PAN3

Chr 13

poly(A) specific ribonuclease subunit PAN3

PAN3 encodes a regulatory subunit of the poly(A)-nuclease deadenylation complex that shortens poly(A) tails and promotes mRNA turnover by recruiting the catalytic subunit PAN2 to target mRNAs. Mutations cause autosomal recessive intellectual disability with seizures and variable additional features including microcephaly and growth retardation. The gene is highly constrained against loss-of-function variants (pLI >0.99), indicating that haploinsufficient mutations are likely pathogenic even when inherited recessively.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.15
Clinical SummaryPAN3
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.15LOEUF
pLI 1.000
Z-score 5.72
OE 0.05 (0.020.15)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint
2.52Z-score
OE missense 0.66 (0.600.73)
285 obs / 432.2 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.05 (0.020.15)
00.351.4
Missense OE0.66 (0.600.73)
00.61.4
Synonymous OE0.97
01.21.6
LoF obs/exp: 2 / 42.0Missense obs/exp: 285 / 432.2Syn Z: 0.31
DN
0.4091th %ile
GOF
0.3986th %ile
LOF
0.81top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.15

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

PAN3 · 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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