CD5L

Chr 1

CD5 molecule like

Also known as: AIM, API6, CT-2, PRO229, SP-ALPHA, Spalpha, hAIM

NCBI Gene: 922 ENSG00000073754 UniProt: O43866 OMIM: 602592

The CD5L protein is secreted by macrophages and acts as a key regulator of lipid synthesis, fatty acid metabolism, and inflammatory responses, while also functioning as a pattern recognition receptor in immune defense. Mutations cause a neurodevelopmental disorder with variable features including intellectual disability, developmental delay, and neurological abnormalities. The condition follows autosomal recessive inheritance and this gene shows very low constraint against loss-of-function variants.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to be involved in cellular defense response. Predicted to act upstream of or within positive regulation of complement-dependent cytotoxicity and regulation of complement activation. Located in cell surface. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.67

Clinical Summary— CD5L

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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

44 VUS of 48 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?

1.67LOEUF

pLI 0.000

Z-score -0.75

OE 1.18 (0.85–1.67)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.06Z-score

OE missense 0.99 (0.88–1.11)

200 obs / 202.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?1.18 (0.85–1.67)

0≤0.351.4

Missense OE?0.99 (0.88–1.11)

0≤0.61.4

Synonymous OE?1.08

0≤1.21.6

LoF obs/exp: 23 / 19.4Missense obs/exp: 200 / 202.4Syn Z: -0.54

This gene — mechanism propensity

0.6260th %ile

GOF

0.6834th %ile

LOF

0.2873th %ile

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

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

48 submitted variants in ClinVar

ClinVar

Classification Summary

VUS44

Likely Benign2

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	44	44
Likely Benign	2	2
Benign	0	0
Total	46	46

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

View in ClinVar →

10 pathogenic / likely-pathogenic (of 15) ClinVar copy-number / structural variants overlap CD5L — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →