NRBP2

Summary

NRBP2 (nuclear receptor binding protein 2, HGNC:19339) is a protein-coding gene on chromosome 8q24.3, encoding Nuclear receptor-binding protein 2 (Q9NSY0). May regulate apoptosis of neural progenitor cells during their differentiation.

Predicted to enable protein serine/threonine kinase activity. Involved in negative regulation of macroautophagy. Predicted to be active in cytoplasm.

Source: NCBI Gene 340371 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 105 total
• MANE Select transcript: NM_178564

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19339
Approved symbol	NRBP2
Name	nuclear receptor binding protein 2
Location	8q24.3
Locus type	gene with protein product
Status	Approved
Aliases	DKFZp434P086
Ensembl gene	ENSG00000185189
Ensembl biotype	protein_coding
OMIM	615563
Entrez	340371

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 7 retained_intron, 4 protein_coding

ENST00000423469, ENST00000442628, ENST00000527545, ENST00000529747, ENST00000530123, ENST00000530347, ENST00000531729, ENST00000532940, ENST00000533093, ENST00000533846, ENST00000859931

RefSeq mRNA: 1 — MANE Select: NM_178564 NM_178564

CCDS: CCDS34959

Canonical transcript exons

ENST00000442628 — 18 exons

Exon	Start	End
ENSE00001671335	143839736	143839825
ENSE00001743478	143839509	143839549
ENSE00002182232	143840706	143840973
ENSE00002184672	143833583	143835730
ENSE00003460178	143837039	143837174
ENSE00003469785	143835967	143836030
ENSE00003508154	143835820	143835875
ENSE00003521994	143839929	143840030
ENSE00003549021	143837407	143837509
ENSE00003587365	143837623	143837755
ENSE00003594691	143839017	143839100
ENSE00003606596	143836127	143836180
ENSE00003613121	143837249	143837299
ENSE00003632545	143839314	143839408
ENSE00003639664	143838680	143838775
ENSE00003640463	143838883	143838938
ENSE00003669701	143839172	143839195
ENSE00003674524	143840107	143840229

Expression profiles

Bgee: expression breadth ubiquitous, 138 present calls, max score 99.22.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.8851 / max 472.2473, expressed in 1779 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
95545	9.8362	1710
95546	6.0363	1570
95542	1.1043	605
95544	0.5597	301
95543	0.3486	158

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cerebellar vermis	UBERON:0004720	99.22	gold quality
sural nerve	UBERON:0015488	98.38	gold quality
spinal cord	UBERON:0002240	98.31	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	98.31	gold quality
tibial nerve	UBERON:0001323	98.12	gold quality
right uterine tube	UBERON:0001302	97.75	gold quality
thymus	UBERON:0002370	97.72	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.85	gold quality
lower esophagus muscularis layer	UBERON:0035833	96.85	gold quality
lower esophagus	UBERON:0013473	96.82	gold quality
substantia nigra	UBERON:0002038	96.75	gold quality
right lobe of liver	UBERON:0001114	96.73	gold quality
mucosa of stomach	UBERON:0001199	96.61	gold quality
right frontal lobe	UBERON:0002810	96.59	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	96.57	gold quality
primary visual cortex	UBERON:0002436	96.23	gold quality
cerebellar hemisphere	UBERON:0002245	96.15	gold quality
quadriceps femoris	UBERON:0001377	96.14	gold quality
cerebellar cortex	UBERON:0002129	96.11	gold quality
muscle layer of sigmoid colon	UBERON:0035805	96.10	gold quality
Ammon’s horn	UBERON:0001954	96.04	gold quality
cerebellum	UBERON:0002037	96.04	gold quality
temporal lobe	UBERON:0001871	95.96	gold quality
amygdala	UBERON:0001876	95.95	gold quality
right coronary artery	UBERON:0001625	95.51	gold quality
left uterine tube	UBERON:0001303	95.49	gold quality
popliteal artery	UBERON:0002250	95.46	gold quality
tibial artery	UBERON:0007610	95.46	gold quality
Brodmann (1909) area 9	UBERON:0013540	95.45	gold quality
descending thoracic aorta	UBERON:0002345	95.26	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.64

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

91 targeting NRBP2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-6753-3P	99.93	66.57	637
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-765	99.84	68.24	2442
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-577	99.78	69.13	2479
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-199A-3P	99.75	70.48	929
HSA-MIR-199B-3P	99.75	70.48	929
HSA-MIR-3129-5P	99.75	70.46	914

Literature-anchored findings (GeneRIF, showing 3)

• Data show that NRBP2 protein levels increase as neural progenitor cells differentiate, and its down regulation renders neural progenitor cells more vulnerable to apoptosis, which suggest a role in stem cell survival. (PMID:18619852)
• The altered expression of NRBP2 and CALCOCO2 is associated with left ventricular dysfunction parameters in human dilated cardiomyopathy. (PMID:31009519)
• TRG16, targeted by miR-765, inhibits breast cancer stem cell-like properties via regulating the NF-kappaB pathway. (PMID:35648115)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	nrbp2b	ENSDARG00000009626
danio_rerio	nrbp2a	ENSDARG00000032951
mus_musculus	Nrbp2	ENSMUSG00000075590
rattus_norvegicus	Nrbp2	ENSRNOG00000029535
drosophila_melanogaster	Madm	FBGN0027497
drosophila_melanogaster	Wnk	FBGN0037098
caenorhabditis_elegans		WBGENE00006941
caenorhabditis_elegans	hpo-11	WBGENE00010427

Paralogs (6): WNK1 (ENSG00000060237), NRBP1 (ENSG00000115216), WNK4 (ENSG00000126562), DSTYK (ENSG00000133059), WNK2 (ENSG00000165238), WNK3 (ENSG00000196632)

Protein

Protein identifiers

Nuclear receptor-binding protein 2 — Q9NSY0 (reviewed: Q9NSY0)

Alternative names: Transformation-related gene 16 protein

All UniProt accessions (3): E9PR11, Q9NSY0, H0YCB1

UniProt curated annotations — full annotation on UniProt →

Function. May regulate apoptosis of neural progenitor cells during their differentiation.

Subcellular location. Cytoplasm.

Domain organisation. The protein kinase domain is predicted to be catalytically inactive.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Similarity. Belongs to the protein kinase superfamily. Ser/Thr protein kinase family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q9NSY0-3	1	yes
Q9NSY0-2	2
Q9NSY0-4	3
Q9NSY0-5	4

RefSeq proteins (1): NP_848659* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR042697	NRBP2_PK	Domain
IPR050588	WNK_Ser-Thr_kinase	Family

Pfam: PF00069

UniProt features (14 total): splice variant 6, compositionally biased region 2, modified residue 2, chain 1, domain 1, sequence conflict 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NSY0-F1	79.50	0.34

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): 409, 411

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 103 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_DN, GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_DN, GOBP_NEGATIVE_REGULATION_OF_NEURON_APOPTOTIC_PROCESS, GOBP_REGULATION_OF_AUTOPHAGY, CHIARADONNA_NEOPLASTIC_TRANSFORMATION_KRAS_DN, GOBP_NEUROGENESIS, GOBP_REGULATION_OF_WNT_SIGNALING_PATHWAY, GGCNKCCATNK_UNKNOWN, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_MACROAUTOPHAGY, GOBP_NEGATIVE_REGULATION_OF_AUTOPHAGY, GOBP_REGULATION_OF_CATABOLIC_PROCESS, GOBP_CANONICAL_WNT_SIGNALING_PATHWAY, GOBP_DNA_DAMAGE_RESPONSE, GOBP_NEGATIVE_REGULATION_OF_MACROAUTOPHAGY

GO Biological Process (6): DNA damage response (GO:0006974), negative regulation of macroautophagy (GO:0016242), neuron differentiation (GO:0030182), negative regulation of neuron apoptotic process (GO:0043524), protein phosphorylation (GO:0006468), nervous system development (GO:0007399)

GO Molecular Function (4): protein serine/threonine kinase activity (GO:0004674), ATP binding (GO:0005524), protein kinase activity (GO:0004672), protein binding (GO:0005515)

GO Cellular Component (1): cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular response to stress	1
negative regulation of autophagy	1
macroautophagy	1
regulation of macroautophagy	1
cell differentiation	1
generation of neurons	1
negative regulation of apoptotic process	1
regulation of neuron apoptotic process	1
neuron apoptotic process	1
phosphorylation	1
protein modification process	1
system development	1
protein kinase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
binding	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

454 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NRBP2	PUF60	Q9UHX1	544
NRBP2	SRFBP1	Q8NEF9	471
NRBP2	PYCR3	Q53H96	459
NRBP2	LONP2	Q86WA8	434
NRBP2	EXOSC4	Q9NPD3	413
NRBP2	METTL25B	Q96FB5	413
NRBP2	TMEM53	Q6P2H8	401
NRBP2	BTBD2	Q9BX70	385
NRBP2	EPPK1	P58107	381
NRBP2	ARMH1	Q6PIY5	379
NRBP2	OTULIN	Q96BN8	377
NRBP2	KRABD3	A5PL33	362
NRBP2	CNN2	Q99439	352
NRBP2	RNF220	Q5VTB9	346
NRBP2	TTF2	Q9UNY4	338

IntAct

23 interactions, top by confidence:

A	B	Type	Score
NRBP2	TSC22D4	psi-mi:“MI:0915”(physical association)	0.840
PHF19	EED	psi-mi:“MI:0914”(association)	0.730
CA10	WDHD1	psi-mi:“MI:0914”(association)	0.640
TSC22D4	TSC22D2	psi-mi:“MI:0914”(association)	0.640
PHF19	EPOP	psi-mi:“MI:0914”(association)	0.530
PDK1	VWA8	psi-mi:“MI:0914”(association)	0.350
NEDD1	ATP5MF-PTCD1	psi-mi:“MI:0914”(association)	0.350
RAP1B	KLC1	psi-mi:“MI:0914”(association)	0.350
PB2		psi-mi:“MI:0914”(association)	0.350
TSC22D4	TBL1X	psi-mi:“MI:0914”(association)	0.350
PHF19	EED	psi-mi:“MI:0914”(association)	0.350
IL16	CAMK1	psi-mi:“MI:0914”(association)	0.350
NRBP2	HAX1	psi-mi:“MI:0914”(association)	0.350
TSC22D4	PSMA7	psi-mi:“MI:0914”(association)	0.350
TSC22D3	SH3PXD2B	psi-mi:“MI:0914”(association)	0.350
NRBP1	PDPK1	psi-mi:“MI:0914”(association)	0.350
TSC22D4	LANCL1	psi-mi:“MI:0914”(association)	0.350
LANCL1	TBC1D9B	psi-mi:“MI:0914”(association)	0.350
CA10	ENTPD5	psi-mi:“MI:0914”(association)	0.350

BioGRID (79): NRBP2 (Two-hybrid), NRBP2 (Affinity Capture-MS), NRBP2 (Affinity Capture-MS), NRBP2 (Affinity Capture-MS), NRBP2 (Affinity Capture-MS), NRBP2 (Affinity Capture-MS), NRBP2 (Affinity Capture-MS), NRBP2 (Affinity Capture-MS), NRBP2 (Affinity Capture-MS), NRBP2 (Affinity Capture-MS), NRBP2 (Affinity Capture-MS), NRBP2 (Affinity Capture-MS), NRBP2 (Affinity Capture-MS), NRBP2 (Affinity Capture-MS), NRBP2 (Affinity Capture-MS)

ESM2 similar proteins: A2AJ88, B3MRI9, B3NY03, B4H3U8, B4IL64, B4JLX2, B4L535, B4M709, B4N1W9, B4Q0P3, B5DKS8, D3ZEF4, O08703, O08962, O35219, O54853, P25848, P59111, P97414, Q02331, Q12809, Q14999, Q17QV9, Q21534, Q3TRM4, Q5BK26, Q5R667, Q5RCJ3, Q5RDS0, Q5TEA3, Q67E00, Q67E01, Q6CF18, Q6ZV29, Q7TNL3, Q7TT23, Q8IY17, Q8N2I9, Q8RY24, Q8VE73

Diamond homologs: A0A078CGE6, A2AQW0, A2QHV0, A2YMV6, A9RVK2, A9SY39, C4YRB7, D4A280, M9PGC5, O14305, O24527, O75914, O81472, O88643, P0CY23, P0CY24, P35465, P41892, P83741, Q01577, Q03497, Q08E52, Q0CL79, Q0D541, Q0D598, Q0D847, Q13153, Q13177, Q17850, Q21029, Q29502, Q297L2, Q2QXC6, Q2QYL8, Q2RA93, Q2RBE3, Q2ULU3, Q2V338, Q2VWQ3, Q39008

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	75
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1983 predictions. Top by Δscore:

Variant	Effect	Δscore
8:143835965:A:AC	donor_gain	1.0000
8:143835966:C:CC	donor_gain	1.0000
8:143837034:CTCA:C	donor_loss	1.0000
8:143837035:TCACC:T	donor_loss	1.0000
8:143837036:CA:C	donor_loss	1.0000
8:143837037:A:AC	donor_gain	1.0000
8:143837037:AC:A	donor_gain	1.0000
8:143837037:ACCTT:A	donor_loss	1.0000
8:143837038:C:CT	donor_gain	1.0000
8:143837038:CC:C	donor_gain	1.0000
8:143837038:CCT:C	donor_gain	1.0000
8:143837038:CCTTT:C	donor_gain	1.0000
8:143837246:CAC:C	donor_loss	1.0000
8:143837248:C:CT	donor_loss	1.0000
8:143837298:ACCTG:A	acceptor_loss	1.0000
8:143837300:C:CA	acceptor_loss	1.0000
8:143837301:T:A	acceptor_loss	1.0000
8:143837304:CA:C	acceptor_gain	1.0000
8:143837305:A:AC	acceptor_gain	1.0000
8:143837305:A:C	acceptor_gain	1.0000
8:143837398:A:AC	donor_gain	1.0000
8:143837399:C:CC	donor_gain	1.0000
8:143837399:CTG:C	donor_gain	1.0000
8:143837403:TCA:T	donor_loss	1.0000
8:143837404:CAC:C	donor_loss	1.0000
8:143837405:A:AC	donor_gain	1.0000
8:143837406:C:A	donor_loss	1.0000
8:143837406:C:CC	donor_gain	1.0000
8:143837406:CCG:C	donor_gain	1.0000
8:143837505:GAGGT:G	acceptor_gain	1.0000

AlphaMissense

3302 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:143838900:C:A	G243W	1.000
8:143839324:C:A	K190N	1.000
8:143839324:C:G	K190N	1.000
8:143839331:A:G	L188P	1.000
8:143839334:C:A	G187V	1.000
8:143839334:C:T	G187D	1.000
8:143839537:A:G	W153R	1.000
8:143839537:A:T	W153R	1.000
8:143839546:A:G	W150R	1.000
8:143839546:A:T	W150R	1.000
8:143839778:G:C	F134L	1.000
8:143839778:G:T	F134L	1.000
8:143839779:A:G	F134S	1.000
8:143839780:A:G	F134L	1.000
8:143840154:A:G	W69R	1.000
8:143840154:A:T	W69R	1.000
8:143840724:C:A	W37C	1.000
8:143840724:C:G	W37C	1.000
8:143840725:C:G	W37S	1.000
8:143840726:A:G	W37R	1.000
8:143840726:A:T	W37R	1.000
8:143835845:A:G	L471P	0.999
8:143835987:A:G	L454P	0.999
8:143837252:A:T	V375D	0.999
8:143837646:G:T	A317D	0.999
8:143837655:A:G	L314P	0.999
8:143837697:A:G	L300P	0.999
8:143837706:G:T	A297D	0.999
8:143837738:G:C	C286W	0.999
8:143837739:C:T	C286Y	0.999

dbSNP variants (sampled 300 via entrez): RS1000186951 (8:143838538 T>C), RS1000541986 (8:143829341 C>G,T), RS1000757052 (8:143833693 T>G), RS1001148691 (8:143834209 G>A), RS1001941474 (8:143839211 A>G), RS1002241182 (8:143830163 C>T), RS1002245188 (8:143839426 G>A,C), RS1002395894 (8:143835392 C>A,T), RS1002480055 (8:143839635 G>C), RS1002660564 (8:143829949 A>G), RS1002910740 (8:143832190 A>G), RS1002916130 (8:143842404 C>A), RS1003121042 (8:143836866 C>T), RS1003332666 (8:143831989 T>C), RS1004034214 (8:143840540 C>T)

Disease associations

OMIM: gene MIM:615563 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — NRBP family

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases methylation, increases expression	4
Cyclosporine	decreases expression, decreases methylation	3
Tobacco Smoke Pollution	decreases expression	2
Aflatoxin B1	affects expression, decreases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	decreases expression	1
bisphenol F	affects cotreatment, decreases expression	1
bufotalin	decreases expression	1
methylmercuric chloride	decreases expression	1
11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid	increases abundance, affects methylation	1
hydroquinone	increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
abrine	decreases expression	1
jinfukang	increases expression, affects cotreatment	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Leflunomide	decreases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	increases methylation	1
Cannabinoids	affects methylation, increases abundance	1
Cisplatin	affects cotreatment, increases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Doxorubicin	decreases expression	1
Indomethacin	affects cotreatment, decreases expression	1
Smoke	decreases expression	1
Valproic Acid	decreases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, decreases expression	1
Antirheumatic Agents	increases expression	1
Okadaic Acid	decreases expression	1
Acrylamide	decreases expression	1

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1Z6	Abcam HeLa NRBP2 KO	Cancer cell line	Female
CVCL_TB05	HAP1 NRBP2 (-) 1	Cancer cell line	Male
CVCL_TB06	HAP1 NRBP2 (-) 2	Cancer cell line	Male
CVCL_TB07	HAP1 NRBP2 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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