PAN2

Chr 12AR

poly(A) specific ribonuclease subunit PAN2

Also known as: DEDCRF, USP52

The protein functions as a deadenylase and catalytic subunit of the polyadenylate binding protein dependent poly(A) nuclease complex, acting as a magnesium-dependent 3' to 5' exoribonuclease involved in cytoplasmic mRNA degradation. Biallelic mutations cause autosomal recessive developmental delay with variable cardiac and renal congenital anomalies and dysmorphic facies. The gene is highly constrained against loss-of-function variants (pLI 0.94, LOEUF 0.32), indicating that haploinsufficiency is likely not tolerated in the general population.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.321 OMIM phenotype
Clinical SummaryPAN2
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Gene-Disease Validity (ClinGen)
syndromic complex neurodevelopmental disorder · ARModerate

Moderate evidence — consider for supplementary testing

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.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint
0.32LOEUF
pLI 0.936
Z-score 5.86
OE 0.19 (0.120.32)
Highly constrained

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

Missense Constraint
3.18Z-score
OE missense 0.66 (0.610.71)
448 obs / 681.3 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.19 (0.120.32)
00.351.4
Missense OE0.66 (0.610.71)
00.61.4
Synonymous OE0.89
01.21.6
LoF obs/exp: 12 / 61.6Missense obs/exp: 448 / 681.3Syn Z: 1.36
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
moderatePAN2-related neurodevelopmental disorder with multiple congenital anomaliesOTHERAR

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

DN
0.3594th %ile
GOF
0.3094th %ile
LOF
0.67top 25%

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.

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

0 submitted variants 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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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