PNRC1

Summary

PNRC1 (proline rich nuclear receptor coactivator 1, HGNC:17278) is a protein-coding gene on chromosome 6q15, encoding Proline-rich nuclear receptor coactivator 1 (Q12796). Nuclear receptor coactivator.

Predicted to be involved in nuclear-transcribed mRNA catabolic process, nonsense-mediated decay. Predicted to be active in P-body and nucleus.

Source: NCBI Gene 10957 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 58 total
• MANE Select transcript: NM_006813

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17278
Approved symbol	PNRC1
Name	proline rich nuclear receptor coactivator 1
Location	6q15
Locus type	gene with protein product
Status	Approved
Aliases	B4-2, PRR2
Ensembl gene	ENSG00000146278
Ensembl biotype	protein_coding
OMIM	606714
Entrez	10957

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000336032, ENST00000354922, ENST00000369472

RefSeq mRNA: 1 — MANE Select: NM_006813 NM_006813

CCDS: CCDS5018

Canonical transcript exons

ENST00000336032 — 2 exons

Exon	Start	End
ENSE00000974836	89080751	89081434
ENSE00001344490	89083753	89085160

Expression profiles

Bgee: expression breadth ubiquitous, 290 present calls, max score 99.04.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 481.1587 / max 15549.6060, expressed in 1828 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
68861	432.2977	1828
68862	44.0091	1792
68867	1.4356	669
204097	1.4023	593
68863	1.2086	748
68868	0.7002	343
68864	0.1051	38

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	99.04	gold quality
mucosa of stomach	UBERON:0001199	99.00	gold quality
left uterine tube	UBERON:0001303	98.95	gold quality
gastrocnemius	UBERON:0001388	98.85	gold quality
left ovary	UBERON:0002119	98.85	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.78	gold quality
right ovary	UBERON:0002118	98.76	gold quality
popliteal artery	UBERON:0002250	98.72	gold quality
tibial artery	UBERON:0007610	98.72	gold quality
muscle of leg	UBERON:0001383	98.66	gold quality
colonic epithelium	UBERON:0000397	98.58	gold quality
gall bladder	UBERON:0002110	98.56	gold quality
monocyte	CL:0000576	98.54	gold quality
leukocyte	CL:0000738	98.49	gold quality
mononuclear cell	CL:0000842	98.49	gold quality
upper leg skin	UBERON:0004262	98.48	gold quality
omental fat pad	UBERON:0010414	98.46	gold quality
skin of hip	UBERON:0001554	98.43	gold quality
peritoneum	UBERON:0002358	98.42	gold quality
adipose tissue of abdominal region	UBERON:0007808	98.31	gold quality
aorta	UBERON:0000947	98.23	gold quality
right lung	UBERON:0002167	98.19	gold quality
cartilage tissue	UBERON:0002418	98.19	gold quality
adrenal tissue	UBERON:0018303	98.13	gold quality
muscle organ	UBERON:0001630	98.06	gold quality
right adrenal gland cortex	UBERON:0035827	98.02	gold quality
blood	UBERON:0000178	98.01	gold quality
granulocyte	CL:0000094	98.00	gold quality
right adrenal gland	UBERON:0001233	97.94	gold quality
left adrenal gland	UBERON:0001234	97.90	gold quality

Single-cell (SCXA)

Detected in 16 experiment(s), a significant marker in 9.

Experiment	Marker?	Max mean expression
E-MTAB-10287	yes	49.14
E-CURD-122	yes	44.67
E-CURD-46	yes	37.10
E-CURD-88	yes	36.06
E-MTAB-9221	yes	33.05
E-MTAB-9543	yes	19.44
E-HCAD-10	yes	18.33
E-MTAB-6701	yes	10.20
E-GEOD-111727	no	996.76
E-HCAD-8	no	686.85
E-CURD-84	no	423.52
E-HCAD-4	no	81.87
E-HCAD-6	no	43.74
E-HCAD-1	no	6.29
E-CURD-112	no	2.02

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR, ESRRA, FOXO3, NR3C1, NR5A1

miRNA regulators (miRDB)

115 targeting PNRC1, 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-126-5P	100.00	72.71	3180
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-190A-3P	100.00	80.35	5520
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-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-548P	99.98	72.25	3784
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-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-23A-3P	99.95	74.24	3163

Literature-anchored findings (GeneRIF, showing 6)

• PNRC and Grb2, by interacting with each other, can suppress nuclear receptor-mediated regulation and growth factor-mediated regulation in human breast tissue (PMID:15122321)
• Functional analysis of the 5’ flanking region of the human PNRC gene by deletion mutagenesis, transient transfection and luciferase assays revealed that the -123/+27 region is the minimal promoter of the human PNRC gene. (PMID:18281297)
• Three human PNRC splicing variants designated PNRC1c, PNRC1d and PNRC1f, are identified. (PMID:18703122)
• RFX1 specifically bind to promoter region and negatively regulate the transcription of the human PNRC gene. (PMID:19334528)
• PNRC1 ablates the enhanced proliferation triggered by established oncogenes such as RAS and MYC These observations uncover a previously undescribed mechanism of tumor suppression, whereby the cytoplasmic decapping machinery is hauled within nucleoli, tightly regulating ribosomal RNA maturation. (PMID:30373810)
• miR-199a Targeting PNRC1 to Promote Keratinocyte Proliferation and Invasion in Cholesteatoma. (PMID:34825000)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	pnrc1	ENSDARG00000043904
mus_musculus	Pnrc1	ENSMUSG00000040128
rattus_norvegicus	Pnrc1	ENSRNOG00000007793
drosophila_melanogaster	aqz	FBGN0286516

Paralogs (1): PNRC2 (ENSG00000189266)

Protein

Protein identifiers

Proline-rich nuclear receptor coactivator 1 — Q12796 (reviewed: Q12796)

Alternative names: Proline-rich protein 2, Protein B4-2

All UniProt accessions (2): Q12796, Q49A59

UniProt curated annotations — full annotation on UniProt →

Function. Nuclear receptor coactivator. May play a role in signal transduction.

Subunit / interactions. Interacts with many nuclear receptors including AR, ESR1, ESRRA, ESRRG, NR3C1/GR, NR5A1, PGR, TR, RAR and RXR. Interacts with GRB2.

Subcellular location. Nucleus.

Tissue specificity. Expressed in liver, lung, fat and NK/T cells.

Domain organisation. The interaction between PNRC1 and nuclear receptors is dependent on the SH3 binding motif.

Similarity. Belongs to the PNRC family. PNRC1 subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q12796-1	1	yes
Q12796-2	2

RefSeq proteins (1): NP_006804* (*=MANE)

Domains & families (InterPro)

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

Pfam: PF15365

UniProt features (13 total): compositionally biased region 3, region of interest 2, mutagenesis site 2, short sequence motif 2, chain 1, sequence conflict 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q12796-F1	58.87	0.04

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 (2):

Position	Phenotype
287	abolishes the interaction with the nuclear receptors; when associated with a-290.
290	abolishes the interaction with the nuclear receptors; when associated with a-287.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 359 (showing top): chr6q15, ATF_B, TAATAAT_MIR126, TGCGCANK_UNKNOWN, MODULE_45, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, TATTATA_MIR374, CREBP1_Q2, TGACCTY_ERR1_Q2, SARRIO_EPITHELIAL_MESENCHYMAL_TRANSITION_DN, HINATA_NFKB_TARGETS_KERATINOCYTE_UP, CREB_Q4, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_SUSTAINDED_IN_ERYTHROCYTE_UP, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_ERYTHROCYTE_UP, LINDSTEDT_DENDRITIC_CELL_MATURATION_B

GO Biological Process (2): nuclear-transcribed mRNA catabolic process, nonsense-mediated decay (GO:0000184), mRNA metabolic process (GO:0016071)

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

GO Cellular Component (2): P-body (GO:0000932), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
nuclear-transcribed mRNA catabolic process	1
RNA metabolic process	1
binding	1
cytoplasmic ribonucleoprotein granule	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

622 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PNRC1	C4BPA	P04003	778
PNRC1	ESR1	P03372	508
PNRC1	CHD7	Q9P2D1	507
PNRC1	PRR4	Q16378	499
PNRC1	STATH	P02808	448
PNRC1	SRSF6	Q13247	447
PNRC1	HTN1	P15515	437
PNRC1	NDUFA6	P56556	431
PNRC1	INS	P01308	429
PNRC1	TRIM5	Q9C035	427
PNRC1	PGR	P06401	423
PNRC1	LGALS4	P56470	419
PNRC1	DCP1A	Q9NPI6	402
PNRC1	TNFRSF21	O75509	397
PNRC1	TRIM22	Q8IYM9	397

IntAct

19 interactions, top by confidence:

A	B	Type	Score
PNRC1	POLR3F	psi-mi:“MI:0915”(physical association)	0.530
PNRC1	POLR3F	psi-mi:“MI:0407”(direct interaction)	0.530
POLR3F	PNRC1	psi-mi:“MI:0915”(physical association)	0.530
PNRC1	NPM1	psi-mi:“MI:0915”(physical association)	0.400
PNRC1	PNRC1	psi-mi:“MI:0915”(physical association)	0.370
UPF1	PNRC1	psi-mi:“MI:0915”(physical association)	0.370
PNRC1	MAPK8	psi-mi:“MI:0915”(physical association)	0.370
RARA	PNRC1	psi-mi:“MI:0915”(physical association)	0.370
Edc4	C4BPA	psi-mi:“MI:0914”(association)	0.350
DCP1A	TBX3	psi-mi:“MI:0914”(association)	0.350
CRKL	SOS1	psi-mi:“MI:0914”(association)	0.350
PNRC1	EDC4	psi-mi:“MI:0914”(association)	0.350
DDX6	PAK4	psi-mi:“MI:0914”(association)	0.350
ARHGAP18	CLTB	psi-mi:“MI:0914”(association)	0.350
CLTA	CLTB	psi-mi:“MI:0914”(association)	0.350
PNRC1		psi-mi:“MI:0915”(physical association)	0.000

BioGRID (25): PNRC1 (Affinity Capture-MS), PNRC1 (Affinity Capture-RNA), PNRC1 (Affinity Capture-MS), PNRC1 (Affinity Capture-MS), PNRC1 (Affinity Capture-MS), PNRC1 (Affinity Capture-MS), DCP1A (Affinity Capture-MS), EDC4 (Affinity Capture-MS), PNRC1 (Proximity Label-MS), PNRC1 (Affinity Capture-MS), PNRC1 (Affinity Capture-MS), PNRC1 (Affinity Capture-MS), PNRC1 (Two-hybrid), PNRC1 (Two-hybrid), PNRC1 (Two-hybrid)

ESM2 similar proteins: A2VDP0, A3AWH5, B1B5D5, B4FAF3, B5X392, B7TWP7, F4IVV0, F4J424, F4JHN2, F4KGY6, Q0D5G4, Q0P5K1, Q0VCW6, Q10JI3, Q10Q07, Q12796, Q28FE5, Q2NND9, Q32KY7, Q3KR53, Q5R4E9, Q5R9C3, Q5RJT0, Q5XH28, Q5ZMB7, Q66HE1, Q66KH8, Q68EQ8, Q6AYU0, Q6LA42, Q6NXH3, Q6NZP2, Q86WP2, Q8GRN0, Q8GY65, Q8GYT8, Q8GYX2, Q922M7, Q94CK6, Q9BVC5

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

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	57
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

408 predictions. Top by Δscore:

Variant	Effect	Δscore
6:89081429:A:T	donor_gain	1.0000
6:89081309:G:GT	donor_gain	0.9900
6:89081432:GAG:G	donor_gain	0.9900
6:89081434:GGT:G	donor_loss	0.9900
6:89081435:G:T	donor_loss	0.9900
6:89081436:T:G	donor_loss	0.9900
6:89082651:AGTGC:A	donor_gain	0.9900
6:89083750:TAG:T	acceptor_loss	0.9900
6:89083751:A:G	acceptor_loss	0.9900
6:89083752:G:GT	acceptor_loss	0.9900
6:89082650:T:TA	donor_gain	0.9800
6:89083751:A:AG	acceptor_gain	0.9800
6:89083752:G:GG	acceptor_gain	0.9800
6:89081428:G:GT	donor_gain	0.9700
6:89081369:G:GT	donor_gain	0.9600
6:89083752:GGTT:G	acceptor_gain	0.9600
6:89083752:GGTTT:G	acceptor_gain	0.9600
6:89081435:G:GG	donor_gain	0.9500
6:89081727:G:GT	donor_gain	0.9500
6:89082164:GA:G	donor_gain	0.9500
6:89083751:AG:A	acceptor_gain	0.9500
6:89083752:GG:G	acceptor_gain	0.9500
6:89083752:GGT:G	acceptor_gain	0.9500
6:89082082:TTCC:T	donor_gain	0.9400
6:89082089:T:G	donor_gain	0.9400
6:89080976:T:A	donor_gain	0.9200
6:89080978:C:G	donor_gain	0.9200
6:89081834:G:GT	donor_gain	0.9200
6:89083173:T:TA	donor_gain	0.9200
6:89083174:A:AA	donor_gain	0.9200

AlphaMissense

2099 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:89084062:T:C	F284L	1.000
6:89084063:T:C	F284S	1.000
6:89084063:T:G	F284C	1.000
6:89084064:T:A	F284L	1.000
6:89084064:T:G	F284L	1.000
6:89084110:T:A	W300R	1.000
6:89084110:T:C	W300R	1.000
6:89084112:G:C	W300C	1.000
6:89084112:G:T	W300C	1.000
6:89084168:T:C	L319S	1.000
6:89084180:T:C	L323P	1.000
6:89084054:G:A	G281E	0.999
6:89084065:A:C	S285R	0.999
6:89084067:T:A	S285R	0.999
6:89084067:T:G	S285R	0.999
6:89084072:C:A	P287Q	0.999
6:89084074:C:T	P288S	0.999
6:89084075:C:A	P288H	0.999
6:89084081:C:A	P290H	0.999
6:89084090:T:A	L293H	0.999
6:89084092:C:T	P294S	0.999
6:89084093:C:A	P294Q	0.999
6:89084098:C:T	P296S	0.999
6:89084099:C:A	P296H	0.999
6:89084101:C:A	P297T	0.999
6:89084101:C:T	P297S	0.999
6:89084102:C:A	P297H	0.999
6:89084102:C:G	P297R	0.999
6:89084111:G:C	W300S	0.999
6:89084171:A:T	K320I	0.999

dbSNP variants (sampled 300 via entrez): RS1000545109 (6:89081796 G>A), RS1000610051 (6:89082490 G>A), RS1001227809 (6:89080752 T>G), RS1001596882 (6:89082999 TTTGTTG>T,TTTG), RS1001712011 (6:89085627 T>C), RS1001720072 (6:89080665 A>G), RS1001947037 (6:89082124 A>G), RS1002324333 (6:89081433 A>C), RS1002547038 (6:89080189 T>C), RS1002599791 (6:89084387 T>C), RS1002631438 (6:89081683 C>A), RS1002846675 (6:89080177 T>C), RS1003009631 (6:89079810 C>T), RS1003339544 (6:89082709 G>A), RS1003350718 (6:89079890 T>C)

Disease associations

OMIM: gene MIM:606714 | 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
GCST008839_573	Height	3.000000e-09

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Estradiol	affects binding, increases reaction, decreases expression, affects expression	5
(+)-JQ1 compound	increases expression	4
bisphenol A	affects folding, decreases reaction, affects cotreatment, decreases methylation, increases expression (+1 more)	3
sodium arsenite	decreases expression, increases expression	2
cobaltous chloride	increases expression	2
Resveratrol	affects cotreatment, decreases expression	2
Arsenic Trioxide	increases expression	2
Tretinoin	increases expression	2
Valproic Acid	affects expression, decreases expression	2
Cyclosporine	decreases expression, increases expression	2
Cadmium Chloride	decreases expression, increases expression	2
Genistein	affects binding, increases reaction, decreases expression	2
GSK-J4	increases expression	1
afuresertib	increases expression	1
FR900359	increases phosphorylation	1
TAK-243	increases sumoylation	1
biochanin A	affects binding, increases reaction	1
daidzein	affects binding, increases reaction	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
lead acetate	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
nickel chloride	increases expression	1
zinc chromate	increases abundance, increases expression	1
ochratoxin A	decreases expression	1
cupric chloride	decreases expression	1
ciglitazone	affects binding, increases expression	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	increases abundance, increases expression	1
CGP 52608	affects binding, increases reaction	1

Clinical trials (associated diseases)

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