PAN2

Chr 12AR

poly(A) specific ribonuclease subunit PAN2

Also known as: DEDCRF, USP52

NCBI Gene: 9924ENSG00000135473UniProt: Q9HBH5

This gene encodes a deadenylase that functions as the catalytic subunit of the polyadenylate binding protein dependent poly(A) nuclease complex. The encoded protein is a magnesium dependent 3' to 5' exoribonuclease that is involved in the degradation of cytoplasmic mRNAs. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]

Primary Disease Associations & Inheritance

Developmental delay with variable cardiac and renal congenital anomalies and dysmorphic faciesMIM #621384
AR
151
ClinVar variants
12
Pathogenic / LP
0.94
pLI score· haploinsufficient
0
Active trials
Clinical Summary— PAN2
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.94). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
12 Pathogenic / Likely Pathogenic· 135 VUS of 151 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
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.
0.32LOEUF
pLI 0.936
Z-score 5.86
OE 0.19 (0.12–0.32)
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.
3.18Z-score
OE missense 0.66 (0.61–0.71)
448 obs / 681.3 exp
Constrained

Highly missense-constrained (top ~0.1%)

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.0.19 (0.12–0.32)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.66 (0.61–0.71)
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.0.89
0≤1.21.6
LoF obs/exp: 12 / 61.6Missense obs/exp: 448 / 681.3Syn Z: 1.36

ClinVar Variant Classifications

151 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic9
Likely Pathogenic3
VUS135
Likely Benign2
Benign2
9
Pathogenic
3
Likely Pathogenic
135
VUS
2
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
1
7
0
9
Likely Pathogenic
1
0
2
0
3
VUS
5
126
4
0
135
Likely Benign
0
2
0
0
2
Benign
0
1
0
1
2
Total7130131151

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

View in ClinVar →

Protein Context — Lollipop Plot

PAN2 · protein map & ClinVar variants

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

Gene2Phenotype Curations

PAN2-related neurodevelopmental disorder with multiple congenital anomalies

moderate
ARUndeterminedAbsent Gene Product
Dev. Disorders
G2P ↗
splice acceptor variantframeshift variantstop gained

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Developmental delay with variable cardiac and renal congenital anomalies and dysmorphic facies

MIM #621384

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Expanding the phenome and variome of skeletal dysplasia.
Maddirevula S et al.·Genet Med
2018
Deubiquitylase USP52 Promotes Bladder Cancer Progression by Modulating Ferroptosis through Stabilizing SLC7A11/xCT.
Liu J et al.·Adv Sci (Weinh)
2024
Biallelic PAN2 variants in individuals with a syndromic neurodevelopmental disorder and multiple congenital anomalies.
Reuter MS et al.·Eur J Hum Genet
2022
Novel Missense Variant in the PAN2 Gene Associated With Congenital Anomalies and Neurodevelopmental Delay: Expanding the Phenotypic and Mutational Spectrum of PAN2-Related Disorders.
Çoğulu Ö et al.·Birth Defects Res
2025Case report
Establishment of human pancreatic ductal cells in a long-term culture.
Ulrich AB et al.·Pancreas
2000
Impact of Attending Physicians' Comments on Residents' Workloads in the Emergency Department: Results from Two J(^o^)PAN Randomized Controlled Trials.
Kuriyama A et al.·PLoS One
2016
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