APC2

Chr 19AR

APC regulator of WNT signaling pathway 2

APC2 encodes a component of the anaphase-promoting complex that regulates cell cycle progression by targeting specific proteins like mitotic cyclins for degradation through ubiquitination. Biallelic mutations cause autosomal recessive intellectual developmental disorder and complex cortical dysplasia with other brain malformations. The gene is highly constrained against loss-of-function variants (pLI 1.0, LOEUF 0.23), consistent with its essential role in cell division.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.232 OMIM phenotypes
Clinical SummaryAPC2
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Gene-Disease Validity (ClinGen)
lissencephaly spectrum disorders · ARStrong

Strong evidence — appropriate for clinical testing

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.
Some data sources returned errors (1)

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.23LOEUF
pLI 1.000
Z-score 6.24
OE 0.12 (0.070.23)
Highly constrained

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

Missense Constraint
0.75Z-score
OE missense 0.94 (0.890.98)
1015 obs / 1084.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.12 (0.070.23)
00.351.4
Missense OE0.94 (0.890.98)
00.61.4
Synonymous OE1.14
01.21.6
LoF obs/exp: 7 / 58.5Missense obs/exp: 1015 / 1084.9Syn Z: -2.43
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongAPC2-related lissencephaly, subcortical heterotopia, and global developmental delayLOFAR

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

DN
0.4189th %ile
GOF
0.5170th %ile
LOF
0.75top 10%

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

APC2 · 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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