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 regulation of complement activation. Predicted to act upstream of or within positive regulation of complement-dependent cytotoxicity. Located in cell surface. [provided by Alliance of Genome Resources, Jun 2026]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.67

LOEUF

Multiple*

Mechanism· predicted

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

Background carrier burden — how many people carry a rare variant somewhere in CD5L?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 160

472 rare PASS variants

Rare truncating (LoF)

1 in 2,100

72 rare PASS variants

Rare synonymous (reference)

1 in 300

204 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CD5L. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 200	1 in 2,600
South Asian	~43k	1 in 110	1 in 580
Remaining (unassigned)	~30k	1 in 160	1 in 1,300
European (Finnish)	~27k	1 in 1,400	1 in 950
Admixed American	~22k	1 in 180	1 in 1,200
African / African American	~21k	1 in 120	1 in 930
East Asian	~20k	1 in 210	1 in 1,400
Ashkenazi Jewish	~13k	1 in 330	1 in 1,200
Middle Eastern	~2,884	1 in 120	≈ 1 in 720

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 5 of 6 coding exons well covered in gnomAD exomes; exon 6 marginal. Genomes: all 6.? see exons ↓