PRRC2A

Chr 6

proline rich coiled-coil 2A

NCBI Gene: 7916ENSG00000204469UniProt: P48634

May play a role in the regulation of pre-mRNA splicing

459
ClinVar variants
7
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— PRRC2A
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
7 Pathogenic / Likely Pathogenic· 370 VUS of 459 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.19LOEUF
pLI 1.000
Z-score 8.62
OE 0.12 (0.07–0.19)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.18Z-score
OE missense 1.01 (0.97–1.06)
1323 obs / 1304.3 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.12 (0.07–0.19)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.01 (0.97–1.06)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.02
0≤1.21.6
LoF obs/exp: 13 / 111.0Missense obs/exp: 1323 / 1304.3Syn Z: -0.44

ClinVar Variant Classifications

459 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic4
Likely Pathogenic3
VUS370
Likely Benign41
Benign41
4
Pathogenic
3
Likely Pathogenic
370
VUS
41
Likely Benign
41
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
4
0
4
Likely Pathogenic
0
0
3
0
3
VUS
0
365
5
0
370
Likely Benign
0
18
5
18
41
Benign
0
25
3
13
41
Total04082031459

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

View in ClinVar →

Protein Context — Lollipop Plot

PRRC2A · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Genome-Wide Identification of N6-Methyladenosine Associated SNPs as Potential Functional Variants for Type 1 Diabetes.
Chen Y et al.·Front Endocrinol (Lausanne)
2022Functional
Unraveling the genetic susceptibility of irritable bowel syndrome: integrative genome-wide analyses in 845 492 individuals: a diagnostic study.
Huang W et al.·Int J Surg
2025Meta-analysis
Distinct sex-specific DNA methylation differences in Alzheimer's disease.
C Silva T et al.·Alzheimers Res Ther
2022Meta-analysis
Association Analysis of the MHC in Lupus Nephritis.
Xu R et al.·J Am Soc Nephrol
2017
Genetic Commonalities Between Metabolic Syndrome and Rheumatic Diseases Through Disease Interactome Modules.
Shi Y et al.·J Cell Mol Med
2025
Allelic expression imbalance of CDKN2A variants in childhood acute lymphoblastic leukemia.
Tang Z et al.·Cell Oncol (Dordr)
2025
Relationship between genetically determined telomere length and glioma risk.
Saunders CN et al.·Neuro Oncol
2022
PRRC2A and BCL2L11 gene variants influence risk of non-Hodgkin lymphoma: results from the InterLymph consortium.
Nieters A et al.·Blood
2012
Interactions within the MHC contribute to the genetic architecture of celiac disease.
Goudey B et al.·PLoS One
2017
Genetic variations in MOV10 and CACNB2 are associated with hypertension in a Chinese Han population.
Hong GL et al.·Genet Mol Res
2013
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools