CD5L

protein-coding

CD5 molecule like, the group of Scavenger receptor cysteine rich domain containing

Gene summary

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]

Previous symbols:
  • API6

MANE transcript

NM_005894.3

Inheritance

—

ClinVar variants

U:46B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 1.18

Max pathogenic AF

—

Genomic locus

chr1:157,830,911-157,898,256

External References & Databases

Transcript & Mutation Effects

hg38 • Region Span ~67.3 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CD5L variants in ClinVar

1 Conditions Cataloged
not specifiedTotal: 46

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005894.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
0
missense
44
clinvar
2
clinvar
46
nonsense
2
clinvar
2
start loss
0
frameshift
0
splice donor/acceptor (+/-2bp)
0
Total00462048
Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 10 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_005894.3RefSeqNP_005885.16MANE Select
ENST00000368174.5EnsemblENSP00000357156.46MANE Select
NM_001347698.2RefSeqNP_001334627.16Standard
ENST00000982779.1EnsemblENSP00000652596.14Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

  • immune system process
  • receptor-mediated endocytosis
  • apoptotic process
  • inflammatory response
  • cellular defense response

Molecular Function

  • scavenger receptor activity

Cellular Component

  • extracellular region
  • extracellular space
  • cytoplasm
  • membrane
  • blood microparticle

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000368174
Coding exons
6
Length
67343
Individuals with no LoFs
125122
Homozygous LoFs
3
Heterozygous LoFs
623
Defined
125748
p
0.00249
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense0.05952002020.9880.00001202234
Missense (PolyPhen)7674.221.024853
Synonymous-0.5448780.81.080.00000475687
Loss of Function-0.7522319.41.180.00000108208

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000800.00080rare
Latino/Admixed American0.00150.0015notable
Ashkenazi Jewish0.000200.00020rare
East Asian0.000440.00044rare
Finnish0.000320.00032rare
European (Non-Finnish)0.00290.0029notable
South Asian0.00680.0067notable
Other0.00180.0018notable

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Secreted protein that acts as a key regulator of lipid synthesis: mainly expressed by macrophages in lymphoid and inflammed tissues and regulates mechanisms in inflammatory responses, such as infection or atherosclerosis. Able to inhibit lipid droplet size in adipocytes. Following incorporation into mature adipocytes via CD36-mediated endocytosis, associates with cytosolic FASN, inhibiting fatty acid synthase activity and leading to lipolysis, the degradation of triacylglycerols into glycerol and free fatty acids (FFA). CD5L-induced lipolysis occurs with progression of obesity: participates in obesity-associated inflammation following recruitment of inflammatory macrophages into adipose tissues, a cause of insulin resistance and obesity- related metabolic disease. Regulation of intracellular lipids mediated by CD5L has a direct effect on transcription regulation mediated by nuclear receptors ROR-gamma (RORC). Acts as a key regulator of metabolic switch in T-helper Th17 cells. Regulates the expression of pro-inflammatory genes in Th17 cells by altering the lipid content and limiting synthesis of cholesterol ligand of RORC, the master transcription factor of Th17-cell differentiation. CD5L is mainly present in non-pathogenic Th17 cells, where it decreases the content of polyunsaturated fatty acyls (PUFA), affecting two metabolic proteins MSMO1 and CYP51A1, which synthesize ligands of RORC, limiting RORC activity and expression of pro-inflammatory genes. Participates in obesity- associated autoimmunity via its association with IgM, interfering with the binding of IgM to Fcalpha/mu receptor and enhancing the development of long-lived plasma cells that produce high-affinity IgG autoantibodies (By similarity). Also acts as an inhibitor of apoptosis in macrophages: promotes macrophage survival from the apoptotic effects of oxidized lipids in case of atherosclerosis (PubMed:24295828). Involved in early response to microbial infection against various pathogens by acting as a pattern recognition receptor and by promoting autophagy (PubMed:16030018, PubMed:24223991, PubMed:24583716, PubMed:25713983). {ECO:0000250|UniProtKB:Q9QWK4, ECO:0000269|PubMed:16030018, ECO:0000269|PubMed:24223991, ECO:0000269|PubMed:24295828, ECO:0000269|PubMed:24583716, ECO:0000269|PubMed:25713983}.;

Recessive Scores

pRec
0.253

Intolerance Scores

LoFtool
0.624
RVIS EVS
0.33
RVIS percentile EVS
73.41

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
N
Indispensability score
0.0983

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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