SAPCD2

Chr 9

suppressor APC domain containing 2

Also known as: C9orf140, p42.3

The protein regulates mitotic spindle orientation in retinal progenitor cells and controls cell cortex localization of other proteins involved in cell division. Mutations cause autosomal recessive microcephaly, short stature, and intellectual disability. The gene shows low constraint against loss-of-function variants, which is consistent with the recessive inheritance pattern.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 0.89
Clinical SummarySAPCD2
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.89LOEUF
pLI 0.004
Z-score 1.86
OE 0.45 (0.250.89)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.83Z-score
OE missense 0.81 (0.710.94)
131 obs / 160.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.45 (0.250.89)
00.351.4
Missense OE0.81 (0.710.94)
00.61.4
Synonymous OE0.93
01.21.6
LoF obs/exp: 6 / 13.3Missense obs/exp: 131 / 160.8Syn Z: 0.47
DN
0.7133th %ile
GOF
0.7127th %ile
LOF
0.3841th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

SAPCD2 · 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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