NXF2B

Summary

NXF2B (nuclear RNA export factor 2B, HGNC:23984) 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 728343 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 27 total
• MANE Select transcript: NM_001099686

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23984
Approved symbol	NXF2B
Name	nuclear RNA export factor 2B
Location	Xq22.1
Locus type	gene with protein product
Status	Approved
Aliases	bA353J17.1
Ensembl gene	ENSG00000269437
Ensembl biotype	protein_coding
Entrez	728343

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 retained_intron

ENST00000489531, ENST00000602195, ENST00000604395

RefSeq mRNA: 1 — MANE Select: NM_001099686 NM_001099686

CCDS: CCDS43979

Canonical transcript exons

ENST00000602195 — 23 exons

Exon	Start	End
ENSE00002976390	102369963	102370152
ENSE00002979739	102369199	102369282
ENSE00002989649	102368058	102368165
ENSE00003000229	102365224	102365331
ENSE00003058561	102368286	102368374
ENSE00003084900	102365463	102365518
ENSE00003091967	102369586	102369736
ENSE00003096179	102368531	102368600
ENSE00003105958	102363980	102364052
ENSE00003115966	102364791	102364906
ENSE00003122684	102368983	102369087
ENSE00003135730	102379994	102380089
ENSE00003140595	102367769	102367878
ENSE00003144428	102365045	102365103
ENSE00003146804	102364653	102364695
ENSE00003159400	102368787	102368867
ENSE00003183073	102366054	102366090
ENSE00003208093	102365605	102365673
ENSE00003543318	102360792	102360852
ENSE00003723933	102363263	102363445
ENSE00003822645	102438553	102438674
ENSE00003978264	102360395	102360645
ENSE00003978265	102439870	102440008

Expression profiles

Bgee: expression breadth broad, 85 present calls, max score 85.52.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.52	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.93	gold quality
right uterine tube	UBERON:0001302	81.07	gold quality
pituitary gland	UBERON:0000007	75.16	gold quality
adenohypophysis	UBERON:0002196	73.48	gold quality
left testis	UBERON:0004533	70.01	gold quality
testis	UBERON:0000473	69.63	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	68.23	gold quality
right testis	UBERON:0004534	67.55	gold quality
fallopian tube	UBERON:0003889	61.32	gold quality
right lung	UBERON:0002167	59.47	gold quality
hypothalamus	UBERON:0001898	54.79	gold quality
ganglionic eminence	UBERON:0004023	54.75	gold quality
left uterine tube	UBERON:0001303	53.90	gold quality
right hemisphere of cerebellum	UBERON:0014890	52.21	gold quality
islet of Langerhans	UBERON:0000006	51.86	gold quality
cerebellar hemisphere	UBERON:0002245	51.84	gold quality
cerebellum	UBERON:0002037	51.80	gold quality
cerebellar cortex	UBERON:0002129	51.74	gold quality
nucleus accumbens	UBERON:0001882	50.59	gold quality
caudate nucleus	UBERON:0001873	48.72	gold quality
brain	UBERON:0000955	48.23	gold quality
primary visual cortex	UBERON:0002436	48.09	gold quality
temporal lobe	UBERON:0001871	47.90	gold quality
superior frontal gyrus	UBERON:0002661	47.87	gold quality
amygdala	UBERON:0001876	47.86	gold quality
sural nerve	UBERON:0015488	47.44	silver quality
fundus of stomach	UBERON:0001160	47.03	gold quality
putamen	UBERON:0001874	46.31	gold quality
cortical plate	UBERON:0005343	45.58	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.23

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

18 targeting NXF2B, 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-4795-3P	100.00	74.62	4024
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-147B-5P	99.45	70.62	2432
HSA-MIR-149-5P	99.25	67.16	1315
HSA-MIR-3125	99.14	68.49	2269
HSA-MIR-3916	98.99	68.04	2155
HSA-MIR-6859-5P	98.99	68.07	2049
HSA-MIR-4764-5P	98.88	65.53	894
HSA-MIR-6794-3P	98.76	66.99	894
HSA-MIR-583	98.71	67.44	1791
HSA-MIR-138-5P	98.43	70.49	1292
HSA-MIR-4299	98.28	66.96	850
HSA-MIR-4483	98.09	64.12	1642
HSA-MIR-1293	96.16	64.69	916
HSA-MIR-1306-3P	87.45	66.21	44

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), NXF2 (ENSG00000269405)

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_001093156* (*=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: 23 (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, chrXq22, GOBP_RNA_EXPORT_FROM_NUCLEUS, GOBP_MRNA_EXPORT_FROM_NUCLEUS, BRUINS_UVC_RESPONSE_VIA_TP53_GROUP_B, GOBP_POLY_A_PLUS_MRNA_EXPORT_FROM_NUCLEUS, GOBP_INTRACELLULAR_TRANSPORT, GOBP_MRNA_TRANSPORT, GOBP_ESTABLISHMENT_OF_RNA_LOCALIZATION, MIR4795_3P

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
NXF2B	NXT1	Q9UKK6	987
NXF2B	NUTF2	P13662	887
NXF2B	NXT2	Q9NPJ8	857
NXF2B	FMR1	Q06787	828
NXF2B	NUP153	P49790	709
NXF2B	NUP62	P37198	701
NXF2B	NUP214	P35658	687
NXF2B	FMR1NB	Q8N0W7	641
NXF2B	TNPO2	O14787	638
NXF2B	NUP98	P52948	633
NXF2B	TAF7L	Q5H9L4	618
NXF2B	NPAS4	Q8IUM7	599
NXF2B	PIWIL1	Q96J94	592
NXF2B	HNRNPUL1	Q9BUJ2	589
NXF2B	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

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	21
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3218 predictions. Top by Δscore:

Variant	Effect	Δscore
X:102360646:C:CC	acceptor_gain	1.0000
X:102363261:A:AC	donor_gain	1.0000
X:102363262:C:CC	donor_gain	1.0000
X:102363441:ACAGA:A	acceptor_gain	1.0000
X:102363442:CAGA:C	acceptor_gain	1.0000
X:102363442:CAGAC:C	acceptor_gain	1.0000
X:102363443:AGA:A	acceptor_gain	1.0000
X:102363444:GA:G	acceptor_gain	1.0000
X:102363445:ACTGG:A	acceptor_loss	1.0000
X:102363446:C:CC	acceptor_gain	1.0000
X:102364053:C:CC	acceptor_gain	1.0000
X:102364786:CTCA:C	donor_loss	1.0000
X:102364787:TCA:T	donor_loss	1.0000
X:102364788:CACCG:C	donor_loss	1.0000
X:102364789:A:AC	donor_gain	1.0000
X:102364790:C:CC	donor_gain	1.0000
X:102364790:C:G	donor_loss	1.0000
X:102364790:CCGT:C	donor_gain	1.0000
X:102364902:CAGGT:C	acceptor_gain	1.0000
X:102364903:AGGT:A	acceptor_gain	1.0000
X:102364904:GGT:G	acceptor_gain	1.0000
X:102364905:GT:G	acceptor_gain	1.0000
X:102364907:C:CC	acceptor_gain	1.0000
X:102364907:C:CG	acceptor_loss	1.0000
X:102364909:G:C	acceptor_gain	1.0000
X:102365039:A:AC	donor_gain	1.0000
X:102365040:C:CC	donor_gain	1.0000
X:102365043:A:AC	donor_gain	1.0000
X:102365044:C:CC	donor_gain	1.0000
X:102365044:CAGGG:C	donor_gain	1.0000

AlphaMissense

4189 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:102364018:G:C	F518L	0.986
X:102364018:G:T	F518L	0.986
X:102364020:A:G	F518L	0.986
X:102367810:G:C	N330K	0.985
X:102367810:G:T	N330K	0.985
X:102368061:A:C	N306K	0.983
X:102368061:A:T	N306K	0.983
X:102368155:A:G	L275S	0.979
X:102368071:A:G	L303P	0.978
X:102368062:T:A	N306I	0.976
X:102365471:G:C	F395L	0.973
X:102365471:G:T	F395L	0.973
X:102365473:A:G	F395L	0.973
X:102366064:A:C	L353W	0.973
X:102368071:A:T	L303H	0.973
X:102367826:A:G	L325P	0.971
X:102368063:T:G	N306H	0.971
X:102363284:A:G	M585T	0.970
X:102368149:A:G	L277S	0.970
X:102360804:G:C	F608L	0.968
X:102360804:G:T	F608L	0.968
X:102360806:A:G	F608L	0.968
X:102368554:A:G	L234P	0.967
X:102360833:A:G	W599R	0.966
X:102360833:A:T	W599R	0.966
X:102366064:A:G	L353S	0.966
X:102368560:A:T	L232H	0.966
X:102367820:A:G	L327P	0.963
X:102368062:T:G	N306T	0.963
X:102369055:A:C	F167L	0.963

dbSNP variants (sampled 300 via entrez): RS10717019 (X:102374922 GA>G), RS1074809 (X:102416061 C>A), RS111565386 (X:102367395 T>C,G), RS111568334 (X:102433903 T>C), RS111593567 (X:102368703 G>GGT), RS111611048 (X:102389648 A>G), RS112512671 (X:102411025 A>C), RS112687938 (X:102397046 T>G), RS112804446 (X:102409913 C>T), RS112971909 (X:102380403 T>A), RS113034029 (X:102399361 C>T), RS113153946 (X:102439634 A>G), RS113264019 (X:102417092 A>T), RS113516503 (X:102432716 A>T), RS113641907 (X:102417396 G>C)

Disease associations

OMIM: gene `` | 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
GCST009391_130	Metabolite levels	2.000000e-06
GCST009391_2052	Metabolite levels	2.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0010355	diacylglycerol 36:2 measurement
EFO:0010345	cholesteryl ester 18:2 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

2 total (human), top 2 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases methylation	1
S-Nitrosoglutathione	decreases expression	1

Clinical trials (associated diseases)

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