SPATA13
Chr 13spermatogenesis associated 13
Also known as: ARHGEF29, ASEF2
SPATA13 encodes a guanine nucleotide exchange factor that activates RHO family GTPases (RHOA, RAC1, CDC42) to regulate cell migration, adhesion, and plasma membrane projection assembly. Mutations cause autosomal recessive intellectual disability with macrocephaly and seizures, typically presenting in early childhood. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.462), suggesting some intolerance to complete protein loss.
Limited evidence — not for standalone diagnostic reporting
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Moderately missense-constrained (top ~2.5%)
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
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
337 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 37 | 0 | 37 |
Likely Pathogenic | 0 | 0 | 3 | 0 | 3 |
VUS | 0 | 200 | 30 | 0 | 230 |
Likely Benign | 0 | 17 | 12 | 10 | 39 |
Benign | 0 | 5 | 3 | 1 | 9 |
Conflicting | — | 1 | |||
| Total | 0 | 222 | 85 | 11 | 319 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
SPATA13 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools