XCL2

Chr 1

X-C motif chemokine ligand 2

Also known as: SCM-1b, SCM1B, SCYC2

NCBI Gene: 6846 ENSG00000143185 UniProt: Q9UBD3 OMIM: 604828

The XCL2 protein functions as a chemokine with specific chemotactic activity for lymphocytes, binding to CCR chemokine receptors and mediating antimicrobial immune responses. This gene has low constraint against loss-of-function variants (pLI 0.009, LOEUF 1.79), and no established disease associations or inheritance patterns have been reported for XCL2 mutations in the current literature.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to enable CCR chemokine receptor binding activity and chemokine activity. Predicted to be involved in several processes, including antimicrobial humoral immune response mediated by antimicrobial peptide; cell chemotaxis; and chemokine-mediated signaling pathway. Predicted to be located in extracellular region. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.78

Clinical Summary— XCL2

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Population Constraint (gnomAD)

Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

16 VUS of 20 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.78LOEUF

pLI 0.009

Z-score 0.28

OE 0.84 (0.37–1.78)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.32Z-score

OE missense 1.11 (0.92–1.36)

69 obs / 61.9 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.84 (0.37–1.78)

0≤0.351.4

Missense OE?1.11 (0.92–1.36)

0≤0.61.4

Synonymous OE?1.18

0≤1.21.6

LoF obs/exp: 3 / 3.6Missense obs/exp: 69 / 61.9Syn Z: -0.72

This gene — mechanism propensity

0.87top 5%

GOF

0.5759th %ile

LOF

0.09100th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction 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.

ClinVar Variant Classifications

20 submitted variants in ClinVar

ClinVar

Classification Summary

VUS16

Likely Benign2

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	16	0	16
Likely Benign	1	1	2
Benign	0	0	0
Total	17	1	18

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

View in ClinVar →

20 pathogenic / likely-pathogenic (of 31) ClinVar copy-number / structural variants overlap XCL2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →