PRB4

Summary

PRB4 (proline rich protein BstNI subfamily 4, HGNC:9340) is a protein-coding gene on chromosome 12p13.2, encoding Basic salivary proline-rich protein 4 (P10163).

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 peptides before secretion from the parotid glands. Multiple alleles of this gene exhibiting variations in the length of the tandem repeats have been identified. The reference genome encodes the “Small” allele. This gene is located in a cluster of closely related salivary proline-rich proteins on chromosome 12. Alternative splicing results in multiple transcript variants encoding different isoforms that may undergo similar proteolytic processing.

Source: NCBI Gene 5545 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 64 total
• MANE Select transcript: NM_002723

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9340
Approved symbol	PRB4
Name	proline rich protein BstNI subfamily 4
Location	12p13.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000230657
Ensembl biotype	protein_coding
OMIM	180990
Entrez	5545

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 6 protein_coding

ENST00000279575, ENST00000445719, ENST00000621732, ENST00000885866, ENST00000885867, ENST00000885868

RefSeq mRNA: 2 — MANE Select: NM_002723 NM_001261399, NM_002723

CCDS: CCDS58208, CCDS8641

Canonical transcript exons

ENST00000279575 — 4 exons

Exon	Start	End
ENSE00000993655	11310335	11310436
ENSE00000993658	11308221	11308882
ENSE00001614033	11309370	11309405
ENSE00003896549	11307077	11307199

Expression profiles

Bgee: expression breadth broad, 32 present calls, max score 94.91.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 229.3570 / max 416571.2354, expressed in 19 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
129645	228.4633	17
129644	0.6031	5
129642	0.1054	1
129643	0.0926	2
129646	0.0443	1
129647	0.0422	2
129641	0.0062	1

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
olfactory segment of nasal mucosa	UBERON:0005386	94.91	gold quality
colonic epithelium	UBERON:0000397	66.54	silver quality
tonsil	UBERON:0002372	52.96	gold quality
bone marrow	UBERON:0002371	52.07	gold quality
bone marrow cell	CL:0002092	51.53	gold quality
liver	UBERON:0002107	38.30	silver quality
urinary bladder	UBERON:0001255	37.83	silver quality
skin of abdomen	UBERON:0001416	37.83	gold quality
zone of skin	UBERON:0000014	37.72	gold quality
skin of leg	UBERON:0001511	37.42	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
skeletal muscle tissue	UBERON:0001134	34.84	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
muscle tissue	UBERON:0002385	32.13	gold quality
calcaneal tendon	UBERON:0003701	31.93	gold quality
primary visual cortex	UBERON:0002436	31.71	gold quality
corpus callosum	UBERON:0002336	30.99	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
blood	UBERON:0000178	29.63	gold quality
prefrontal cortex	UBERON:0000451	29.62	gold quality
lymph node	UBERON:0000029	29.15	silver quality
lung	UBERON:0002048	28.92	gold quality
leukocyte	CL:0000738	28.68	gold quality
cortex of kidney	UBERON:0001225	28.44	silver quality
duodenum	UBERON:0002114	28.14	gold quality
monocyte	CL:0000576	27.55	gold quality
islet of Langerhans	UBERON:0000006	27.07	gold quality
left testis	UBERON:0004533	26.99	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NSD1, SOX10

miRNA regulators (miRDB)

8 targeting PRB4, 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-548AT-5P	99.96	70.83	2666
HSA-MIR-4420	99.82	70.08	1624
HSA-MIR-181B-2-3P	99.81	70.06	1646
HSA-MIR-181B-3P	99.81	70.06	1646
HSA-MIR-4452	99.50	68.45	1493
HSA-MIR-183-3P	99.41	69.41	1598
HSA-MIR-1272	99.34	68.79	878
HSA-MIR-6748-3P	97.20	65.66	836

Literature-anchored findings (GeneRIF, showing 1)

• Two heterozygous mutations of po gene were identified: S63F and N131Y in Charcot-Marie-Tooth disease. (PMID:17294201)

Cross-species orthologs

0 orthologs

Paralogs (6): PRR4 (ENSG00000111215), PRB2 (ENSG00000121335), PRH2 (ENSG00000134551), PRB3 (ENSG00000197870), PRH1 (ENSG00000231887), PRB1 (ENSG00000251655)

Protein

Protein identifiers

Basic salivary proline-rich protein 4 — P10163 (reviewed: P10163)

Alternative names: Parotid o protein, Salivary proline-rich protein II-1

All UniProt accessions (2): E7EXA8, E9PAL0

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Secreted.

Post-translational modifications. N-glycosylated. 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 found on at least Gln-46, Gln-48, Gln-67, Gln-88; Gln-90; Gln-193; Gln-288 Gln-214 and Gln-295, preferentially in diabetic, and head and neck cancer patients.

Polymorphism. The number of repeats is polymorphic and varies among different alleles. Allele S (short), allele M (medium) and allele L (long) contain 6, 7 and 9 tandem repeats respectively.

RefSeq proteins (2): NP_001248328, NP_002714* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026086	Pro-rich	Family

Pfam: PF15240

UniProt features (50 total): sequence conflict 14, repeat 10, glycosylation site 8, sequence variant 6, compositionally biased region 5, chain 3, region of interest 2, signal peptide 1, peptide 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P10163-F1	51.77	0.00

Functional residue map

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

Glycosylation sites (8): 66, 87, 108, 150, 171, 192, 213, 234

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 42 (showing top): MODULE_52, ENK_UV_RESPONSE_KERATINOCYTE_UP, MODULE_64, MODULE_16, MODULE_66, MODULE_118, MODULE_289, MODULE_379, MODULE_157, MODULE_88, KANG_IMMORTALIZED_BY_TERT_DN, MODULE_287, MODULE_6, MODULE_242, MODULE_18

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (1): 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

0 interactions, top by confidence (×1000):

IntAct

0 interactions, top by confidence:

BioGRID (6): PRB4 (Two-hybrid), PRB4 (Two-hybrid), PRB4 (Two-hybrid), PRB4 (Protein-peptide), PRB4 (Co-fractionation), PRB4 (Co-fractionation)

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, P10163, Q04118, Q16378

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
NSD1	“up-regulates quantity by expression”	PRB4	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	46
Likely benign	11
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

521 predictions. Top by Δscore:

Variant	Effect	Δscore
12:11308883:C:CC	acceptor_gain	1.0000
12:11308878:CTTTC:C	acceptor_gain	0.9900
12:11308879:TTTC:T	acceptor_gain	0.9900
12:11308881:TCC:T	acceptor_loss	0.9900
12:11308882:CCTGG:C	acceptor_loss	0.9900
12:11308883:C:CA	acceptor_loss	0.9900
12:11308884:T:A	acceptor_loss	0.9900
12:11308892:G:C	acceptor_gain	0.9900
12:11309366:TTA:T	donor_loss	0.9900
12:11309367:TACCT:T	donor_loss	0.9900
12:11309368:A:C	donor_loss	0.9900
12:11309369:CCTGA:C	donor_loss	0.9900
12:11309403:CAT:C	acceptor_gain	0.9900
12:11309404:ATCT:A	acceptor_loss	0.9900
12:11309405:TC:T	acceptor_loss	0.9900
12:11309406:C:CA	acceptor_loss	0.9900
12:11309406:C:CC	acceptor_gain	0.9900
12:11309407:T:C	acceptor_loss	0.9900
12:11310330:TTTAC:T	donor_loss	0.9900
12:11310331:TTACC:T	donor_loss	0.9900
12:11310332:TAC:T	donor_loss	0.9900
12:11310333:AC:A	donor_loss	0.9900
12:11310334:C:G	donor_loss	0.9900
12:11310334:CCT:C	donor_gain	0.9900
12:11310336:TTC:T	donor_gain	0.9900
12:11310352:G:C	donor_gain	0.9900
12:11308880:TTC:T	acceptor_gain	0.9800
12:11308881:TC:T	acceptor_gain	0.9800
12:11308882:CC:C	acceptor_gain	0.9800
12:11308892:G:GC	acceptor_gain	0.9800

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000199978 (12:11306593 G>A), RS1000575347 (12:11307448 C>T), RS1000842520 (12:11311105 C>A,T), RS1001878593 (12:11310023 G>A,T), RS1003799516 (12:11309052 T>G), RS1004173146 (12:11309253 G>A,T), RS1004420723 (12:11309303 G>A), RS1004473037 (12:11309531 C>A), RS1005426003 (12:11308033 G>T), RS1006599170 (12:11312401 A>G), RS1006995918 (12:11310718 G>A), RS1007295574 (12:11311775 A>G), RS1007375850 (12:11310943 T>C), RS1007741993 (12:11311630 C>A,T), RS1007822646 (12:11307136 C>G)

Disease associations

OMIM: gene MIM:180990 | 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
bisphenol A	decreases methylation	1
CGP 52608	affects binding, increases reaction	1
Grape Seed Proanthocyanidins	affects cotreatment, decreases expression	1
bisphenol S	decreases methylation	1
Air Pollutants	increases abundance, increases expression	1
Benzo(a)pyrene	increases methylation	1
Catechin	affects cotreatment, decreases expression	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

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