PAN3

Chr 13

poly(A) specific ribonuclease subunit PAN3

NCBI Gene: 255967 ENSG00000152520 UniProt: Q58A45

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.

ResearchSummary from RefSeq, UniProt

Contributes to poly(A)-specific ribonuclease activity. Involved in nuclear-transcribed mRNA poly(A) tail shortening. Part of PAN complex. [provided by Alliance of Genome Resources, Jun 2026]

ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.15

LOEUF· LoF intol.

LOF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.15LOEUF

pLI 1.000

Z-score 5.72

OE 0.05 (0.02–0.15)

Highly constrained

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

Missense Constraint?

2.52Z-score

OE missense 0.66 (0.60–0.73)

285 obs / 432.2 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.05 (0.02–0.15)

0≤0.351.4

Missense OE?0.66 (0.60–0.73)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

LoF obs/exp: 2 / 42.0Missense obs/exp: 285 / 432.2Syn Z: 0.31

Background carrier burden — how many people carry a rare variant somewhere in PAN3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 110

953 rare PASS variants

Rare truncating (LoF)

1 in 3,800

65 rare PASS variants

Rare synonymous (reference)

1 in 86

466 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PAN3. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 110	1 in 5,200
South Asian	~43k	1 in 71	1 in 1,300
Remaining (unassigned)	~30k	1 in 94	1 in 5,200
European (Finnish)	~27k	1 in 190	≈ 1 in 13,000
Admixed American	~22k	1 in 91	1 in 4,100
African / African American	~21k	1 in 64	1 in 2,200
East Asian	~20k	1 in 100	none seen
Ashkenazi Jewish	~13k	1 in 220	≈ 1 in 5,600
Middle Eastern	~2,884	1 in 73	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 17 of 19 coding exons well covered in gnomAD exomes; exons 1, 14 marginal. Genomes: all 19.? see exons ↓