PRG2

protein-coding

proteoglycan 2, pro eosinophil major basic protein, the group of C-type lectin domain containing

Gene summary

The protein encoded by this gene is the predominant constituent of the crystalline core of the eosinophil granule. High levels of the proform of this protein are also present in placenta and pregnancy serum, where it exists as a complex with several other proteins including pregnancy-associated plasma protein A (PAPPA), angiotensinogen (AGT), and C3dg. This protein may be involved in antiparasitic defense mechanisms as a cytotoxin and helminthotoxin, and in immune hypersensitivity reactions. The encoded protein contains a peptide that displays potent antimicrobial activity against Gram-positive bacteria, Gram-negative bacteria, and fungi. It is directly implicated in epithelial cell damage, exfoliation, and bronchospasm in allergic diseases. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2014]

MANE transcript

NM_002728.6

Inheritance

—

ClinVar variants

U:33B:4

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.68

Max pathogenic AF

—

Genomic locus

chr11:57,386,780-57,390,650

External References & Databases

Ensembl (ENSG00000186652)

Transcript & Mutation Effects

hg38 • Region Span ~3.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PRG2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 35

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002728.6. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous					1 clinvar	1
missense			32 clinvar	3 clinvar		35
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	33	3	1	37

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 29 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002728.6	RefSeq	NP_002719.3	5	MANE Select
ENST00000311862.10	Ensembl	ENSP00000312134.5	5	MANE Select
NM_001243245.3	RefSeq	NP_001230174.1	5	Standard
NM_001302926.2	RefSeq	NP_001289855.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Asthma - Homo sapiens (human)
Neutrophil degranulation
Innate Immune System
Immune System

Biological Process

defense response to bacterium
neutrophil degranulation

Molecular Function

heparin binding
extracellular matrix structural constituent conferring compression resistance
carbohydrate binding

Cellular Component

extracellular region
transport vesicle
collagen-containing extracellular matrix
extracellular exosome
ficolin-1-rich granule lumen

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000311862
Coding exons: 5
Length: 3864
Individuals with no LoFs: 125519
Homozygous LoFs: 0
Heterozygous LoFs: 63
Defined: 125582
p: 0.000251

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.315	115	125	0.921	0.00000717	1422
Missense (PolyPhen)		28	32.321	0.8663		422
Synonymous	0.0194	45	45.2	0.996	0.00000253	426
Loss of Function	0.966	7	10.4	0.676	5.09e-7	117

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0034	0.0035	notable
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.0000088	0.0000088	rare
South Asian	0.000098	0.000098	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Cytotoxin and helminthotoxin. Also induces non-cytolytic histamine release from human basophils. Involved in antiparasitic defense mechanisms and immune hypersensitivity reactions. The proform acts as a proteinase inhibitor, reducing the activity of PAPPA. {ECO:0000269|PubMed:10913121}.;

Recessive Scores

pRec: 0.103

Intolerance Scores

LoFtool: 0.846
RVIS EVS: -0.11
RVIS percentile EVS: 45.26

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.580

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium