CD68

protein-coding

CD68 molecule, the group of CD molecules|Scavenger receptors|Lysosome associated membrane proteins

Gene summary

This gene encodes a 110-kD transmembrane glycoprotein that is highly expressed by human monocytes and tissue macrophages. It is a member of the lysosomal/endosomal-associated membrane glycoprotein (LAMP) family. The protein primarily localizes to lysosomes and endosomes with a smaller fraction circulating to the cell surface. It is a type I integral membrane protein with a heavily glycosylated extracellular domain and binds to tissue- and organ-specific lectins or selectins. The protein is also a member of the scavenger receptor family. Scavenger receptors typically function to clear cellular debris, promote phagocytosis, and mediate the recruitment and activation of macrophages. Alternative splicing results in multiple transcripts encoding different isoforms. [provided by RefSeq, Jul 2008]

MANE transcript

NM_001251.3

Inheritance

—

ClinVar variants

U:67B:9

Top phenotype

Breast-ovarian cancer, familial, susceptibility to, 2

gnomAD constraint

pLI —, LoF o/e 0.72

Max pathogenic AF

—

Genomic locus

chr17:7,579,491-7,582,111

External References & Databases

Ensembl (ENSG00000129226)

Transcript & Mutation Effects

hg38 • Region Span ~2.6 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 CD68 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 62

not providedTotal: 7

Breast-ovarian cancer, familial, susceptibility to, 2Total: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001251.3. 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.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				3 clinvar	2 clinvar	5
missense			61 clinvar	2 clinvar	2 clinvar	65
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			6 clinvar			6
Total	0	0	67	5	4	76

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 19 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001251.3	RefSeq	NP_001242.2	6	MANE Select
ENST00000250092.11	Ensembl	ENSP00000250092.6	6	MANE Select
NM_001040059.2	RefSeq	NP_001035148.1	6	Standard
ENST00000380498.10	Ensembl	ENSP00000369867.6	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Lysosome - Homo sapiens (human)
Macrophage markers
Macrophage markers
Neutrophil degranulation
Innate Immune System

Biological Process

neutrophil degranulation

Cellular Component

plasma membrane
endosome membrane
membrane
integral component of membrane
azurophil granule membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000250092
Coding exons: 6
Length: 2645
Individuals with no LoFs: 125707
Homozygous LoFs: 0
Heterozygous LoFs: 40
Defined: 125747
p: 0.000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.365	187	202	0.928	0.0000106	2276
Missense (PolyPhen)		53	71.544	0.7408		872
Synonymous	-0.633	92	84.6	1.09	0.00000489	777
Loss of Function	1.01	11	15.3	0.721	9.82e-7	140

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00037	0.00037	rare
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00038	0.00038	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00016	0.00016	rare
South Asian	0.00016	0.00016	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Could play a role in phagocytic activities of tissue macrophages, both in intracellular lysosomal metabolism and extracellular cell-cell and cell-pathogen interactions. Binds to tissue- and organ-specific lectins or selectins, allowing homing of macrophage subsets to particular sites. Rapid recirculation of CD68 from endosomes and lysosomes to the plasma membrane may allow macrophages to crawl over selectin-bearing substrates or other cells.;

Recessive Scores

pRec: 0.807

Intolerance Scores

LoFtool: 0.792
RVIS EVS: 0.46
RVIS percentile EVS: 78.59

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.799

Gene Damage Prediction

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