XKR6

Chr 8

XK related 6

Also known as: C8orf21, C8orf5, C8orf7, XRG6

NCBI Gene: 286046 ENSG00000171044 UniProt: Q5GH73

The XKR6 protein is predicted to be involved in apoptotic processes during development, including the exposure of phosphatidylserine on apoptotic cell surfaces and the engulfment of apoptotic cells, and is located in cellular membranes including the plasma membrane. Mutations in XKR6 cause neurodevelopmental disorders, though the specific phenotypes and inheritance patterns are not well-established in the provided data. This gene is highly constrained against loss-of-function variants (pLI = 0.999, LOEUF = 0.186), suggesting that complete loss of function is likely incompatible with normal development.

ResearchSummary from RefSeq

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]

ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.19

LOEUF· LoF intol.

Multiple*

Mechanism· predicted

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 OE?0.04 (0.01–0.19)

0≤0.351.4

Missense OE?0.71 (0.64–0.78)

0≤0.61.4

Synonymous OE?1.27

0≤1.21.6

LoF obs/exp: 1 / 25.5Missense obs/exp: 262 / 370.9Syn Z: -2.65

Background carrier burden — how many people carry a rare variant somewhere in XKR6?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 92

993 rare PASS variants

Rare truncating (LoF)

1 in 2,700

53 rare PASS variants

Rare synonymous (reference)

1 in 110

602 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for XKR6. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 100	1 in 4,500
South Asian	~43k	1 in 58	1 in 1,200
Remaining (unassigned)	~30k	1 in 82	1 in 2,000
European (Finnish)	~27k	1 in 160	≈ 1 in 12,000
Admixed American	~22k	1 in 70	1 in 3,800
African / African American	~21k	1 in 64	1 in 2,500
East Asian	~20k	1 in 71	1 in 2,000
Ashkenazi Jewish	~13k	1 in 220	none seen
Middle Eastern	~2,884	1 in 47	≈ 1 in 2,000

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 3 coding exons well covered in gnomAD exomes and genomes.? see exons ↓