CD68

Chr 17

CD68 molecule

Also known as: GP110, LAMP4, SCARD1

NCBI Gene: 968 ENSG00000129226 UniProt: P34810 OMIM: 153634

This gene encodes a transmembrane glycoprotein that functions as a scavenger receptor on macrophages, mediating phagocytosis, lysosomal metabolism, and macrophage homing to specific tissues through binding to lectins and selectins. The gene is not highly constrained against loss-of-function variants and has not been established as a cause of Mendelian disease. CD68 serves primarily as a macrophage marker in clinical and research settings.

OMIM ResearchSummary from RefSeq, UniProt

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]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.19

Clinical Summary— CD68

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

60 VUS of 82 total submissions

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Clinical Trials

10 active or recruiting trials — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.19LOEUF

pLI 0.000

Z-score 1.01

OE 0.72 (0.45–1.19)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.37Z-score

OE missense 0.93 (0.82–1.05)

187 obs / 201.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.72 (0.45–1.19)

0≤0.351.4

Missense OE?0.93 (0.82–1.05)

0≤0.61.4

Synonymous OE?1.09

0≤1.21.6

LoF obs/exp: 11 / 15.3Missense obs/exp: 187 / 201.6Syn Z: -0.63

This gene — mechanism propensity

0.7132th %ile

GOF

0.6835th %ile

LOF

0.2969th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median

GOFprediction above median

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

82 submitted variants in ClinVar

ClinVar

Classification Summary

VUS60

Likely Benign6

Benign4

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	60	0	0	60
Likely Benign	2	1	3	6
Benign	2	0	2	4
Total	64	1	5	70

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

20 pathogenic / likely-pathogenic (of 30) ClinVar copy-number / structural variants overlap CD68 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →