NRIP2

Summary

NRIP2 (nuclear receptor interacting protein 2, HGNC:23078) is a protein-coding gene on chromosome 12p13.33, encoding Nuclear receptor-interacting protein 2 (Q9BQI9). Down-regulates transcriptional activation by nuclear receptors such as NR1F2.

Predicted to enable aspartic-type endopeptidase activity. Predicted to be involved in proteolysis. Predicted to act upstream of or within Notch signaling pathway and negative regulation of transcription by RNA polymerase II. Located in cytoplasm.

Source: NCBI Gene 83714 — RefSeq curated summary.

At a glance

• MANE Select transcript: NM_031474

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23078
Approved symbol	NRIP2
Name	nuclear receptor interacting protein 2
Location	12p13.33
Locus type	gene with protein product
Status	Approved
Aliases	DKFZP761G1913
Ensembl gene	ENSG00000053702
Ensembl biotype	protein_coding
OMIM	621054
Entrez	83714

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000337508, ENST00000542386, ENST00000542990

RefSeq mRNA: 1 — MANE Select: NM_031474 NM_031474

CCDS: CCDS8514

Canonical transcript exons

ENST00000337508 — 6 exons

Exon	Start	End
ENSE00000452451	2834642	2835035
ENSE00000452452	2828332	2828414
ENSE00000713161	2827625	2827677
ENSE00000713198	2827926	2828047
ENSE00000713200	2830708	2830860
ENSE00002304626	2825348	2827299

Expression profiles

Bgee: expression breadth ubiquitous, 215 present calls, max score 97.90.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.3635 / max 148.3898, expressed in 180 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
128972	0.6594	159
128973	0.4816	88
128971	0.1172	59
128970	0.1054	45

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
olfactory bulb	UBERON:0002264	97.90	gold quality
cerebellar hemisphere	UBERON:0002245	93.73	gold quality
cerebellar cortex	UBERON:0002129	93.69	gold quality
cerebellum	UBERON:0002037	93.10	gold quality
right hemisphere of cerebellum	UBERON:0014890	92.96	gold quality
tibial nerve	UBERON:0001323	89.75	gold quality
sural nerve	UBERON:0015488	88.07	gold quality
popliteal artery	UBERON:0002250	85.47	gold quality
tibial artery	UBERON:0007610	85.47	gold quality
trigeminal ganglion	UBERON:0001675	84.34	gold quality
right coronary artery	UBERON:0001625	84.20	gold quality
pons	UBERON:0000988	84.07	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.91	gold quality
putamen	UBERON:0001874	83.42	gold quality
lateral globus pallidus	UBERON:0002476	83.07	gold quality
apex of heart	UBERON:0002098	82.30	gold quality
dorsal root ganglion	UBERON:0000044	82.02	gold quality
blood vessel layer	UBERON:0004797	81.96	gold quality
cerebellar vermis	UBERON:0004720	80.68	silver quality
coronary artery	UBERON:0001621	80.61	gold quality
left coronary artery	UBERON:0001626	80.45	gold quality
caudate nucleus	UBERON:0001873	79.85	gold quality
renal glomerulus	UBERON:0000074	79.75	gold quality
type B pancreatic cell	CL:0000169	79.72	gold quality
aorta	UBERON:0000947	79.51	gold quality
metanephric glomerulus	UBERON:0004736	79.48	gold quality
cortex of kidney	UBERON:0001225	79.37	gold quality
metanephros cortex	UBERON:0010533	79.37	gold quality
globus pallidus	UBERON:0001875	79.15	gold quality
metanephros	UBERON:0000081	78.89	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.56

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

100 targeting NRIP2, 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-6851-5P	100.00	65.63	1294
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-221-5P	99.86	65.45	1052
HSA-MIR-8073	99.86	65.21	1118
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-30B-3P	99.70	65.76	2325
HSA-MIR-3689A-3P	99.70	65.73	2306
HSA-MIR-3689B-3P	99.70	65.71	2311
HSA-MIR-3689C	99.70	65.71	2311
HSA-MIR-6779-5P	99.70	65.76	2363
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-4527	99.66	67.43	714
HSA-MIR-651-5P	99.64	68.49	1104

Literature-anchored findings (GeneRIF, showing 1)

• Results show that NRIP2 was significantly up-regulated in Colorectal cancer initiating cells (CCICs) from both cell lines and primary colorectal cancer tissues, and identified it as a novel molecule acting in Wnt pathway. The interaction between NRIP2 and RORbeta activates downstream target HBP1 and is probably involved in CCIC self-renewal. (PMID:28137278)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	nrip2	ENSDARG00000079985
mus_musculus	Nrip2	ENSMUSG00000001520
rattus_norvegicus	Nrip2	ENSRNOG00000063347
drosophila_melanogaster	rngo	FBGN0030753
caenorhabditis_elegans		WBGENE00015308

Paralogs (4): UBAC2 (ENSG00000134882), DDI1 (ENSG00000170967), NRIP3 (ENSG00000175352), DDI2 (ENSG00000197312)

Protein

Protein identifiers

Nuclear receptor-interacting protein 2 — Q9BQI9 (reviewed: Q9BQI9)

All UniProt accessions (3): F5H065, F5H2G5, Q9BQI9

UniProt curated annotations — full annotation on UniProt →

Function. Down-regulates transcriptional activation by nuclear receptors such as NR1F2.

Subunit / interactions. Interacts with NR1F2, RARA and THRB in a ligand-dependent manner.

Subcellular location. Nucleus.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9BQI9-1	1	yes
Q9BQI9-2	2

RefSeq proteins (1): NP_113662* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR019103	Peptidase_aspartic_DDI1-type	Domain
IPR021109	Peptidase_aspartic_dom_sf	Homologous_superfamily
IPR033821	NRIP_C	Domain

Pfam: PF09668

UniProt features (8 total): compositionally biased region 2, sequence conflict 2, chain 1, region of interest 1, short sequence motif 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BQI9-F1	66.91	0.20

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 77 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_DN, FOSTER_TOLERANT_MACROPHAGE_DN, MODULE_301, GGGNNTTTCC_NFKB_Q6_01, TGGAAA_NFAT_Q4_01, GOBP_PROTEOLYSIS, GOMF_PEPTIDASE_ACTIVITY, GOMF_ASPARTIC_TYPE_PEPTIDASE_ACTIVITY, GOBP_NEGATIVE_REGULATION_OF_TRANSCRIPTION_BY_RNA_POLYMERASE_II, GOBP_NEGATIVE_REGULATION_OF_NUCLEOBASE_CONTAINING_COMPOUND_METABOLIC_PROCESS, CTIP_DN.V1_DN, MIR1827, MIR7106_5P, MIR4700_5P, MIR183_5P

GO Biological Process (3): negative regulation of transcription by RNA polymerase II (GO:0000122), proteolysis (GO:0006508), Notch signaling pathway (GO:0007219)

GO Molecular Function (2): aspartic-type endopeptidase activity (GO:0004190), protein binding (GO:0005515)

GO Cellular Component (2): nucleus (GO:0005634), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
protein metabolic process	1
cell surface receptor signaling pathway	1
endopeptidase activity	1
aspartic-type peptidase activity	1
binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

636 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NRIP2	SUSD5	O60279	533
NRIP2	GRIP2	Q9C0E4	528
NRIP2	TEX52	A6NCN8	505
NRIP2	IQSEC3	Q9UPP2	463
NRIP2	DYRK4	Q9NR20	435
NRIP2	ZNF454	Q8N9F8	432
NRIP2	XIRP1	Q702N8	419
NRIP2	ZNF540	Q8NDQ6	418
NRIP2	TSPAN9	O75954	414
NRIP2	RHNO1	Q9BSD3	409
NRIP2	A0A2Q2T6B6	A0A2Q2T6B6	407
NRIP2	TESC	Q96BS2	402
NRIP2	CRACR2A	Q9BSW2	393
NRIP2	NRIP1	P48552	388
NRIP2	MROH1	Q8NDA8	388

IntAct

19 interactions, top by confidence:

A	B	Type	Score
HDAC7	NRIP2	psi-mi:“MI:0915”(physical association)	0.600
NRIP2	HDAC7	psi-mi:“MI:0915”(physical association)	0.600
BANP	NRIP2	psi-mi:“MI:0915”(physical association)	0.560
NRIP2	BANP	psi-mi:“MI:0915”(physical association)	0.560
ZNF76	NRIP2	psi-mi:“MI:0915”(physical association)	0.560
NRIP2	SF3A2	psi-mi:“MI:0915”(physical association)	0.400
CCNG2	NRIP2	psi-mi:“MI:0915”(physical association)	0.370
NRIP2	ELF5	psi-mi:“MI:0915”(physical association)	0.370
NRIP2	BANP	psi-mi:“MI:0915”(physical association)	0.000
NRIP2	HDAC7	psi-mi:“MI:0915”(physical association)	0.000
ZNF76	NRIP2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (9): NRIP2 (Two-hybrid), HDAC7 (Two-hybrid), ZNF76 (Two-hybrid), BANP (Two-hybrid), NRIP2 (Biochemical Activity), NRIP2 (Proximity Label-MS), NRIP2 (Affinity Capture-MS), NRIP2 (Two-hybrid), NRIP2 (Two-hybrid)

ESM2 similar proteins: A0A087WVF3, A0A087WXS9, A0A087X179, A0A087X1G2, A6NDS4, A6NER0, A6QPT6, B9A6J9, M3WHG5, O14771, O15482, O15553, O19110, O76081, P0C7X1, P0C7X3, P0C7X4, P35125, P48778, P48967, P79209, Q13670, Q15697, Q2TBC4, Q3T191, Q3UZD7, Q4R2Z8, Q5DRQ5, Q5SSQ6, Q5XFX8, Q69ZB3, Q6DHY5, Q6IPX1, Q6ZMN8, Q8BLR5, Q8BWA8, Q8IYF1, Q8IZP1, Q8JZW5, Q8N7G0

Diamond homologs: A0JPP7, A1CDT9, A1DCU5, A2ADY9, I7HUG0, P0CS14, P0CS15, P40087, Q0CJ13, Q0U3Y6, Q10256, Q17569, Q1DNB9, Q1EBV4, Q2H085, Q2T9Z1, Q2USD7, Q497D6, Q4WGS4, Q54JB0, Q5AY89, Q5TDH0, Q6BK42, Q6CFI3, Q6CNS3, Q6FQE9, Q6TH22, Q754R2, Q7S906, Q7ZYA7, Q8WTU0, Q95JI3, Q9BQI9, Q9DAF3, Q5R7G1, Q9JHR9, Q9JJR9, Q9NQ35

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

803 predictions. Top by Δscore:

Variant	Effect	Δscore
12:2827687:CAATT:C	acceptor_gain	1.0000
12:2827691:T:C	acceptor_gain	1.0000
12:2827691:T:TC	acceptor_gain	1.0000
12:2828327:CTTA:C	donor_loss	1.0000
12:2828328:TTA:T	donor_loss	1.0000
12:2828329:TACCC:T	donor_loss	1.0000
12:2828330:A:AC	donor_gain	1.0000
12:2828330:AC:A	donor_gain	1.0000
12:2828330:ACC:A	donor_gain	1.0000
12:2828330:ACCCC:A	donor_loss	1.0000
12:2828331:C:CC	donor_gain	1.0000
12:2828331:C:CT	donor_loss	1.0000
12:2828331:CC:C	donor_gain	1.0000
12:2828331:CCC:C	donor_gain	1.0000
12:2828412:GCA:G	acceptor_gain	1.0000
12:2828413:CA:C	acceptor_gain	1.0000
12:2828413:CAC:C	acceptor_gain	1.0000
12:2828414:AC:A	acceptor_loss	1.0000
12:2828415:C:CC	acceptor_gain	1.0000
12:2828416:T:G	acceptor_loss	1.0000
12:2830868:C:CT	acceptor_gain	1.0000
12:2830869:A:T	acceptor_gain	1.0000
12:2830871:C:CT	acceptor_gain	1.0000
12:2830873:C:CT	acceptor_gain	1.0000
12:2830874:A:T	acceptor_gain	1.0000
12:2834636:CCTCA:C	donor_loss	1.0000
12:2834637:CTCA:C	donor_loss	1.0000
12:2834638:TCACC:T	donor_loss	1.0000
12:2834639:CA:C	donor_loss	1.0000
12:2834640:A:AC	donor_gain	1.0000

AlphaMissense

1805 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:2828386:A:T	V175D	0.988
12:2828364:A:C	N182K	0.984
12:2828364:A:T	N182K	0.984
12:2834711:G:C	F91L	0.982
12:2834711:G:T	F91L	0.982
12:2834713:A:G	F91L	0.982
12:2827237:G:C	F272L	0.976
12:2827237:G:T	F272L	0.976
12:2827239:A:G	F272L	0.976
12:2828359:A:G	I184T	0.975
12:2827292:A:T	I254N	0.974
12:2830718:A:T	V162D	0.967
12:2827238:A:G	F272S	0.963
12:2827937:G:T	A230E	0.963
12:2827238:A:C	F272C	0.955
12:2827651:C:G	G243R	0.955
12:2827970:A:G	L219P	0.954
12:2828359:A:C	I184S	0.950
12:2830713:A:G	C164R	0.949
12:2828359:A:T	I184N	0.948
12:2827299:A:G	C252R	0.947
12:2827659:A:G	F240S	0.947
12:2827650:C:T	G243D	0.946
12:2828365:T:A	N182I	0.941
12:2827292:A:C	I254S	0.940
12:2827638:A:G	L247P	0.938
12:2828366:T:A	N182Y	0.938
12:2827650:C:A	G243V	0.933
12:2830711:G:C	C164W	0.930
12:2834712:A:C	F91C	0.929

dbSNP variants (sampled 300 via entrez): RS1000043980 (12:2829941 G>A,T), RS1000330666 (12:2830958 C>A,G,T), RS1000642943 (12:2828802 A>G), RS1001730519 (12:2835658 T>TA), RS1001824460 (12:2828147 C>G,T), RS1001987471 (12:2824915 A>C), RS1002075084 (12:2835455 C>T), RS1002339865 (12:2833834 G>C), RS1002673120 (12:2834393 A>G), RS1002828548 (12:2829184 T>G), RS1002880831 (12:2829474 A>G), RS1002935008 (12:2832619 G>A), RS1003044589 (12:2827221 C>G,T), RS1003098833 (12:2827425 T>A,C), RS1003398029 (12:2832974 A>G)

Disease associations

OMIM: gene MIM:621054 | 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)

CTD chemical–gene interactions

11 total (human), top 11 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Silicon Dioxide	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
butyraldehyde	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Nickel	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Asbestos, Serpentine	increases methylation	1
Asbestos, Crocidolite	increases methylation	1
Copper Sulfate	increases expression	1

Clinical trials (associated diseases)

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