PRR4

Summary

PRR4 (proline rich 4, HGNC:18020) is a protein-coding gene on chromosome 12p13.2, encoding Proline-rich protein 4 (Q16378).

This gene encodes a member of the proline-rich protein family that lacks a conserved repetitive domain. This protein may play a role in protective functions in the eye. Alternative splicing result in multiple transcript variants. Read-through transcription also exists between this gene and the upstream PRH1 (proline-rich protein HaeIII subfamily 1) gene.

Source: NCBI Gene 11272 — RefSeq curated summary.

At a glance

• MANE Select transcript: NM_007244

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18020
Approved symbol	PRR4
Name	proline rich 4
Location	12p13.2
Locus type	gene with protein product
Status	Approved
Aliases	LPRP
Ensembl gene	ENSG00000111215
Ensembl biotype	protein_coding
OMIM	605359
Entrez	11272

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 4 protein_coding, 4 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000228811, ENST00000535024, ENST00000539179, ENST00000539285, ENST00000540107, ENST00000540808, ENST00000542658, ENST00000542881, ENST00000544994

RefSeq mRNA: 2 — MANE Select: NM_007244 NM_001098538, NM_007244

CCDS: CCDS41756, CCDS55804

Canonical transcript exons

ENST00000228811 — 4 exons

Exon	Start	End
ENSE00003526535	10849374	10849475
ENSE00003737631	10847045	10847367
ENSE00003744244	10845849	10845950
ENSE00003825551	10848372	10848407

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 99.81.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 152.6771 / max 84452.9382, expressed in 65 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
129587	152.5149	64
129586	0.1622	11

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
olfactory segment of nasal mucosa	UBERON:0005386	99.81	gold quality
saliva-secreting gland	UBERON:0001044	97.91	gold quality
minor salivary gland	UBERON:0001830	97.72	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	94.77	gold quality
skin of leg	UBERON:0001511	91.37	gold quality
zone of skin	UBERON:0000014	88.78	gold quality
duodenum	UBERON:0002114	86.67	gold quality
primary visual cortex	UBERON:0002436	86.26	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	86.00	gold quality
skin of abdomen	UBERON:0001416	85.92	gold quality
substantia nigra	UBERON:0002038	85.31	gold quality
Ammon’s horn	UBERON:0001954	85.08	gold quality
right ovary	UBERON:0002118	83.27	gold quality
amygdala	UBERON:0001876	83.23	gold quality
hypothalamus	UBERON:0001898	83.18	gold quality
temporal lobe	UBERON:0001871	83.15	gold quality
Brodmann (1909) area 9	UBERON:0013540	83.08	gold quality
pituitary gland	UBERON:0000007	83.00	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	82.77	gold quality
thoracic mammary gland	UBERON:0005200	82.60	gold quality
right frontal lobe	UBERON:0002810	82.58	gold quality
prostate gland	UBERON:0002367	82.56	gold quality
tonsil	UBERON:0002372	82.53	gold quality
tibial nerve	UBERON:0001323	82.48	gold quality
adenohypophysis	UBERON:0002196	82.23	gold quality
cerebral cortex	UBERON:0000956	82.21	gold quality
right lobe of liver	UBERON:0001114	82.18	gold quality
anterior cingulate cortex	UBERON:0009835	82.09	gold quality
right lobe of thyroid gland	UBERON:0001119	82.04	gold quality
brain	UBERON:0000955	81.99	gold quality

Single-cell (SCXA)

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

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

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

3 targeting PRR4, 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-1252-5P	100.00	69.80	2774
HSA-MIR-4727-5P	99.23	67.55	1154
HSA-MIR-6738-3P	99.03	67.14	1326

Literature-anchored findings (GeneRIF, showing 3)

• Lacrimal proline rich 4 (LPRR4) protein in the tear fluid is a potential biomarker of dry eye syndrome. (PMID:23272196)
• A new PRR4 isoform designated as PRR4-N3 in addition to PRR4 (gi154448886) and pHL E1F1 (gi1050983) was identified in human tear proteome. (PMID:24782455)
• High expression of lacrimal proline-rich protein 4 (PRR4) was found in reflex tears. (PMID:26173177)

Cross-species orthologs

0 orthologs

Paralogs (6): PRB2 (ENSG00000121335), PRH2 (ENSG00000134551), PRB3 (ENSG00000197870), PRB4 (ENSG00000230657), PRH1 (ENSG00000231887), PRB1 (ENSG00000251655)

Protein

Protein identifiers

Proline-rich protein 4 — Q16378 (reviewed: Q16378)

Alternative names: Lacrimal proline-rich protein, Nasopharyngeal carcinoma-associated proline-rich protein 4

All UniProt accessions (3): A0A087WY73, Q16378, F5H178

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Secreted.

Tissue specificity. Abundantly expressed in lacrimal gland where it is found in the acinar cells but not in the intralobular ducts. Also found in the submandibular gland, the parotid and sublingual glands.

Isoforms (2)

UniProt ID	Names	Canonical?
Q16378-1	1	yes
Q16378-2	2

RefSeq proteins (2): NP_001092008, NP_009175* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026086	Pro-rich	Family

Pfam: PF15240

UniProt features (10 total): compositionally biased region 3, sequence variant 2, signal peptide 1, chain 1, region of interest 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q16378-F1	63.60	0.07

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 62 (showing top): GOBP_SENSORY_PERCEPTION_OF_LIGHT_STIMULUS, MODULE_88, GOBP_SENSORY_PERCEPTION, MODULE_6, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_DN, RIZKI_TUMOR_INVASIVENESS_3D_UP, MODULE_55, YOSHIMURA_MAPK8_TARGETS_UP, RICKMAN_HEAD_AND_NECK_CANCER_D, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_DN, MODULE_129, PURBEY_TARGETS_OF_CTBP1_NOT_SATB1_DN, IL21_UP.V1_UP, BANP_TARGET_GENES, BARX1_TARGET_GENES

GO Biological Process (1): visual perception (GO:0007601)

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
sensory perception of light stimulus	1
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

318 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRR4	LACRT	Q9GZZ8	665
PRR4	LCN1	P31025	646
PRR4	STATH	P02808	620
PRR4	PRND	Q9UKY0	608
PRR4	OPRPN	P85047	581
PRR4	SCGB2A1	O75556	577
PRR4	CST4	P01036	571
PRR4	PIP	P12273	541
PRR4	LYZL1	Q6UWQ5	526
PRR4	PNRC1	Q12796	499
PRR4	ZG16B	Q96DA0	477
PRR4	LYZ	P00695	474
PRR4	MUC7	Q8TAX7	469
PRR4	SCGB1D1	O95968	447
PRR4	LTF	P02788	447

IntAct

62 interactions, top by confidence:

A	B	Type	Score
SMARCE1	ARID1A	psi-mi:“MI:0914”(association)	0.840
RPL10A	RRP8	psi-mi:“MI:0914”(association)	0.640
SGTB	PRR4	psi-mi:“MI:0915”(physical association)	0.560
MIEF1	PRR4	psi-mi:“MI:0915”(physical association)	0.560
LAT	PRR4	psi-mi:“MI:0915”(physical association)	0.560
PRR4	UBQLN2	psi-mi:“MI:0915”(physical association)	0.560
PRR4	UBQLN1	psi-mi:“MI:0915”(physical association)	0.560
PRR4	MIEF1	psi-mi:“MI:0915”(physical association)	0.560
PRR4	SGTB	psi-mi:“MI:0915”(physical association)	0.560
GET3	PRR4	psi-mi:“MI:0915”(physical association)	0.560
DDX31	IGLL5	psi-mi:“MI:0914”(association)	0.530
HBM	SCGB2A1	psi-mi:“MI:0914”(association)	0.530
EGFL8	MPO	psi-mi:“MI:0914”(association)	0.530
POLR2D	POLR2M	psi-mi:“MI:0914”(association)	0.530
MUC7	PRR4	psi-mi:“MI:0915”(physical association)	0.370
SNX27	IGLL5	psi-mi:“MI:0914”(association)	0.350
	SCGB1D1	psi-mi:“MI:0914”(association)	0.350
KCNIP4	SCGB1D1	psi-mi:“MI:0914”(association)	0.350
NSD2	PFKFB2	psi-mi:“MI:0914”(association)	0.350
PIK3CA	SCGB2A1	psi-mi:“MI:0914”(association)	0.350
GOLGA8A	ZNF320	psi-mi:“MI:0914”(association)	0.350
GNG8	POTEF	psi-mi:“MI:0914”(association)	0.350
OR13C3	POTEF	psi-mi:“MI:0914”(association)	0.350

BioGRID (63): PRR4 (Affinity Capture-MS), PRR4 (Affinity Capture-MS), PRR4 (Affinity Capture-MS), PRR4 (Affinity Capture-MS), PRR4 (Affinity Capture-MS), PRR4 (Affinity Capture-MS), PRR4 (Affinity Capture-MS), PRR4 (Affinity Capture-MS), PRR4 (Two-hybrid), UBQLN1 (Two-hybrid), UBQLN2 (Two-hybrid), SGTB (Two-hybrid), ASNA1 (Two-hybrid), LAT (Two-hybrid), PRR4 (Affinity Capture-MS)

ESM2 similar proteins: A0A0G2K6Z9, A0A1B0GVQ3, A1E959, A1E960, A1YQ91, A1YQ92, A1YQ93, A1YQ94, A7RJ12, B3A0S0, D3Z9M3, E9PXT9, G1UB67, K9N4Q4, O35979, O35985, P02667, P03417, P06651, P13432, P18897, P19902, P23051, P26020, P28875, P55796, P79139, P83474, P86727, Q003G9, Q01493, Q0P4F6, Q10906, Q10928, Q16378, Q17RF5, Q23933, Q3HS83, Q5A0W9, Q66652

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

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

6524 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

852 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:10849409:A:T	L10H	0.967
12:10849403:G:T	A12D	0.966
12:10849421:A:T	L6H	0.966
12:10849421:A:C	L6R	0.961
12:10849409:A:C	L10R	0.958
12:10849424:A:C	L5R	0.955
12:10849396:G:C	S14R	0.951
12:10849396:G:T	S14R	0.951
12:10849398:T:G	S14R	0.951
12:10849415:A:T	V8E	0.949
12:10849412:A:T	V9D	0.948
12:10849409:A:G	L10P	0.947
12:10849427:A:T	V4D	0.945
12:10849400:A:G	L13P	0.936
12:10849406:A:G	L11P	0.933
12:10849406:A:C	L11R	0.927
12:10849424:A:T	L5Q	0.925
12:10849421:A:G	L6P	0.924
12:10849430:A:C	L3R	0.908
12:10849424:A:G	L5P	0.905
12:10849404:C:G	A12P	0.897
12:10849406:A:T	L11Q	0.890
12:10849433:A:C	L2R	0.882
12:10849433:A:G	L2P	0.880
12:10849430:A:T	L3Q	0.875
12:10849433:A:T	L2Q	0.866
12:10849400:A:C	L13R	0.840
12:10849391:G:T	A16D	0.827
12:10849400:A:T	L13Q	0.792
12:10849419:A:G	S7P	0.779

dbSNP variants (sampled 300 via entrez): RS1000031797 (12:10848772 A>G), RS1000610820 (12:10845620 T>A,C), RS1001867228 (12:10848695 A>C), RS1002375718 (12:10847429 T>C), RS1002462002 (12:10850209 A>G), RS1002583832 (12:10850490 C>A), RS1002806472 (12:10847685 T>C), RS1003147232 (12:10851002 T>C), RS1004480589 (12:10846262 T>G), RS1004866093 (12:10846506 G>A), RS1005586611 (12:10849843 T>C), RS1005824139 (12:10849733 T>C), RS1005937944 (12:10851081 GTGTT>G), RS1005990346 (12:10850839 A>C), RS1006773814 (12:10851011 C>A,T)

Disease associations

OMIM: gene MIM:605359 | 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

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	increases abundance, increases expression	2
Benzo(a)pyrene	decreases expression, increases methylation	2
Cadmium Chloride	decreases expression, increases abundance	2
2,2’,4,4’,5-brominated diphenyl ether	decreases expression	1
jinfukang	decreases expression	1
Acetaminophen	increases expression	1
Cadmium	decreases expression, increases abundance	1
Cisplatin	decreases expression	1
Estradiol	affects cotreatment, increases expression	1
Silicon Dioxide	decreases expression	1
Smoke	increases abundance, increases expression	1
Tunicamycin	increases expression	1
Cyclosporine	increases methylation	1
Aflatoxin B1	decreases methylation	1
Thapsigargin	increases expression	1
S-Nitrosoglutathione	increases expression	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

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