CD163

protein-coding

CD163 molecule, the group of CD molecules|Scavenger receptor cysteine rich domain containing|Scavenger receptors

Gene summary

The protein encoded by this gene is a member of the scavenger receptor cysteine-rich (SRCR) superfamily, and is exclusively expressed in monocytes and macrophages. It functions as an acute phase-regulated receptor involved in the clearance and endocytosis of hemoglobin/haptoglobin complexes by macrophages, and may thereby protect tissues from free hemoglobin-mediated oxidative damage. This protein may also function as an innate immune sensor for bacteria and inducer of local inflammation. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Aug 2011]

MANE transcript

NM_203416.4

Inheritance

—

ClinVar variants

U:111B:15

Top phenotype

Lung adenocarcinoma

gnomAD constraint

pLI —, LoF o/e 0.3

Max pathogenic AF

—

Genomic locus

chr12:7,470,811-7,503,893

External References & Databases

Ensembl (ENSG00000177575)

Transcript & Mutation Effects

hg38 • Region Span ~33.1 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 CD163 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 112

not providedTotal: 11

Lung adenocarcinomaTotal: 2

Squamous cell carcinomaTotal: 1

Multisystem inflammatory syndrome in childrenTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_203416.4. 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.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			3 clinvar	2 clinvar	5 clinvar	10
missense			105 clinvar	6 clinvar	2 clinvar	113
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	111	8	7	126

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 45 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_203416.4	RefSeq	NP_981961.2	16	MANE Select
ENST00000432237.3	Ensembl	ENSP00000403885.2	16	MANE Select
NM_001370145.1	RefSeq	NP_001357074.1	16	Standard
NM_001370146.1	RefSeq	NP_001357075.1	15	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Macrophage markers
Protein alkylation leading to liver fibrosis
Macrophage markers
TWEAK
Vesicle-mediated transport

Biological Process

receptor-mediated endocytosis
acute-phase response

Molecular Function

scavenger receptor activity
protein binding

Cellular Component

extracellular region
plasma membrane
integral component of plasma membrane
external side of plasma membrane
endocytic vesicle membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000359156
Coding exons: 16
Length: 33081
Individuals with no LoFs: 125699
Homozygous LoFs: 0
Heterozygous LoFs: 44
Defined: 125743
p: 0.000175

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.51	455	633	0.719	0.0000329	7537
Missense (PolyPhen)		137	251.76	0.54417		3081
Synonymous	0.335	221	227	0.972	0.0000123	2227
Loss of Function	4.95	17	57.6	0.295	0.00000262	696

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.00038	0.00029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00021	0.00021	rare
South Asian	0.00020	0.00020	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Acute phase-regulated receptor involved in clearance and endocytosis of hemoglobin/haptoglobin complexes by macrophages and may thereby protect tissues from free hemoglobin-mediated oxidative damage. May play a role in the uptake and recycling of iron, via endocytosis of hemoglobin/haptoglobin and subsequent breakdown of heme. Binds hemoglobin/haptoglobin complexes in a calcium-dependent and pH-dependent manner. Exhibits a higher affinity for complexes of hemoglobin and multimeric haptoglobin of HP*1F phenotype than for complexes of hemoglobin and dimeric haptoglobin of HP*1S phenotype. Induces a cascade of intracellular signals that involves tyrosine kinase-dependent calcium mobilization, inositol triphosphate production and secretion of IL6 and CSF1. Isoform 3 exhibits the higher capacity for ligand endocytosis and the more pronounced surface expression when expressed in cells.;

Recessive Scores

pRec: 0.234

Intolerance Scores

RVIS EVS: -0.11
RVIS percentile EVS: 45.61

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.131

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium