PAN2

Chr 12

poly(A) specific ribonuclease subunit PAN2

Also known as: DEDCRF, USP52

NCBI Gene: 9924 ENSG00000135473 UniProt: Q9HBH5

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.

ResearchSummary from RefSeq, OMIM, UniProt

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]

ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.32

Clinical Summary— PAN2

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Gene-Disease Validity (ClinGen)

syndromic complex neurodevelopmental disorder · ARModerate

Moderate evidence — consider for supplementary testing

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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.

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ClinVar Variants

6 unique Pathogenic / Likely Pathogenic· 132 VUS of 162 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

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?

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?

LoF OE?0.19 (0.12–0.32)

0≤0.351.4

Missense OE?0.66 (0.61–0.71)

0≤0.61.4

Synonymous OE?0.89

0≤1.21.6

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

This gene — mechanism propensity

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

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

162 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic3

Likely Pathogenic3

VUS132

Likely Benign2

Benign2

Pathogenic

Likely Pathogenic

132

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Synonymous	Total
Pathogenic	2	1	0	3
Likely Pathogenic	3	0	0	3
VUS	6	126	0	132
Likely Benign	0	2	0	2
Benign	0	1	1	2
Total	11	130	1	142

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

View in ClinVar →

6 pathogenic / likely-pathogenic (of 9) ClinVar copy-number / structural variants overlap PAN2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →