XKR9
Chr 8XK related 9
Also known as: XRG9, hXKR9
XKR9 encodes a phospholipid scramblase that promotes phosphatidylserine exposure on apoptotic cell surfaces, serving as a signal for cellular engulfment during programmed cell death. Mutations in XKR9 cause Birk-Barel syndrome, characterized by intellectual disability, congenital microcephaly, and dysmorphic features, with autosomal recessive inheritance. The gene shows very high constraint against loss-of-function variants (pLI ~0), indicating that complete loss of function is likely not tolerated.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Tolerant to missense variation
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.
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
108 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 | 33 | 0 | 33 |
Likely Pathogenic | 0 | 0 | 1 | 0 | 1 |
VUS | 0 | 51 | 7 | 0 | 58 |
Likely Benign | 0 | 4 | 2 | 0 | 6 |
Benign | 0 | 0 | 1 | 0 | 1 |
| Total | 0 | 55 | 44 | 0 | 99 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
XKR9 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
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