XCL1

Chr 1

X-C motif chemokine ligand 1

Also known as: ATAC, LPTN, LTN, SCM-1, SCM-1a, SCM1, SCM1A, SCYC1

NCBI Gene: 6375 ENSG00000143184 UniProt: P47992 OMIM: 600250

The encoded protein is a C-chemokine that exhibits chemotactic activity specifically for lymphocytes and mediates medullary accumulation of thymic dendritic cells, contributing to regulatory T cell development and self-tolerance establishment. This gene shows low constraint against loss-of-function variants (pLI 0.001, LOEUF 1.87), and no definitive human disease associations have been established in the provided data. The inheritance pattern for any potential disease would be expected to follow autosomal patterns given its chromosomal location.

OMIM ResearchSummary from RefSeq, UniProt

This antimicrobial gene encodes a member of the chemokine superfamily. Chemokines function in inflammatory and immunological responses, inducing leukocyte migration and activation. The encoded protein is a member of the C-chemokine subfamily, retaining only two of four cysteines conserved in other chemokines, and is thought to be specifically chemotactic for T cells. This gene and a closely related family member are located on the long arm of chromosome 1. [provided by RefSeq, Sep 2014]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.87

Clinical Summary— XCL1

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

13 VUS of 17 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

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?

1.87LOEUF

pLI 0.001

Z-score -0.16

OE 1.09 (0.51–1.87)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.13Z-score

OE missense 1.05 (0.85–1.29)

64 obs / 61.2 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.09 (0.51–1.87)

0≤0.351.4

Missense OE?1.05 (0.85–1.29)

0≤0.61.4

Synonymous OE?0.78

0≤1.21.6

LoF obs/exp: 4 / 3.7Missense obs/exp: 64 / 61.2Syn Z: 0.86

This gene — mechanism propensity

0.73top 25%

GOF

0.4874th %ile

LOF

0.1994th %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

17 submitted variants in ClinVar

ClinVar

Classification Summary

VUS13

Benign1

VUS

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	13	13
Likely Benign	0	0
Benign	1	1
Total	14	14

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 XCL1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →