XKR7

Chr 20

XK related 7

Also known as: C20orf159, dJ310O13.4

NCBI Gene: 343702 ENSG00000260903 UniProt: Q5GH72

The protein is predicted to be involved in apoptotic processes during development, including phosphatidylserine exposure on apoptotic cell surfaces and engulfment of apoptotic cells, and is located in cellular membranes including the plasma membrane. This gene is highly constrained against loss-of-function variants (pLI 0.91, LOEUF 0.38), but no definitive human disease associations have been established to date. Clinical significance of variants in this gene remains unclear pending further research.

Summary from RefSeq

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Active trials

Pubs (1 yr)

P/LP submissions

P/LP missense

0.38

LOEUF

Multiple*

Mechanism· predicted

Clinical Summary— XKR7

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.91). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

16 unique Pathogenic / Likely Pathogenic· 92 VUS of 109 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint

0.38LOEUF

pLI 0.908

Z-score 3.31

OE 0.12 (0.05–0.38)

Highly constrained

More LoF-intolerant than ~75% of genes

Missense Constraint

1.57Z-score

OE missense 0.76 (0.69–0.84)

256 obs / 337.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios

LoF OE0.12 (0.05–0.38)

0≤0.351.4

Missense OE0.76 (0.69–0.84)

0≤0.61.4

Synonymous OE0.85

0≤1.21.6

LoF obs/exp: 2 / 16.5Missense obs/exp: 256 / 337.0Syn Z: 1.41

0.5378th %ile

GOF

0.72top 25%

LOF

0.56top 25%

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and loss-of-function). 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.

GOFprediction above median

LOFLOEUF 0.38

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.