PACRG

protein-coding

parkin coregulated, the group of Armadillo like helical domain containing

Gene summary

This gene encodes a protein that is conserved across metazoans. In vertebrates, this gene is linked in a head-to-head arrangement with the adjacent parkin gene, which is associated with autosomal recessive juvenile Parkinson's disease. These genes are co-regulated in various tissues and they share a bi-directional promoter. Both genes are associated with susceptibility to leprosy. The parkin co-regulated gene protein forms a large molecular complex with chaperones, including heat shock proteins 70 and 90, and chaperonin components. This protein is also a component of Lewy bodies in Parkinson's disease patients, and it suppresses unfolded Pael receptor-induced neuronal cell death. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

MANE transcript

NM_001080379.2

Inheritance

—

ClinVar variants

U:42B:4

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.77

Max pathogenic AF

—

Genomic locus

chr6:162,727,132-163,315,500

External References & Databases

Ensembl (ENSG00000112530)

Transcript & Mutation Effects

hg38 • Region Span ~588.4 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 PACRG variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 42

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001080379.2. 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	2 clinvar	3
missense			41 clinvar	1 clinvar		42
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	42	2	2	46

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 33 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001080379.2	RefSeq	NP_001073848.1	5	MANE Select
ENST00000366888.7	Ensembl	ENSP00000355854.2	5	MANE Select
NM_001080378.2	RefSeq	NP_001073847.1	5	Standard
NM_152410.3	RefSeq	NP_689623.2	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

spermatid development
cellular response to unfolded protein
negative regulation of cell death

Molecular Function

G protein-coupled receptor binding
actin binding
Hsp70 protein binding
heat shock protein binding
ubiquitin protein ligase binding

Cellular Component

nucleus
cytosol
vesicle
neuron projection
cell body

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000337019
Coding exons: 6
Length: 588361
Individuals with no LoFs: 125698
Homozygous LoFs: 0
Heterozygous LoFs: 50
Defined: 125748
p: 0.000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.884	130	162	0.804	0.00000881	1928
Missense (PolyPhen)		51	62.412	0.81715		702
Synonymous	-0.482	70	65.0	1.08	0.00000404	573
Loss of Function	0.850	12	15.6	0.768	0.00000106	162

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00044	0.00044	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00028	0.00028	rare
South Asian	0.000065	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Suppresses cell death induced by accumulation of unfolded Pael receptor (Pael-R, a substrate of Parkin). Facilitates the formation of inclusions consisting of Pael-R, molecular chaperones, protein degradation molecules and itself when proteasome is inhibited. May play an important role in the formation of Lewy bodies and protection of dopaminergic neurons against Parkinson disease. {ECO:0000269|PubMed:14532270}.;

Recessive Scores

pRec: 0.173

Intolerance Scores

LoFtool: 0.348
RVIS EVS: -0.4
RVIS percentile EVS: 26.53

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.797

Gene Damage Prediction

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