PRG3

Summary

PRG3 (proteoglycan 3, pro eosinophil major basic protein 2, HGNC:9363) is a protein-coding gene on chromosome 11q12.1, encoding Proteoglycan 3 (Q9Y2Y8). Possesses similar cytotoxic and cytostimulatory activities to PRG2/MBP.

An extracellular matrix structural constituent conferring compression resistance. Involved in several processes, including granulocyte activation; histamine biosynthetic process; and regulation of gene expression. Located in collagen-containing extracellular matrix.

Source: NCBI Gene 10394 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 16 total
• MANE Select transcript: NM_006093

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9363
Approved symbol	PRG3
Name	proteoglycan 3, pro eosinophil major basic protein 2
Location	11q12.1
Locus type	gene with protein product
Status	Approved
Aliases	MBPH, MBP2
Ensembl gene	ENSG00000156575
Ensembl biotype	protein_coding
OMIM	606814
Entrez	10394

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000287143

RefSeq mRNA: 1 — MANE Select: NM_006093 NM_006093

CCDS: CCDS7954

Canonical transcript exons

ENST00000287143 — 6 exons

Exon	Start	End
ENSE00001027249	57378681	57378812
ENSE00001027250	57379494	57379807
ENSE00001027251	57377725	57377836
ENSE00001172351	57376769	57376908
ENSE00001174601	57381114	57381150
ENSE00001189789	57380648	57380781

Expression profiles

Bgee: expression breadth broad, 46 present calls, max score 97.85.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0948 / max 51.3153, expressed in 8 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
119732	0.0948	8

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
trabecular bone tissue	UBERON:0002483	97.85	gold quality
bone marrow	UBERON:0002371	90.85	gold quality
bone marrow cell	CL:0002092	80.58	gold quality
tibialis anterior	UBERON:0001385	58.15	silver quality
pancreatic ductal cell	CL:0002079	58.12	silver quality
ileal mucosa	UBERON:0000331	57.75	silver quality
oocyte	CL:0000023	57.54	silver quality
spleen	UBERON:0002106	54.03	gold quality
deltoid	UBERON:0001476	51.74	gold quality
blood	UBERON:0000178	51.05	gold quality
epithelial cell of pancreas	CL:0000083	50.87	gold quality
quadriceps femoris	UBERON:0001377	49.34	gold quality
Brodmann (1909) area 46	UBERON:0006483	49.30	gold quality
cervix squamous epithelium	UBERON:0006922	49.20	gold quality
hair follicle	UBERON:0002073	49.18	gold quality
olfactory bulb	UBERON:0002264	48.92	gold quality
myocardium	UBERON:0002349	48.87	gold quality
type B pancreatic cell	CL:0000169	48.83	gold quality
cardiac muscle of right atrium	UBERON:0003379	48.55	gold quality
CA1 field of hippocampus	UBERON:0003881	48.50	gold quality
vastus lateralis	UBERON:0001379	48.25	gold quality
left ventricle myocardium	UBERON:0006566	48.24	gold quality
orbitofrontal cortex	UBERON:0004167	48.20	gold quality
upper arm skin	UBERON:0004263	48.06	gold quality
cervix epithelium	UBERON:0004801	48.04	gold quality
oviduct epithelium	UBERON:0004804	48.00	gold quality
tongue squamous epithelium	UBERON:0006919	47.92	gold quality
mucosa of urinary bladder	UBERON:0001259	47.80	gold quality
metanephric glomerulus	UBERON:0004736	47.45	gold quality
thymus	UBERON:0002370	47.42	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-9801	yes	28498.77
E-ANND-3	no	1.64

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 1)

• contains 2 cysteine disulfide linkages (Cys20-Cys115 and Cys92-Cys107) and 6 cysteine residues with free sulfhydryl groups (Cys2, Cys23, Cys42, Cys43, Cys68, and Cys96). Amino acid positions are not based on the full-length protein sequence. (PMID:17136616)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Prg3	ENSMUSG00000027072
rattus_norvegicus	Prg3	ENSRNOG00000037908

Paralogs (1): PRG2 (ENSG00000186652)

Protein

Protein identifiers

Proteoglycan 3 — Q9Y2Y8 (reviewed: Q9Y2Y8)

Alternative names: Eosinophil major basic protein homolog, Prepro-major basic protein homolog

All UniProt accessions (1): Q9Y2Y8

UniProt curated annotations — full annotation on UniProt →

Function. Possesses similar cytotoxic and cytostimulatory activities to PRG2/MBP. In vitro, stimulates neutrophil superoxide production and IL8 release, and histamine and leukotriene C4 release from basophils.

Subcellular location. Cytoplasmic granule.

Tissue specificity. Expressed in bone marrow. Not detected in placenta.

RefSeq proteins (1): NP_006084* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001304	C-type_lectin-like	Domain
IPR002352	Eosinophil_major_basic	Family
IPR016186	C-type_lectin-like/link_sf	Homologous_superfamily
IPR016187	CTDL_fold	Homologous_superfamily
IPR018378	C-type_lectin_CS	Conserved_site
IPR033816	EMBP_CTLD	Domain
IPR050111	C-type_lectin/snaclec_domain	Family

Pfam: PF00059

UniProt features (7 total): disulfide bond 2, sequence variant 2, signal peptide 1, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y2Y8-F1	77.26	0.54

Functional residue map

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

Disulfide bonds (2): 128–223, 200–215

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-6798695	Neutrophil degranulation

MSigDB gene sets: 112 (showing top): REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_POSITIVE_REGULATION_OF_INTERLEUKIN_8_PRODUCTION, GOCC_SECRETORY_GRANULE, GOBP_SUPEROXIDE_METABOLIC_PROCESS, DARWICHE_SKIN_TUMOR_PROMOTER_UP, DARWICHE_PAPILLOMA_RISK_LOW_UP, DARWICHE_PAPILLOMA_RISK_HIGH_UP, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION, DARWICHE_SQUAMOUS_CELL_CARCINOMA_UP, GOBP_LEUKOTRIENE_BIOSYNTHETIC_PROCESS, GOBP_ORGANIC_ACID_BIOSYNTHETIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_TRANSLATION, GOBP_TRANSLATION, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS

GO Biological Process (8): histamine biosynthetic process (GO:0001694), immune response (GO:0006955), negative regulation of translation (GO:0017148), leukotriene biosynthetic process (GO:0019370), positive regulation of interleukin-8 production (GO:0032757), neutrophil activation (GO:0042119), superoxide anion generation (GO:0042554), basophil activation (GO:0045575)

GO Molecular Function (2): extracellular matrix structural constituent conferring compression resistance (GO:0030021), carbohydrate binding (GO:0030246)

GO Cellular Component (4): extracellular region (GO:0005576), extracellular matrix (GO:0031012), specific granule lumen (GO:0035580), tertiary granule lumen (GO:1904724)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Innate Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
granulocyte activation	2
histamine metabolic process	1
biogenic amine biosynthetic process	1
immune system process	1
response to stimulus	1
translation	1
regulation of translation	1
negative regulation of gene expression	1
negative regulation of protein metabolic process	1
leukotriene metabolic process	1
icosanoid biosynthetic process	1
positive regulation of cytokine production	1
interleukin-8 production	1
regulation of interleukin-8 production	1
superoxide metabolic process	1
extracellular matrix structural constituent	1
binding	1
cellular anatomical structure	1
external encapsulating structure	1
secretory granule lumen	1
specific granule	1
intracellular organelle lumen	1
tertiary granule	1

Protein interactions and networks

STRING

268 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRG3	IL5	P05113	578
PRG3	EPX	P11678	389
PRG3	GPC3	P51654	370
PRG3	SHCBP1L	Q9BZQ2	354
PRG3	HBM	Q6B0K9	326
PRG3	OBP2B	Q9NPH6	292
PRG3	NRDE2	Q9H7Z3	285
PRG3	IGFLR1	Q9H665	280
PRG3	ZNF134	P52741	272
PRG3	CHDH	Q8NE62	272
PRG3	CPNE2	Q96FN4	272
PRG3	TNPO2	O14787	269
PRG3	MPP1	Q00013	268
PRG3	TXNDC2	Q86VQ3	260
PRG3	A0A2Q2T6B6	A0A2Q2T6B6	248
PRG3	ZNF160	Q9HCG1	248

IntAct

5 interactions, top by confidence:

A	B	Type	Score
PRG3	ZNF324	psi-mi:“MI:0914”(association)	0.530
CRYBB3	H1-4	psi-mi:“MI:0914”(association)	0.350
PRG3	VGF	psi-mi:“MI:0914”(association)	0.350
PRG3	IGLL5	psi-mi:“MI:0914”(association)	0.350

BioGRID (74): FUT11 (Affinity Capture-MS), ZMYND19 (Affinity Capture-MS), GALNS (Affinity Capture-MS), ARMC8 (Affinity Capture-MS), GID4 (Affinity Capture-MS), MKLN1 (Affinity Capture-MS), EOGT (Affinity Capture-MS), LDLR (Affinity Capture-MS), RMND5A (Affinity Capture-MS), RANBP10 (Affinity Capture-MS), GID8 (Affinity Capture-MS), PCSK5 (Affinity Capture-MS), TXNDC16 (Affinity Capture-MS), ITGB5 (Affinity Capture-MS), ATP12A (Affinity Capture-MS)

ESM2 similar proteins: A5PJC7, O88200, O88201, P01377, P04004, P0DV84, P13727, P22032, P22272, P22273, P22458, P22934, P23132, P25118, P35230, P35709, P40967, P55068, P83515, P84618, Q01114, Q06141, Q06154, Q28062, Q29191, Q3U4N7, Q568T5, Q60696, Q60943, Q61361, Q61878, Q62713, Q62715, Q62716, Q63189, Q6RUU0, Q6UW15, Q6UXB4, Q7Z442, Q8C351

Diamond homologs: A1XRN2, B1A4M7, B1A4N2, B1A4N8, B1A4P2, B1A4P6, B1A4P7, B1A4P8, B1A4P9, B1A4Q0, B1A4Q2, B1A4Q3, B1A4Q5, B1A4Q6, B1A4Q8, B1A4Q9, B1A4R0, B1A4R4, B2D1Y0, C0STK6, P0DQP8, P12842, P21755, P21756, P35246, P81077, P82142, Q6RXL1, Q8AXS4, Q8AYA2, Q95L88, Q9TT06, Q9Y2Y8, A7X3W1, A7X3W6, A7X3Z4, A7X3Z7, B0VXV2, B4XSY4, B4XSY5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	14
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

1480 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:57376865:G:C	F221L	0.989
11:57376865:G:T	F221L	0.989
11:57376867:A:G	F221L	0.989
11:57377789:A:C	F185L	0.982
11:57377789:A:T	F185L	0.982
11:57377791:A:G	F185L	0.982
11:57379506:A:C	F121L	0.980
11:57379506:A:T	F121L	0.980
11:57379508:A:G	F121L	0.980
11:57376898:C:A	W210C	0.976
11:57376898:C:G	W210C	0.976
11:57377813:C:A	W177C	0.973
11:57377813:C:G	W177C	0.973
11:57378705:C:A	W161C	0.971
11:57378705:C:G	W161C	0.971
11:57377780:C:A	W188C	0.966
11:57377780:C:G	W188C	0.966
11:57379499:C:G	A124P	0.959
11:57378707:A:G	W161R	0.958
11:57378707:A:T	W161R	0.958
11:57377819:A:C	F175L	0.957
11:57377819:A:T	F175L	0.957
11:57377821:A:G	F175L	0.957
11:57378753:G:C	N145K	0.949
11:57378753:G:T	N145K	0.949
11:57376900:A:G	W210R	0.946
11:57376900:A:T	W210R	0.946
11:57377815:A:G	W177R	0.943
11:57377815:A:T	W177R	0.943
11:57377782:A:G	W188R	0.942

dbSNP variants (sampled 300 via entrez): RS1000018362 (11:57381978 G>A,T), RS1000603115 (11:57381729 TG>T), RS1001496687 (11:57378398 G>A), RS1003572712 (11:57380008 G>A), RS1003942659 (11:57380036 C>T), RS1004785182 (11:57378049 A>G,T), RS1004838859 (11:57377720 C>G), RS1005772981 (11:57382365 G>A), RS1005945444 (11:57382606 C>A,T), RS1006953605 (11:57382015 A>G,T), RS1007717070 (11:57377365 G>T), RS1007728408 (11:57377664 G>A,T), RS1008293758 (11:57376484 T>C), RS1008312241 (11:57378474 A>G), RS1008380926 (11:57380950 T>C)

Disease associations

OMIM: gene MIM:606814 | 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
Benzo(a)pyrene	affects methylation, increases methylation	2
benzo(e)pyrene	increases methylation	1
clothianidin	increases expression	1
Arsenic Trioxide	increases expression	1
Iron	decreases expression	1
Methapyrilene	increases methylation	1
Tretinoin	increases expression	1
Gold Compounds	decreases expression	1

Clinical trials (associated diseases)

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