PACRG

Chr 6

parkin coregulated

Also known as: BUG21, GLUP, HAK005771, PACRG2.1, PARK2CRG, pf12

NCBI Gene: 135138 ENSG00000112530 UniProt: Q96M98 OMIM: 608427

PACRG encodes a microtubule inner protein required for motile cilia beating and also suppresses neuronal cell death induced by unfolded proteins. Mutations cause primary ciliary dyskinesia with autosomal recessive inheritance, affecting respiratory function and ciliary motility. The gene shows minimal constraint to loss-of-function variants and forms molecular complexes with chaperones that may be protective in neurodegenerative processes.

OMIM ResearchSummary from RefSeq, UniProt

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]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.24

Clinical Summary— PACRG

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

9 unique Pathogenic / Likely Pathogenic· 57 VUS of 83 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.24LOEUF

pLI 0.000

Z-score 0.85

OE 0.77 (0.49–1.24)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.88Z-score

OE missense 0.80 (0.70–0.93)

130 obs / 161.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.77 (0.49–1.24)

0≤0.351.4

Missense OE?0.80 (0.70–0.93)

0≤0.61.4

Synonymous OE?1.08

0≤1.21.6

LoF obs/exp: 12 / 15.6Missense obs/exp: 130 / 161.6Syn Z: -0.48

This gene — mechanism propensity

0.6259th %ile

GOF

0.5072th %ile

LOF

0.3454th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

83 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic6

Likely Pathogenic3

VUS57

Likely Benign7

Benign5

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	1	0	5	0	6
Likely Pathogenic	0	2	1	0	3
VUS	0	41	16	0	57
Likely Benign	0	1	5	1	7
Benign	0	0	3	2	5
Total	1	44	30	3	78

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

47 pathogenic / likely-pathogenic (of 73) ClinVar copy-number / structural variants overlap PACRG — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →