NRBF2

Summary

NRBF2 (nuclear receptor binding factor 2, HGNC:19692) is a protein-coding gene on chromosome 10q21.3, encoding Nuclear receptor-binding factor 2 (Q96F24). May modulate transcriptional activation by target nuclear receptors. It is a selective cancer dependency (DepMap: 13.9% of cell lines).

Involved in autophagy. Located in cytoplasm and phosphatidylinositol 3-kinase complex, class III.

Source: NCBI Gene 29982 — RefSeq curated summary.

At a glance

• GWAS associations: 32
• Clinical variants (ClinVar): 35 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 13.9% of screened cell lines
• MANE Select transcript: NM_030759

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19692
Approved symbol	NRBF2
Name	nuclear receptor binding factor 2
Location	10q21.3
Locus type	gene with protein product
Status	Approved
Aliases	DKFZp564C1664, FLJ30395, COPR1, COPR2
Ensembl gene	ENSG00000148572
Ensembl biotype	protein_coding
OMIM	616477
Entrez	29982

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 5 protein_coding

ENST00000277746, ENST00000435510, ENST00000857328, ENST00000932225, ENST00000963003

RefSeq mRNA: 2 — MANE Select: NM_030759 NM_001282405, NM_030759

CCDS: CCDS60537, CCDS7268

Canonical transcript exons

ENST00000277746 — 4 exons

Exon	Start	End
ENSE00000985963	63146209	63146293
ENSE00000985964	63152150	63152190
ENSE00001272071	63153511	63155024
ENSE00001900579	63133328	63133500

Expression profiles

Bgee: expression breadth ubiquitous, 277 present calls, max score 94.45.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 34.5480 / max 585.1871, expressed in 1818 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
105167	33.0838	1816
105168	1.1121	578
105166	0.3521	140

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	94.45	gold quality
blood	UBERON:0000178	93.34	gold quality
amniotic fluid	UBERON:0000173	91.86	gold quality
leukocyte	CL:0000738	91.30	gold quality
monocyte	CL:0000576	91.17	gold quality
mononuclear cell	CL:0000842	91.04	gold quality
calcaneal tendon	UBERON:0003701	90.84	gold quality
right lobe of liver	UBERON:0001114	90.64	gold quality
granulocyte	CL:0000094	90.33	gold quality
bone marrow	UBERON:0002371	90.08	gold quality
tendon	UBERON:0000043	88.94	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.89	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.84	gold quality
hindlimb stylopod muscle	UBERON:0004252	88.48	gold quality
bone element	UBERON:0001474	88.38	gold quality
palpebral conjunctiva	UBERON:0001812	88.13	gold quality
islet of Langerhans	UBERON:0000006	88.07	gold quality
stromal cell of endometrium	CL:0002255	87.58	gold quality
liver	UBERON:0002107	87.53	gold quality
tendon of biceps brachii	UBERON:0008188	87.38	gold quality
gastrocnemius	UBERON:0001388	87.29	gold quality
placenta	UBERON:0001987	87.24	gold quality
muscle of leg	UBERON:0001383	87.10	gold quality
gall bladder	UBERON:0002110	87.08	gold quality
parotid gland	UBERON:0001831	86.95	gold quality
rectum	UBERON:0001052	86.80	gold quality
bone marrow cell	CL:0002092	86.44	gold quality
cartilage tissue	UBERON:0002418	86.44	gold quality
omental fat pad	UBERON:0010414	86.17	gold quality
vermiform appendix	UBERON:0001154	86.14	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

102 targeting NRBF2, 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-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-329-3P	99.91	66.56	1234
HSA-MIR-362-3P	99.91	66.38	1267
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-652-5P	99.91	67.49	505
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 13.9% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 11)

• The activation domain, their small size (COPR1, 26.9 kDa; COPR2, 32.4 kDa), and strict dependence on AF-2 for interaction distinguish COPR1 and COPR2 from the SMRT/NCoR type of corepressor and may dampen rather than repress NR-mediated gene expression. (PMID:15610520)
• NRBF2 regulates macroautophagy as a component of Vps34 Complex I. (PMID:24785657)
• Nrbf2 may interact with the Atg14L-containing Beclin 1-Vps34 protein complex to modulate protein-protein interactions within the complex. (PMID:25086043)
• Polymorphisms in a putative enhancer at the 10q21.2 Breast Cancer Risk Locus regulate NRBF2 expression, implicating this gene in the etiology of breast cancer. (PMID:26073781)
• Here we show that a putative fifth subunit, nuclear receptor binding factor 2 (NRBF2), is a tightly bound component of the class III phosphatidylinositol 3-kinase complex I that profoundly affects its activity and architecture. NRBF2 is a homodimer and drives the dimerization of the larger PI3KC3-C1 complex, with implications for the higher-order organization of the preautophagosomal structure. (PMID:27385829)
• Atg38 and its human ortholog NRBF2, accessory components of complex I consisting of Vps15-Vps34-Vps30/Atg6-Atg14 (yeast) and PIK3R4/VPS15-PIK3C3/VPS34-BECN1/Beclin 1-ATG14 (human), were characterized. (PMID:27630019)
• This study reveals NRBF2 as a critical molecular switch of PtdIns3K and autophagy activation, and its on/off state is precisely controlled by MTORC1 through phosphorylation. (PMID:28059666)
• NRBF2 plays an important role in regulating degradation of APP-C-terminal fragments through modulating autophagy. (PMID:28980867)
• implicates NRBF2 deficiency as a risk factor for cognitive impairment associated with AD, but also support the idea of NRBF2 as a potential therapeutic target for Alzheimer’s Disease (PMID:31775806)
• PI3KC3 complex subunit NRBF2 is required for apoptotic cell clearance to restrict intestinal inflammation. (PMID:32160108)
• NRBF2-mediated autophagy contributes to metabolite replenishment and radioresistance in glioblastoma. (PMID:36333468)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	nrbf2b	ENSDARG00000023591
mus_musculus	Nrbf2	ENSMUSG00000075000
rattus_norvegicus	Nrbf2	ENSRNOG00000000641
rattus_norvegicus	AABR07072761.1	ENSRNOG00000030494
drosophila_melanogaster	CG42554	FBGN0260756

Protein

Protein identifiers

Nuclear receptor-binding factor 2 — Q96F24 (reviewed: Q96F24)

Alternative names: Comodulator of PPAR and RXR

All UniProt accessions (1): Q96F24

UniProt curated annotations — full annotation on UniProt →

Function. May modulate transcriptional activation by target nuclear receptors. Can act as transcriptional activator (in vitro). Involved in starvation-induced autophagy probably by its association with PI3K complex I (PI3KC3-C1). However, effects has been described variably. Involved in the induction of starvation-induced autophagy. Stabilizes PI3KC3-C1 assembly and enhances ATG14-linked lipid kinase activity of PIK3C3. Proposed to negatively regulate basal and starvation-induced autophagy and to inhibit PIK3C3 activity by modulating interactions in PI3KC3-C1. May be involved in autophagosome biogenesis. May play a role in neural progenitor cell survival during differentiation.

Subunit / interactions. Interacts with PPARA, PPARD and PPARG. Interacts with RARA, RARG and RXRA in the presence of bound ligand. Interacts with SCOC. Associates with the PI3K complex I (PI3KC3-C1); the direct binding partner in the complex is reported variably as PIK3R4 or ATG14.

Subcellular location. Nucleus. Cytoplasm. Cytoplasmic vesicle. Autophagosome.

Tissue specificity. Detected in keratinocytes, liver and placenta. Expressed in a subset of cells in pediatric medulloblastoma.

Isoforms (3)

UniProt ID	Names	Canonical?
Q96F24-1	1, COPR2, Comodulator of PPAR and RXR 2	yes
Q96F24-2	2, COPR1, Comodulator of PPAR and RXR 1
Q96F24-3	3

RefSeq proteins (2): NP_001269334, NP_110386* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR015056	NRBF2_C	Domain
IPR033393	NRBF2_MIT	Domain
IPR039679	NRBF2	Family

Pfam: PF08961, PF17169

UniProt features (16 total): helix 3, sequence conflict 2, compositionally biased region 2, modified residue 2, splice variant 2, chain 1, region of interest 1, mutagenesis site 1, coiled-coil region 1, short sequence motif 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
4ZEY	X-RAY DIFFRACTION	1.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96F24-F1	73.75	0.43

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 (2): 113, 268

Mutagenesis-validated functional residues (1):

Position	Phenotype
144–145	decreased interaction with nuclear receptors.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-383280	Nuclear Receptor transcription pathway

MSigDB gene sets: 199 (showing top): GGTGTGT_MIR329, GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, chr10q21, CAGCTG_AP4_Q5, RICKMAN_TUMOR_DIFFERENTIATED_WELL_VS_POORLY_DN, AAAGGGA_MIR204_MIR211, HIF1_Q3, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, CTCAAGA_MIR526B, IVANOVA_HEMATOPOIESIS_EARLY_PROGENITOR, TTTGCAC_MIR19A_MIR19B, GOCC_AUTOPHAGOSOME, GOCC_TRANSFERASE_COMPLEX_TRANSFERRING_PHOSPHORUS_CONTAINING_GROUPS, GOCC_TRANSFERASE_COMPLEX, GOCC_MEMBRANE_PROTEIN_COMPLEX

GO Biological Process (2): autophagy (GO:0006914), response to endoplasmic reticulum stress (GO:0034976)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (6): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), autophagosome (GO:0005776), cytoplasmic vesicle (GO:0031410), phosphatidylinositol 3-kinase complex, class III (GO:0035032), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Generic Transcription Pathway	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
catabolic process	1
transmembrane transport	1
process utilizing autophagic mechanism	1
cellular response to stress	1
binding	1
nuclear lumen	1
intracellular anatomical structure	1
vacuole	1
cytoplasm	1
intracellular vesicle	1
phosphatidylinositol 3-kinase complex	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

660 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NRBF2	ATG14	Q6ZNE5	995
NRBF2	PIK3C3	Q8NEB9	995
NRBF2	PIK3R4	Q99570	995
NRBF2	BECN1	Q14457	994
NRBF2	AMBRA1	Q9C0C7	924
NRBF2	UVRAG	Q9P2Y5	910
NRBF2	ATG101	Q9BSB4	627
NRBF2	ATG13	O75143	620
NRBF2	RUBCN	Q92622	607
NRBF2	RB1CC1	Q8TDY2	593
NRBF2	WIPI2	Q9Y4P8	546
NRBF2	VPS33A	Q96AX1	540
NRBF2	ZFYVE1	Q9HBF4	534
NRBF2	ULK1	O75385	520
NRBF2	ATG3	Q9NT62	518

IntAct

78 interactions, top by confidence:

A	B	Type	Score
ATG14	BECN1	psi-mi:“MI:0914”(association)	0.980
NRBF2	PIK3R4	psi-mi:“MI:0915”(physical association)	0.920
NRBF2	BECN1	psi-mi:“MI:0914”(association)	0.860
NRBF2	PIK3C3	psi-mi:“MI:0915”(physical association)	0.850
NRBF2	PIK3C3	psi-mi:“MI:0914”(association)	0.850
PIK3C3	NRBF2	psi-mi:“MI:0914”(association)	0.850
PIK3R4	PIK3C3	psi-mi:“MI:0914”(association)	0.830
BECN1	ZWINT	psi-mi:“MI:0914”(association)	0.750
SEC24D	SEC23A	psi-mi:“MI:0914”(association)	0.690
SPTLC1	SPTLC2	psi-mi:“MI:0914”(association)	0.680
SEC13	SEC16A	psi-mi:“MI:0914”(association)	0.640
NRBF2	C1orf216	psi-mi:“MI:0915”(physical association)	0.560
C1orf216	NRBF2	psi-mi:“MI:0915”(physical association)	0.560
NRBF2	CDC23	psi-mi:“MI:0915”(physical association)	0.560
CCNC	NRBF2	psi-mi:“MI:0915”(physical association)	0.560
PRKAA2	NRBF2	psi-mi:“MI:0915”(physical association)	0.560
KDM1A	NRBF2	psi-mi:“MI:0915”(physical association)	0.560
NRBF2	GALT	psi-mi:“MI:0914”(association)	0.530
SFRP2	MAEA	psi-mi:“MI:0914”(association)	0.530

BioGRID (137): C1orf216 (Two-hybrid), NRBF2 (Affinity Capture-MS), PIK3R4 (Affinity Capture-MS), PIK3C3 (Affinity Capture-MS), CALCOCO2 (Affinity Capture-MS), TGFBRAP1 (Affinity Capture-MS), BECN1 (Affinity Capture-MS), GALT (Affinity Capture-MS), ATG14 (Affinity Capture-MS), SOGA3 (Affinity Capture-MS), PPARA (Two-hybrid), NRBF2 (Proximity Label-MS), NRBF2 (Proximity Label-MS), NRBF2 (Proximity Label-MS), NRBF2 (Proximity Label-MS)

ESM2 similar proteins: A1A5R8, A3LU54, A7RNG8, E9QHE3, F1N5V1, F4HWE6, F4JTJ2, L0R819, O94763, P08638, P18106, P25558, P32913, P33981, P35761, P36168, P38187, P38830, P38853, P50090, P53253, Q04052, Q06001, Q06623, Q12513, Q3B7M7, Q4KLY4, Q4R945, Q5R4C9, Q5R9J5, Q5RFA9, Q5VX52, Q642A0, Q68FF0, Q6AY22, Q6BS08, Q6NSI8, Q803I4, Q8S3U9, Q8TFN2

Diamond homologs: Q5R4C9, Q8VCQ3, Q96F24, Q9QYK3

SIGNOR signaling

7 interactions.

A	Effect	B	Mechanism
MTOR	“up-regulates activity”	NRBF2	phosphorylation
mTORC1	“up-regulates activity”	NRBF2	phosphorylation
NRBF2	“down-regulates activity”	PIK3R4	binding
NRBF2	“down-regulates activity”	PIK3C3	binding
NRBF2	“down-regulates activity”	“Vps34 Complex I”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 70 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
Antigen Presentation: Folding, assembly and peptide loading of class I MHC	7	54.0×	1e-08
Macroautophagy	9	20.4×	9e-08
COPII-mediated vesicle transport	5	16.0×	8e-04
Autophagy	5	14.5×	1e-03
SARS-CoV-2 activates/modulates innate and adaptive immune responses	8	14.0×	1e-05
SARS-CoV-2-host interactions	6	14.0×	3e-04
ER to Golgi Anterograde Transport	5	13.0×	1e-03
Class I MHC mediated antigen processing & presentation	8	11.0×	5e-05

GO biological processes:

GO term	Partners	Fold	FDR
regulation of macroautophagy	6	28.2×	3e-05
autophagosome maturation	5	27.9×	1e-04
cellular response to glucose starvation	5	26.8×	1e-04
autophagosome assembly	5	17.8×	5e-04
intracellular protein transport	7	7.2×	2e-03
cell division	9	6.6×	5e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	29
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

796 predictions. Top by Δscore:

Variant	Effect	Δscore
10:63133497:CCTGG:C	donor_loss	1.0000
10:63133499:TGG:T	donor_loss	1.0000
10:63133501:G:GC	donor_loss	1.0000
10:63133502:T:A	donor_loss	1.0000
10:63146290:GCAG:G	donor_gain	1.0000
10:63146293:GGT:G	donor_loss	1.0000
10:63146294:G:C	donor_loss	1.0000
10:63146295:TGA:T	donor_loss	1.0000
10:63146296:GAG:G	donor_loss	1.0000
10:63152145:A:AG	acceptor_gain	1.0000
10:63152148:A:AG	acceptor_gain	1.0000
10:63152148:A:T	acceptor_loss	1.0000
10:63152149:G:GC	acceptor_gain	1.0000
10:63152149:GC:G	acceptor_gain	1.0000
10:63152149:GCA:G	acceptor_gain	1.0000
10:63152149:GCAT:G	acceptor_gain	1.0000
10:63152149:GCATA:G	acceptor_gain	1.0000
10:63133474:G:GT	donor_gain	0.9900
10:63133496:ACCTG:A	donor_gain	0.9900
10:63133497:CCTG:C	donor_gain	0.9900
10:63133498:CTG:C	donor_gain	0.9900
10:63133499:TG:T	donor_gain	0.9900
10:63133500:GG:G	donor_gain	0.9900
10:63133501:G:GG	donor_gain	0.9900
10:63146207:A:AG	acceptor_gain	0.9900
10:63146208:G:GG	acceptor_gain	0.9900
10:63146294:G:GG	donor_gain	0.9900
10:63146372:T:G	acceptor_gain	0.9900
10:63146378:A:G	acceptor_gain	0.9900
10:63152146:A:G	acceptor_gain	0.9900

AlphaMissense

1896 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:63146225:G:C	R16T	0.998
10:63146226:A:C	R16S	0.998
10:63146226:A:T	R16S	0.998
10:63146212:C:G	H12D	0.997
10:63153534:A:C	Q60H	0.997
10:63153534:A:T	Q60H	0.997
10:63133493:T:A	L8H	0.996
10:63146214:T:A	H12Q	0.996
10:63146214:T:G	H12Q	0.996
10:63153524:T:C	L57P	0.996
10:63153530:T:C	L59S	0.996
10:63146266:G:C	A30P	0.995
10:63152156:T:C	L41P	0.995
10:63146209:G:A	A11T	0.994
10:63146210:C:A	A11D	0.994
10:63146212:C:A	H12N	0.994
10:63146230:G:C	A18P	0.994
10:63152164:G:C	A44P	0.994
10:63133493:T:C	L8P	0.993
10:63154136:T:A	L261H	0.993
10:63154145:T:C	L264S	0.993
10:63146219:A:C	Q14P	0.992
10:63146224:A:G	R16G	0.992
10:63146225:G:T	R16I	0.992
10:63146278:C:G	H34D	0.992
10:63146210:C:T	A11V	0.991
10:63146231:C:A	A18E	0.991
10:63146267:C:A	A30D	0.991
10:63133497:C:A	N9K	0.990
10:63133497:C:G	N9K	0.990

dbSNP variants (sampled 300 via entrez): RS1000001717 (10:63133481 TGGAA>T), RS1000030529 (10:63134200 G>A), RS1000149949 (10:63140514 C>T), RS1000235627 (10:63139978 GAA>G,GA,GAAA), RS1000235957 (10:63146317 A>G), RS1000462399 (10:63152328 A>G), RS1000520015 (10:63133738 C>G,T), RS1000627840 (10:63138709 A>C,T), RS1000748177 (10:63152698 G>T), RS1000804622 (10:63145087 A>C), RS1000862438 (10:63146763 CT>C,CTT), RS1000881070 (10:63151292 A>G), RS1000912085 (10:63151595 C>A), RS1001174759 (10:63144712 G>A,T), RS1001241649 (10:63141235 T>G)

Disease associations

OMIM: gene MIM:616477 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

32 associations (top):

Study	Trait	p-value
GCST001276_14	Liver enzyme levels (alkaline phosphatase)	6.000000e-23
GCST002184_9	Mean platelet volume	3.000000e-18
GCST002446_4	Plasma omega-6 polyunsaturated fatty acid levels (linoleic acid)	8.000000e-09
GCST002448_4	Plasma omega-6 polyunsaturated fatty acid levels (adrenic acid)	7.000000e-07
GCST004602_184	Mean corpuscular volume	4.000000e-17
GCST004630_239	Mean corpuscular hemoglobin	3.000000e-18
GCST004946_80	Schizophrenia	5.000000e-09
GCST006414_135	Atrial fibrillation	2.000000e-12
GCST007201_114	Schizophrenia	1.000000e-08
GCST008074_110	Triglyceride levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	2.000000e-16
GCST008074_13	Triglyceride levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	1.000000e-06
GCST008074_44	Triglyceride levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	2.000000e-24
GCST008076_32	Triglyceride levels	1.000000e-12
GCST008076_68	Triglyceride levels	2.000000e-07
GCST008078_138	LDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	9.000000e-08
GCST008078_47	LDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	1.000000e-06
GCST008079_134	LDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	2.000000e-06
GCST008083_153	Triglyceride levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	2.000000e-17
GCST008083_74	Triglyceride levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	2.000000e-10
GCST008083_78	Triglyceride levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	2.000000e-29
GCST008084_179	HDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	2.000000e-06
GCST008087_135	Triglyceride levels in current drinkers	1.000000e-08
GCST008087_54	Triglyceride levels in current drinkers	1.000000e-06
GCST008087_83	Triglyceride levels in current drinkers	5.000000e-16
GCST012251_2	Macular telangiectasia type 2	9.000000e-08
GCST012252_9	Macular telangiectasia type 2	5.000000e-08
GCST90002385_480	High light scatter reticulocyte count	7.000000e-16
GCST90002386_401	High light scatter reticulocyte percentage of red cells	1.000000e-12
GCST90002390_489	Mean corpuscular hemoglobin	1.000000e-42
GCST90002392_613	Mean corpuscular volume	3.000000e-42

EFO canonical traits (11, from GWAS)

EFO ID	Trait name
EFO:0004533	alkaline phosphatase measurement
EFO:0005680	omega-6 polyunsaturated fatty acid measurement
EFO:0004527	mean corpuscular hemoglobin
EFO:0004530	triglyceride measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004329	alcohol drinking
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:1002009	macular telangiectasia type 2
EFO:0007986	reticulocyte count
EFO:0004305	erythrocyte count
EFO:0004532	serum gamma-glutamyl transferase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295924 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, affects cotreatment, increases abundance	2
Arsenic	affects methylation, affects cotreatment, increases abundance, increases expression	2
Valproic Acid	decreases methylation	2
Cyclosporine	increases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
FR900359	decreases phosphorylation	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
arsenite	affects binding, increases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
cobaltous chloride	increases expression	1
butyraldehyde	increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
perfluorooctane sulfonic acid	increases expression	1
K 7174	increases expression	1
ICG 001	affects expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	increases expression	1
PCI 5002	affects cotreatment, increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Benzo(a)pyrene	decreases methylation	1
Caffeine	affects phosphorylation	1
Dimethyl Sulfoxide	increases expression	1
Drugs, Chinese Herbal	increases expression	1
Estradiol	affects binding, increases reaction	1
Manganese	affects cotreatment, increases abundance, increases expression	1
Phenobarbital	affects expression	1
Smoke	decreases expression	1
Dronabinol	decreases expression	1
Thiram	increases expression	1
Tobacco Smoke Pollution	increases expression	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
CHEMBL4118692	Binding	Binding affinity to NRBF2 in human NCI-H23 cells at 1 uM by mass spectrometry based pull down assay	Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. — Bioorg Med Chem

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B1Z5	Abcam HeLa NRBF2 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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