PARN

Chr 16ARAD

poly(A)-specific ribonuclease

Also known as: DAN, DKCB6, PFBMFT4

NCBI Gene: 5073ENSG00000140694UniProt: O95453

The protein encoded by this gene is a 3'-exoribonuclease, with similarity to the RNase D family of 3'-exonucleases. It prefers poly(A) as the substrate, hence, efficiently degrades poly(A) tails of mRNAs. Exonucleolytic degradation of the poly(A) tail is often the first step in the decay of eukaryotic mRNAs. This protein is also involved in silencing of certain maternal mRNAs during oocyte maturation and early embryonic development, as well as in nonsense-mediated decay (NMD) of mRNAs that contain premature stop codons. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2008]

Primary Disease Associations & Inheritance

Dyskeratosis congenita, autosomal recessive 6MIM #616353
AR
Pulmonary fibrosis and/or bone marrow failure syndrome, telomere-related, 4MIM #616371
AD
569
ClinVar variants
58
Pathogenic / LP
0.00
pLI score
1
Active trials
Clinical Summary— PARN
🧬
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
58 Pathogenic / Likely Pathogenic· 288 VUS of 569 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.52LOEUF
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?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.
0.79Z-score
OE missense 0.88 (0.79–0.97)
285 obs / 325.3 exp
Tolerant

Mild missense constraint

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.0.33 (0.22–0.52)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.88 (0.79–0.97)
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.0.93
0≤1.21.6
LoF obs/exp: 14 / 42.2Missense obs/exp: 285 / 325.3Syn Z: 0.57

ClinVar Variant Classifications

569 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic30
Likely Pathogenic28
VUS288
Likely Benign218
Benign4
Conflicting1
30
Pathogenic
28
Likely Pathogenic
288
VUS
218
Likely Benign
4
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
8
0
22
0
30
Likely Pathogenic
23
0
5
0
28
VUS
5
238
42
3
288
Likely Benign
0
0
140
78
218
Benign
0
0
4
0
4
Conflicting
—1
Total3623821381569

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.

Gene2Phenotype Curations

PARN-related dyskeratosis congenita

definitive
ARLoss Of FunctionAbsent Gene Product, Altered Gene Product Structure
Dev. DisordersCancer
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Dyskeratosis congenita, autosomal recessive 6

MIM #616353

Molecular basis of disorder known

Autosomal recessive

Pulmonary fibrosis and/or bone marrow failure syndrome, telomere-related, 4

MIM #616371

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — PARN
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Germline PARN Variants in Telomere Biology Disorders and Challenges in Variant Curation.
Nurelegne HT et al.·Mol Genet Genomic Med
2025
Poly (A)-specific ribonuclease (PARN): More than just "mRNA stock clearing".
Nanjappa DP et al.·Life Sci
2021Review
Modulation of poly(A)-specific ribonuclease (PARN): current knowledge and perspectives.
Balatsos NA et al.·Curr Med Chem
2012Review
Optical Genomic Mapping and Next-Generation Sequencing Identified Retrotransposon Insertion and Missense Variant Disrupting PARN Gene in Dyskeratosis Congenita.
Cao Q et al.·Hum Mutat
2025Case report
PARN Modulates Y RNA Stability and Its 3'-End Formation.
Shukla S et al.·Mol Cell Biol
2017
Telomere biology disorders: time for moving towards the clinic?
Batista LFZ et al.·Trends Mol Med
2022Review
Interstitial lung diseases associated with mutations of poly(A)-specific ribonuclease: A multicentre retrospective study.
Philippot Q et al.·Respirology
2022
RNA Analysis Uncovers Pathogenic PARN Variant in Dyskeratosis Congenita.
Akimova D et al.·Clin Genet
2026Case report
How genetic defects in piRNA trimming contribute to male infertility.
Mann JM et al.·Andrology
2023Review
From incomplete penetrance with normal telomere length to severe disease and telomere shortening in a family with monoallelic and biallelic PARN pathogenic variants.
Dodson LM et al.·Hum Mutat
2019
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
Idiopathic Interstitial Pneumopathy/Pneumopathy Interstitial DiffusePaediatric and Adult Patients

RaDiCo PID Cohort (RaDiCo-ILD Cohort in English)

RECRUITING
NCT04238871Institut National de la Santé Et de la Recherche Médicale, FranceStarted 2017-06-21

External Resources

Links to major genomics databases and tools