PNRC2

Summary

PNRC2 (proline rich nuclear receptor coactivator 2, HGNC:23158) is a protein-coding gene on chromosome 1p36.11, encoding Proline-rich nuclear receptor coactivator 2 (Q9NPJ4). Involved in nonsense-mediated mRNA decay (NMD) by acting as a bridge between the mRNA decapping complex and the NMD machinery. It is a selective cancer dependency (DepMap: 10.5% of cell lines).

Involved in nuclear-transcribed mRNA catabolic process, nonsense-mediated decay. Located in Golgi apparatus; P-body; and nucleoplasm.

Source: NCBI Gene 55629 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 10 total
• Cancer dependency (DepMap): dependent in 10.5% of screened cell lines
• MANE Select transcript: NM_017761

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23158
Approved symbol	PNRC2
Name	proline rich nuclear receptor coactivator 2
Location	1p36.11
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000189266
Ensembl biotype	protein_coding
OMIM	611882
Entrez	55629

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 13 protein_coding

ENST00000334351, ENST00000374468, ENST00000471915, ENST00000579103, ENST00000647887, ENST00000904192, ENST00000904193, ENST00000904194, ENST00000912545, ENST00000912546, ENST00000912547, ENST00000912548, ENST00000912549

RefSeq mRNA: 1 — MANE Select: NM_017761 NM_017761

CCDS: CCDS246

Canonical transcript exons

ENST00000334351 — 3 exons

Exon	Start	End
ENSE00001336314	23961440	23963462
ENSE00001375617	23959828	23959998
ENSE00001463599	23960929	23961134

Expression profiles

Bgee: expression breadth ubiquitous, 288 present calls, max score 99.51.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 29.1934 / max 713.6013, expressed in 1806 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
1376	28.2135	1805
1374	0.4390	214
1375	0.3075	150
1373	0.2334	90

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
germinal epithelium of ovary	UBERON:0001304	99.51	gold quality
mucosa of sigmoid colon	UBERON:0004993	99.11	gold quality
colonic mucosa	UBERON:0000317	98.92	gold quality
parietal pleura	UBERON:0002400	98.85	gold quality
pleura	UBERON:0000977	98.72	gold quality
trabecular bone tissue	UBERON:0002483	98.68	gold quality
cauda epididymis	UBERON:0004360	98.61	gold quality
visceral pleura	UBERON:0002401	98.59	gold quality
mammary duct	UBERON:0001765	98.46	gold quality
lower lobe of lung	UBERON:0008949	98.44	gold quality
mucosa of urinary bladder	UBERON:0001259	98.41	gold quality
epithelium of nasopharynx	UBERON:0001951	98.41	gold quality
renal medulla	UBERON:0000362	98.40	gold quality
superficial temporal artery	UBERON:0001614	98.38	gold quality
metanephric glomerulus	UBERON:0004736	98.38	gold quality
secondary oocyte	CL:0000655	98.37	gold quality
colonic epithelium	UBERON:0000397	98.34	gold quality
epithelium of mammary gland	UBERON:0003244	98.33	gold quality
lymph node	UBERON:0000029	98.31	gold quality
ventricular zone	UBERON:0003053	98.30	gold quality
calcaneal tendon	UBERON:0003701	98.30	gold quality
vena cava	UBERON:0004087	98.28	gold quality
renal glomerulus	UBERON:0000074	98.25	gold quality
amniotic fluid	UBERON:0000173	98.25	gold quality
corpus epididymis	UBERON:0004359	98.23	gold quality
jejunal mucosa	UBERON:0000399	98.17	gold quality
esophagus squamous epithelium	UBERON:0006920	98.12	gold quality
kidney epithelium	UBERON:0004819	98.10	gold quality
cardia of stomach	UBERON:0001162	98.08	gold quality
caput epididymis	UBERON:0004358	98.05	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-7037	yes	574.43
E-MTAB-6386	no	711.47
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F1, NFYA

miRNA regulators (miRDB)

96 targeting PNRC2, 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-4262	100.00	73.26	3931
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-4503	99.85	71.45	1869

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 10.5% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 5)

• Not only PNRC2 but also the corepressor TLE1 functioned as ERRgamma coactivator in a reporter gene analysis. (PMID:14651967)
• PNRC2 plays an essential role in mammalian Nonsense-mediated mRNA decay (NMD), mediating the interaction between the NMD machinery and the decapping complex. (PMID:19150429)
• PNRC2 acts in synergy with Dcp1a to stimulate the decapping activity of Dcp2 by bridging the interaction between Dcp1a and Dcp2. (PMID:23085078)
• GR and PNRC2 interact in a ligand-dependent manner to recruit UPF1 for rapid mRNA degradation (PMID:25775514)
• UPF1 interacts with PNRC2 and that it triggers 5’-3’ exonucleolytic decay of reporter transcripts in tethering assays. PNRC2 is probably an important mRNA decapping factor but that it does not appear to be required for nonsense-mediated mRNA decay. (PMID:29348139)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	pnrc2	ENSDARG00000053291
mus_musculus	Pnrc2	ENSMUSG00000028675
rattus_norvegicus	Pnrc2	ENSRNOG00000070268
drosophila_melanogaster	aqz	FBGN0286516

Paralogs (1): PNRC1 (ENSG00000146278)

Protein

Protein identifiers

Proline-rich nuclear receptor coactivator 2 — Q9NPJ4 (reviewed: Q9NPJ4)

All UniProt accessions (2): Q9NPJ4, J3KS97

UniProt curated annotations — full annotation on UniProt →

Function. Involved in nonsense-mediated mRNA decay (NMD) by acting as a bridge between the mRNA decapping complex and the NMD machinery. May act by targeting the NMD machinery to the P-body and recruiting the decapping machinery to aberrant mRNAs. Required for UPF1/RENT1 localization to the P-body. Plays a role in glucocorticoid receptor-mediated mRNA degradation by interacting with the glucocorticoid receptor NR3C1 in a ligand-dependent manner when it is bound to the 5’ UTR of target mRNAs and recruiting the RNA helicase UPF1 and the mRNA-decapping enzyme DCP1A, leading to RNA decay. Also acts as a nuclear receptor coactivator. May play a role in controlling the energy balance between energy storage and energy expenditure.

Subunit / interactions. Interacts with UPF1/RENT1; preferentially interacts with hyperphosphorylated form. Interacts with DCP1A. Interacts with many nuclear receptors including ESR1, ESRRA, ESRRG, NR3C1/GR, NR5A1, PGR, TR, RAR and RXR.

Subcellular location. Nucleus. Cytoplasm. P-body.

Tissue specificity. Expressed in heart, lung, muscle and brain.

Domain organisation. The interaction between PNRC2 and nuclear receptors is dependent on the SH3 binding motif.

Similarity. Belongs to the PNRC family. PNRC2 subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NPJ4-1	1	yes
Q9NPJ4-2	2

RefSeq proteins (1): NP_060231* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026780	PNRC1/2	Family
IPR028322	PNRC-like_rgn	Conserved_site

Pfam: PF15365

UniProt features (15 total): mutagenesis site 4, region of interest 3, compositionally biased region 3, helix 2, chain 1, short sequence motif 1, splice variant 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
5KQ4	X-RAY DIFFRACTION	2.56
4B6H	X-RAY DIFFRACTION	2.6
5KQ1	X-RAY DIFFRACTION	3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NPJ4-F1	67.55	0.18

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Mutagenesis-validated functional residues (4):

Position	Phenotype
104	abolishes the interaction with the nuclear receptors but not decapping enzyme; when associated with a-101.
108	abolishes the interaction with dcp1a.
114	abolishes the interaction with dcp1a.
101	abolishes the interaction with the nuclear receptors but not decapping enzyme; when associated with a-104.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-975957	Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC)

MSigDB gene sets: 129 (showing top): HORIUCHI_WTAP_TARGETS_DN, CMYB_01, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, CHANDRAN_METASTASIS_DN, YY1_Q6, FISCHER_G2_M_CELL_CYCLE, WTGAAAT_UNKNOWN, GARY_CD5_TARGETS_DN, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, FISCHER_DREAM_TARGETS, SENESE_HDAC1_TARGETS_UP, GOBP_NUCLEAR_TRANSCRIBED_MRNA_CATABOLIC_PROCESS_NONSENSE_MEDIATED_DECAY, GRYDER_PAX3FOXO1_ENHANCERS_IN_TADS, BURTON_ADIPOGENESIS_11, REACTOME_METABOLISM_OF_RNA

GO Biological Process (3): nuclear-transcribed mRNA catabolic process, nonsense-mediated decay (GO:0000184), deadenylation-independent decapping of nuclear-transcribed mRNA (GO:0031087), mRNA metabolic process (GO:0016071)

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

GO Cellular Component (6): P-body (GO:0000932), nucleus (GO:0005634), nucleoplasm (GO:0005654), Golgi apparatus (GO:0005794), cytosol (GO:0005829), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Nonsense-Mediated Decay (NMD)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
intracellular membrane-bounded organelle	2
cytoplasm	2
nuclear-transcribed mRNA catabolic process	1
nuclear-transcribed mRNA catabolic process, deadenylation-independent decay	1
mRNA methylguanosine-cap decapping	1
RNA metabolic process	1
binding	1
cytoplasmic ribonucleoprotein granule	1
nuclear lumen	1
endomembrane system	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

743 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PNRC2	DCP1A	Q9NPI6	980
PNRC2	UPF1	Q92900	953
PNRC2	SMG5	Q9UPR3	951
PNRC2	ESRRG	P62508	854
PNRC2	COMMD7	Q86VX2	826
PNRC2	A0A2R8Y455	A0A2R8Y455	826
PNRC2	IARS1	P41252	813
PNRC2	SMG7	Q92540	792
PNRC2	TLE1	Q04724	764
PNRC2	SMG6	Q86US8	719
PNRC2	DCP2	Q8IU60	716
PNRC2	SMG8	Q8ND04	695
PNRC2	SMG9	Q9H0W8	664
PNRC2	UPF2	Q9HAU5	661
PNRC2	SMG1	Q96Q15	611

IntAct

46 interactions, top by confidence:

A	B	Type	Score
DCP2	DCP1A	psi-mi:“MI:0914”(association)	0.950
PNRC2	DCP1A	psi-mi:“MI:0915”(physical association)	0.940
DCP1A	PNRC2	psi-mi:“MI:0915”(physical association)	0.940
PNRC2	DCP1A	psi-mi:“MI:0403”(colocalization)	0.940
dcp1	dcp2	psi-mi:“MI:0915”(physical association)	0.790
DCP1A	UPF1	psi-mi:“MI:0914”(association)	0.780
UPF1	DCP1A	psi-mi:“MI:0914”(association)	0.780
PNRC2	UPF1	psi-mi:“MI:0915”(physical association)	0.620
PNRC2	UPF1	psi-mi:“MI:0914”(association)	0.620
UPF1	PNRC2	psi-mi:“MI:0915”(physical association)	0.620
UPF1	PNRC2	psi-mi:“MI:0914”(association)	0.620
ESRRG	PNRC2	psi-mi:“MI:0915”(physical association)	0.560
PNRC2	GALK1	psi-mi:“MI:0915”(physical association)	0.560
GALK1	PNRC2	psi-mi:“MI:0915”(physical association)	0.560
BANP	PNRC2	psi-mi:“MI:0915”(physical association)	0.560
PNRC2	EDC4	psi-mi:“MI:0914”(association)	0.530
NR5A1	PNRC2	psi-mi:“MI:0915”(physical association)	0.490
PNRC2	ESR1	psi-mi:“MI:0915”(physical association)	0.490
PNRC2	NR5A1	psi-mi:“MI:0915”(physical association)	0.490

BioGRID (38): DCP1A (Two-hybrid), PNRC2 (Reconstituted Complex), PNRC2 (Two-hybrid), PNRC2 (Biochemical Activity), dcp2 (Co-crystal Structure), dcp1 (Co-crystal Structure), PNRC2 (Two-hybrid), PNRC2 (Two-hybrid), ESRRG (Two-hybrid), DCP1A (Two-hybrid), PNRC2 (Negative Genetic), PNRC2 (Affinity Capture-RNA), DCP1A (Affinity Capture-MS), NF2 (Affinity Capture-MS), DCP1B (Affinity Capture-MS)

ESM2 similar proteins: A0A0Q3PY21, A2VDP0, A2XYN9, A3AWH5, A3C057, B1B5D3, B1B5D4, B1B5D5, B4FAF3, B5X392, B6TNQ7, B7TWP7, C0RWW9, F4IVV0, F4J424, F4JHN2, O82117, Q0J995, Q0VCW6, Q10JI3, Q10Q07, Q3KR53, Q53KW9, Q5R9C3, Q5RJT0, Q5XH28, Q5Z9E5, Q5ZMB7, Q653Z5, Q66HE1, Q66KH8, Q68EQ8, Q6AWY4, Q6LA42, Q6NZP2, Q6YVY6, Q8GRN0, Q8LGD5, Q922M7, Q9BVC5

Diamond homologs: B5X392, B7TWP7, Q0VCW6, Q12796, Q5XH28, Q5ZMB7, Q63647, Q66HE1, Q66KH8, Q68EQ8, Q9CR73, Q9NPJ4

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 21 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 Receptor transcription pathway	6	70.7×	2e-08

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	9
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

287 predictions. Top by Δscore:

Variant	Effect	Δscore
1:23959995:G:GG	donor_gain	1.0000
1:23959995:GTCA:G	donor_loss	1.0000
1:23959996:TCA:T	donor_gain	1.0000
1:23959997:CA:C	donor_gain	1.0000
1:23959999:G:GG	donor_gain	1.0000
1:23960000:TAA:T	donor_loss	1.0000
1:23960001:AA:A	donor_loss	0.9900
1:23960928:GCTA:G	acceptor_gain	0.9900
1:23961434:TTGTA:T	acceptor_loss	0.9900
1:23961435:TGTA:T	acceptor_loss	0.9900
1:23961436:GTAG:G	acceptor_loss	0.9900
1:23961437:TA:T	acceptor_loss	0.9900
1:23961438:A:AT	acceptor_loss	0.9900
1:23960002:AGTAG:A	donor_loss	0.9800
1:23961131:AAAG:A	donor_loss	0.9800
1:23961132:AAGGT:A	donor_loss	0.9800
1:23961133:AGG:A	donor_loss	0.9800
1:23961134:GG:G	donor_loss	0.9800
1:23961135:G:GA	donor_loss	0.9800
1:23961136:T:G	donor_loss	0.9800
1:23961036:G:GT	donor_gain	0.9700
1:23961098:T:TA	donor_gain	0.9700
1:23961099:AGTGG:A	donor_gain	0.9700
1:23961438:A:AG	acceptor_gain	0.9700
1:23961439:G:GG	acceptor_gain	0.9700
1:23961439:GGT:G	acceptor_gain	0.9700
1:23960060:G:GT	donor_gain	0.9600
1:23961433:C:G	acceptor_gain	0.9600
1:23959963:G:GT	donor_gain	0.9500
1:23959979:T:A	donor_gain	0.9500

AlphaMissense

924 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:23961749:T:C	F98L	0.999
1:23961751:T:A	F98L	0.999
1:23961751:T:G	F98L	0.999
1:23961797:T:A	W114R	0.999
1:23961797:T:C	W114R	0.999
1:23961799:G:C	W114C	0.999
1:23961799:G:T	W114C	0.999
1:23961750:T:C	F98S	0.998
1:23961777:T:A	L107H	0.998
1:23961861:T:C	L135P	0.998
1:23961750:T:G	F98C	0.997
1:23961849:T:C	L131P	0.997
1:23961861:T:A	L135H	0.997
1:23961779:C:T	P108S	0.996
1:23961780:C:A	P108H	0.996
1:23961798:G:C	W114S	0.996
1:23961849:T:A	L131H	0.996
1:23961741:G:A	G95D	0.995
1:23961752:A:C	S99R	0.995
1:23961754:T:A	S99R	0.995
1:23961754:T:G	S99R	0.995
1:23961762:C:A	P102Q	0.995
1:23961779:C:A	P108T	0.995
1:23961786:C:A	P110Q	0.995
1:23961789:C:A	P111Q	0.995
1:23961785:C:T	P110S	0.994
1:23961852:A:T	K132I	0.994
1:23961853:A:C	K132N	0.994
1:23961853:A:T	K132N	0.994
1:23961738:C:A	A94D	0.993

dbSNP variants (sampled 300 via entrez): RS1000069111 (1:23959732 C>T), RS1000070763 (1:23959619 A>C,G,T), RS1001070607 (1:23960730 G>A), RS1001080465 (1:23960570 C>T), RS1001732850 (1:23958692 C>A), RS1001744091 (1:23958411 G>T), RS1002232993 (1:23962394 A>G), RS1002585507 (1:23961880 TAAGAC>T), RS1003910024 (1:23960147 C>G,T), RS1004914331 (1:23963695 T>C), RS1004968185 (1:23963495 T>C), RS1005385621 (1:23959602 G>A), RS1005586061 (1:23959219 G>A,C), RS1006084005 (1:23963216 G>GTT), RS1006718229 (1:23963879 TTG>T)

Disease associations

OMIM: gene MIM:611882 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST001762_851	Obesity-related traits	2.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0003940	physical activity

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases methylation	2
Estradiol	decreases expression, affects binding, increases reaction, affects cotreatment	2
Tetrachlorodibenzodioxin	decreases expression	2
aristolochic acid I	decreases expression	1
bisphenol F	affects cotreatment, increases expression	1
dicrotophos	decreases expression	1
alpha phellandrene	increases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	decreases expression, increases activity, affects binding	1
lead acetate	decreases expression	1
CGP 52608	affects binding, increases reaction	1
K 7174	increases expression	1
abrine	increases expression	1
jinfukang	decreases expression	1
Resveratrol	increases expression, affects cotreatment	1
Zoledronic Acid	increases expression	1
Leflunomide	decreases expression	1
Acetaldehyde	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Doxorubicin	increases expression	1
Indomethacin	affects cotreatment, increases expression	1
Methotrexate	increases expression	1
Phenobarbital	affects expression	1
Plant Extracts	affects cotreatment, increases expression	1
Progesterone	affects cotreatment, decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Valproic Acid	decreases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1

Clinical trials (associated diseases)

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