NCBP3

Summary

NCBP3 (nuclear cap binding subunit 3, HGNC:24612) is a protein-coding gene on chromosome 17p13.2, encoding Nuclear cap-binding protein subunit 3 (Q53F19). Associates with NCBP1/CBP80 to form an alternative cap-binding complex (CBC) which plays a key role in mRNA export.

Enables RNA 7-methylguanosine cap binding activity and mRNA binding activity. Involved in defense response to virus; mRNA export from nucleus; and snRNA export from nucleus. Located in cytoplasm and nuclear speck. Part of nuclear cap binding activity complex.

Source: NCBI Gene 55421 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 74 total
• MANE Select transcript: NM_001114118

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24612
Approved symbol	NCBP3
Name	nuclear cap binding subunit 3
Location	17p13.2
Locus type	gene with protein product
Status	Approved
Aliases	HSA277841, ELG
Ensembl gene	ENSG00000074356
Ensembl biotype	protein_coding
OMIM	616624
Entrez	55421

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 3 protein_coding, 2 protein_coding_CDS_not_defined, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000389005, ENST00000572988, ENST00000574379, ENST00000574911, ENST00000575815, ENST00000576523, ENST00000577169, ENST00000936723

RefSeq mRNA: 2 — MANE Select: NM_001114118 NM_001114118, NM_001398494

CCDS: CCDS45578

Canonical transcript exons

ENST00000389005 — 13 exons

Exon	Start	End
ENSE00002651024	3802158	3813279
ENSE00002664066	3846041	3846246
ENSE00003459184	3825767	3825843
ENSE00003497775	3829243	3829368
ENSE00003510581	3818263	3818572
ENSE00003535986	3821249	3821352
ENSE00003541074	3816116	3816270
ENSE00003547106	3824942	3825050
ENSE00003572000	3821953	3822052
ENSE00003576029	3843086	3843151
ENSE00003594945	3840100	3840205
ENSE00003650157	3814322	3814483
ENSE00003692479	3826087	3826215

Expression profiles

Bgee: expression breadth ubiquitous, 264 present calls, max score 93.62.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 29.2409 / max 1264.3588, expressed in 1819 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
163880	29.2409	1819

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	93.62	gold quality
body of pancreas	UBERON:0001150	93.45	gold quality
sural nerve	UBERON:0015488	93.26	gold quality
tibial nerve	UBERON:0001323	91.98	gold quality
rectum	UBERON:0001052	91.34	gold quality
buccal mucosa cell	CL:0002336	91.31	gold quality
ganglionic eminence	UBERON:0004023	91.07	gold quality
right ovary	UBERON:0002118	91.01	gold quality
ventricular zone	UBERON:0003053	90.99	gold quality
left ovary	UBERON:0002119	90.97	gold quality
monocyte	CL:0000576	90.93	gold quality
skin of abdomen	UBERON:0001416	90.87	gold quality
skin of leg	UBERON:0001511	90.85	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	90.77	gold quality
small intestine Peyer’s patch	UBERON:0003454	90.68	gold quality
transverse colon	UBERON:0001157	90.51	gold quality
lower esophagus mucosa	UBERON:0035834	90.49	gold quality
left testis	UBERON:0004533	90.45	gold quality
right testis	UBERON:0004534	90.42	gold quality
mononuclear cell	CL:0000842	90.38	gold quality
metanephros cortex	UBERON:0010533	90.34	gold quality
minor salivary gland	UBERON:0001830	90.23	gold quality
leukocyte	CL:0000738	90.14	gold quality
body of stomach	UBERON:0001161	90.14	gold quality
endocervix	UBERON:0000458	89.85	gold quality
stromal cell of endometrium	CL:0002255	89.79	gold quality
right lobe of thyroid gland	UBERON:0001119	89.78	gold quality
ectocervix	UBERON:0012249	89.74	gold quality
body of uterus	UBERON:0009853	89.60	gold quality
esophagus mucosa	UBERON:0002469	89.37	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.22

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTCF

Literature-anchored findings (GeneRIF, showing 4)

• NCBP3 binds mRNA, associates with components of the mRNA processing machinery and contributes to poly(A) RNA export. Study proposes the existence of an alternative cap-binding complex involving NCBP1 and NCBP3 that plays a key role in mRNA biogenesis. (PMID:26382858)
• NCBP3/SNHG6 inhibits GBX2 transcription in a histone modification manner to facilitate the malignant biological behaviour of glioma cells. (PMID:32618493)
• Affinity proteomic dissection of the human nuclear cap-binding complex interactome. (PMID:32960270)
• NCBP3 positively impacts mRNA biogenesis. (PMID:32960271)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	ncbp3	ENSDARG00000044597
mus_musculus	Ncbp3	ENSMUSG00000020783
rattus_norvegicus	Ncbp3	ENSRNOG00000018550

Protein

Protein identifiers

Nuclear cap-binding protein subunit 3 — Q53F19 (reviewed: Q53F19)

Alternative names: Protein ELG

All UniProt accessions (3): Q53F19, K7ELP6, K7EQA5

UniProt curated annotations — full annotation on UniProt →

Function. Associates with NCBP1/CBP80 to form an alternative cap-binding complex (CBC) which plays a key role in mRNA export. NCBP3 serves as adapter protein linking the capped RNAs (m7GpppG-capped RNA) to NCBP1/CBP80. Unlike the conventional CBC with NCBP2 which binds both small nuclear RNA (snRNA) and messenger (mRNA) and is involved in their export from the nucleus, the alternative CBC with NCBP3 does not bind snRNA and associates only with mRNA thereby playing a role in only mRNA export. The alternative CBC is particularly important in cellular stress situations such as virus infections and the NCBP3 activity is critical to inhibit virus growth.

Subunit / interactions. Component of an alternative cap-binding complex (CBC) composed of NCBP1/CBP80 and NCBP3. Interacts with SRRT, KPNA3, THOC5 and EIF4A3.

Subcellular location. Nucleus. Cytoplasm.

Similarity. Belongs to the NCBP3 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q53F19-1	1	yes
Q53F19-2	2

RefSeq proteins (2): NP_001107590, NP_001385423 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR019416	NCBP3	Family

Pfam: PF10309

UniProt features (33 total): compositionally biased region 10, modified residue 7, region of interest 5, cross-link 4, mutagenesis site 2, chain 1, splice variant 1, sequence conflict 1, helix 1, short sequence motif 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
8BY6	ELECTRON MICROSCOPY	3.19

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q53F19-F1	63.46	0.14

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 (11): 25, 73, 209, 210, 413, 415, 620, 12, 70, 186, 541

Mutagenesis-validated functional residues (2):

Position	Phenotype
134	minor loss of 7-methylguanosine-containing mrna cap binding.
155–158	complete loss of 7-methylguanosine-containing mrna cap binding.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 159 (showing top): TTTGTAG_MIR520D, GOBP_NUCLEAR_TRANSPORT, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, GOBP_NUCLEOBASE_CONTAINING_COMPOUND_TRANSPORT, GOBP_RNA_CAPPING, EVI1_01, GOBP_MRNA_TRANSCRIPTION, GOBP_DEFENSE_RESPONSE_TO_VIRUS, TCCAGAT_MIR5165P, BASAKI_YBX1_TARGETS_DN, GOBP_NUCLEAR_EXPORT, GOBP_RNA_LOCALIZATION, SPIELMAN_LYMPHOBLAST_EUROPEAN_VS_ASIAN_DN, DEURIG_T_CELL_PROLYMPHOCYTIC_LEUKEMIA_UP, MARIADASON_RESPONSE_TO_BUTYRATE_SULINDAC_6

GO Biological Process (8): 7-methylguanosine mRNA capping (GO:0006370), mRNA export from nucleus (GO:0006406), snRNA export from nucleus (GO:0006408), regulatory ncRNA-mediated post-transcriptional gene silencing (GO:0035194), mRNA transcription by RNA polymerase II (GO:0042789), defense response to virus (GO:0051607), mRNA processing (GO:0006397), mRNA transport (GO:0051028)

GO Molecular Function (5): RNA cap binding (GO:0000339), RNA 7-methylguanosine cap binding (GO:0000340), RNA binding (GO:0003723), mRNA binding (GO:0003729), protein binding (GO:0005515)

GO Cellular Component (5): nucleus (GO:0005634), cytoplasm (GO:0005737), nuclear cap binding complex (GO:0005846), nuclear speck (GO:0016607), RNA cap binding complex (GO:0034518)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA export from nucleus	2
RNA binding	2
mRNA processing	1
7-methylguanosine RNA capping	1
gene expression	1
mRNA transport	1
snRNA transport	1
post-transcriptional gene silencing	1
regulatory ncRNA-mediated gene silencing	1
transcription by RNA polymerase II	1
mRNA transcription	1
defense response	1
response to virus	1
RNA processing	1
mRNA metabolic process	1
RNA transport	1
RNA cap binding	1
nucleic acid binding	1
binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1
RNA cap binding complex	1
nuclear ribonucleoprotein granule	1
intracellular protein-containing complex	1

Protein interactions and networks

STRING

1732 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NCBP3	NCBP1	Q09161	795
NCBP3	THOC2	Q8NI27	688
NCBP3	NCBP2	P52298	659
NCBP3	THOC3	Q96J01	628
NCBP3	THOC1	Q96FV9	624
NCBP3	THOC5	Q13769	613
NCBP3	FYTTD1	Q96QD9	611
NCBP3	HNRNPUL2	Q1KMD3	583
NCBP3	SRRT	Q9BXP5	582
NCBP3	ZC3H11A	O75152	580
NCBP3	RBM7	Q9Y580	574
NCBP3	A0A0A6YYJ8	A0A0A6YYJ8	570
NCBP3	THOC6	Q86W42	569
NCBP3	LUC7L2	Q9Y383	569
NCBP3	PHAX	Q9H814	541

IntAct

128 interactions, top by confidence:

A	B	Type	Score
PDIK1L	CTDSPL2	psi-mi:“MI:0914”(association)	0.840
	NCBP1	psi-mi:“MI:0914”(association)	0.760
VPS29	VPS26C	psi-mi:“MI:0914”(association)	0.760
KPNA4	NCBP3	psi-mi:“MI:0915”(physical association)	0.740
NCBP3	LENG8	psi-mi:“MI:0915”(physical association)	0.740
NCBP3	NCBP1	psi-mi:“MI:0915”(physical association)	0.720
NCBP1	NCBP3	psi-mi:“MI:0915”(physical association)	0.720
SNIP1	NCBP3	psi-mi:“MI:0915”(physical association)	0.660
NCBP1	KPNA3	psi-mi:“MI:0914”(association)	0.640
NCBP2	KPNA3	psi-mi:“MI:0914”(association)	0.640
PNN	CASC3	psi-mi:“MI:0914”(association)	0.640
THOC1	DDX39A	psi-mi:“MI:0914”(association)	0.640
NCBP3		psi-mi:“MI:0915”(physical association)	0.590
NCBP3		psi-mi:“MI:0407”(direct interaction)	0.590
	NCBP3	psi-mi:“MI:0915”(physical association)	0.590
	NCBP3	psi-mi:“MI:0407”(direct interaction)	0.590
NCBP3	KPNA3	psi-mi:“MI:0914”(association)	0.530
NCBP3	SAP18	psi-mi:“MI:0914”(association)	0.530
GSPT2	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
LUC7L2	CASC3	psi-mi:“MI:0914”(association)	0.530
SNIP1	CASC3	psi-mi:“MI:0914”(association)	0.530
PAIP2B	CASC3	psi-mi:“MI:0914”(association)	0.530
WSB2	UBB	psi-mi:“MI:0914”(association)	0.530
SNRPC	SNRPGP15	psi-mi:“MI:0914”(association)	0.530
EZH1	EPOP	psi-mi:“MI:0914”(association)	0.530
SRSF3	CASC3	psi-mi:“MI:0914”(association)	0.530
CPSF6	DDX39A	psi-mi:“MI:0914”(association)	0.480
NCBP3	LRRK2	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (207): C17orf85 (Affinity Capture-MS), C17orf85 (Affinity Capture-MS), C17orf85 (Affinity Capture-MS), C17orf85 (Affinity Capture-MS), C17orf85 (Affinity Capture-MS), C17orf85 (Affinity Capture-MS), C17orf85 (Affinity Capture-MS), C17orf85 (Affinity Capture-MS), C17orf85 (Affinity Capture-MS), C17orf85 (Affinity Capture-MS), C17orf85 (Affinity Capture-MS), PLEC (Co-fractionation), C17orf85 (Affinity Capture-MS), C17orf85 (Proximity Label-MS), RPL6 (Affinity Capture-MS)

ESM2 similar proteins: A0JNI5, A2AJT4, A2AQ19, A4IFB1, B1H1X4, D3ZTQ1, O43290, P35269, Q05519, Q12872, Q13435, Q3THK3, Q3UJB0, Q3UQU0, Q3USH5, Q4V7C9, Q53F19, Q568R1, Q5EA53, Q5HZB6, Q5PQQ2, Q5R539, Q5RAD5, Q5XIW8, Q5ZM19, Q66I22, Q6AY96, Q6DDA4, Q6GLZ8, Q6INH5, Q6ZPZ3, Q8BZR9, Q8CFC7, Q8K194, Q8N2M8, Q8N5F7, Q8TF01, Q8VHI6, Q8WVK2, Q923D5

Diamond homologs: Q53F19, Q5ZM19, Q6DE94, Q6DFQ2, Q803E1, Q8BZR9, O74460

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
NCBP3	up-regulates	mRNA_nuclear_export
NCBP3	“up-regulates activity”	“messenger RNA”	relocalization

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 130 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 Mature Transcript to Cytoplasm	15	65.6×	7e-23
mRNA 3’-end processing	21	47.5×	4e-28
RNA Polymerase II Transcription Termination	17	42.9×	3e-22
Transport of Mature mRNA derived from an Intron-Containing Transcript	22	38.5×	1e-27
mRNA Splicing	18	22.7×	3e-18
Processing of Capped Intron-Containing Pre-mRNA	24	22.7×	2e-24
Transport of the SLBP Dependant Mature mRNA	6	21.9×	1e-05
mRNA Polyadenylation	19	19.2×	7e-18

GO biological processes:

GO term	Partners	Fold	FDR
RNA export from nucleus	5	39.0×	1e-05
negative regulation of mRNA splicing, via spliceosome	6	38.3×	9e-07
mRNA export from nucleus	15	37.0×	1e-17
alternative mRNA splicing, via spliceosome	5	28.1×	6e-05
nuclear-transcribed mRNA catabolic process, nonsense-mediated decay	6	23.4×	2e-05
regulation of alternative mRNA splicing, via spliceosome	10	20.4×	8e-09
RNA splicing	24	17.6×	1e-20
mRNA splicing, via spliceosome	22	16.8×	2e-18

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	61
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2732 predictions. Top by Δscore:

Variant	Effect	Δscore
17:3815640:A:C	acceptor_gain	1.0000
17:3816110:CAGTA:C	donor_loss	1.0000
17:3816111:AGTAC:A	donor_loss	1.0000
17:3816112:GTA:G	donor_loss	1.0000
17:3816113:TA:T	donor_loss	1.0000
17:3816114:A:AG	donor_loss	1.0000
17:3816115:C:CT	donor_loss	1.0000
17:3818568:TAGCC:T	acceptor_gain	1.0000
17:3818569:AGCC:A	acceptor_gain	1.0000
17:3818569:AGCCC:A	acceptor_gain	1.0000
17:3818570:GCC:G	acceptor_gain	1.0000
17:3818570:GCCC:G	acceptor_gain	1.0000
17:3818571:CC:C	acceptor_gain	1.0000
17:3818571:CCC:C	acceptor_gain	1.0000
17:3818571:CCCT:C	acceptor_gain	1.0000
17:3818572:CC:C	acceptor_gain	1.0000
17:3818573:C:CC	acceptor_gain	1.0000
17:3818583:T:C	acceptor_gain	1.0000
17:3818588:C:CT	acceptor_gain	1.0000
17:3821269:G:GT	donor_gain	1.0000
17:3821349:CTTC:C	acceptor_gain	1.0000
17:3821350:TTC:T	acceptor_gain	1.0000
17:3821353:C:CC	acceptor_gain	1.0000
17:3821354:T:C	acceptor_loss	1.0000
17:3821361:A:AC	acceptor_gain	1.0000
17:3821361:A:C	acceptor_gain	1.0000
17:3821946:GACTC:G	donor_loss	1.0000
17:3821947:ACTCA:A	donor_loss	1.0000
17:3821948:CTCA:C	donor_loss	1.0000
17:3821949:TCACC:T	donor_loss	1.0000

AlphaMissense

4093 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:3818296:G:T	A426D	1.000
17:3818341:A:G	I411T	1.000
17:3818350:A:G	L408P	1.000
17:3818356:A:G	L406P	1.000
17:3821342:A:C	Y303D	1.000
17:3821347:C:G	R301P	1.000
17:3821349:C:A	K300N	1.000
17:3821349:C:G	K300N	1.000
17:3821352:C:A	W299C	1.000
17:3821352:C:G	W299C	1.000
17:3821961:G:C	S296R	1.000
17:3821961:G:T	S296R	1.000
17:3821962:C:A	S296I	1.000
17:3821963:T:G	S296R	1.000
17:3821965:A:G	L295P	1.000
17:3821965:A:T	L295H	1.000
17:3821968:A:C	I294S	1.000
17:3821968:A:G	I294T	1.000
17:3821971:C:A	G293V	1.000
17:3821971:C:T	G293E	1.000
17:3821972:C:G	G293R	1.000
17:3821972:C:T	G293R	1.000
17:3821983:C:T	G289E	1.000
17:3821992:G:T	P286Q	1.000
17:3821993:G:A	P286S	1.000
17:3821994:A:C	N285K	1.000
17:3821994:A:T	N285K	1.000
17:3821998:C:A	G284V	1.000
17:3821998:C:T	G284E	1.000
17:3821999:C:A	G284W	1.000

dbSNP variants (sampled 300 via entrez): RS1000069755 (17:3828683 G>A), RS1000091540 (17:3847060 T>A), RS1000203582 (17:3832579 C>G,T), RS1000268612 (17:3828938 G>A,C,T), RS1000400669 (17:3848075 A>G), RS1000450715 (17:3823279 C>A,T), RS1000508038 (17:3826892 G>A), RS1000522085 (17:3811952 G>C), RS1000685847 (17:3806142 G>A), RS1000804374 (17:3840622 G>T), RS1000827435 (17:3838704 T>C), RS1000894970 (17:3837522 G>C), RS1000920196 (17:3840339 T>A), RS1000960740 (17:3834601 C>A,T), RS1000996356 (17:3821120 T>C)

Disease associations

OMIM: gene MIM:616624 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST012291_6	Schizophrenia, bipolar disorder or recurrent major depressive disorder	2.000000e-06
GCST012292_3	Schizophrenia, bipolar disorder or recurrent major depressive disorder x sex interaction	7.000000e-07
GCST012295_2	Schizophrenia, bipolar disorder or recurrent major depressive disorder x sex interaction	7.000000e-07
GCST012298_2	Schizophrenia, bipolar disorder or major depressive disorder x sex interaction	1.000000e-06
GCST012301_2	Schizophrenia, bipolar disorder or major depressive disorder x sex interaction	1.000000e-06
GCST90002394_509	Monocyte percentage of white cells	4.000000e-09

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004952	disease recurrence
EFO:0008343	sex interaction measurement
EFO:0007989	monocyte percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases methylation, affects expression	2
FR900359	affects phosphorylation	1
TAK-243	decreases sumoylation	1
benzo(e)pyrene	decreases methylation	1
coumarin	affects phosphorylation	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
ICG 001	increases expression	1
Temozolomide	increases expression	1
Atrazine	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Caffeine	increases phosphorylation	1
Lead	affects expression	1
Methapyrilene	decreases methylation	1
Phthalic Acids	increases methylation	1
Ribonucleotides	affects binding	1
Smoke	decreases expression	1
Cyclosporine	increases expression	1

Clinical trials (associated diseases)

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