PRH1

Summary

PRH1 (proline rich protein HaeIII subfamily 1, HGNC:9366) 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. Multiple distinct alleles of this locus including the parotid isoelectric-focusing variant slow (PIF-s), the parotid acidic protein (Pa), and the double band slow (Db-s) isoforms have been characterized. The reference genome encodes the Db-s 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. Co-transcription of this gene with adjacent genes has been observed. Alternate splicing of this gene results in multiple transcript variants encoding different isoforms.

Source: NCBI Gene 5554 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 408 total
• MANE Select transcript: NM_001393989

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9366
Approved symbol	PRH1
Name	proline rich protein HaeIII subfamily 1
Location	12p13.2
Locus type	gene with protein product
Status	Approved
Aliases	Pa
Ensembl gene	ENSG00000231887
Ensembl biotype	protein_coding
OMIM	168730
Entrez	5554

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 7 protein_coding_CDS_not_defined, 4 protein_coding

ENST00000534923, ENST00000536086, ENST00000538332, ENST00000541175, ENST00000541456, ENST00000541977, ENST00000543626, ENST00000546265, ENST00000546317, ENST00000703543, ENST00000850905

RefSeq mRNA: 2 — MANE Select: NM_001393989 NM_001291314, NM_001393989

CCDS: CCDS76533

Canonical transcript exons

ENST00000543626 — 4 exons

Exon	Start	End
ENSE00001743404	10880965	10881056
ENSE00002234451	10884154	10884255
ENSE00002323704	10882217	10882698
ENSE00003821401	10883061	10883096

Expression profiles

Bgee: expression breadth ubiquitous, 138 present calls, max score 94.39.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 202.9143 / max 199764.5565, expressed in 1805 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
129593	177.6434	21
129605	24.7269	1805
129590	0.1393	5
129594	0.1108	3
129591	0.0940	4
129589	0.0571	3
129592	0.0501	4
129596	0.0260	4
129595	0.0230	3
129597	0.0181	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	94.39	gold quality
testis	UBERON:0000473	93.49	gold quality
right testis	UBERON:0004534	93.42	gold quality
corpus callosum	UBERON:0002336	93.38	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	93.16	gold quality
adrenal tissue	UBERON:0018303	92.25	gold quality
calcaneal tendon	UBERON:0003701	90.34	gold quality
bone marrow cell	CL:0002092	88.95	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.55	gold quality
bone marrow	UBERON:0002371	84.43	gold quality
tonsil	UBERON:0002372	84.38	gold quality
colonic epithelium	UBERON:0000397	82.29	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	81.37	gold quality
skeletal muscle tissue	UBERON:0001134	81.12	gold quality
placenta	UBERON:0001987	80.13	gold quality
muscle tissue	UBERON:0002385	79.83	gold quality
sural nerve	UBERON:0015488	79.37	gold quality
right ovary	UBERON:0002118	78.80	gold quality
uterine cervix	UBERON:0000002	78.70	gold quality
ovary	UBERON:0000992	78.39	gold quality
pituitary gland	UBERON:0000007	78.30	gold quality
adenohypophysis	UBERON:0002196	78.23	gold quality
liver	UBERON:0002107	78.18	gold quality
adrenal gland	UBERON:0002369	77.72	gold quality
urinary bladder	UBERON:0001255	77.59	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	77.50	gold quality
left ovary	UBERON:0002119	77.39	gold quality
spinal cord	UBERON:0002240	77.22	gold quality
endometrium	UBERON:0001295	77.09	gold quality
tibial nerve	UBERON:0001323	77.02	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.08

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ID4

Literature-anchored findings (GeneRIF, showing 3)

• Compared with African-Americans, all Caucasians had significantly greater Streptococcus mutans colonization, but only Db-negative Caucasians had significantly more caries. Alleles linked to Db may explain racial differences in caries experience. (PMID:18037651)
• 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), PRH2 (ENSG00000134551), PRB3 (ENSG00000197870), PRB4 (ENSG00000230657), 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 (3): A0A087WV42, A0A087WYF5, A0A087WYT0

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 (2): NP_001278243, NP_001380918* (*=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: 37 (showing top): YAGI_AML_WITH_INV_16_TRANSLOCATION, RICKMAN_HEAD_AND_NECK_CANCER_D, SU_SALIVARY_GLAND, WNT_UP.V1_DN, BANP_TARGET_GENES, BARX1_TARGET_GENES, BCL6B_TARGET_GENES, CREB3L4_TARGET_GENES, DYRK1A_TARGET_GENES, GLI3_TARGET_GENES, HES4_TARGET_GENES, HMG20B_TARGET_GENES, HOXB4_TARGET_GENES, ID2_TARGET_GENES, IRF5_TARGET_GENES

GO Biological Process (0):

GO Molecular Function (0):

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
cellular anatomical structure	1

Protein interactions and networks

STRING

1556 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRH1	CRY1	Q16526	936
PRH1	PRB4	P02813	916
PRH1	PRB1	P04280	890
PRH1	CRY2	Q49AN0	885
PRH1	PIF1	Q9H611	883
PRH1	PRB2	P02811	864
PRH1	DET1	Q7L5Y6	860
PRH1	C4BPA	P04003	769
PRH1	ZNF346	Q9UL40	715
PRH1	RB1	P06400	699
PRH1	DDB1	Q16531	642
PRH1	BBX	Q8WY36	620
PRH1	EPRS1	P07814	554
PRH1	CDKN2A	P42771	523
PRH1	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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	349
Likely benign	44
Benign	9

Top pathogenic / likely-pathogenic (0)

SpliceAI

6708 predictions. Top by Δscore:

Variant	Effect	Δscore
12:10847365:CAT:C	acceptor_gain	1.0000
12:10848405:CAT:C	acceptor_gain	1.0000
12:10849379:T:C	donor_gain	1.0000
12:10882695:CCAT:C	acceptor_gain	1.0000
12:10882696:CATC:C	acceptor_gain	1.0000
12:10884148:TCTTA:T	donor_loss	1.0000
12:10884149:CTTAC:C	donor_loss	1.0000
12:10884150:TTACC:T	donor_loss	1.0000
12:10884151:TAC:T	donor_loss	1.0000
12:10884152:A:AT	donor_loss	1.0000
12:10884153:C:CT	donor_loss	1.0000
12:10884153:CCTT:C	donor_gain	1.0000
12:10884275:CCTT:C	acceptor_gain	1.0000
12:10929334:GAAG:G	donor_gain	1.0000
12:10929338:G:GG	donor_gain	1.0000
12:10929338:GTA:G	donor_loss	1.0000
12:10973719:CAG:C	acceptor_gain	1.0000
12:10973721:GC:G	acceptor_loss	1.0000
12:10973722:C:CC	acceptor_gain	1.0000
12:10973722:CTA:C	acceptor_loss	1.0000
12:11121181:C:CC	acceptor_gain	1.0000
12:10847363:TACAT:T	acceptor_gain	0.9900
12:10847367:TC:T	acceptor_loss	0.9900
12:10847368:C:CA	acceptor_loss	0.9900
12:10847368:C:CC	acceptor_gain	0.9900
12:10847370:G:C	acceptor_gain	0.9900
12:10847370:G:GC	acceptor_gain	0.9900
12:10847372:G:GC	acceptor_gain	0.9900
12:10848369:TA:T	donor_loss	0.9900
12:10848406:ATCTA:A	acceptor_loss	0.9900

AlphaMissense

1170 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000006978 (12:11012944 A>G), RS1000018596 (12:11153149 T>C), RS1000019666 (12:11084869 G>A,C), RS1000027601 (12:10990609 G>A), RS1000054132 (12:10889803 C>T), RS1000056131 (12:11058849 A>G), RS1000064453 (12:10912880 G>T), RS1000069827 (12:10930588 G>A,C), RS1000071498 (12:11004147 T>A,C), RS1000085744 (12:10977405 G>A), RS1000088591 (12:10896756 G>A,T), RS1000094361 (12:11163691 T>A,C), RS1000095397 (12:11159133 A>G), RS1000099420 (12:11173496 G>T), RS1000110891 (12:10880903 G>A)

Disease associations

OMIM: gene MIM:168730 | 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

8 total (human), top 8 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
triphenyl phosphate	affects expression	1
beta-lapachone	increases expression	1
CGP 52608	affects binding, increases reaction	1
abrine	increases expression	1
Sunitinib	increases expression	1
Cyclosporine	increases methylation	1
Aflatoxin B1	decreases methylation	1
Antirheumatic Agents	increases expression	1

Clinical trials (associated diseases)

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