NXF2

Summary

NXF2 (nuclear RNA export factor 2, HGNC:8072) is a protein-coding gene on chromosome Xq22.1, encoding Nuclear RNA export factor 2 (Q9GZY0). Involved in the export of mRNA from the nucleus to the cytoplasm.

This gene encodes a member of a family of nuclear RNA export proteins. The encoded protein is associated with the nuclear envelope and aids in the export of mRNAs. There is a closely related paralog of this gene located adjacent on chromosome X and on the opposite strand.

Source: NCBI Gene 56001 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 23 total
• MANE Select transcript: NM_022053

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8072
Approved symbol	NXF2
Name	nuclear RNA export factor 2
Location	Xq22.1
Locus type	gene with protein product
Status	Approved
Aliases	CT39, TAPL-2
Ensembl gene	ENSG00000269405
Ensembl biotype	protein_coding
OMIM	300315
Entrez	56001

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000604790, ENST00000625106

RefSeq mRNA: 1 — MANE Select: NM_022053 NM_022053

CCDS: CCDS14497

Canonical transcript exons

ENST00000625106 — 23 exons

Exon	Start	End
ENSE00002976619	102322420	102322462
ENSE00002988286	102321597	102321652
ENSE00003038209	102318950	102319057
ENSE00003041047	102316963	102317152
ENSE00003051200	102318028	102318132
ENSE00003071344	102321025	102321061
ENSE00003075268	102322012	102322070
ENSE00003097227	102321784	102321891
ENSE00003127091	102318741	102318829
ENSE00003155313	102322209	102322324
ENSE00003156480	102318515	102318584
ENSE00003162589	102318248	102318328
ENSE00003171532	102319237	102319346
ENSE00003175915	102317379	102317529
ENSE00003182715	102317833	102317916
ENSE00003199564	102323063	102323135
ENSE00003213904	102321442	102321510
ENSE00003612842	102326263	102326323
ENSE00003615206	102323670	102323852
ENSE00003756442	102326470	102326722
ENSE00003757498	102307026	102307121
ENSE00003759595	102248437	102248558
ENSE00003760324	102247167	102247238

Expression profiles

Bgee: expression breadth broad, 46 present calls, max score 84.57.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.57	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.29	gold quality
right testis	UBERON:0004534	82.07	gold quality
testis	UBERON:0000473	80.33	gold quality
left testis	UBERON:0004533	79.79	gold quality
right uterine tube	UBERON:0001302	72.88	gold quality
pituitary gland	UBERON:0000007	62.42	gold quality
adenohypophysis	UBERON:0002196	59.77	gold quality
fallopian tube	UBERON:0003889	49.85	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	49.58	gold quality
hypothalamus	UBERON:0001898	47.34	gold quality
ganglionic eminence	UBERON:0004023	47.22	gold quality
islet of Langerhans	UBERON:0000006	44.43	gold quality
nucleus accumbens	UBERON:0001882	42.76	gold quality
right lung	UBERON:0002167	42.23	gold quality
temporal lobe	UBERON:0001871	42.15	gold quality
amygdala	UBERON:0001876	42.03	gold quality
putamen	UBERON:0001874	41.23	gold quality
caudate nucleus	UBERON:0001873	40.88	gold quality
superior frontal gyrus	UBERON:0002661	40.84	gold quality
sural nerve	UBERON:0015488	40.75	gold quality
brain	UBERON:0000955	40.54	gold quality
ventricular zone	UBERON:0003053	39.91	gold quality
cerebellum	UBERON:0002037	39.50	silver quality
cerebellar cortex	UBERON:0002129	39.48	silver quality
cerebellar hemisphere	UBERON:0002245	39.42	silver quality
apex of heart	UBERON:0002098	37.81	silver quality
prefrontal cortex	UBERON:0000451	37.74	gold quality
right hemisphere of cerebellum	UBERON:0014890	37.57	silver quality
Ammon’s horn	UBERON:0001954	37.54	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-CURD-11	yes	422.32
E-ANND-3	no	0.98

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 2)

• Data do not support role for NXF2 in male infertility. (PMID:18258234)
• Low NXF2 expression is associated with leukemia. (PMID:24002123)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	nxf1b	ENSDARG00000055076
danio_rerio	nxf1a	ENSDARG00000086017
mus_musculus	Nxf2	ENSMUSG00000009941
mus_musculus	Nxf7	ENSMUSG00000031410
rattus_norvegicus	Nxf2	ENSRNOG00000011729
rattus_norvegicus	Nxf7	ENSRNOG00000023256
drosophila_melanogaster	nxf4	FBGN0051501
caenorhabditis_elegans		WBGENE00003834
caenorhabditis_elegans		WBGENE00003835

Paralogs (3): NXF3 (ENSG00000147206), NXF1 (ENSG00000162231), NXF2B (ENSG00000269437)

Protein

Protein identifiers

Nuclear RNA export factor 2 — Q9GZY0 (reviewed: Q9GZY0)

Alternative names: Cancer/testis antigen 39, TAP-like protein 2

All UniProt accessions (1): Q9GZY0

UniProt curated annotations — full annotation on UniProt →

Function. Involved in the export of mRNA from the nucleus to the cytoplasm.

Subunit / interactions. Interacts with NXT1, NXT2, E1B-AP5, the REF proteins and with nucleoporins, Nup62, Nup153 and Nup214. Interacts with LUZP4.

Subcellular location. Nucleus. Nucleoplasm. Cytoplasm.

Tissue specificity. Expressed almost exclusively in testis. Also expressed in several cancers.

Domain organisation. The NTF2 domain heterodimerizes with NXT1 and NXT2. The formation of NXF1/NXT1 heterodimers is required for NXF2-mediated nuclear mRNA export. The leucine-rich repeats and the NTF2-domain are essential for the export of mRNA from the nucleus. The C-terminal fragment, containing the TAP domain (also called UBA-like domain) and part of the NTF2-like domain, named the NPC-binding domain, mediates direct interactions with nucleoporin-FG-repeats and is necessary and sufficient for localization of NXF2 to the nuclear rim. The RNA-binding domain is a non-canonical RNP-type domain.

Similarity. Belongs to the NXF family.

RefSeq proteins (1): NP_071336* (*=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 (12 total): repeat 4, domain 3, mutagenesis site 3, chain 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9GZY0-F1	76.73	0.53

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): 34

Mutagenesis-validated functional residues (3):

Position	Phenotype
599	suppresses fg-nucleoporin binding.
600	has no effect on fg-nucleoporin binding.
598	has no effect on fg-nucleoporin binding.

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: 57 (showing top): GOBP_NUCLEAR_TRANSPORT, REACTOME_PROCESSING_OF_CAPPED_INTRON_CONTAINING_PRE_MRNA, GOBP_NUCLEOBASE_CONTAINING_COMPOUND_TRANSPORT, GOBP_NUCLEAR_EXPORT, GOBP_RNA_LOCALIZATION, REACTOME_METABOLISM_OF_RNA, DODD_NASOPHARYNGEAL_CARCINOMA_DN, chrXq22, GOBP_RNA_EXPORT_FROM_NUCLEUS, GOBP_MRNA_EXPORT_FROM_NUCLEUS, GOBP_POLY_A_PLUS_MRNA_EXPORT_FROM_NUCLEUS, GOBP_INTRACELLULAR_TRANSPORT, GOBP_MRNA_TRANSPORT, GOBP_ESTABLISHMENT_OF_RNA_LOCALIZATION, PRC1_BMI_UP.V1_UP

GO Biological Process (4): mRNA export from nucleus (GO:0006406), poly(A)+ mRNA export from nucleus (GO:0016973), RNA transport (GO:0050658), mRNA transport (GO:0051028)

GO Molecular Function (3): RNA binding (GO:0003723), nucleic acid binding (GO:0003676), protein binding (GO:0005515)

GO Cellular Component (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), nuclear RNA export factor complex (GO:0042272)

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
cellular anatomical structure	3
binding	2
RNA export from nucleus	1
gene expression	1
mRNA transport	1
mRNA export from nucleus	1
nucleic acid transport	1
establishment of RNA localization	1
RNA transport	1
nucleic acid binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1
nuclear protein-containing complex	1

Protein interactions and networks

STRING

1038 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NXF2	NXT1	Q9UKK6	987
NXF2	NUTF2	P13662	887
NXF2	NXT2	Q9NPJ8	857
NXF2	FMR1	Q06787	828
NXF2	NUP153	P49790	709
NXF2	NUP62	P37198	701
NXF2	NUP214	P35658	687
NXF2	FMR1NB	Q8N0W7	641
NXF2	TNPO2	O14787	638
NXF2	NUP98	P52948	633
NXF2	TAF7L	Q5H9L4	618
NXF2	NPAS4	Q8IUM7	599
NXF2	PIWIL1	Q96J94	592
NXF2	HNRNPUL1	Q9BUJ2	589
NXF2	CT45A1	Q5HYN5	570

IntAct

18 interactions, top by confidence:

A	B	Type	Score
NXF2B	NXT2	psi-mi:“MI:0915”(physical association)	0.680
NXF2B	NXT1	psi-mi:“MI:0915”(physical association)	0.670
ZC3HC1	TPR	psi-mi:“MI:0914”(association)	0.640
KLHL22	TMEM223	psi-mi:“MI:0914”(association)	0.640
NXF2B	HEXB	psi-mi:“MI:0915”(physical association)	0.560
NXF2B	Nxt1	psi-mi:“MI:0915”(physical association)	0.400
NXF2B	MEIOC	psi-mi:“MI:0914”(association)	0.350
LNX1	LRFN4	psi-mi:“MI:0914”(association)	0.350
NXF5	LRP6	psi-mi:“MI:0914”(association)	0.350
NXT2	MYO1G	psi-mi:“MI:0914”(association)	0.350
NXT2	NXF2B	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (116): LUZP4 (Affinity Capture-Western), NXF2 (Affinity Capture-MS), NXF2 (Affinity Capture-MS), NXF2B (Affinity Capture-MS), C17orf104 (Affinity Capture-MS), DVL2 (Affinity Capture-MS), GLE1 (Affinity Capture-MS), STOX2 (Affinity Capture-MS), NXF2B (Affinity Capture-MS), DVL3 (Affinity Capture-MS), NXF2B (Affinity Capture-MS), ZNF106 (Affinity Capture-MS), FAM120B (Affinity Capture-MS), RGPD8 (Affinity Capture-MS), NXT2 (Affinity Capture-MS)

ESM2 similar proteins: A0A1L1SUL6, A4QJJ7, A4QK16, A6H5F6, A6MM34, A6NH52, A6NMK7, A7M939, A8SEA1, A8W3M5, B0Z4S1, B0Z505, B0Z589, B0Z5H3, B1AR13, B1NWE8, B2LMJ1, O19048, O19137, O95639, P0C7P0, P0DI19, P46292, P60335, P83870, P83871, P98138, Q09G48, Q0G9M1, Q0WMV8, Q15365, Q1KXW1, Q332Y0, Q5E9A3, Q5FVR7, Q5R654, Q63789, Q66KE3, Q68S08, Q6DJP7

Diamond homologs: O35381, O88984, P49911, P58797, Q1RMS5, Q5R752, Q8ILI6, Q92688, Q99JX7, Q9GZY0, Q9H1B4, Q9H4D5, Q9U1H9, Q9UBU9, Q9XVS8, Q3SZC6

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
NXF2	“form complex”	“NXF2-NXT1 mRNA nuclear export factor complex”	binding
NXF2	“form complex”	“NXF2-NXT2 mRNA nuclear export factor complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 15 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.

GO biological processes:

GO term	Partners	Fold	FDR
mRNA export from nucleus	5	105.6×	8e-08

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	12
Likely benign	10
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

3263 predictions. Top by Δscore:

Variant	Effect	Δscore
X:102316961:A:AG	acceptor_gain	1.0000
X:102316962:G:GA	acceptor_gain	1.0000
X:102316962:GT:G	acceptor_gain	1.0000
X:102316962:GTT:G	acceptor_gain	1.0000
X:102316962:GTTGC:G	acceptor_gain	1.0000
X:102317148:AGACA:A	donor_gain	1.0000
X:102317149:GACA:G	donor_gain	1.0000
X:102317149:GACAG:G	donor_gain	1.0000
X:102317150:ACA:A	donor_gain	1.0000
X:102317151:CA:C	donor_gain	1.0000
X:102317151:CAGTA:C	donor_loss	1.0000
X:102317152:AGT:A	donor_loss	1.0000
X:102317153:G:GG	donor_gain	1.0000
X:102317153:GTAA:G	donor_loss	1.0000
X:102317376:C:G	acceptor_gain	1.0000
X:102317377:A:AG	acceptor_gain	1.0000
X:102317377:A:AT	acceptor_loss	1.0000
X:102317378:G:GG	acceptor_gain	1.0000
X:102317378:GC:G	acceptor_gain	1.0000
X:102317378:GCA:G	acceptor_gain	1.0000
X:102317378:GCACT:G	acceptor_gain	1.0000
X:102317497:G:GT	donor_gain	1.0000
X:102317511:G:GT	donor_gain	1.0000
X:102317512:A:T	donor_gain	1.0000
X:102317527:ACAG:A	donor_loss	1.0000
X:102317528:CAGTG:C	donor_loss	1.0000
X:102317530:G:GG	donor_gain	1.0000
X:102317530:GTGA:G	donor_loss	1.0000
X:102317531:T:A	donor_loss	1.0000
X:102317533:AG:A	donor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1004119 (X:102271994 G>C), RS111321456 (X:102322975 T>C), RS111490714 (X:102259080 G>T), RS111517590 (X:102268697 T>C), RS111526062 (X:102259154 T>A), RS111596280 (X:102270808 A>T), RS111745824 (X:102280498 T>A), RS111827009 (X:102319484 T>C), RS112277003 (X:102271572 G>T), RS112304666 (X:102280518 T>C), RS112311440 (X:102269045 C>T), RS112503794 (X:102294071 A>G,T), RS112693256 (X:102288274 G>A), RS113143377 (X:102267566 A>C), RS113298099 (X:102269046 G>A)

Disease associations

OMIM: gene MIM:300315 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

7 total (human), top 7 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
perfluorooctanoic acid	increases expression	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
Decitabine	increases expression	1
Arsenicals	decreases expression	1
Dihydrotestosterone	increases expression	1
Valproic Acid	decreases methylation	1

Clinical trials (associated diseases)

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