SAPCD2

Chr 9

suppressor APC domain containing 2

Also known as: C9orf140, p42.3

NCBI Gene: 89958ENSG00000186193UniProt: Q86UD0

Involved in negative regulation of protein localization to cell cortex and positive regulation of cell population proliferation. Located in several cellular components, including apical cortex; apical junction complex; and nuclear lumen. [provided by Alliance of Genome Resources, Jul 2025]

0
Active trials
87
Pathogenic / LP
173
ClinVar variants
3
Pubs (1 yr)
0.8
Missense Z
0.89
LOEUF
Clinical Summary— SAPCD2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
87 Pathogenic / Likely Pathogenic· 80 VUS of 173 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.89LOEUF
pLI 0.004
Z-score 1.86
OE 0.45 (0.25–0.89)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.83Z-score
OE missense 0.81 (0.71–0.94)
131 obs / 160.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.45 (0.25–0.89)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.81 (0.71–0.94)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.93
0≤1.21.6
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

173 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic82
Likely Pathogenic5
VUS80
Likely Benign4
Conflicting2
82
Pathogenic
5
Likely Pathogenic
80
VUS
4
Likely Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
82
0
82
Likely Pathogenic
0
0
5
0
5
VUS
0
72
8
0
80
Likely Benign
0
3
0
1
4
Benign
0
0
0
0
0
Conflicting
—2
Total075951173

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

View 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.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
The Function and Regulation of SAPCD2 in Physiological and Oncogenic Processes
Baker AL et al.·J Cancer
2022
SAPCD2 promotes neuroblastoma progression by altering the subcellular distribution of E2F7
Zhang ZM et al.·Cell Death Dis
2022
Identification of ARHGEF38, NETO2, GOLM1, and SAPCD2 Associated With Prostate Cancer Progression by Bioinformatic Analysis and Experimental Validation
Sun Z et al.·Front Cell Dev Biol
2021
YY1-inudced activation of lncRNA DUXAP8 promotes proliferation and suppresses apoptosis of triple negative breast cancer cells through upregulating SAPCD2.
Yang Z et al.·Cancer Biol Ther
2021
Integrating differential gene expression and Mendelian randomization analyses reveal novel gene for prognosis, immune response, and drug sensitivity in lung cancer
Li M et al.·Discov Oncol
2025
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients