	98.36	65.74	1776
HSA-MIR-4684-5P	98.29	67.99	1650
HSA-MIR-10226	98.25	66.50	811
HSA-MIR-506-5P	98.02	67.41	1065
HSA-MIR-4446-3P	97.91	64.29	991
HSA-MIR-4294	97.86	65.72	1110
HSA-MIR-1285-3P	97.72	67.02	1932
HSA-MIR-5189-5P	97.72	66.96	1814
HSA-MIR-612	97.26	65.95	1597
HSA-MIR-6860	97.21	66.31	1656

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 43.7% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 2)

• 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)
• Here, the authors identify cellular nuclear transport factor 2 (NTF2)-like export protein 1 (NXT1) as a novel binding partner of nucleoprotein (NP) that stimulates NP-mediated nuclear export via the CRM1-dependent pathway. (PMID:27483302)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Nxt1	ENSMUSG00000036992
rattus_norvegicus	Nxt1	ENSRNOG00000004700
drosophila_melanogaster	Nxt1	FBGN0028411
caenorhabditis_elegans	nxt-1	WBGENE00003836

Paralogs (2): NXT2 (ENSG00000101888), NUTF2 (ENSG00000102898)

Protein

Protein identifiers

NTF2-related export protein 1 — Q9UKK6 (reviewed: Q9UKK6)

Alternative names: Protein p15

All UniProt accessions (1): Q9UKK6

UniProt curated annotations — full annotation on UniProt →

Function. Stimulator of protein export for NES-containing proteins. Also plays a role in the nuclear export of U1 snRNA, tRNA, and mRNA. The NXF1-NXT1 heterodimer is involved in the export of HSP70 mRNA in conjunction with ALYREF/THOC4 and THOC5.

Subunit / interactions. Heterodimer with NXF1. Forms a complex with RANGAP1, RANBP2/NUP358 and NXF1. Interacts (via NTF2 domain) with NXF1. Stabilizes the NTF2 domain of NXF1 by heterodimerization. The formation of NXF1-NXT1 heterodimers is required for the NXF1-mediated nuclear mRNA export. Preferentially binds Ran-GTP. Associates with NXF2, NXF3 and NXF5. Does not bind nucleoporins (NPC) directly, its association to NPC is mediated by NXF1.

Subcellular location. Nucleus. Nucleus speckle. Cytoplasm.

RefSeq proteins (1): NP_037380* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002075	NTF2_dom	Domain
IPR018222	Nuclear_transport_factor_2_euk	Domain
IPR032710	NTF2-like_dom_sf	Homologous_superfamily
IPR045875	NTF2	Family

Pfam: PF02136

UniProt features (18 total): strand 7, helix 3, turn 2, mutagenesis site 2, initiator methionine 1, chain 1, domain 1, modified residue 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
9I8A	X-RAY DIFFRACTION	1.5
1JKG	X-RAY DIFFRACTION	1.9
1JN5	X-RAY DIFFRACTION	2.8
4WYK	X-RAY DIFFRACTION	3.4
6E5U	X-RAY DIFFRACTION	3.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UKK6-F1	94.40	0.88

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 (1): 2

Mutagenesis-validated functional residues (2):

Position	Phenotype
114	70% reduction in mrna export activity.
134	57% reduction in mrna export activity and loss of nuclear rim staining.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-159236	Transport of Mature mRNA derived from an Intron-Containing Transcript

MSigDB gene sets: 168 (showing top): GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOMF_GTPASE_BINDING, GOBP_NUCLEAR_TRANSPORT, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_1, REACTOME_PROCESSING_OF_CAPPED_INTRON_CONTAINING_PRE_MRNA, GOBP_NUCLEOBASE_CONTAINING_COMPOUND_TRANSPORT, DODD_NASOPHARYNGEAL_CARCINOMA_UP, FISCHER_DREAM_TARGETS, SA_G1_AND_S_PHASES, GOBP_NUCLEAR_EXPORT, GRYDER_PAX3FOXO1_ENHANCERS_IN_TADS, DANG_BOUND_BY_MYC, GOBP_RNA_LOCALIZATION

GO Biological Process (6): mRNA export from nucleus (GO:0006406), protein export from nucleus (GO:0006611), poly(A)+ mRNA export from nucleus (GO:0016973), RNA export from nucleus (GO:0006405), nucleocytoplasmic transport (GO:0006913), protein transport (GO:0015031)

GO Molecular Function (2): small GTPase binding (GO:0031267), protein binding (GO:0005515)

GO Cellular Component (8): nucleus (GO:0005634), nuclear pore (GO:0005643), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), nuclear speck (GO:0016607), nuclear RNA export factor complex (GO:0042272), nuclear pore central transport channel (GO:0044613)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
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
nuclear export	2
RNA export from nucleus	1
gene expression	1
mRNA transport	1
intracellular protein transport	1
mRNA export from nucleus	1
RNA transport	1
nuclear transport	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
GTPase binding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear envelope	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1
nuclear ribonucleoprotein granule	1
nuclear pore	1

Protein interactions and networks

STRING

992 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NXT1	NXF1	Q9UBU9	999
NXT1	NXF2B	Q9GZY0	987
NXT1	NXF3	Q9H4D5	983
NXT1	NUTF2	P13662	967
NXT1	HNRNPUL1	Q9BUJ2	895
NXT1	NXF5	Q9H1B4	888
NXT1	NUP214	P35658	870
NXT1	NUP62	P37198	866
NXT1	ALYREF	Q86V81	866
NXT1	NUP98	P52948	837
NXT1	XPO1	O14980	795
NXT1	THOC5	Q13769	792
NXT1	FYTTD1	Q96QD9	789
NXT1	NUP153	P49790	787
NXT1	RAE1	P78406	770

IntAct

69 interactions, top by confidence:

A	B	Type	Score
NXF3	NXT1	psi-mi:“MI:0915”(physical association)	0.950
NXT1	NXF3	psi-mi:“MI:0915”(physical association)	0.950
NXF1	NXT1	psi-mi:“MI:0407”(direct interaction)	0.910
NXF1	NXT1	psi-mi:“MI:0915”(physical association)	0.910
NXT1	NXF1	psi-mi:“MI:0915”(physical association)	0.910
DDX6	EDC4	psi-mi:“MI:0914”(association)	0.820
NXF1	NXT2	psi-mi:“MI:0914”(association)	0.790
STAU1	NXT1	psi-mi:“MI:0915”(physical association)	0.720
NXT1	STAU1	psi-mi:“MI:0915”(physical association)	0.720
NXF2B	NXT1	psi-mi:“MI:0915”(physical association)	0.670
CHTOP	NXF1	psi-mi:“MI:0914”(association)	0.650
BZW2	ENDOD1	psi-mi:“MI:0914”(association)	0.640
NXT1	PAXIP1	psi-mi:“MI:0915”(physical association)	0.560
PAXIP1	NXT1	psi-mi:“MI:0915”(physical association)	0.560
FBXO16	NXT1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (56): NXT1 (Two-hybrid), NXT1 (Two-hybrid), NXF3 (Two-hybrid), NXF3 (Two-hybrid), NXT1 (Two-hybrid), NXT1 (Co-fractionation), NXT1 (Affinity Capture-MS), NXT1 (Affinity Capture-MS), NXT1 (Affinity Capture-MS), NXT1 (Affinity Capture-MS), NXT1 (Affinity Capture-MS), NXT1 (Affinity Capture-MS), NXT1 (Affinity Capture-MS), NXT1 (Two-hybrid), NXF3 (Two-hybrid)

ESM2 similar proteins: A6QNX3, B2GV77, P09851, P20936, P50904, P61970, P61971, P61972, Q1JP79, Q29425, Q2KI42, Q2KIW0, Q2TBL9, Q32KP9, Q3UNA4, Q4R4K5, Q4R5H6, Q5E9J4, Q5F415, Q5FVJ7, Q5R8G4, Q5R8I6, Q5RB36, Q5RES2, Q5RKN4, Q5ZLH0, Q6PC62, Q8BG32, Q8BUH1, Q8IUI8, Q8K0F1, Q8MJJ1, Q92747, Q93034, Q99PD4, Q9CQC8, Q9CZQ9, Q9D5V5, Q9DAI2, Q9ES56

Diamond homologs: A6QNX3, B2GV77, Q2KIW0, Q3UNA4, Q5ZLH0, Q9NPJ8, Q9QZV9, Q9UKK6, Q9V3H8, Q9U757, Q9XJ54, Q10100, Q9C7F5, Q9FZK4, Q6FRC6, Q75AA5

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
NXT1	“form complex”	“NXF2-NXT1 mRNA nuclear export factor complex”	binding
NXT1	“form complex”	“NXF5-NXT1 mRNA nuclear export factor complex”	binding
NXT1	“form complex”	“NXF3-NXT1 mRNA nuclear export factor complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 36 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 the SLBP independent Mature mRNA	6	85.1×	3e-09
Transport of the SLBP Dependant Mature mRNA	6	82.8×	3e-09
Transport of Mature mRNA derived from an Intron-Containing Transcript	11	72.8×	7e-17
Transport of Mature mRNA Derived from an Intronless Transcript	6	70.9×	5e-09

GO biological processes:

GO term	Partners	Fold	FDR
poly(A)+ mRNA export from nucleus	5	108.7×	5e-08
mRNA export from nucleus	11	104.9×	3e-18

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	11
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
442830	GRCh37/hg19 20p11.23-11.1(chr20:18500917-25847320)x1	Pathogenic

SpliceAI

548 predictions. Top by Δscore:

Variant	Effect	Δscore
20:23351059:CAGGT:C	donor_loss	0.9900
20:23351060:AGG:A	donor_loss	0.9900
20:23351061:GGTA:G	donor_loss	0.9900
20:23351062:G:T	donor_loss	0.9900
20:23351063:T:G	donor_loss	0.9900
20:23353969:A:AG	acceptor_gain	0.9900
20:23353970:C:G	acceptor_gain	0.9900
20:23353979:A:AG	acceptor_gain	0.9900
20:23353980:G:GG	acceptor_gain	0.9900
20:23353980:GC:G	acceptor_gain	0.9900
20:23353980:GCCCC:G	acceptor_gain	0.9900
20:23353980:GCC:G	acceptor_gain	0.9800
20:23353980:GCCC:G	acceptor_gain	0.9800
20:23350845:A:T	donor_gain	0.9700
20:23350878:GA:G	donor_gain	0.9700
20:23352447:GTTA:G	donor_gain	0.9700
20:23352448:TTAT:T	donor_gain	0.9700
20:23352450:A:AG	donor_gain	0.9700
20:23353976:T:TA	acceptor_gain	0.9700
20:23353976:TGCAG:T	acceptor_gain	0.9700
20:23353977:GCA:G	acceptor_loss	0.9700
20:23353978:CA:C	acceptor_loss	0.9700
20:23353979:A:AC	acceptor_loss	0.9700
20:23351062:G:GG	donor_gain	0.9600
20:23352450:A:G	donor_gain	0.9600
20:23352482:A:T	donor_gain	0.9600
20:23353247:AT:A	donor_gain	0.9500
20:23353977:GCAGC:G	acceptor_gain	0.9500
20:23353978:CAGCC:C	acceptor_gain	0.9500
20:23350880:G:GG	donor_gain	0.9400

AlphaMissense

927 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:23354180:T:A	W47R	0.999
20:23354180:T:C	W47R	0.999
20:23354187:G:A	G49D	0.999
20:23354187:G:T	G49V	0.999
20:23354243:A:C	S68R	0.999
20:23354245:C:A	S68R	0.999
20:23354245:C:G	S68R	0.999
20:23354331:G:A	G97E	0.999
20:23354373:A:C	Q111P	0.999
20:23354417:T:A	W126R	0.999
20:23354417:T:C	W126R	0.999
20:23354442:G:C	R134P	0.999
20:23354099:T:C	F20L	0.998
20:23354101:T:A	F20L	0.998
20:23354101:T:G	F20L	0.998
20:23354175:T:C	L45P	0.998
20:23354181:G:C	W47S	0.998
20:23354182:G:C	W47C	0.998
20:23354182:G:T	W47C	0.998
20:23354184:A:T	N48I	0.998
20:23354186:G:C	G49R	0.998
20:23354186:G:T	G49C	0.998
20:23354249:T:C	F70L	0.998
20:23354251:C:A	F70L	0.998
20:23354251:C:G	F70L	0.998
20:23354280:T:A	V80D	0.998
20:23354313:T:A	V91D	0.998
20:23354331:G:T	G97V	0.998
20:23354366:T:C	F109L	0.998
20:23354367:T:C	F109S	0.998

dbSNP variants (sampled 300 via entrez): RS1000670789 (20:23350291 C>A,T), RS1001187758 (20:23350468 C>T), RS1001526409 (20:23354570 C>G,T), RS1001557683 (20:23354884 G>A), RS1001789624 (20:23349594 T>C), RS1002071623 (20:23349325 C>T), RS1002560472 (20:23353145 T>C), RS1002919503 (20:23352742 C>T), RS1003532935 (20:23351493 T>C,G), RS1003611013 (20:23351785 C>T), RS1005039145 (20:23350690 T>A,C), RS1005407639 (20:23351697 A>G), RS1005465148 (20:23355136 C>T), RS1005633936 (20:23349946 A>G), RS1006494737 (20:23353843 G>A,T)

Disease associations

OMIM: gene MIM:605811 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST001762_751	Obesity-related traits	6.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004730	hormone measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance, increases expression	2
Estradiol	affects expression, increases expression	2
Nickel	increases expression	2
Cyclosporine	increases expression	2
Aflatoxin B1	increases expression	2
Cadmium Chloride	decreases expression	2
methylparaben	increases expression	1
afimoxifene	decreases reaction, increases expression	1
zinc chromate	decreases expression, increases abundance	1
manganese chloride	increases abundance, increases expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
chloropicrin	decreases expression	1
ICG 001	increases expression	1
abrine	increases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	decreases expression, increases response to substance	1
jinfukang	affects cotreatment, decreases expression	1
(+)-JQ1 compound	decreases expression	1
Temozolomide	increases expression	1
Arsenic	increases expression, increases abundance	1
Atrazine	decreases expression	1
Benzo(a)pyrene	increases expression	1
Cisplatin	affects cotreatment, decreases expression	1
Demecolcine	decreases expression	1
Estrogens	decreases reaction, increases expression	1
Formaldehyde	decreases expression	1
Manganese	increases abundance, increases expression	1
Phenobarbital	affects expression	1
Smoke	decreases expression	1
Dronabinol	decreases expression	1
Tobacco Smoke Pollution	increases expression	1

Clinical trials (associated diseases)

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