NCBP2

Summary

NCBP2 (nuclear cap binding protein subunit 2, HGNC:7659) is a protein-coding gene on chromosome 3q29, encoding Nuclear cap-binding protein subunit 2 (P52298). Component of the cap-binding complex (CBC), which binds co-transcriptionally 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)…. It is a common-essential gene (DepMap: required in 99.8% 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 has an RNP domain commonly found in RNA binding proteins, and contains the cap-binding activity. The CBC promotes pre-mRNA splicing, 3’-end processing, RNA nuclear export, and nonsense-mediated mRNA decay. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 22916 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 20 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 99.8% of screened cell lines (common-essential)
• MANE Select transcript: NM_007362

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7659
Approved symbol	NCBP2
Name	nuclear cap binding protein subunit 2
Location	3q29
Locus type	gene with protein product
Status	Approved
Aliases	NIP1, CBP20, Cbc2
Ensembl gene	ENSG00000114503
Ensembl biotype	protein_coding
OMIM	605133
Entrez	22916

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 7 protein_coding, 4 retained_intron, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000321256, ENST00000411704, ENST00000422610, ENST00000427641, ENST00000428425, ENST00000447325, ENST00000452404, ENST00000455953, ENST00000463783, ENST00000467803, ENST00000468923, ENST00000479647, ENST00000482976

RefSeq mRNA: 4 — MANE Select: NM_007362 NM_001042540, NM_001308036, NM_001410857, NM_007362

CCDS: CCDS3323, CCDS46986, CCDS77878, CCDS93446

Canonical transcript exons

ENST00000321256 — 4 exons

Exon	Start	End
ENSE00001056985	196942426	196942528
ENSE00001746919	196935406	196937082
ENSE00003539773	196939251	196939432
ENSE00003554682	196937510	196937648

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 98.36.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 56.7747 / max 673.4212, expressed in 1823 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
46390	53.3458	1823
46389	2.1115	1267
46388	0.9871	694
46387	0.3302	137

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ganglionic eminence	UBERON:0004023	98.36	gold quality
cortical plate	UBERON:0005343	98.33	gold quality
ventricular zone	UBERON:0003053	98.15	gold quality
secondary oocyte	CL:0000655	96.22	gold quality
embryo	UBERON:0000922	95.88	gold quality
nucleus accumbens	UBERON:0001882	95.46	gold quality
stromal cell of endometrium	CL:0002255	95.36	gold quality
caudate nucleus	UBERON:0001873	95.22	gold quality
rectum	UBERON:0001052	95.14	gold quality
islet of Langerhans	UBERON:0000006	95.13	gold quality
amygdala	UBERON:0001876	95.10	gold quality
putamen	UBERON:0001874	95.06	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	94.71	gold quality
right adrenal gland cortex	UBERON:0035827	94.70	gold quality
lymph node	UBERON:0000029	94.66	gold quality
right adrenal gland	UBERON:0001233	94.63	gold quality
left adrenal gland	UBERON:0001234	94.60	gold quality
endometrium epithelium	UBERON:0004811	94.54	gold quality
gall bladder	UBERON:0002110	94.49	gold quality
left adrenal gland cortex	UBERON:0035825	94.38	gold quality
spinal cord	UBERON:0002240	94.36	gold quality
muscle layer of sigmoid colon	UBERON:0035805	94.22	gold quality
adrenal cortex	UBERON:0001235	94.21	gold quality
adrenal tissue	UBERON:0018303	94.20	gold quality
lower esophagus muscularis layer	UBERON:0035833	94.19	gold quality
pericardium	UBERON:0002407	94.18	gold quality
lower esophagus	UBERON:0013473	94.18	gold quality
adrenal gland	UBERON:0002369	94.12	gold quality
endometrium	UBERON:0001295	94.05	gold quality
smooth muscle tissue	UBERON:0001135	93.99	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-6911	no	536.99
E-MTAB-7606	no	379.02
E-MTAB-5061	no	3.57
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

70 targeting NCBP2, 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-4682	100.00	68.89	1258
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-4302	99.89	67.94	1187
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-4420	99.82	70.08	1624
HSA-MIR-181B-2-3P	99.81	70.06	1646
HSA-MIR-181B-3P	99.81	70.06	1646
HSA-MIR-4639-5P	99.81	67.37	1028
HSA-MIR-4320	99.75	65.80	793
HSA-MIR-518A-5P	99.70	69.01	2209
HSA-MIR-527	99.70	69.01	2209
HSA-MIR-1283	99.69	72.42	3009
HSA-MIR-7161-5P	99.68	68.92	1592

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.8% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 9)

• 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)
• 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)
• 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)
• determined how importin-beta binds to the cap-binding complex (CBC) through its CBP20 subunit (PMID:19668212)
• A novel alternative splice variant of CBP20, termed CBP20S, has an in-frame deletion, leading to the translation of a protein lacking most of the RNA recognition motif (RRM). (PMID:21326824)
• NCBP2 is not required for cell viability and poly(A) RNA export. (PMID:26382858)
• Affinity proteomic dissection of the human nuclear cap-binding complex interactome. (PMID:32960270)
• m7G-related genes-NCBP2 and EIF4E3 determine immune contexture in head and neck squamous cell carcinoma by regulating CCL4/CCL5 expression. (PMID:37067401)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ncbp2	ENSDARG00000014898
mus_musculus	Ncbp2	ENSMUSG00000022774
rattus_norvegicus	Ncbp2	ENSRNOG00000001746
drosophila_melanogaster	Cbp20	FBGN0022943
caenorhabditis_elegans	ncbp-2	WBGENE00009141

Paralogs (1): NCBP2L (ENSG00000170935)

Protein

Protein identifiers

Nuclear cap-binding protein subunit 2 — P52298 (reviewed: P52298)

Alternative names: 20 kDa nuclear cap-binding protein, Cell proliferation-inducing gene 55 protein, NCBP 20 kDa subunit, NCBP-interacting protein 1

All UniProt accessions (5): C9JKF4, C9JQX9, P52298, F6WVI0, F8WE41

UniProt curated annotations — full annotation on UniProt →

Function. Component of the cap-binding complex (CBC), which binds co-transcriptionally 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, thereby being 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, NCBP2/CBP20 recognizes and binds capped RNAs (m7GpppG-capped RNA) but requires NCBP1/CBP80 to stabilize the movement of its N-terminal loop and lock the CBC into a high affinity cap-binding state with the cap structure. The conventional cap-binding complex with NCBP2 binds both small nuclear RNA (snRNA) and messenger (mRNA) and is involved in their export from the nucleus.

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 with PHAX/RNUXA, NCBP1/CBP80, NCBP2/CBP20, RAN, XPO1 and m7G-capped RNA. Interacts with PHAX/RNUXA, EIF4G1, HNRNPF, HNRNPH1 and ALYREF/THOC4/ALY. Interacts with SRRT/ARS2 and KPNA3.

Subcellular location. Nucleus. Cytoplasm.

Similarity. Belongs to the RRM NCBP2 family.

Isoforms (3)

UniProt ID	Names	Canonical?
P52298-1	1	yes
P52298-2	2
P52298-3	3

RefSeq proteins (4): NP_001036005, NP_001294965, NP_001397786, NP_031388* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000504	RRM_dom	Domain
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR027157	NCBP2	Family
IPR034148	NCBP2_RRM	Domain
IPR035979	RBD_domain_sf	Homologous_superfamily

Pfam: PF00076

UniProt features (50 total): mutagenesis site 13, helix 8, strand 8, binding site 5, modified residue 4, turn 4, splice variant 2, initiator methionine 1, chain 1, domain 1, sequence conflict 1, region of interest 1, compositionally biased region 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-P52298-F1	93.82	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.

Ligand- & substrate-binding residues (5): 20; 43; 112–116; 123–127; 133–134

Post-translational modifications (4): 2, 13, 18, 146

Mutagenesis-validated functional residues (13):

Position	Phenotype
20	abolishes mrna cap-binding.
20	strongly impairs mrna cap-binding.
25	does not affect mrna cap-binding.
43	abolishes mrna cap-binding.
43	does not affect mrna cap-binding.
46	does not affect mrna cap-binding.
83	abolishes mrna cap-binding.
85	impairs mrna cap-binding.
112	does not affect mrna cap-binding.
114	does not affect mrna cap-binding.
116	abolishes mrna cap-binding.
119	does not affect mrna cap-binding.
138	does not affect mrna cap-binding.

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: 305 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_UP, MORF_MTA1, GOBP_CYTOPLASMIC_TRANSLATION, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, PAL_PRMT5_TARGETS_UP, GOBP_POSITIVE_REGULATION_OF_MRNA_PROCESSING, GOBP_ALTERNATIVE_MRNA_SPLICING_VIA_SPLICEOSOME, REACTOME_SIGNALING_BY_FGFR, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, GOBP_TRANSLATIONAL_INITIATION, MORF_HDAC2, MODULE_16

GO Biological Process (23): nuclear-transcribed mRNA catabolic process, nonsense-mediated decay (GO:0000184), alternative mRNA splicing, via spliceosome (GO:0000380), mRNA splicing, via spliceosome (GO:0000398), cap-dependent translational initiation (GO:0002191), 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), 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), mRNA cis splicing, via spliceosome (GO:0045292), positive regulation of RNA export from nucleus (GO:0046833), mRNA processing (GO:0006397), regulation of translation (GO:0006417), regulatory ncRNA-mediated gene silencing (GO:0031047), mRNA transport (GO:0051028)

GO Molecular Function (8): RNA cap binding (GO:0000339), RNA 7-methylguanosine cap binding (GO:0000340), DNA binding (GO:0003677), RNA binding (GO:0003723), mRNA binding (GO:0003729), snRNA binding (GO:0017069), nucleic acid binding (GO:0003676), protein binding (GO:0005515)

GO Cellular Component (7): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), nuclear cap binding complex (GO:0005846), RNA cap binding complex (GO:0034518), ciliary basal body (GO:0036064)

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
RNA export from nucleus	3
RNA binding	3
cellular anatomical structure	3
mRNA splicing, via spliceosome	2
mRNA processing	2
mRNA metabolic process	2
RNA processing	2
nucleic acid binding	2
binding	2
nuclear-transcribed mRNA catabolic process	1
RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	1
cytoplasmic translational initiation	1
cap-dependent translation initiation factor activity	1
gene expression	1
mRNA transport	1
snRNA transport	1
translational initiation	1
regulation of translation	1
RNA metabolic 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
transcription by RNA polymerase II	1
mRNA transcription	1
positive regulation of nucleobase-containing compound transport	1
positive regulation of nucleocytoplasmic transport	1
regulation of RNA export from nucleus	1
RNA cap binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

2994 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NCBP2	NCBP1	Q09161	999
NCBP2	SRRT	Q9BXP5	973
NCBP2	CTIF	O43310	928
NCBP2	EIF4G1	Q04637	907
NCBP2	EIF4E	P06730	899
NCBP2	PHAX	Q9H814	897
NCBP2	UPF2	Q9HAU5	866
NCBP2	PABPN1	Q86U42	859
NCBP2	UPF3A	Q9H1J1	857
NCBP2	XPO1	O14980	757
NCBP2	UPF1	Q92900	750
NCBP2	MTREX	P42285	702
NCBP2	SF3B4	Q15427	700
NCBP2	SNRPC	P09234	694
NCBP2	CDC5L	Q99459	678

IntAct

136 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 (191): LZTS2 (Two-hybrid), NCBP2 (Affinity Capture-MS), ADPRHL2 (Co-fractionation), NCBP1 (Co-fractionation), NCBP2 (Co-fractionation), SYNCRIP (Co-fractionation), NCBP2 (Affinity Capture-MS), ZBTB48 (Affinity Capture-MS), KPNA2 (Affinity Capture-MS), KPNA3 (Affinity Capture-MS), KPNA4 (Affinity Capture-MS), NCBP1 (Affinity Capture-MS), NUP98 (Affinity Capture-MS), RPL10 (Affinity Capture-MS), STX3 (Affinity Capture-MS)

ESM2 similar proteins: A2SW84, A6PVI3, A8Y1R8, B0W939, B1WC40, B3LYP1, B3P0D7, B4GLK8, B4IBA4, B4JUT1, B4KCD5, B4LZ88, B4M205, B4NB54, B4PL68, B4QV17, B5G279, B7P877, C0H859, C1BY64, C6Y4C0, O94290, P25555, P36629, P40565, P52298, P52299, Q00916, Q05AT9, Q08920, Q177H0, Q1HE01, Q293V6, Q3ZBJ1, Q4IE79, Q54KR9, Q5ZKR5, Q6DES0, Q6FNF9, Q754W7

Diamond homologs: A0A0D1C8Z4, A2SW84, A6PVI3, A8Y1R8, B0W939, B1WC40, B3LYP1, B3P0D7, B4GLK8, B4IBA4, B4JUT1, B4KCD5, B4LZ88, B4M205, B4NB54, B4PL68, B4QV17, B5DGI7, B5G279, B7P877, C0H859, C0HFE5, C1BY64, O35698, O89086, P19684, P27476, P33240, P52298, P52299, P60824, P60825, P60826, P62995, P62996, P62997, P78795, P98179, Q05AT9, Q08920

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
NCBP2	“form complex”	“Cap-binding complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 92 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
HIV Transcription Elongation	5	24.3×	5e-05
Dengue Virus Genome Translation and Replication	5	23.0×	7e-05
mRNA Splicing	13	20.7×	5e-12
mRNA 3’-end processing	7	20.0×	3e-06
RNA Polymerase II Transcription Termination	6	19.1×	2e-05
Formation of HIV-1 elongation complex containing HIV-1 Tat	5	18.8×	1e-04
Tat-mediated elongation of the HIV-1 transcript	5	18.8×	1e-04
Formation of HIV elongation complex in the absence of HIV Tat	5	18.0×	2e-04

GO biological processes:

GO term	Partners	Fold	FDR
U2-type prespliceosome assembly	5	38.1×	3e-05
spliceosomal complex assembly	5	36.7×	3e-05
mRNA export from nucleus	8	28.8×	9e-08
nuclear-transcribed mRNA catabolic process, nonsense-mediated decay	5	28.5×	8e-05
mRNA splicing, via spliceosome	16	17.9×	3e-13
regulation of alternative mRNA splicing, via spliceosome	5	14.9×	1e-03
RNA splicing	11	11.8×	4e-07
mRNA processing	8	7.7×	7e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

1147 predictions. Top by Δscore:

Variant	Effect	Δscore
3:196937552:AAAG:A	donor_gain	1.0000
3:196939252:C:CA	donor_gain	1.0000
3:196939282:T:TA	donor_gain	1.0000
3:196939429:CACC:C	acceptor_gain	1.0000
3:196939431:CC:C	acceptor_gain	1.0000
3:196939432:CC:C	acceptor_gain	1.0000
3:196939433:CTAG:C	acceptor_loss	1.0000
3:196937079:GAACC:G	acceptor_loss	0.9900
3:196937080:AACCT:A	acceptor_loss	0.9900
3:196937081:ACCTT:A	acceptor_loss	0.9900
3:196937082:CCTTT:C	acceptor_loss	0.9900
3:196937083:C:A	acceptor_loss	0.9900
3:196937084:T:A	acceptor_loss	0.9900
3:196937547:T:TA	donor_gain	0.9900
3:196939196:C:CT	donor_gain	0.9900
3:196939205:G:C	donor_gain	0.9900
3:196939211:C:A	donor_gain	0.9900
3:196939249:A:AC	donor_gain	0.9900
3:196939250:C:CC	donor_gain	0.9900
3:196939392:CAG:C	donor_gain	0.9900
3:196939428:TCACC:T	acceptor_gain	0.9900
3:196939429:CACCC:C	acceptor_gain	0.9900
3:196939433:C:CC	acceptor_gain	0.9900
3:196939434:T:A	acceptor_loss	0.9900
3:196942379:G:C	donor_gain	0.9900
3:196942387:G:A	donor_gain	0.9900
3:196942399:C:A	donor_gain	0.9900
3:196942419:C:A	donor_gain	0.9900
3:196942420:CCTCA:C	donor_loss	0.9900
3:196942421:CTCA:C	donor_loss	0.9900

AlphaMissense

1018 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:196937540:C:A	R123S	1.000
3:196937540:C:G	R123S	1.000
3:196937541:C:A	R123M	1.000
3:196937541:C:G	R123T	1.000
3:196937583:C:G	R109P	1.000
3:196939256:A:C	F85L	1.000
3:196939256:A:T	F85L	1.000
3:196939257:A:G	F85S	1.000
3:196939258:A:G	F85L	1.000
3:196939259:A:C	C84W	1.000
3:196939260:C:T	C84Y	1.000
3:196939261:A:G	C84R	1.000
3:196939262:G:C	F83L	1.000
3:196939262:G:T	F83L	1.000
3:196939263:A:G	F83S	1.000
3:196939264:A:G	F83L	1.000
3:196939266:C:A	G82V	1.000
3:196939266:C:T	G82E	1.000
3:196939297:C:G	G72R	1.000
3:196939371:A:G	L47P	1.000
3:196939377:C:T	G45E	1.000
3:196939380:A:T	V44D	1.000
3:196937517:C:T	G131E	0.999
3:196937526:C:T	G128E	0.999
3:196937527:C:G	G128R	0.999
3:196937527:C:T	G128R	0.999
3:196937530:G:T	R127S	0.999
3:196937532:C:T	G126D	0.999
3:196937533:C:G	G126R	0.999
3:196937552:A:C	F119L	0.999

dbSNP variants (sampled 300 via entrez): RS1000108563 (3:196941161 G>A,C,T), RS1000352863 (3:196936214 GA>G), RS1000807537 (3:196940812 T>G), RS1000859702 (3:196941070 T>G), RS1000883245 (3:196935395 C>G), RS1001237265 (3:196941428 C>G), RS1001251725 (3:196935165 C>T), RS1001268638 (3:196941693 C>A,G,T), RS1001383458 (3:196935765 T>G), RS1001881886 (3:196936098 T>C), RS1003253449 (3:196944136 A>G), RS1003487448 (3:196943571 C>A), RS1003562695 (3:196942548 C>A,G), RS1003593663 (3:196942656 G>A), RS1003610362 (3:196943901 C>A,T)

Disease associations

OMIM: gene MIM:605133 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST003542_204	Night sleep phenotypes	9.000000e-06
GCST008758_42	Pre-treatment viral load in HIV-1 infection	2.000000e-17
GCST010725_2	Malaria	8.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010125	viral load

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL4665589 (PROTEIN COMPLEX), CHEMBL6066873 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.78	Kd	1.678	nM	CHEMBL3752910
8.64	ED50	2.293	nM	CHEMBL3752910

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 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	2149895: Binding affinity to human NCBP2 incubated for 45 mins by Kinobead based pull down assay	kd	0.0017	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression	2
trichostatin A	affects cotreatment, increases expression	2
cobaltous chloride	decreases expression	2
aristolochic acid I	decreases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	affects binding, increases reaction	1
bleomycetin	increases expression	1
N,N,N’,N’-tetrakis(2-pyridylmethyl)ethylenediamine	increases expression	1
tamibarotene	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
bisphenol B	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	increases expression	1
bisphenol AF	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Acetaminophen	decreases expression	1
Cadmium	increases abundance, increases expression	1
Cisplatin	increases expression	1
Diethylstilbestrol	decreases expression	1
Nickel	increases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	decreases expression	1
Cyclosporine	decreases expression	1
Aflatoxin B1	increases methylation	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652937	Binding	Binding affinity to human NCBP2 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)

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