CD40LG

Chr X

CD40 ligand

Also known as: CD154, CD40L, HIGM1, IGM, IMD3, T-BAM, TNFSF5, TRAP

NCBI Gene: 959 ENSG00000102245 UniProt: P29965

The protein encoded by CD40LG is expressed on T cell surfaces and functions as a cytokine ligand for CD40, costimulating T cell proliferation and mediating immunoglobulin class switching in B cells. Mutations cause X-linked hyper-IgM syndrome, characterized by recurrent infections due to impaired antibody class switching. The gene shows X-linked recessive inheritance and is moderately constrained against loss-of-function variants.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene is expressed on the surface of T cells. It regulates B cell function by engaging CD40 on the B cell surface. A defect in this gene results in an inability to undergo immunoglobulin class switch and is associated with hyper-IgM syndrome. [provided by RefSeq, Jul 2008]

GeneReviews ResearchGenerating clinical summary…

LOEUF 0.56

Clinical Summary— CD40LG

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Gene-Disease Validity (ClinGen)

hyper-IgM syndrome type 1 · XLDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.72) — some intolerance to loss-of-function variants.

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ClinVar Variants

108 unique Pathogenic / Likely Pathogenic· 80 VUS of 338 total submissions

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Clinical Trials

2 active or recruiting trials — potential therapeutic options may be available

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GeneReview available — CD40LG

Authoritative clinical overview · Recommended first read

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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.56LOEUF

pLI 0.721

Z-score 2.39

OE 0.12 (0.04–0.56)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.30Z-score

OE missense 0.63 (0.51–0.78)

61 obs / 97.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.12 (0.04–0.56)

0≤0.351.4

Missense OE?0.63 (0.51–0.78)

0≤0.61.4

Synonymous OE?0.79

0≤1.21.6

LoF obs/exp: 1 / 8.5Missense obs/exp: 61 / 97.1Syn Z: 1.03

ClinVar Variant Classifications

338 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic78

Likely Pathogenic30

VUS80

Likely Benign88

Benign30

Conflicting10

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	58	11	9	0	78
Likely Pathogenic	13	14	3	0	30
VUS	2	69	8	1	80
Likely Benign	0	4	40	44	88
Benign	0	10	7	13	30
Conflicting	—				10
Total	73	108	67	58	316

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

View in ClinVar →

96 pathogenic / likely-pathogenic (of 99) ClinVar copy-number / structural variants overlap CD40LG — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →