PRG4

proteoglycan 4

Basic information

Region (hg38): 1:186296279-186314567

Previous symbols: [ "CACP" ]

Links

ENSG00000116690

∙ NCBI:10216 ∙ OMIM:604283 ∙ HGNC:9364 ∙ Uniprot:Q92954 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

camptodactyly-arthropathy-coxa vara-pericarditis syndrome (Strong), mode of inheritance: AR
camptodactyly-arthropathy-coxa vara-pericarditis syndrome (Definitive), mode of inheritance: AR
camptodactyly-arthropathy-coxa vara-pericarditis syndrome (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Camptodactyly-arthropathy-coxa vara-pericarditis syndrome	AR	Cardiovascular	The disorder may be recognizable by noncardiac manifestations, but individuals frequently develop pericarditis refractory to other treatments and requiring pericardiectomy, and awareness may allow early detection and efficient targeted medical management	Cardiovascular; Musculoskeletal	940709; 656159; 6866038; 6870971; 4083939; 3964320; 3964321; 8835575; 9550484; 10545950; 11102929; 16429407; 21565623

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PRG4 gene.

Inborn_genetic_diseases (209 variants)
not_provided (40 variants)
Camptodactyly-arthropathy-coxa_vara-pericarditis_syndrome (37 variants)
PRG4-related_disorder (16 variants)
not_specified (2 variants)
See_cases (2 variants)
Fetal_akinesia_deformation_sequence_1 (1 variants)
Arthrogryposis_multiplex_congenita (1 variants)
Abnormality_of_the_skeletal_system (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PRG4 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000005807.6. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous				27 clinvar	2 clinvar	29
missense			196 clinvar	21 clinvar	1 clinvar	218
nonsense	5 clinvar	4 clinvar				9
start loss						0
frameshift	22 clinvar	11 clinvar				33
splice donor/acceptor (+/-2bp)		1 clinvar				1
Total	27	16	196	48	3

Highest pathogenic variant AF is 0.000142625

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PRG4	protein_coding	protein_coding	ENST00000445192	12	18290

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.70e-8	0.998	125644	0	104	125748	0.000414

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.296	758	735	1.03	0.0000365	8930
Missense in Polyphen		77	93.497	0.82356		1313
Synonymous	-0.698	278	264	1.05	0.0000138	3066
Loss of Function	2.80	19	37.5	0.507	0.00000170	605

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00395	0.00386
Ashkenazi Jewish	0.00	0.00
East Asian	0.000272	0.000272
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000141	0.000141
Middle Eastern	0.000272	0.000272
South Asian	0.000492	0.000457
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: FUNCTION: Plays a role in boundary lubrication within articulating joints. Prevents protein deposition onto cartilage from synovial fluid by controlling adhesion-dependent synovial growth and inhibiting the adhesion of synovial cells to the cartilage surface.;
Disease: DISEASE: Camptodactyly-arthropathy-coxa vara-pericarditis syndrome (CACP) [MIM:208250]: An autosomal recessive disorder characterized by the association of congenital or early-onset camptodactyly and non-inflammatory arthropathy with synovial hyperplasia. Individuals with CACP have normal appearing joints at birth but with advancing age develop joint failure, non-inflammatory synoviocyte hyperplasia and subintimal fibrosis of the synovial capsule. Some patients also manifest progressive coxa vara deformity and/or non-inflammatory pericardial or pleural effusions. {ECO:0000269|PubMed:10545950}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Intolerance Scores

loftool: 0.905
rvis_EVS: 1.5
rvis_percentile_EVS: 95.39

Haploinsufficiency Scores

pHI: 0.145
hipred: N
hipred_score: 0.273
ghis

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: N
gene_indispensability_score: 0.145

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Prg4
Phenotype: skeleton phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); limbs/digits/tail phenotype;

Gene ontology

Biological process: receptor-mediated endocytosis;immune response;cell population proliferation
Cellular component: collagen-containing extracellular matrix
Molecular function: scavenger receptor activity;extracellular matrix structural constituent conferring compression resistance;polysaccharide binding