PRB2

Summary

PRB2 (proline rich protein BstNI subfamily 2, HGNC:9338) is a protein-coding gene on chromosome 12p13.2, encoding Basic salivary proline-rich protein 2 (P02812).

This gene encodes a member of the heterogeneous family of basic, proline-rich, human salivary glycoproteins. The encoded preproprotein undergoes proteolytic processing to generate one or more mature isoforms before secretion from the parotid glands. Multiple alleles of this gene exhibiting variations in the length of the tandem repeats, polymorphic cleavage sites and polymorphic stop codons have been identified. This gene is located in a cluster of closely related salivary proline-rich proteins on chromosome 12.

Source: NCBI Gene 653247 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 148 total
• MANE Select transcript: NM_006248

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9338
Approved symbol	PRB2
Name	proline rich protein BstNI subfamily 2
Location	12p13.2
Locus type	gene with protein product
Status	Approved
Aliases	PRPPRB1, Ps, cP7
Ensembl gene	ENSG00000121335
Ensembl biotype	protein_coding
OMIM	168810
Entrez	653247

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000389362, ENST00000545829, ENST00000565533

RefSeq mRNA: 1 — MANE Select: NM_006248 NM_006248

CCDS: CCDS41757

Canonical transcript exons

ENST00000389362 — 4 exons

Exon	Start	End
ENSE00001524753	11391540	11391648
ENSE00001598885	11392794	11393977
ENSE00003623705	11394495	11394530
ENSE00003842975	11395466	11395567

Expression profiles

Bgee: expression breadth ubiquitous, 110 present calls, max score 75.72.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 3.2896 / max 5966.8395, expressed in 7 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
129673	3.2896	7
129666	0.6592	2
129667	0.4370	1
129665	0.4150	1
129669	0.3630	1
129668	0.3610	3
129671	0.0866	2
129670	0.0790	1
206620	0.0499	1
206621	0.0376	1

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
caudate nucleus	UBERON:0001873	75.72	gold quality
nucleus accumbens	UBERON:0001882	75.29	gold quality
primary visual cortex	UBERON:0002436	74.60	gold quality
putamen	UBERON:0001874	74.40	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	72.95	gold quality
superior frontal gyrus	UBERON:0002661	70.53	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	70.26	gold quality
Brodmann (1909) area 9	UBERON:0013540	69.61	gold quality
right frontal lobe	UBERON:0002810	69.53	gold quality
anterior cingulate cortex	UBERON:0009835	67.47	gold quality
Ammon’s horn	UBERON:0001954	66.70	gold quality
cerebral cortex	UBERON:0000956	66.60	gold quality
corpus callosum	UBERON:0002336	66.39	gold quality
frontal cortex	UBERON:0001870	64.82	gold quality
tonsil	UBERON:0002372	63.19	gold quality
adrenal tissue	UBERON:0018303	62.45	gold quality
prefrontal cortex	UBERON:0000451	61.55	gold quality
temporal lobe	UBERON:0001871	61.41	gold quality
amygdala	UBERON:0001876	61.33	gold quality
brain	UBERON:0000955	61.20	gold quality
hypothalamus	UBERON:0001898	60.52	gold quality
skin of leg	UBERON:0001511	59.13	gold quality
zone of skin	UBERON:0000014	57.80	gold quality
skin of abdomen	UBERON:0001416	56.06	gold quality
bone marrow	UBERON:0002371	55.51	gold quality
sural nerve	UBERON:0015488	52.84	gold quality
colonic epithelium	UBERON:0000397	50.49	gold quality
bone marrow cell	CL:0002092	50.34	gold quality
substantia nigra	UBERON:0002038	50.06	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	45.04	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.96

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

9 targeting PRB2, 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-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-944	99.82	70.85	3042
HSA-MIR-15B-3P	97.85	66.68	974
HSA-MIR-4639-3P	97.54	67.12	787
HSA-MIR-6748-3P	97.20	65.66	836
HSA-MIR-6759-3P	96.94	68.31	823
HSA-MIR-616-3P	96.82	66.99	784

Literature-anchored findings (GeneRIF, showing 3)

• Ezh2 competes with HDAC1 in binding to pRb2/p130, disrupting their occupancy on the cyclin A promoter. (PMID:15077161)
• Our studies suggested that pRb2/p130-complexes bind to the ER-alpha promoter and could be involved in the transcriptional regulation of the ER-alpha gene by altering chromatin structure and DNA methylation pattern. (PMID:15923424)
• pRb2/p130 cytoplasmic delocalization can lead to cell cycle deregulation (PMID:25205458)

Cross-species orthologs

0 orthologs

Paralogs (6): PRR4 (ENSG00000111215), PRH2 (ENSG00000134551), PRB3 (ENSG00000197870), PRB4 (ENSG00000230657), PRH1 (ENSG00000231887), PRB1 (ENSG00000251655)

Protein

Protein identifiers

Basic salivary proline-rich protein 2 — P02812 (reviewed: P02812)

Alternative names: Con1 glycoprotein

All UniProt accessions (2): H3BR58, P02812

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Secreted.

Post-translational modifications. N- and O-glycosylated. In head and neck cancer patients, O-glycosylated with glucosylgalactosyl carbohydrate moiety. This modification would require prior hydroxylation on the lysine residue. Proteolytically cleaved at the tripeptide Xaa-Pro-Gln, where Xaa in the P(3) position is mostly lysine. The endoprotease may be of microbial origin. Pyroglutamate formation occurs on terminal Gln residues of cleaved peptides. Pyroglutamate formation found on at least Gln-398 and Gln-400.

Polymorphism. The number of repeats is polymorphic and varies among different alleles.

Miscellaneous. Peptides IB-9 and P-E are the same peptide.

RefSeq proteins (1): NP_006239* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026086	Pro-rich	Family

Pfam: PF15240

UniProt features (46 total): repeat 15, compositionally biased region 9, chain 6, glycosylation site 4, sequence conflict 4, modified residue 3, region of interest 2, sequence variant 2, signal peptide 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P02812-F1	47.03	0.02

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 (3): 17, 24, 52

Glycosylation sites (4): 168, 230, 232, 272

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 7 (showing top): WP_SPINAL_CORD_INJURY, TRAVAGLINI_LUNG_SEROUS_CELL, WP_PLEURAL_MESOTHELIOMA, ZNF320_TARGET_GENES, DAZARD_UV_RESPONSE_CLUSTER_G24, chr12p13, CROMER_METASTASIS_UP

GO Biological Process (0):

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

GO Cellular Component (1): extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

9 interactions, top by confidence:

A	B	Type	Score
PRB2	ASPH	psi-mi:“MI:0915”(physical association)	0.560
PRB2	MIEF2	psi-mi:“MI:0915”(physical association)	0.560
GTF2B	CST4	psi-mi:“MI:0914”(association)	0.530
CLK1	PIGR	psi-mi:“MI:0914”(association)	0.350
ASPH	PRB2	psi-mi:“MI:0915”(physical association)	0.000
MIEF2	PRB2	psi-mi:“MI:0915”(physical association)	0.000

ESM2 similar proteins: A0A087WUL8, A0A1D9BZF0, B2SU53, F8W0I5, H0YM25, O36421, O46383, P02812, P02849, P02895, P03211, P04280, P04927, P04928, P06916, P08116, P08676, P08726, P09593, P0DPF3, P0DX00, P12027, P13813, P13822, P14708, P16230, P17437, P21850, Q01033, Q01042, Q03400, Q04118, Q1HVF7, Q26005, Q27905, Q3BBV0, Q3KSS4, Q4WW98, Q54G14, Q5MJ10

Diamond homologs: P02810, P02812, P04280, Q04118, Q16378, P10163

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	133
Likely benign	13
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

239 predictions. Top by Δscore:

Variant	Effect	Δscore
12:11393973:ATTTC:A	acceptor_gain	1.0000
12:11393974:TTTC:T	acceptor_gain	1.0000
12:11393975:TTC:T	acceptor_gain	1.0000
12:11393975:TTCC:T	acceptor_loss	1.0000
12:11393976:TC:T	acceptor_gain	1.0000
12:11393977:CC:C	acceptor_gain	1.0000
12:11393977:CCTG:C	acceptor_loss	1.0000
12:11393978:C:CC	acceptor_gain	1.0000
12:11393978:C:T	acceptor_gain	1.0000
12:11393979:T:C	acceptor_loss	1.0000
12:11393986:C:CT	acceptor_gain	1.0000
12:11393987:A:T	acceptor_gain	1.0000
12:11394490:TTTA:T	donor_loss	0.9900
12:11394491:TTA:T	donor_loss	0.9900
12:11394492:TA:T	donor_loss	0.9900
12:11395461:TTTA:T	donor_loss	0.9900
12:11395462:TTA:T	donor_loss	0.9900
12:11395463:TA:T	donor_loss	0.9900
12:11395465:C:CA	donor_loss	0.9900
12:11392788:TCATA:T	donor_loss	0.9800
12:11392789:CATA:C	donor_loss	0.9800
12:11392790:ATACC:A	donor_loss	0.9800
12:11392791:TA:T	donor_loss	0.9800
12:11392792:A:AT	donor_loss	0.9800
12:11392793:C:CT	donor_loss	0.9800
12:11394528:CAT:C	acceptor_gain	0.9800
12:11394529:ATCTA:A	acceptor_loss	0.9800
12:11394531:C:CC	acceptor_gain	0.9800
12:11394531:CTAG:C	acceptor_loss	0.9800
12:11394532:T:C	acceptor_loss	0.9800

AlphaMissense

2567 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:11395504:G:T	A9D	0.948
12:11395516:A:C	L5R	0.946
12:11395513:A:C	L6R	0.938
12:11395488:G:C	S14R	0.934
12:11395488:G:T	S14R	0.934
12:11395490:T:G	S14R	0.934
12:11395516:A:G	L5P	0.901
12:11395516:A:T	L5Q	0.901
12:11395495:G:T	A12D	0.892
12:11395513:A:G	L6P	0.876
12:11395507:A:T	V8E	0.863
12:11395513:A:T	L6Q	0.863
12:11395505:C:G	A9P	0.832
12:11395525:A:C	L2R	0.831
12:11395519:A:T	I4N	0.824
12:11395492:A:G	L13P	0.808
12:11395525:A:T	L2Q	0.803
12:11395498:A:G	L11P	0.796
12:11395498:A:C	L11R	0.792
12:11395525:A:G	L2P	0.790
12:11395501:A:C	L10W	0.740
12:11395501:A:G	L10S	0.736
12:11395519:A:G	I4T	0.734
12:11393472:T:A	Q202H	0.727
12:11393472:T:G	Q202H	0.727
12:11393535:T:A	Q181H	0.722
12:11393535:T:G	Q181H	0.722
12:11393520:T:A	Q186H	0.715
12:11393520:T:G	Q186H	0.715
12:11395519:A:C	I4S	0.711

dbSNP variants (sampled 300 via entrez): RS1000050133 (12:11396670 A>T), RS1000144511 (12:11396843 T>C), RS1001613411 (12:11355159 A>G), RS1001834186 (12:11356720 G>A), RS1001941977 (12:11356950 G>A,C,T), RS1002392883 (12:11395687 G>A,T), RS1002486068 (12:11395959 G>A), RS1002501604 (12:11351986 G>A,C), RS1003040034 (12:11354792 C>A), RS1004046205 (12:11394713 G>A), RS1004869310 (12:11355292 C>A,T), RS1005307269 (12:11355684 G>A,C,T), RS1005474766 (12:11397065 A>G,T), RS1005528772 (12:11397233 A>G,T), RS1005900671 (12:11354180 A>C)

Disease associations

OMIM: gene MIM:168810 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST001346_2	Response to gemcitabine in pancreatic cancer	1.000000e-06
GCST002126_12	Periodontitis (CDC/AAP)	9.000000e-06
GCST003542_165	Night sleep phenotypes	6.000000e-06
GCST004485_40	Survival in pancreatic cancer	1.000000e-06
GCST90011898_9	Alanine aminotransferase levels	8.000000e-13

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0000638	overall survival

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2900174	PRB2		0.00	0

CTD chemical–gene interactions

5 total (human), top 5 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
perfluorooctanoic acid	increases expression	1
perfluoro-n-nonanoic acid	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Benzo(a)pyrene	increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

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