CD163
Chr 12CD163 molecule
Also known as: M130, MM130, SCARI1
The CD163 protein functions as an acute phase-regulated receptor on macrophages that clears hemoglobin/haptoglobin complexes through endocytosis, protecting tissues from free hemoglobin-mediated oxidative damage and facilitating iron recycling. Mutations cause autosomal recessive macrophage activation syndrome and hemophagocytic lymphohistiocytosis, typically presenting in early childhood with severe inflammatory episodes. The gene is highly constrained against loss-of-function variants (LOEUF 0.44), indicating intolerance to protein-disrupting mutations.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Moderately missense-constrained (top ~2.5%)
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.
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
195 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 43 | 0 | 43 |
Likely Pathogenic | 0 | 0 | 2 | 0 | 2 |
VUS | 0 | 104 | 9 | 1 | 114 |
Likely Benign | 0 | 7 | 0 | 2 | 9 |
Benign | 0 | 4 | 1 | 5 | 10 |
| Total | 0 | 115 | 55 | 8 | 178 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
CD163 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Time-restricted Eating Versus Daily Continuous Calorie Restriction on Body Weight and Colorectal Cancer Risk Markers
RECRUITINGA Study of Adipose Tissue in Adaptive Responses to Exercise
ACTIVE NOT RECRUITINGDapagliflozin on Renal Morphology and Renal Perfusion in Patients One Year After Kidney Transplantation
RECRUITINGMaternal Probiotic Intervention to Improve Gut Health-Trial II-Pakistan
RECRUITINGThe Microbial Impact on Intestinal Fibrosis and the Associated Immune Microenvironment in Crohn's Disease
NOT YET RECRUITINGMaternal Probiotic Intervention to Improve Gut Health - Trial II - Bangladesh
ENROLLING BY INVITATIONEGR2 and NLRP3 Pathways in Obstructive Sleep Apnea-Related Cognitive and Mood Disorders
RECRUITINGEarly Life Malnutrition, Environmental Enteric Dysfunction and Microbiome Trajectories
RECRUITINGThe BEGIN Study Bifidobacterium Infantis to Newborns: Effects of Modulating the Gut Microbial Composition on Growth, Immune Function and Inflammatory Conditions - a Randomized Placebo-controlled Double-blinded Intervention Trial
RECRUITINGPrediction of Malignant Transformation of Oral Leukoplakia Using a MAGE-A-based Immunoscore
RECRUITINGMaternal Probiotic Intervention to Improve Gut Health - Trial II - Burkina Faso (MPIGH-II)
RECRUITINGResidual Disease MEMory in PSOriasis Skin During EnstiLAR® and Narrow-band Ultraviolet B Therapy: The MEMPSOLAR Study
ACTIVE NOT RECRUITINGExternal Resources
Links to major genomics databases and tools