PRH2

Summary

PRH2 (proline rich protein HaeIII subfamily 2, HGNC:9367) is a protein-coding gene on chromosome 12p13.2, encoding Salivary acidic proline-rich phosphoprotein 1/2 (P02810). PRP’s act as highly potent inhibitors of crystal growth of calcium phosphates.

This gene encodes a member of the heterogeneous family of proline-rich salivary glycoproteins. The encoded preproprotein undergoes proteolytic processing to generate one or more mature isoforms before secretion from the parotid and submandibular/sublingual glands. In western population this locus is commonly biallelic and encodes proline-rich protein (PRP) isoforms, PRP-1 and PRP-2. The reference genome encodes the PRP-1 allele. Certain alleles of this gene are associated with susceptibility to dental caries. This gene is located in a cluster of closely related salivary proline-rich proteins on chromosome 12.

Source: NCBI Gene 5555 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 12 total
• MANE Select transcript: NM_001110213

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9367
Approved symbol	PRH2
Name	proline rich protein HaeIII subfamily 2
Location	12p13.2
Locus type	gene with protein product
Status	Approved
Aliases	Pr
Ensembl gene	ENSG00000134551
Ensembl biotype	protein_coding
OMIM	168790
Entrez	5555

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000381847, ENST00000396400, ENST00000850893

RefSeq mRNA: 1 — MANE Select: NM_001110213 NM_001110213

CCDS: CCDS8636

Canonical transcript exons

ENST00000396400 — 4 exons

Exon	Start	End
ENSE00001404901	10930662	10931080
ENSE00002305151	10932226	10934845
ENSE00004282629	10929236	10929337
ENSE00004282631	10930269	10930304

Expression profiles

Bgee: expression breadth ubiquitous, 130 present calls, max score 84.78.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 263.1773 / max 198399.2627, expressed in 34 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
124189	263.1552	34
124188	0.0221	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.78	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	83.88	gold quality
tonsil	UBERON:0002372	73.15	gold quality
placenta	UBERON:0001987	72.68	gold quality
bone marrow cell	CL:0002092	71.02	gold quality
bone marrow	UBERON:0002371	70.88	gold quality
corpus callosum	UBERON:0002336	70.24	gold quality
quadriceps femoris	UBERON:0001377	69.42	gold quality
adrenal tissue	UBERON:0018303	69.25	gold quality
thymus	UBERON:0002370	68.91	silver quality
cerebellar vermis	UBERON:0004720	67.75	gold quality
calcaneal tendon	UBERON:0003701	63.95	gold quality
colonic epithelium	UBERON:0000397	62.78	silver quality
cerebellar hemisphere	UBERON:0002245	60.99	gold quality
cerebellar cortex	UBERON:0002129	60.86	gold quality
sural nerve	UBERON:0015488	60.84	silver quality
cerebellum	UBERON:0002037	60.78	gold quality
liver	UBERON:0002107	60.25	gold quality
right hemisphere of cerebellum	UBERON:0014890	59.61	gold quality
right testis	UBERON:0004534	58.61	gold quality
ventricular zone	UBERON:0003053	58.32	gold quality
primary visual cortex	UBERON:0002436	58.21	gold quality
skeletal muscle tissue	UBERON:0001134	56.60	gold quality
ovary	UBERON:0000992	56.35	gold quality
right lobe of liver	UBERON:0001114	55.59	gold quality
saliva-secreting gland	UBERON:0001044	55.27	gold quality
ganglionic eminence	UBERON:0004023	55.08	gold quality
left ovary	UBERON:0002119	54.86	gold quality
mucosa of transverse colon	UBERON:0004991	54.79	gold quality
right ovary	UBERON:0002118	54.76	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.85

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

112 targeting PRH2, 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-12118	100.00	65.88	1270
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-150-5P	99.99	66.69	1976
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-6891-5P	99.98	66.53	1372
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-570-3P	99.96	72.41	4910
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-144-3P	99.94	73.98	2698
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942

Literature-anchored findings (GeneRIF, showing 2)

• We investigated whether PRH1 and PRH2 polymorphisms in saliva acidic proline-rich protein (PRP) receptors for indigenous bacteria match and predict individual differences in the development of caries..They instead developed 3.9-fold more caries than P1 children from plaque accumulation in general when treated with orthodontic multibrackets; and had basic PRP polymorphisms and low DMBT1-mediated S. mutans adhesion (PMID:29191562)
• Human PRH1, PRH2 susceptibility and resistance and Streptococcus mutans virulence phenotypes specify different microbial profiles in caries. (PMID:38364699)

Cross-species orthologs

0 orthologs

Paralogs (6): PRR4 (ENSG00000111215), PRB2 (ENSG00000121335), PRB3 (ENSG00000197870), PRB4 (ENSG00000230657), PRH1 (ENSG00000231887), PRB1 (ENSG00000251655)

Protein

Protein identifiers

Salivary acidic proline-rich phosphoprotein 1/2 — P02810 (reviewed: P02810)

Alternative names: Db-s, PRP-1/PRP-2, Parotid acidic protein, Parotid double-band protein, Parotid isoelectric focusing variant protein, Parotid proline-rich protein 1/2, Pr1/Pr2, Protein C

All UniProt accessions (1): P02810

UniProt curated annotations — full annotation on UniProt →

Function. PRP’s act as highly potent inhibitors of crystal growth of calcium phosphates. They provide a protective and reparative environment for dental enamel which is important for the integrity of the teeth.

Subcellular location. Secreted.

Post-translational modifications. Proteolytically cleaved; PRP-2, PRP-1, PIF-S and Db-S yield PRP-4, PRP-3 (protein A), PIF-F and Db-F, respectively. A hexuronic acid was shown to be linked to Ser-33 in about 40% of the polypeptides. Neither the structure of the carbohydrate (whether glucuronic acid or an isomer of), nor the linkage (whether a glycoside or an ester) has been definitely established.

Polymorphism. Sequence shown is that of allele PRH1-PIF, which is the most frequent allele (68% of the population). The PRH1-DB allele (about 16% of the population) has an insertion of 21 repeated amino acids compared to the PRH1-PIF allele. Allele PRH2-2, also known as PR-2, allele PRH2-1 is also known as PR-1 or protein C, and allele PRH2-3 as PR-1’. In contrast to all other PRH1 and PRH2 alleles, the PRH1-PA allele (16%) is not proteolytically cleaved.

RefSeq proteins (1): NP_001103683* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026086	Pro-rich	Family

Pfam: PF15240

UniProt features (25 total): sequence variant 6, modified residue 4, compositionally biased region 4, chain 3, glycosylation site 2, mutagenesis site 2, region of interest 2, signal peptide 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P02810-F1	67.27	0.10

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 (4): 17, 24, 33, 38

Glycosylation sites (2): 33, 38

Mutagenesis-validated functional residues (2):

Position	Phenotype
24	decreased phosphorylation by fam20c; when associated with a-38.
38	decreased phosphorylation by fam20c; when associated with a-24.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 29 (showing top): MODULE_123, ZWANG_EGF_INTERVAL_UP, RAPA_EARLY_UP.V1_DN, ZNF274_TARGET_GENES, MIR1250_3P, MIR374A_5P, MIR374B_5P, MIR511_5P, MIR4528, MIR4700_5P, MIR12132, MIR2116_5P, MIR6791_5P, MIR6783_5P, MIR4292

GO Biological Process (0):

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

GO Cellular Component (2): obsolete extracellular space (GO:0005615), 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

1556 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRH2	CRY1	Q16526	936
PRH2	PRB4	P02813	916
PRH2	PRB1	P04280	890
PRH2	CRY2	Q49AN0	885
PRH2	PIF1	Q9H611	883
PRH2	PRB2	P02811	864
PRH2	DET1	Q7L5Y6	860
PRH2	C4BPA	P04003	769
PRH2	ZNF346	Q9UL40	715
PRH2	RB1	P06400	699
PRH2	DDB1	Q16531	642
PRH2	BBX	Q8WY36	620
PRH2	EPRS1	P07814	554
PRH2	CDKN2A	P42771	523
PRH2	WHR1	P49842	511

IntAct

12 interactions, top by confidence:

A	B	Type	Score
EHMT2	WIZ	psi-mi:“MI:0914”(association)	0.730
PRKAB2	PRKAB2	psi-mi:“MI:0914”(association)	0.550
PRH1	MUC7	psi-mi:“MI:0915”(physical association)	0.510
FAM20C	PRH1	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
AXL		psi-mi:“MI:0914”(association)	0.350
PRKX	AIP	psi-mi:“MI:0914”(association)	0.350
GABARAP		psi-mi:“MI:0914”(association)	0.350
CCP110	A2ML1	psi-mi:“MI:0914”(association)	0.350
CCP110	KIF2A	psi-mi:“MI:0914”(association)	0.350

BioGRID (20): PRH1 (Affinity Capture-RNA), PRH1 (Affinity Capture-MS), PRH1 (Affinity Capture-MS), PRH1 (Two-hybrid), PRH1 (Two-hybrid), PRH1 (Two-hybrid), PRH1 (Two-hybrid), PRH1 (Two-hybrid), PRH1 (Two-hybrid), PRH1 (Two-hybrid), PRH1 (Two-hybrid), EHMT2 (Affinity Capture-MS), PRH1 (Affinity Capture-MS), EHMT1 (Affinity Capture-MS), PRH1 (Affinity Capture-MS)

ESM2 similar proteins: A0A2H4S6M4, A2XT03, C0HM81, C9JFL3, J4WMI6, O31510, O94426, P02810, P04474, P04706, P06600, P06680, P08297, P10163, P10165, P16329, P17816, P19470, P21749, P37705, P50439, P54643, P86960, Q00451, Q00725, Q01642, Q01643, Q01644, Q01645, Q04118, Q0WV37, Q20689, Q25055, Q27270, Q32L04, Q5U1W2, Q61900, Q62266, Q62267, Q63532

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

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
CSNK1D	up-regulates	PRH1	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	11
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

120 predictions. Top by Δscore:

Variant	Effect	Δscore
12:10929334:GAAG:G	donor_gain	1.0000
12:10929338:G:GG	donor_gain	1.0000
12:10929338:GTA:G	donor_loss	1.0000
12:10929333:TGAAG:T	donor_gain	0.9900
12:10929334:GAAGG:G	donor_gain	0.9900
12:10929336:AG:A	donor_gain	0.9900
12:10929337:GG:G	donor_gain	0.9900
12:10929339:T:A	donor_loss	0.9900
12:10930263:TTCTA:T	acceptor_loss	0.9900
12:10930264:TCTA:T	acceptor_loss	0.9900
12:10930265:CTAG:C	acceptor_loss	0.9900
12:10930266:TA:T	acceptor_loss	0.9900
12:10930267:A:AG	acceptor_gain	0.9900
12:10930267:A:AT	acceptor_loss	0.9900
12:10930268:G:GG	acceptor_gain	0.9900
12:10930268:GAT:G	acceptor_gain	0.9900
12:10930302:CAGG:C	donor_loss	0.9900
12:10930303:AGG:A	donor_loss	0.9900
12:10930304:GG:G	donor_loss	0.9900
12:10930305:G:GA	donor_loss	0.9900
12:10930306:T:G	donor_loss	0.9900
12:10930651:A:AG	acceptor_gain	0.9900
12:10930652:A:AG	acceptor_gain	0.9900
12:10930657:CACA:C	acceptor_loss	0.9900
12:10930658:A:AG	acceptor_gain	0.9900
12:10930660:A:AG	acceptor_gain	0.9900
12:10930660:AGAT:A	acceptor_gain	0.9900
12:10930661:G:GG	acceptor_gain	0.9900
12:10930661:G:GT	acceptor_loss	0.9900
12:10930661:GAT:G	acceptor_gain	0.9900

AlphaMissense

1040 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:10929299:C:A	A9D	0.983
12:10929287:T:G	L5R	0.980
12:10929290:T:G	L6R	0.977
12:10929308:C:A	A12D	0.970
12:10929287:T:A	L5Q	0.969
12:10929296:T:A	V8E	0.963
12:10929278:T:A	L2H	0.958
12:10929284:T:A	I4N	0.957
12:10929287:T:C	L5P	0.957
12:10929313:A:C	S14R	0.957
12:10929315:C:A	S14R	0.957
12:10929315:C:G	S14R	0.957
12:10929290:T:A	L6Q	0.956
12:10929302:T:C	L10P	0.952
12:10929290:T:C	L6P	0.950
12:10929302:T:G	L10R	0.950
12:10929281:T:G	L3R	0.942
12:10929305:T:C	L11P	0.935
12:10929278:T:G	L2R	0.930
12:10929284:T:C	I4T	0.920
12:10929281:T:A	L3Q	0.914
12:10929305:T:G	L11R	0.912
12:10929302:T:A	L10Q	0.910
12:10929278:T:C	L2P	0.909
12:10929298:G:C	A9P	0.908
12:10929284:T:G	I4S	0.905
12:10929307:G:C	A12P	0.880
12:10929305:T:A	L11Q	0.855
12:10929292:T:C	S7P	0.835
12:10929314:G:A	S14N	0.799

dbSNP variants (sampled 300 via entrez): RS1000069827 (12:10930588 G>A,C), RS1001449726 (12:10934001 T>A), RS1002495156 (12:10934524 C>T), RS1002780396 (12:10934921 A>C,G), RS1004108685 (12:10928766 T>A), RS1004453108 (12:10933595 A>C), RS1004880507 (12:10934582 C>A), RS1004912984 (12:10934337 G>A), RS1005616272 (12:10931494 T>C), RS1005911847 (12:10932833 TG>T), RS1005922186 (12:10933282 G>C), RS1006590301 (12:10930365 T>C), RS1006862371 (12:10927488 G>C), RS1007030997 (12:10930141 G>T), RS1008716964 (12:10934187 T>C)

Disease associations

OMIM: gene MIM:168790 | 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

6 total (human), top 6 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
Aspirin	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	decreases methylation	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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