PARN

Chr 16ARAD

poly(A)-specific ribonuclease

Also known as: DAN, DKCB6, PFBMFT4

NCBI Gene: 5073ENSG00000140694UniProt: O95453OMIM: 604212

The protein is a 3'-exoribonuclease that degrades poly(A) tails of mRNAs, representing the first step in mRNA decay, and is also involved in nonsense-mediated decay and silencing of maternal mRNAs during early development. Mutations cause dyskeratosis congenita and pulmonary fibrosis with bone marrow failure syndrome, both telomere-related disorders with autosomal recessive inheritance. The gene is highly intolerant to loss-of-function variants (LOEUF 0.52), reflecting its essential role in RNA metabolism.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismAR/ADLOEUF 0.522 OMIM phenotypes
Clinical Summary— PARN
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Gene-Disease Validity (ClinGen)
pulmonary fibrosis and/or bone marrow failure, Telomere-related, 4 · SDDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.33) despite low pLI — interpret in context.
📋
ClinVar Variants
49 unique Pathogenic / Likely Pathogenic· 194 VUS of 400 total submissions
Explore recent and relevant literature in Research Assistant →
📖
GeneReview available — PARN
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
0.52LOEUF
pLI 0.000
Z-score 4.02
OE 0.33 (0.22–0.52)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.79Z-score
OE missense 0.88 (0.79–0.97)
285 obs / 325.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.33 (0.22–0.52)
0≤0.351.4
Missense OE0.88 (0.79–0.97)
0≤0.61.4
Synonymous OE0.93
0≤1.21.6
LoF obs/exp: 14 / 42.2Missense obs/exp: 285 / 325.3Syn Z: 0.57
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitivePARN-related dyskeratosis congenitaLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.5575th %ile
GOF
0.4085th %ile
LOF
0.3647th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Literature Evidence

LOFWe found an additional new missense variant (encoding p.Lys421Arg) in a proband of European ancestry. PARN is among the 20% of genes with the lowest prevalence of rare variants that are likely to disrupt normal function (mutation-intolerant genes)14, consistent with the identified variants causing hPMID:25848748

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

400 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic30
Likely Pathogenic19
VUS194
Likely Benign138
Benign6
Conflicting8
30
Pathogenic
19
Likely Pathogenic
194
VUS
138
Likely Benign
6
Benign
8
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
20
0
10
0
30
Likely Pathogenic
16
0
3
0
19
VUS
4
164
24
2
194
Likely Benign
0
2
84
52
138
Benign
0
2
4
0
6
Conflicting
—8
Total4016812554395

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

View in ClinVar →

Protein Context — Lollipop Plot

PARN · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients