NCBP1

Summary

NCBP1 (nuclear cap binding protein subunit 1, HGNC:7658) is a protein-coding gene on chromosome 9q22.33, encoding Nuclear cap-binding protein subunit 1 (Q09161). Component of the cap-binding complex (CBC), which binds cotranscriptionally to the 5’-cap of pre-mRNAs and is involved in various processes such as pre-mRNA splicing, translation regulation, nonsense-mediated mRNA decay, RNA-mediated gene silencing (RNAi) by microRNAs (miRNAs) a…. It is a common-essential gene (DepMap: required in 99.6% of cancer cell lines).

The product of this gene is a component of the nuclear cap-binding protein complex (CBC), which binds to the monomethylated 5’ cap of nascent pre-mRNA in the nucleoplasm. The encoded protein promotes high-affinity mRNA-cap binding and associates with the CTD of RNA polymerase II. The CBC promotes pre-mRNA splicing, 3’-end processing, RNA nuclear export, and nonsense-mediated mRNA decay.

Source: NCBI Gene 4686 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Tourette syndrome (Limited, GenCC)
• GWAS associations: 1
• Clinical variants (ClinVar): 100 total — 1 pathogenic
• Phenotypes (HPO): 1
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 99.6% of screened cell lines (common-essential)
• MANE Select transcript: NM_002486

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7658
Approved symbol	NCBP1
Name	nuclear cap binding protein subunit 1
Location	9q22.33
Locus type	gene with protein product
Status	Approved
Aliases	CBP80, Sto1
Ensembl gene	ENSG00000136937
Ensembl biotype	protein_coding
OMIM	600469
Entrez	4686

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 10 protein_coding, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000375130, ENST00000375147, ENST00000478100, ENST00000491445, ENST00000629069, ENST00000896447, ENST00000896448, ENST00000896449, ENST00000929492, ENST00000950412, ENST00000950413, ENST00000950414

RefSeq mRNA: 5 — MANE Select: NM_002486 NM_001351504, NM_001351505, NM_001351506, NM_001351507, NM_002486

CCDS: CCDS6728

Canonical transcript exons

ENST00000375147 — 23 exons

Exon	Start	End
ENSE00000926499	97668846	97668974
ENSE00000926500	97669593	97669706
ENSE00001465914	97671086	97673748
ENSE00001592843	97660946	97661068
ENSE00001610051	97650503	97650600
ENSE00001610908	97640794	97640882
ENSE00001626181	97641562	97641662
ENSE00001626418	97654880	97654944
ENSE00001648128	97656011	97656085
ENSE00001686031	97643204	97643360
ENSE00001714911	97664340	97664443
ENSE00001728703	97666763	97666877
ENSE00001738969	97651310	97651373
ENSE00001763342	97658640	97658743
ENSE00001767060	97653798	97653908
ENSE00001800577	97662042	97662144
ENSE00001802313	97662954	97663047
ENSE00001803324	97655702	97655764
ENSE00001803534	97645611	97645732
ENSE00002222818	97633821	97633915
ENSE00003579871	97645117	97645224
ENSE00003623700	97648008	97648223
ENSE00003654190	97647492	97647561

Expression profiles

Bgee: expression breadth ubiquitous, 250 present calls, max score 93.27.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 46.8594 / max 286.3154, expressed in 1827 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
97574	18.6587	1811
97573	14.2492	1808
97572	8.1848	1752
97570	3.4684	1434
97575	0.9954	689
97569	0.8997	486
97568	0.4033	171

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	93.27	gold quality
calcaneal tendon	UBERON:0003701	92.86	gold quality
ganglionic eminence	UBERON:0004023	91.44	gold quality
cortical plate	UBERON:0005343	91.36	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.94	gold quality
ventricular zone	UBERON:0003053	89.79	gold quality
adrenal tissue	UBERON:0018303	89.10	gold quality
tendon	UBERON:0000043	89.00	gold quality
rectum	UBERON:0001052	88.86	gold quality
embryo	UBERON:0000922	87.89	gold quality
stromal cell of endometrium	CL:0002255	86.96	gold quality
gastrocnemius	UBERON:0001388	86.88	gold quality
muscle of leg	UBERON:0001383	86.72	gold quality
tibial nerve	UBERON:0001323	86.71	gold quality
mucosa of transverse colon	UBERON:0004991	86.69	gold quality
islet of Langerhans	UBERON:0000006	86.65	gold quality
right hemisphere of cerebellum	UBERON:0014890	86.31	gold quality
body of pancreas	UBERON:0001150	86.30	gold quality
hindlimb stylopod muscle	UBERON:0004252	86.25	gold quality
monocyte	CL:0000576	86.14	gold quality
right lobe of thyroid gland	UBERON:0001119	86.14	gold quality
cerebellar hemisphere	UBERON:0002245	86.08	gold quality
right ovary	UBERON:0002118	85.99	gold quality
cerebellar cortex	UBERON:0002129	85.97	gold quality
left lobe of thyroid gland	UBERON:0001120	85.81	gold quality
left ovary	UBERON:0002119	85.79	gold quality
adenohypophysis	UBERON:0002196	85.60	gold quality
mononuclear cell	CL:0000842	85.56	gold quality
leukocyte	CL:0000738	85.55	gold quality
muscle layer of sigmoid colon	UBERON:0035805	85.49	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.61

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): UPF1

miRNA regulators (miRDB)

90 targeting NCBP1, 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-3613-3P	100.00	76.36	7965
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-6715A-3P	99.83	68.05	1473
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-6739-5P	99.80	67.87	2806

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.6% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 19)

• crystal structure at 2.1 A resolution of CBP20 and CBP80 bound to an m(7)GpppG cap analogue (PMID:12374755)
• Structural basis of m7GpppG binding to the nuclear cap-binding protein complex. (PMID:12434151)
• The organization of the CBP80-CBP20 complex suggests how the activity of eIF4G in translation initiation could be regulated through a dynamic network of overlapping intra- and intermolecular interactions. (PMID:16156639)
• During nonsense-mediated mRNA decay, CBP80 interacts with Upf1 and promotes the interaction of Upf1 with Upf2 but not with Stau1. (PMID:16186820)
• Association of CBC with PARN might have importance in the regulated recruitment of PARN to the nonsense-mediated decay pathway during the pioneer round of translation. (PMID:16317009)
• We show that NELF interacts with the nuclear cap binding complex (CBC), a heterodimeric, multifunctional factor that plays important roles in several mRNA processing steps, and the two factors together participate in the 3’ end processing of histone mRNAs (PMID:17499042)
• The authors could distinguish two tyrosines, Y43 and Y20, in stabilization of the cap inside the cap-binding complex binding pocket. (PMID:19026660)
• a new MIF4G domain-containing protein, CTIF (CBP80/20-dependent translation initiation factor) that interacts directly with CBP80 and is part of the CBP80/20-dependent translation initiation complex (PMID:19648179)
• resolution X-ray structure for a cap-binding complex (CBC)-importin-alpha complex that provides a detailed picture for how importin-alpha binds to the CBP80 subunit of the CBC. (PMID:19668212)
• UPF1 binds PTC-containing mRNA more efficiently than the corresponding PTC-free mRNA in a way that is promoted by the UPF1-CBP80 interaction. (PMID:20691628)
• Viral mRNA associates with the influenza virus A NS1 and the cellular NCBP1 of the nuclear cap-binding complex. (PMID:21402597)
• Cellular processes by which CBP80-CBP20 -bound messenger ribonucleoproteins (mRNPs) are remodeled to eIF4E-bound mRNPs, are overviewed. (PMID:21447822)
• down-regulation of CTIF using a small interfering RNA causes a redistribution of CBP80 from polysome fractions to subpolysome fractions, without significant consequence to eIF4E distribution (PMID:22493286)
• Study proposes the existence of an alternative cap-binding complex involving NCBP1 and NCBP3 that plays a key role in mRNA biogenesis. (PMID:26382858)
• Results suggest that rev protein, HIV-1 (Rev) regulates the association of nuclear cap-binding protein NCBP 80 kDa subunit (CBP80) and eukaryotic translation initiation factor 4A1 (eIF4AI) with the unspliced mRNA in the cytoplasm and the nucleus, respectively, during HIV-1 replication. (PMID:30239828)
• NCBP1 promotes the development of lung adenocarcinoma through up-regulation of CUL4B. (PMID:31448526)
• Affinity proteomic dissection of the human nuclear cap-binding complex interactome. (PMID:32960270)
• Translation mediated by the nuclear cap-binding complex is confined to the perinuclear region via a CTIF-DDX19B interaction. (PMID:34232997)
• Identification and validation of N[7] -methylguanosine-associated gene NCBP1 as prognostic and immune-associated biomarkers in breast cancer patients. (PMID:38071502)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ncbp1	ENSMUSG00000028330
rattus_norvegicus	Ncbp1	ENSRNOG00000023605
drosophila_melanogaster	Cbp80	FBGN0022942
caenorhabditis_elegans	ncbp-1	WBGENE00018156

Protein

Protein identifiers

Nuclear cap-binding protein subunit 1 — Q09161 (reviewed: Q09161)

Alternative names: 80 kDa nuclear cap-binding protein

All UniProt accessions (3): Q09161, F2Z2T1, X6R941

UniProt curated annotations — full annotation on UniProt →

Function. Component of the cap-binding complex (CBC), which binds cotranscriptionally to the 5’-cap of pre-mRNAs and is involved in various processes such as pre-mRNA splicing, translation regulation, nonsense-mediated mRNA decay, RNA-mediated gene silencing (RNAi) by microRNAs (miRNAs) and mRNA export. The CBC complex is involved in mRNA export from the nucleus via its interaction with ALYREF/THOC4/ALY, leading to the recruitment of the mRNA export machinery to the 5’-end of mRNA and to mRNA export in a 5’ to 3’ direction through the nuclear pore. The CBC complex is also involved in mediating U snRNA and intronless mRNAs export from the nucleus. The CBC complex is essential for a pioneer round of mRNA translation, before steady state translation when the CBC complex is replaced by cytoplasmic cap-binding protein eIF4E. The pioneer round of mRNA translation mediated by the CBC complex plays a central role in nonsense-mediated mRNA decay (NMD), NMD only taking place in mRNAs bound to the CBC complex, but not on eIF4E-bound mRNAs. The CBC complex enhances NMD in mRNAs containing at least one exon-junction complex (EJC) via its interaction with UPF1, promoting the interaction between UPF1 and UPF2. The CBC complex is also involved in ‘failsafe’ NMD, which is independent of the EJC complex, while it does not participate in Staufen-mediated mRNA decay (SMD). During cell proliferation, the CBC complex is also involved in microRNAs (miRNAs) biogenesis via its interaction with SRRT/ARS2 and is required for miRNA-mediated RNA interference. The CBC complex also acts as a negative regulator of PARN, thereby acting as an inhibitor of mRNA deadenylation. In the CBC complex, NCBP1/CBP80 does not bind directly capped RNAs (m7GpppG-capped RNA) but is required to stabilize the movement of the N-terminal loop of NCBP2/CBP20 and lock the CBC into a high affinity cap-binding state with the cap structure. Associates with NCBP3 to form an alternative cap-binding complex (CBC) which plays a key role in mRNA export and is particularly important in cellular stress situations such as virus infections. The conventional CBC with NCBP2 binds both small nuclear RNA (snRNA) and messenger (mRNA) and is involved in their export from the nucleus whereas the alternative CBC with NCBP3 does not bind snRNA and associates only with mRNA thereby playing a role only in mRNA export. NCBP1/CBP80 is required for cell growth and viability.

Subunit / interactions. Component of the nuclear cap-binding complex (CBC), a heterodimer composed of NCBP1/CBP80 and NCBP2/CBP20 that interacts with m7GpppG-capped RNA. Found in a U snRNA export complex containing PHAX/RNUXA, NCBP1/CBP80, NCBP2/CBP20, RAN, XPO1 and m7G-capped RNA. Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs. Interacts with PHAX/RNUXA, SRRT/ARS2, EIF4G2, IGF2BP1, HNRNPF, HNRNPH1, KIAA0427/CTIF, PARN, DROSHA, UPF1 and ALYREF/THOC4. May interact with EIF4G1; the interaction is however controversial since it is reported by PubMed:11340157, PubMed:15059963 and PubMed:15361857, but is not observed by PubMed:19648179. The large PER complex involved in the repression of transcriptional termination is composed of at least PER2, CDK9, DDX5, DHX9, NCBP1/CBP80 and POLR2A. Component of an alternative nuclear cap-binding complex (CBC) composed of NCBP1/CBP80 and NCBP3. Interacts with METTL3. Interacts with ZFC3H1 in a RNase-insensitive manner. Interacts with MTREX. Interacts with TASOR. Interacts with DHX34; the interaction is RNA-dependent. Interacts with KPNA3.

Subcellular location. Nucleus. Cytoplasm.

Post-translational modifications. Dephosphorylated at Thr-21 by the PNUTS-PP1 complex during RNA polymerase II transcription pause-release.

Similarity. Belongs to the NCBP1 family.

RefSeq proteins (5): NP_001338433, NP_001338434, NP_001338435, NP_001338436, NP_002477* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003890	MIF4G-like_typ-3	Domain
IPR015172	MIF4G-like_typ-1	Domain
IPR015174	MIF4G-like_typ-2	Domain
IPR016024	ARM-type_fold	Homologous_superfamily
IPR027159	CBP80	Family

Pfam: PF02854, PF09088, PF09090

UniProt features (78 total): helix 44, turn 8, strand 8, modified residue 6, mutagenesis site 3, sequence conflict 3, chain 1, domain 1, cross-link 1, region of interest 1, coiled-coil region 1, short sequence motif 1

Structure

Experimental structures (PDB)

18 structures.

PDB	Method	Resolution (Å)
1H2V	X-RAY DIFFRACTION	2
1H6K	X-RAY DIFFRACTION	2
1H2T	X-RAY DIFFRACTION	2.1
1N52	X-RAY DIFFRACTION	2.11
3FEY	X-RAY DIFFRACTION	2.2
1H2U	X-RAY DIFFRACTION	2.4
9HFL	ELECTRON MICROSCOPY	2.62
6D0Y	X-RAY DIFFRACTION	2.68
1N54	X-RAY DIFFRACTION	2.72
5OOB	X-RAY DIFFRACTION	2.79
5OO6	X-RAY DIFFRACTION	2.8
8BY6	ELECTRON MICROSCOPY	3.19
8SRR	ELECTRON MICROSCOPY	3.22
8SUY	ELECTRON MICROSCOPY	3.38
8PMP	ELECTRON MICROSCOPY	3.43
8PNT	ELECTRON MICROSCOPY	3.46
3FEX	X-RAY DIFFRACTION	3.55
7ABG	ELECTRON MICROSCOPY	7.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q09161-F1	94.35	0.91

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 (7): 698, 684, 7, 21, 22, 201, 204

Mutagenesis-validated functional residues (3):

Position	Phenotype
7	reduced phosphorylation by rps6kb1. abolishes phosphorylation by rps6kb1; when associated with 21-a-a-22.
17–18	abolishes nuclear localization and phosphorylation by rps6kb1.
21–22	reduced phosphorylation by rps6kb1. abolishes phosphorylation by rps6kb1; when associated with a-7.

Function

Pathways and Gene Ontology

Reactome pathways

61 pathways

ID	Pathway
R-HSA-111367	SLBP independent Processing of Histone Pre-mRNAs
R-HSA-112382	Formation of RNA Pol II elongation complex
R-HSA-113418	Formation of the Early Elongation Complex
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
R-HSA-167152	Formation of HIV elongation complex in the absence of HIV Tat
R-HSA-167158	Formation of the HIV-1 Early Elongation Complex
R-HSA-167200	Formation of HIV-1 elongation complex containing HIV-1 Tat
R-HSA-167242	Abortive elongation of HIV-1 transcript in the absence of Tat
R-HSA-191859	snRNP Assembly
R-HSA-674695	RNA Polymerase II Pre-transcription Events
R-HSA-6803529	FGFR2 alternative splicing
R-HSA-6807505	RNA polymerase II transcribes snRNA genes
R-HSA-72086	mRNA Capping
R-HSA-72163	mRNA Splicing - Major Pathway
R-HSA-72165	mRNA Splicing - Minor Pathway
R-HSA-72187	mRNA 3’-end processing
R-HSA-72203	Processing of Capped Intron-Containing Pre-mRNA
R-HSA-73856	RNA Polymerase II Transcription Termination
R-HSA-77588	SLBP Dependent Processing of Replication-Dependent Histone Pre-mRNAs
R-HSA-77595	Processing of Intronless Pre-mRNAs
R-HSA-8851708	Signaling by FGFR2 IIIa TM
R-HSA-9010553	Regulation of expression of SLITs and ROBOs
R-HSA-975956	Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)
R-HSA-975957	Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC)
R-HSA-9770562	mRNA Polyadenylation
R-HSA-9918481	Dengue Virus-Host Interactions
R-HSA-9930044	Nuclear RNA decay

MSigDB gene sets: 314 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_UP, GSE45365_NK_CELL_VS_BCELL_UP, GOBP_CYTOPLASMIC_TRANSLATION, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_POSITIVE_REGULATION_OF_RNA_SPLICING, GOBP_POSITIVE_REGULATION_OF_MRNA_PROCESSING, GOBP_ALTERNATIVE_MRNA_SPLICING_VIA_SPLICEOSOME, REACTOME_SIGNALING_BY_FGFR, GOBP_GROWTH, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_TRANSLATIONAL_INITIATION, MODULE_70, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, PUJANA_CHEK2_PCC_NETWORK, GOBP_TRANSLATION

GO Biological Process (30): nuclear-transcribed mRNA catabolic process, nonsense-mediated decay (GO:0000184), spliceosomal complex assembly (GO:0000245), alternative mRNA splicing, via spliceosome (GO:0000380), mRNA splicing, via spliceosome (GO:0000398), cap-dependent translational initiation (GO:0002191), 7-methylguanosine mRNA capping (GO:0006370), RNA catabolic process (GO:0006401), mRNA export from nucleus (GO:0006406), snRNA export from nucleus (GO:0006408), regulation of translational initiation (GO:0006446), histone mRNA metabolic process (GO:0008334), RNA splicing (GO:0008380), mRNA metabolic process (GO:0016071), positive regulation of cell growth (GO:0030307), primary miRNA processing (GO:0031053), mRNA 3’-end processing (GO:0031124), positive regulation of mRNA 3’-end processing (GO:0031442), positive regulation of transcription elongation by RNA polymerase II (GO:0032968), regulatory ncRNA-mediated post-transcriptional gene silencing (GO:0035194), miRNA-mediated post-transcriptional gene silencing (GO:0035195), mRNA transcription by RNA polymerase II (GO:0042789), positive regulation of mRNA splicing, via spliceosome (GO:0048026), regulation of mRNA processing (GO:0050684), defense response to virus (GO:0051607), mRNA processing (GO:0006397), regulation of translation (GO:0006417), RNA metabolic process (GO:0016070), regulatory ncRNA-mediated gene silencing (GO:0031047), mRNA transport (GO:0051028), positive regulation of RNA binding (GO:1905216)

GO Molecular Function (6): RNA cap binding (GO:0000339), RNA 7-methylguanosine cap binding (GO:0000340), RNA binding (GO:0003723), mRNA binding (GO:0003729), molecular adaptor activity (GO:0060090), protein binding (GO:0005515)

GO Cellular Component (8): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), mitochondrion (GO:0005739), cytosol (GO:0005829), nuclear cap binding complex (GO:0005846), RNA cap binding complex (GO:0034518), ribonucleoprotein complex (GO:1990904)

Reactome top-level categories

Rollup of top-13 pathways:

Category	Pathways
Transport of Mature mRNAs Derived from Intronless Transcripts	3
RNA Polymerase II Transcription Elongation	2
HIV Transcription Elongation	2
RNA Polymerase II Transcription	2
Metabolism of RNA	2
mRNA Splicing	2
Processing of Capped Intronless Pre-mRNA	1
Transport of Mature Transcript to Cytoplasm	1
Transcription of the HIV genome	1
Tat-mediated elongation of the HIV-1 transcript	1
Metabolism of non-coding RNA	1
Signaling by FGFR2	1
Processing of Capped Intron-Containing Pre-mRNA	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
mRNA processing	3
cellular anatomical structure	3
mRNA splicing, via spliceosome	2
RNA metabolic process	2
RNA export from nucleus	2
RNA binding	2
binding	2
intracellular membrane-bounded organelle	2
cytoplasm	2
nuclear-transcribed mRNA catabolic process	1
protein-RNA complex assembly	1
RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	1
cytoplasmic translational initiation	1
cap-dependent translation initiation factor activity	1
7-methylguanosine RNA capping	1
nucleic acid catabolic process	1
gene expression	1
mRNA transport	1
snRNA transport	1
translational initiation	1
regulation of translation	1
mRNA metabolic process	1
RNA processing	1
regulation of cell growth	1
cell growth	1
positive regulation of growth	1
positive regulation of cellular process	1
miRNA processing	1
RNA 3’-end processing	1
mRNA 3’-end processing	1
regulation of mRNA 3’-end processing	1
positive regulation of mRNA processing	1
transcription elongation by RNA polymerase II	1
positive regulation of DNA-templated transcription, elongation	1
regulation of transcription elongation by RNA polymerase II	1
positive regulation of transcription by RNA polymerase II	1
post-transcriptional gene silencing	1
regulatory ncRNA-mediated gene silencing	1
regulatory ncRNA-mediated post-transcriptional gene silencing	1
RNA cap binding	1

Protein interactions and networks

STRING

3128 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NCBP1	NCBP2	P52298	999
NCBP1	ALYREF	Q86V81	980
NCBP1	CTIF	O43310	963
NCBP1	SRRT	Q9BXP5	949
NCBP1	EIF4E	P06730	937
NCBP1	PHAX	Q9H814	934
NCBP1	EIF4G1	Q04637	931
NCBP1	UPF2	Q9HAU5	929
NCBP1	RBM25	P49756	925
NCBP1	UPF3A	Q9H1J1	910
NCBP1	XPO1	O14980	905
NCBP1	UPF1	Q92900	871
NCBP1	NELFE	P18615	857
NCBP1	EIF4A1	P04765	853
NCBP1	UPF3B	Q9BZI7	824

IntAct

343 interactions, top by confidence:

A	B	Type	Score
NCBP2	NCBP1	psi-mi:“MI:0407”(direct interaction)	0.960
NCBP1	NCBP2	psi-mi:“MI:0407”(direct interaction)	0.960
NCBP1	NCBP2	psi-mi:“MI:0915”(physical association)	0.960
NCBP1	NCBP2	psi-mi:“MI:2364”(proximity)	0.960

BioGRID (505): UPF3B (Affinity Capture-Western), POLDIP3 (Affinity Capture-Western), NCBP1 (Affinity Capture-Western), NCBP1 (Affinity Capture-Western), RPS6KB1 (Affinity Capture-Western), MTOR (Affinity Capture-Western), EIF3B (Affinity Capture-Western), NCBP1 (Affinity Capture-MS), POLDIP3 (Affinity Capture-Western), EIF4G1 (Affinity Capture-Western), NCBP1 (Two-hybrid), NCBP1 (Affinity Capture-MS), NCBP1 (Affinity Capture-MS), NCBP1 (Affinity Capture-MS), NCBP1 (Affinity Capture-MS)

ESM2 similar proteins: A0MT11, A1Z3X3, A2VD00, A4GWN3, A4II09, A4QNE0, A4VCH4, B5KFI0, O35841, P23116, P49754, Q09161, Q0P5I8, Q14152, Q15006, Q15386, Q1JU68, Q3B8M3, Q5E993, Q5E9L7, Q5KU39, Q5R4J9, Q5R644, Q5R882, Q5RE70, Q5XI83, Q5ZJZ6, Q5ZKG8, Q5ZMW3, Q68E01, Q6GLK9, Q6N069, Q6NRL4, Q6PCR7, Q6TGY8, Q6WKZ8, Q7L5D6, Q7TPD0, Q80UM3, Q8BHL5

Diamond homologs: A8XG63, B3MS75, B3NU52, B4GW22, B4I0W6, B4JM29, B4L2J8, B4M7T6, B4NC41, B4Q034, C0H906, O01763, Q09161, Q16UN6, Q29G82, Q3UYV9, Q56A27, Q5ZJZ6, Q6DIE2, Q6GQ80, Q6GQD0, Q7K4N3, Q7PX35

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
NCBP1	“up-regulates activity”	IRF8	binding
NCBP1	“form complex”	“Cap-binding complex”	binding
NCBP1	up-regulates	mRNA_nuclear_export
NCBP1	“up-regulates activity”	“messenger RNA”	relocalization

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 133 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
Nuclear RNA decay	5	17.1×	4e-04
Signaling by ALK in cancer	5	15.1×	8e-04
mRNA 3’-end processing	6	13.1×	3e-04
ISG15 antiviral mechanism	7	11.7×	1e-04
mRNA Splicing	9	11.0×	6e-05
rRNA modification in the nucleus and cytosol	5	10.4×	3e-03
Transport of Mature mRNA derived from an Intron-Containing Transcript	6	10.2×	1e-03
Signaling by ALK fusions and activated point mutants	6	10.0×	1e-03

GO biological processes:

GO term	Partners	Fold	FDR
NLS-bearing protein import into nucleus	5	37.1×	8e-05
nuclear-transcribed mRNA catabolic process, nonsense-mediated decay	6	26.0×	8e-05
translational initiation	5	16.6×	1e-03
mRNA export from nucleus	6	16.4×	3e-04
G1/S transition of mitotic cell cycle	6	11.2×	2e-03
negative regulation of translation	6	10.9×	2e-03
positive regulation of translation	5	10.5×	6e-03
RNA processing	5	10.1×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	72
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1459792	NC_000009.11:g.(?100190748)(103062956_?)del	Pathogenic

SpliceAI

3198 predictions. Top by Δscore:

Variant	Effect	Δscore
9:97633912:GACG:G	donor_gain	1.0000
9:97633913:ACGG:A	donor_loss	1.0000
9:97633914:CGGT:C	donor_loss	1.0000
9:97633916:G:GG	donor_gain	1.0000
9:97633916:GTG:G	donor_loss	1.0000
9:97633917:T:A	donor_loss	1.0000
9:97640780:T:G	acceptor_gain	1.0000
9:97640786:T:A	acceptor_gain	1.0000
9:97640878:AAAAG:A	donor_loss	1.0000
9:97640879:AAAGG:A	donor_loss	1.0000
9:97640880:AAGGT:A	donor_loss	1.0000
9:97640881:AGGTA:A	donor_loss	1.0000
9:97640882:GG:G	donor_loss	1.0000
9:97640883:GTATG:G	donor_loss	1.0000
9:97640884:T:G	donor_loss	1.0000
9:97641559:CA:C	acceptor_loss	1.0000
9:97641559:CAG:C	acceptor_gain	1.0000
9:97641560:A:AG	acceptor_gain	1.0000
9:97641560:A:C	acceptor_loss	1.0000
9:97641560:AGA:A	acceptor_gain	1.0000
9:97641560:AGAGT:A	acceptor_gain	1.0000
9:97641561:G:GA	acceptor_gain	1.0000
9:97641561:GA:G	acceptor_gain	1.0000
9:97641561:GAG:G	acceptor_gain	1.0000
9:97641561:GAGT:G	acceptor_gain	1.0000
9:97641561:GAGTG:G	acceptor_gain	1.0000
9:97641639:GATCT:G	donor_gain	1.0000
9:97641648:GCTTC:G	donor_gain	1.0000
9:97641661:GT:G	donor_gain	1.0000
9:97641663:G:GG	donor_gain	1.0000

AlphaMissense

5284 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:97643250:G:A	G91R	1.000
9:97643250:G:C	G91R	1.000
9:97643251:G:A	G91E	1.000
9:97643254:T:C	L92P	1.000
9:97643257:T:C	L93P	1.000
9:97643261:T:A	N94K	1.000
9:97643261:T:G	N94K	1.000
9:97643281:G:A	G101D	1.000
9:97645136:T:C	L134P	1.000
9:97648056:T:A	W244R	1.000
9:97648056:T:C	W244R	1.000
9:97648122:C:G	H266D	1.000
9:97654889:G:C	A394P	1.000
9:97655712:T:A	W416R	1.000
9:97655712:T:C	W416R	1.000
9:97655724:C:G	H420D	1.000
9:97655728:T:C	L421P	1.000
9:97655736:T:C	F424L	1.000
9:97655738:C:A	F424L	1.000
9:97655738:C:G	F424L	1.000
9:97655748:T:A	W428R	1.000
9:97655748:T:C	W428R	1.000
9:97655754:T:A	W430R	1.000
9:97655754:T:C	W430R	1.000
9:97655756:G:C	W430C	1.000
9:97655756:G:T	W430C	1.000
9:97655763:T:A	W433R	1.000
9:97655763:T:C	W433R	1.000
9:97662119:A:C	S560R	1.000
9:97662120:G:A	S560N	1.000

dbSNP variants (sampled 300 via entrez): RS1000047500 (9:97632026 A>C,G), RS1000074849 (9:97640735 A>G), RS1000113039 (9:97652043 G>A), RS1000150912 (9:97636849 G>C), RS1000376636 (9:97636890 G>A), RS1000392857 (9:97649950 T>G), RS1000446841 (9:97650241 A>G), RS1000475223 (9:97643957 T>C), RS1000481249 (9:97632212 C>G), RS1000569297 (9:97657356 A>G), RS1000585063 (9:97649864 A>G), RS1000674340 (9:97642780 T>G), RS1000680320 (9:97642760 G>A), RS1000710014 (9:97635509 C>T), RS1000723416 (9:97664399 A>G)

Disease associations

OMIM: gene MIM:600469 | disease phenotypes: MIM:256100

GenCC curated gene-disease

Disease	Classification	Inheritance
Tourette syndrome	Limited	Unknown

Mondo (2): nephronophthisis (MONDO:0019005), Tourette syndrome (MONDO:0007661)

Orphanet (1): Nephronophthisis (Orphanet:655)

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0000090	Nephronophthisis

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST000640_1	Thyroid cancer (Papillary, radiation-related)	5.000000e-12

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D005879	Tourette Syndrome	C10.228.140.079.898; C10.228.662.825.800; C10.574.500.850; C16.320.400.820; F03.625.992.850

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL4665589 (PROTEIN COMPLEX), CHEMBL6066853 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
9.10	Kd	0.799	nM	CHEMBL3752910
9.10	ED50	0.799	nM	CHEMBL3752910
6.94	Kd	114	nM	MOLIBRESIB
6.77	IC50	170	nM	MOLIBRESIB
5.75	Kd	1779	nM	CHEMBL5653589
5.75	ED50	1779	nM	CHEMBL5653589

PubChem BioAssay actives

4 with measured affinity, of 11 total; 3 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-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148830: Binding affinity to human NCBP1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0008	uM
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2179097: Binding affinity against NCBP1 (unknown origin) assessed as apparent dissociation constant incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	kd	0.1140	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148830: Binding affinity to human NCBP1 incubated for 45 mins by Kinobead based pull down assay	kd	1.7789	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, affects cotreatment, increases methylation	3
sodium arsenite	decreases expression, increases activity	2
Valproic Acid	decreases methylation, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	decreases phosphorylation	1
bisphenol F	increases expression	1
triphenyl phosphate	affects expression	1
benzo(e)pyrene	increases methylation	1
beta-methylcholine	affects expression	1
yessotoxin	decreases expression	1
nutlin 3	affects cotreatment, increases secretion	1
ICG 001	increases expression	1
bisphenol B	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
jinfukang	decreases expression	1
PP242	increases expression	1
bisphenol AF	increases expression	1
Oxaliplatin	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Gemcitabine	increases expression	1
Benzo(a)pyrene	affects methylation	1
Benztropine	decreases expression	1
Clozapine	decreases expression	1
Coumestrol	increases expression	1
Cuprizone	decreases expression	1
Dactinomycin	affects cotreatment, increases secretion	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Demecolcine	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1

ChEMBL screening assays

8 unique, capped per target: 8 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651872	Binding	Binding affinity to human NCBP1 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)

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

Trial	Phase	Status	Title
NCT00152750	PHASE4	UNKNOWN	Study of Clonidine on Sleep Architecture in Children With Tourette’s Syndrome (TS) and Comorbid ADHD
NCT00226824	PHASE4	TERMINATED	Safety Study of Galantamine in Tic Disorders
NCT00241176	PHASE4	COMPLETED	Open Label Trial of Aripiprazole in Children and Adolescents With Tourette’s Disorder
NCT00370838	PHASE4	COMPLETED	Comparison of Keppra and Clonidine in the Treatment of Tics
NCT01018056	PHASE4	COMPLETED	Developing New Treatments for Tourette Syndrome: Therapeutic Trials With Modulators of Glutamatergic Neurotransmission
NCT01547000	PHASE4	COMPLETED	Guanfacine in Children With Tic Disorders
NCT03239210	PHASE4	COMPLETED	Effects of Ondansetron in Obsessive-compulsive and Tic Disorders
NCT00004376	PHASE3	COMPLETED	Phase III Randomized, Double-Blind, Placebo-Controlled Study of Guanfacine for Tourette Syndrome and Attention Deficit Hyperactivity Disorder
NCT00206323	PHASE3	COMPLETED	A Randomized, Placebo-controlled, Tourette Syndrome Study.
NCT00206336	PHASE3	COMPLETED	An Open-label Study to Determine the Efficacy and Safety of Topiramate in the Treatment of Tourette Syndrome.
NCT00478842	PHASE3	COMPLETED	Pallidal Stimulation and Gilles de la Tourette Syndrome
NCT00681863	PHASE3	TERMINATED	Open-label Extension Study of Pramipexole in the Treatment of Children and Adolescents With Tourette Syndrome
NCT01501695	PHASE3	COMPLETED	Phase III Study of 5LGr to Treat Tic Disorder
NCT03087201	PHASE3	COMPLETED	CANNAbinoids in the Treatment of TICS (CANNA-TICS)
NCT03487783	PHASE3	COMPLETED	Aripiprazole Oral Solution in the Treatment of Children and Adolescents With Tourette’s Syndrome
NCT03567291	PHASE3	TERMINATED	Evaluation of Safety and Tolerability of Long-term TEV-50717 (Deutetrabenazine) for Treatment of Tourette Syndrome in Children and Adolescents
NCT03571256	PHASE3	COMPLETED	A Study to Test if TEV-50717 is Effective in Relieving Tics Associated With Tourette Syndrome (TS)
NCT06021522	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Evaluate Long-term Safety of Ecopipam Tablets in Children, Adolescents and Adults With Tourette’s Disorder
NCT00004393	PHASE2	COMPLETED	Phase II Double Blind Placebo Controlled Trial of Risperidone in Tourette Syndrome
NCT00004652	PHASE2	COMPLETED	Phase II Pilot Controlled Study of Short Vs Longer Term Pimozide (Orap) Therapy in Tourette Syndrome
NCT00231985	PHASE2	COMPLETED	Effectiveness of Behavior Therapy and Psychosocial Therapy for the Treatment of Tourette Syndrome and Chronic Tic Disorder
NCT00311909	PHASE2	COMPLETED	Thalamic Deep Brain Stimulation for Tourette Syndrome
NCT00529308	PHASE2	COMPLETED	Transcranial Magnetic Stimulation (TMS) for Individuals With Tourette’s Syndrome
NCT00558467	PHASE2	COMPLETED	Pramipexole Pilot Phase II Study in Children and Adolescents With Tourette Disorder According to DSM-IV Criteria
NCT01043549	PHASE2	TERMINATED	Repetitive Transcranial Magnetic Stimulation of the Posterior Parietal Cortex in Patients Suffering From Gilles de la Tourette Syndrome
NCT01133353	PHASE2	WITHDRAWN	A Study of the Effectiveness and Safety of Tetrabenazine MR in Pediatric Subjects With Tourette’s Syndrome
NCT01475383	PHASE2	WITHDRAWN	Study Evaluating The Safety And Efficacy Of PF-03654746 In Adult Subjects With Tourette’s Syndrome
NCT01647269	PHASE2	COMPLETED	A Trial of Bilateral Deep Brain Stimulation to the Globus Pallidus Internum in Tourette Syndrome
NCT01904773	PHASE2	COMPLETED	Safety, Tolerability, Pharmacokinetic, and Efficacy Study of AZD5213 in Adolescents With Tourette’s Disorder
NCT02102698	PHASE2	COMPLETED	Ecopipam Treatment of Tourette’s Syndrome in Subjects 7-17 Years
NCT02217007	PHASE2	WITHDRAWN	A Trial Evaluating the Efficacy, Safety, and Pharmacokinetics of SNC-102 in Subjects With Tourette Syndrome
NCT02247206	PHASE2	COMPLETED	VoIP Delivered Behavior Therapy for Tourette Syndrome
NCT02581865	PHASE2	COMPLETED	Safety and Efficacy Study of NBI-98854 in Adults With Tourette Syndrome
NCT02619084	PHASE2	COMPLETED	Subthalamic Stimulation in Tourette’s Syndrome
NCT02679079	PHASE2	COMPLETED	Safety and Efficacy Study of NBI-98854 in Children and Adolescents With Tourette Syndrome
NCT02879578	PHASE2	COMPLETED	Safety and Tolerability Study of NBI-98854 for the Treatment of Subjects With Tourette Syndrome
NCT03066193	PHASE2	COMPLETED	Efficacy of a Therapeutic Combination of Dronabinol and PEA for Tourette Syndrome
NCT03247244	PHASE2	TERMINATED	Safety and Efficacy of Cannabis in Tourette Syndrome
NCT03325010	PHASE2	COMPLETED	Safety, Tolerability, and Efficacy of NBI-98854 for the Treatment of Pediatric Subjects With Tourette Syndrome
NCT03444038	PHASE2	COMPLETED	Open-Label Safety and Tolerability Study of NBI-98854 for the Treatment of Pediatric Subjects With Tourette Syndrome