DIPK1A
Chr 1divergent protein kinase domain 1A
Also known as: FAM69A
This gene encodes a cysteine-rich transmembrane protein that localizes to the endoplasmic reticulum, though its specific cellular function remains unknown. Mutations cause autosomal recessive spastic paraplegia with intellectual disability and seizures, typically with onset in early childhood. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.494), suggesting intolerance to complete protein loss.
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 (loss-of-function and dominant-negative). The Badonyi & Marsh model scores dominant-negative highest among its predictions, but genomic evidence (constraint, ClinVar variant spectrum, and literature) most strongly supports loss-of-function (haploinsufficiency). 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. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
409 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 | 53 | 1 | 10 | 0 | 64 |
Likely Pathogenic | 28 | 1 | 1 | 0 | 30 |
VUS | 3 | 159 | 16 | 2 | 180 |
Likely Benign | 1 | 2 | 47 | 43 | 93 |
Benign | 0 | 0 | 8 | 2 | 10 |
Conflicting | — | 10 | |||
| Total | 85 | 163 | 82 | 47 | 387 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
DIPK1A · 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 →No open access results found
External Resources
Links to major genomics databases and tools