XKR6

Chr 8

XK related 6

Also known as: C8orf21, C8orf5, C8orf7, XRG6

NCBI Gene: 286046ENSG00000171044UniProt: Q5GH73

Predicted to be involved in apoptotic process involved in development; engulfment of apoptotic cell; and phosphatidylserine exposure on apoptotic cell surface. Predicted to be located in membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Jul 2025]

0
Active trials
118
Pathogenic / LP
235
ClinVar variants
7
Pubs (1 yr)
2.0
Missense Z
0.19
LOEUF· LoF intolerant
Clinical Summary— XKR6
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
118 Pathogenic / Likely Pathogenic· 112 VUS of 235 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.19LOEUF
pLI 0.999
Z-score 4.50
OE 0.04 (0.01–0.19)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
2.01Z-score
OE missense 0.71 (0.64–0.78)
262 obs / 370.9 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.04 (0.01–0.19)
0≤0.351.4
Missense OE0.71 (0.64–0.78)
0≤0.61.4
Synonymous OE1.27
0≤1.21.6
LoF obs/exp: 1 / 25.5Missense obs/exp: 262 / 370.9Syn Z: -2.65
LOFGOF
DN
0.4487th %ile
GOF
0.6931th %ile
LOF
0.65top 25%

This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and gain-of-function). The Badonyi & Marsh model scores gain-of-function 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.

LOFprediction above median · LOEUF 0.19
GOFprediction 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. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

235 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic114
Likely Pathogenic4
VUS112
Likely Benign5
114
Pathogenic
4
Likely Pathogenic
112
VUS
5
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
114
0
114
Likely Pathogenic
0
0
4
0
4
VUS
0
96
16
0
112
Likely Benign
0
2
0
3
5
Benign
0
0
0
0
0
Total0981343235

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

View in ClinVar →

XKR6 · 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
Trans-ancestry, Bayesian meta-analysis discovers 20 novel risk loci for inflammatory bowel disease in an African American, East Asian and European cohort.
Cordero RY et al.·Hum Mol Genet
2022Cohort
The genetic landscape of primary malignant melanoma of the cervix using integrated bioinformatics analysis and whole-exome sequencing.
Zhou J et al.·Front Oncol
2025
Emotional dysregulation, alexithymia and neuroticism: a systematic review on the genetic basis of a subset of psychological traits
Castellini G et al.·Psychiatr Genet
2022Review
Differentially Methylated DNA Regions and Left Ventricular Hypertrophy in African Americans: A HyperGEN Study
Jones AC et al.·Genes (Basel)
2022
Genome-wide association study identifies Sjogren's risk loci with functional implications in immune and glandular cells
Khatri B et al.·Nat Commun
2022Functional
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