CD68

Summary

CD68 (CD68 molecule, HGNC:1693) is a protein-coding gene on chromosome 17p13.1, encoding Macrosialin (P34810). Could play a role in phagocytic activities of tissue macrophages, both in intracellular lysosomal metabolism and extracellular cell-cell and cell-pathogen interactions.

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.

Source: NCBI Gene 968 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 82 total
• Druggable target: yes
• MANE Select transcript: NM_001251

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1693
Approved symbol	CD68
Name	CD68 molecule
Location	17p13.1
Locus type	gene with protein product
Status	Approved
Aliases	SCARD1, GP110, DKFZp686M18236, LAMP4
Ensembl gene	ENSG00000129226
Ensembl biotype	protein_coding
OMIM	153634
Entrez	968

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 7 protein_coding

ENST00000250092, ENST00000380498, ENST00000584180, ENST00000584502, ENST00000852832, ENST00000965359, ENST00000965360

RefSeq mRNA: 2 — MANE Select: NM_001251 NM_001040059, NM_001251

CCDS: CCDS11114, CCDS58512

Canonical transcript exons

ENST00000250092 — 6 exons

Exon	Start	End
ENSE00000887319	7579810	7580327
ENSE00001549375	7579638	7579726
ENSE00002705835	7581378	7582111
ENSE00003530242	7580466	7580585
ENSE00003570473	7580711	7580783
ENSE00003629740	7580896	7581066

Expression profiles

Bgee: expression breadth ubiquitous, 141 present calls, max score 99.41.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 455.3460 / max 12060.4954, expressed in 1724 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
159268	446.6296	1718
159271	6.4064	558
159273	1.3219	168
159274	0.3879	143
159275	0.2971	105
159272	0.1609	83
159270	0.1423	83

Top tissues by expression

141 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	99.41	gold quality
leukocyte	CL:0000738	99.41	gold quality
granulocyte	CL:0000094	99.31	gold quality
duodenum	UBERON:0002114	99.08	gold quality
vermiform appendix	UBERON:0001154	99.07	gold quality
stromal cell of endometrium	CL:0002255	98.89	gold quality
gall bladder	UBERON:0002110	98.80	gold quality
placenta	UBERON:0001987	98.77	gold quality
right lung	UBERON:0002167	98.74	gold quality
lymph node	UBERON:0000029	98.60	gold quality
blood	UBERON:0000178	98.38	gold quality
spleen	UBERON:0002106	98.28	gold quality
right coronary artery	UBERON:0001625	97.69	gold quality
upper lobe of left lung	UBERON:0008952	97.65	gold quality
descending thoracic aorta	UBERON:0002345	97.42	gold quality
mucosa of stomach	UBERON:0001199	97.32	gold quality
islet of Langerhans	UBERON:0000006	97.20	gold quality
subcutaneous adipose tissue	UBERON:0002190	96.56	gold quality
small intestine Peyer’s patch	UBERON:0003454	96.29	gold quality
adipose tissue	UBERON:0001013	96.14	gold quality
small intestine	UBERON:0002108	96.14	gold quality
thoracic aorta	UBERON:0001515	95.82	gold quality
left coronary artery	UBERON:0001626	95.78	gold quality
omental fat pad	UBERON:0010414	95.60	gold quality
ascending aorta	UBERON:0001496	95.57	gold quality
bone marrow	UBERON:0002371	95.57	gold quality
right adrenal gland cortex	UBERON:0035827	95.42	gold quality
lung	UBERON:0002048	95.38	gold quality
rectum	UBERON:0001052	95.09	gold quality
right adrenal gland	UBERON:0001233	95.06	gold quality

Single-cell (SCXA)

Detected in 32 experiment(s), a significant marker in 31.

Experiment	Marker?	Max mean expression
E-HCAD-15	yes	2777.92
E-MTAB-7407	yes	2707.65
E-CURD-122	yes	2107.63
E-MTAB-6678	yes	1437.58
E-HCAD-1	yes	1426.81
E-MTAB-10042	yes	1154.57
E-CURD-112	yes	774.60
E-ANND-5	yes	681.04
E-MTAB-8530	yes	590.51
E-HCAD-32	yes	475.81
E-MTAB-6701	yes	97.35
E-HCAD-4	yes	77.05
E-MTAB-8410	yes	62.13
E-GEOD-135922	yes	60.93
E-HCAD-10	yes	60.77

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPA, CREB1, ELF1, ESR2, FLI1, IRF4, IRF8, JUN, JUNB, SPI1, TYROBP

miRNA regulators (miRDB)

20 targeting CD68, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-221-5P	99.86	65.45	1052
HSA-MIR-8073	99.86	65.21	1118
HSA-MIR-3680-3P	99.75	72.51	3095
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-4677-5P	99.70	70.09	1940
HSA-MIR-6739-3P	99.22	68.84	1843
HSA-MIR-1286	99.09	66.23	1046
HSA-MIR-7151-3P	99.04	69.72	2370
HSA-MIR-6506-5P	99.04	65.66	1386
HSA-MIR-619-5P	98.57	64.97	1988
HSA-MIR-5089-5P	98.45	66.06	1388
HSA-MIR-5681A	97.99	67.17	1658
HSA-MIR-6742-3P	97.95	64.50	1490
HSA-MIR-22-5P	97.67	68.92	1355
HSA-MIR-6807-5P	97.51	64.25	1046

Literature-anchored findings (GeneRIF, showing 40)

• CD68 was expressed in beta-cells of NOD mice by 14-17 weeks of age, when a large proportion of these cells were infiltrated with lymphocytes and monocytes. (PMID:12397372)
• CD68 expression is down-regulated in lymphoid cells by combinatorial interactions between PU.1 and IRF-4 (PMID:12676954)
• study expands the immunophenotype of granular cell tumor (S100, CD68, protein gene product 9.5, and inhibin-alpha) regardless of location and supports a neural origin (PMID:15214825)
• The expression of CD68 was statistically significantly higher in the aggressive non hodgkin’ lymphoma than in indolent nHL. (PMID:15638380)
• The specificity of CD68 expression in fibroblasts was verified by RT-PCR which also showed some tumor cell types to express CD68 mRNA. (PMID:16888915)
• A marker that may be used to detect macrophages and in the anatomical plane of the fetomaternal junction. (PMID:17052752)
• human CD68 gene expression is associated with changes in Pol II phosphorylation and short-range intrachromosomal gene looping (PMID:17583472)
• High-level expression of CD68 is associated with leiomyosarcomas (PMID:18316565)
• These results suggest that MMP-3 and CD68 cells may play an important role in the pathogenesis of synovial inflammation in ankylosing spondylitis. (PMID:19165649)
• Expression of t-PA, PAI-1, TF, TFPI, TM, CD68 and VE-cadherin were significantly increased in the early symptomatic group, but the level of gene expression in the late symptomatic group was indistinguishable from the asymptomatic group. (PMID:19356953)
• High CD68 and kallikrein 6 expression is associated with glioma progression. (PMID:19661345)
• Significant co-localization of CD36 receptor with cells of the macrophage lineage, such as CD68 positive cells. (PMID:20333725)
• Treatment with etanercept may be involved in vascular and cell proliferations with inhibition of the expression of CD68 and MMP-3 in synovium of rheumatoid arthritis patients. (PMID:20374310)
• Fibrolamellar carcinomas are positive for CD68. (PMID:21113139)
• Data show that the number of TNF-alpha and CD68 positive cells in HIZ was significantly higher than that in the annulus fibrosus around HIZ and in the control. (PMID:21192298)
• Increased numbers of CD68-positive tumor macrophages indicate an adverse overall outcome in Hodgkin lymphoma. (PMID:21266828)
• Results show that levels of CD3epsilon, CD25, CD68, and ICAM-1 mRNA in BCC biopsies may predict risk for new basal cell carcinomas. (PMID:21980389)
• In the intratumoral and peritumoral areas, the expression of CD1a, tryptase, and CD68 was significantly higher in papillary thyroid carcinoma than in thyroid adenomas. (PMID:22007938)
• CD68 and CD163 are prognostic factors for Korean patients with Hodgkin lymphoma (PMID:22044760)
• Statins promote the beneficial remodeling of plaques in diseased mouse arteries through the stimulation of the CCR7 / CD68 emigration pathway in macrophages (PMID:22163030)
• CD163 staining is lower than CD68, with less non-specific staining of background inflammatory cells and Hodgkin cells, therefore is a better marker for Hodgkin lymphoma associated macrophages. (PMID:22289504)
• elderly subjects had twofold higher CD68 and CD206 gene expression (both P < 0.002) than young participants. In both studies, CD68(+) muscle macrophages were not associated with BMI. (PMID:22314623)
• CD68 may have a role in atherosclerotic plaque (PMID:22395501)
• the marker CD68 might accurately predict early outcome of de novo cHL and could be used in combination with c-kit and TiA1 staining. (PMID:22667341)
• Increased CD68 expression was associated with Hodgkin lymphoma (PMID:22948049)
• CSF1R and cd68 gene expression is an independent predictor for progression-free survival of Hodgkin lymphoma patients. (PMID:22955918)
• After bed rest, CD68 expression was increased in LBW (P=0.03) but not in NBW individuals. (PMID:22968485)
• Suggest that the proteins or mRNAs expressed by the proinflammatory CD68(+)MR(-) macrophages may contribute to abdominal aortic aneurysm pathology. (PMID:23241402)
• The CD68-positive cells (those that have not yet developed into foam cells) present in the intima of saphenous vein grafts might serve as a very early marker of graft occlusion. (PMID:23275124)
• Multivariate analysis identified the density of CD163-positive cells as well as the ratio of CD163/CD68 expression as negative predictors for survival of epithelial ovarian cancer patients. (PMID:23289476)
• Follicular lymphoma patients with PSMB1 P11A (G allele) and low CD68 expression have significantly longer progression free survival with bortezomib-rituximab versus rituximab. (PMID:23549871)
• CD68 has a role in poor recurrence-free survival of hepatocellular carcinoma, but CD163 is more related to active hepatitis (PMID:23555776)
• Rhinovirus colocalizes with CD68- and CD11b-positive macrophages following experimental infection in humans. (PMID:23727038)
• The MRC1/CD68 ratio is positively associated with adipose tissue lipogenesis and with muscle mitochondrial gene expression in humans. (PMID:23951013)
• CD68 tumor-associated macrophage marker is not prognostic of clinical outcome in classical Hodgkin lymphoma. (PMID:24067108)
• the distribution of CD68-positive cells during normal brain development may not reflect a supportive role of these microglia in axonogenesis of midterm human fetuses. (PMID:24459672)
• Data indicate the prognostic value of CD68 antigen in Hodgkin lymphoma (HL). (PMID:24766492)
• Data indicate that the high CD68/CD3 ratio identifies a bad prognosis group among muscle-invasive urothelial carcinoma (UC). (PMID:24794251)
• The human CD68 promoter drives green fluorescent protein expression in all CD115(+) monocytes of adult blood, spleen, and bone marrow. (PMID:25030063)
• Microenvironment CD20 + cells seem to play a favorable prognostic role in classical Hodgkin Lymphoma. Depletion of CD20 + cells together with an increase of TAMs identifies a group of patients with high-risk disease. (PMID:25098425)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	cd68	ENSDARG00000055504
rattus_norvegicus	Cd68	ENSRNOG00000037563
drosophila_melanogaster	CG43668	FBGN0263743

Paralogs (3): LAMP2 (ENSG00000005893), LAMP5 (ENSG00000125869), LAMP1 (ENSG00000185896)

Protein

Protein identifiers

Macrosialin — P34810 (reviewed: P34810)

Alternative names: Gp110

All UniProt accessions (3): P34810, J3KRX0, J3KT24

UniProt curated annotations — full annotation on UniProt →

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.

Subcellular location. Cell membrane Endosome membrane. Lysosome membrane.

Tissue specificity. Highly expressed by blood monocytes and tissue macrophages. Also expressed in lymphocytes, fibroblasts and endothelial cells. Expressed in many tumor cell lines which could allow them to attach to selectins on vascular endothelium, facilitating their dissemination to secondary sites.

Post-translational modifications. N- and O-glycosylated.

Similarity. Belongs to the LAMP family.

Isoforms (3)

UniProt ID	Names	Canonical?
P34810-1	Long, CD68.1	yes
P34810-2	Short, CD68.2
P34810-3	3

RefSeq proteins (2): NP_001035148, NP_001242* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002000	Lysosome-assoc_membr_glycop	Family
IPR018134	LAMP_CS	Conserved_site
IPR048528	Lamp2-like_luminal	Domain

Pfam: PF01299

UniProt features (35 total): glycosylation site 9, compositionally biased region 7, sequence variant 4, region of interest 3, topological domain 2, disulfide bond 2, splice variant 2, repeat 2, signal peptide 1, chain 1, transmembrane region 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P34810-F1	74.23	0.50

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Disulfide bonds (2): 169–207, 277–314

Glycosylation sites (9): 88, 96, 118, 126, 164, 199, 246, 261, 279

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-6798695	Neutrophil degranulation
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System

MSigDB gene sets: 297 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_UP, GOBP_CELLULAR_RESPONSE_TO_LIPOPROTEIN_PARTICLE_STIMULUS, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, REACTOME_INNATE_IMMUNE_SYSTEM, SWEET_KRAS_ONCOGENIC_SIGNATURE, GOBP_INFLAMMATORY_RESPONSE, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOCC_VACUOLAR_MEMBRANE, GOCC_SECRETORY_GRANULE, GOBP_CELLULAR_RESPONSE_TO_BIOTIC_STIMULUS, STEARMAN_LUNG_CANCER_EARLY_VS_LATE_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, KEGG_LYSOSOME, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE

GO Biological Process (8): inflammatory response to antigenic stimulus (GO:0002437), negative regulation of dendritic cell antigen processing and presentation (GO:0002605), cellular response to nutrient levels (GO:0031669), autocrine signaling (GO:0035425), response to ethanol (GO:0045471), cellular response to lipopolysaccharide (GO:0071222), establishment of protein localization to organelle (GO:0072594), cellular response to oxidised low-density lipoprotein particle stimulus (GO:0140052)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (10): lysosome (GO:0005764), lysosomal membrane (GO:0005765), plasma membrane (GO:0005886), membrane (GO:0016020), late endosome membrane (GO:0031902), azurophil granule membrane (GO:0035577), cytoplasm (GO:0005737), endosome (GO:0005768), endosome membrane (GO:0010008), cytoplasmic vesicle (GO:0031410)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Innate Immune System	1
Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
inflammatory response	1
immune response	1
dendritic cell antigen processing and presentation	1
negative regulation of antigen processing and presentation	1
regulation of dendritic cell antigen processing and presentation	1
response to nutrient levels	1
cellular response to stimulus	1
cell-cell signaling	1
response to alcohol	1
response to lipopolysaccharide	1
cellular response to molecule of bacterial origin	1
cellular response to lipid	1
cellular response to oxygen-containing compound	1
establishment of protein localization	1
cellular response to low-density lipoprotein particle stimulus	1
binding	1
lytic vacuole	1
lysosome	1
lytic vacuole membrane	1
membrane	1
cell periphery	1
late endosome	1
endosome membrane	1
lysosomal membrane	1
secretory granule membrane	1
azurophil granule	1
intracellular anatomical structure	1
endomembrane system	1
cytoplasmic vesicle	1
endosome	1
cytoplasmic vesicle membrane	1
bounding membrane of organelle	1
cytoplasm	1
intracellular vesicle	1

Protein interactions and networks

STRING

4044 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CD68	CD1A	P06126	903
CD68	CD1E	P15812	903
CD68	CD163	Q86VB7	903
CD68	CD1B	P29016	898
CD68	CD4	P01730	889
CD68	CD8A	P01732	888
CD68	CD1C	P29017	883
CD68	ITGAM	P11215	872
CD68	PTPRC	P08575	871
CD68	CD1D	P15813	871
CD68	MRC1	P22897	870
CD68	GAPDH	P00354	859
CD68	AIF1	P55008	852
CD68	FOXP3	Q9BZS1	851
CD68	TNF	P01375	844

IntAct

43 interactions, top by confidence:

A	B	Type	Score
CD68	TTI1	psi-mi:“MI:0914”(association)	0.640
CD68	LGALS1	psi-mi:“MI:0914”(association)	0.640
CD68	TOMM6	psi-mi:“MI:0915”(physical association)	0.560
CD68	PLEKHB2	psi-mi:“MI:0915”(physical association)	0.560
CD68	SGTB	psi-mi:“MI:0915”(physical association)	0.560
CD68	CLEC2D	psi-mi:“MI:0915”(physical association)	0.560
CD68	TMEM179B	psi-mi:“MI:0915”(physical association)	0.560
CD68	AQP6	psi-mi:“MI:0915”(physical association)	0.560
MUC1	CD68	psi-mi:“MI:0915”(physical association)	0.560
CD68	MAL2	psi-mi:“MI:0915”(physical association)	0.560
CD68	KTN1	psi-mi:“MI:0915”(physical association)	0.560
AGR2	CD68	psi-mi:“MI:0915”(physical association)	0.560
CD68	TNPO2	psi-mi:“MI:0914”(association)	0.530
CD68	RALGDS	psi-mi:“MI:0915”(physical association)	0.370
CD68	CFTR	psi-mi:“MI:0915”(physical association)	0.370
CFTR	CD68	psi-mi:“MI:0915”(physical association)	0.370
	CD68	psi-mi:“MI:0915”(physical association)	0.370
CD68	TCAF2	psi-mi:“MI:0914”(association)	0.350
CD68	TOMM6	psi-mi:“MI:0915”(physical association)	0.000
CD68	PLEKHB2	psi-mi:“MI:0915”(physical association)	0.000
CD68	SGTB	psi-mi:“MI:0915”(physical association)	0.000
CD68	CLEC2D	psi-mi:“MI:0915”(physical association)	0.000
CD68	TMEM179B	psi-mi:“MI:0915”(physical association)	0.000
TOMM6	CD68	psi-mi:“MI:0915”(physical association)	0.000
CD68	AQP6	psi-mi:“MI:0915”(physical association)	0.000
CD68	MUC1	psi-mi:“MI:0915”(physical association)	0.000
MAL2	CD68	psi-mi:“MI:0915”(physical association)	0.000
KTN1	CD68	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (50): RARS (Affinity Capture-MS), BZW2 (Affinity Capture-MS), KIF14 (Affinity Capture-MS), TNPO2 (Affinity Capture-MS), SAAL1 (Affinity Capture-MS), TTI1 (Affinity Capture-MS), COG6 (Affinity Capture-MS), GRN (Affinity Capture-MS), LGALS1 (Affinity Capture-MS), EIF2B5 (Affinity Capture-MS), LGALS3 (Affinity Capture-MS), TUBGCP4 (Affinity Capture-MS), MTX3 (Affinity Capture-MS), GRN (Affinity Capture-MS), KIF14 (Affinity Capture-MS)

ESM2 similar proteins: A1L314, A2VE33, A4FV27, A4IGL3, A8WFR0, A8WH34, O09126, O54715, O60486, O77726, P05300, P13473, P17046, P17047, P31996, P34810, P37176, P40682, P42099, P47983, P47984, P48829, P48834, P49130, Q00193, Q05996, Q12836, Q2KJC3, Q2M385, Q5PPI4, Q5R5V2, Q5RBP9, Q63961, Q6AX53, Q6UX82, Q8BG22, Q8K135, Q8MJJ2, Q90617, Q92854

Diamond homologs: P05300, P11279, P11438, P13473, P14562, P17046, P17047, P34810, P49129, P49130, Q05204, Q90617, P31996

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
ELF1	“up-regulates quantity by expression”	CD68	“transcriptional regulation”
IRF4	“down-regulates quantity by repression”	CD68	“transcriptional regulation”
IRF8	“down-regulates quantity by repression”	CD68	“transcriptional regulation”
SPI1	“down-regulates quantity by repression”	CD68	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

82 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	60
Likely benign	6
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

628 predictions. Top by Δscore:

Variant	Effect	Δscore
17:7580779:AGCAC:A	donor_gain	1.0000
17:7580780:GCAC:G	donor_gain	1.0000
17:7580780:GCACG:G	donor_gain	1.0000
17:7580781:CAC:C	donor_gain	1.0000
17:7580782:AC:A	donor_gain	1.0000
17:7580782:ACGT:A	donor_loss	1.0000
17:7580784:G:GG	donor_gain	1.0000
17:7580785:TAAG:T	donor_loss	1.0000
17:7580788:G:GG	donor_gain	1.0000
17:7580894:A:AG	acceptor_gain	1.0000
17:7580895:G:GG	acceptor_gain	1.0000
17:7580895:GA:G	acceptor_gain	1.0000
17:7580324:A:T	donor_gain	0.9900
17:7580324:AGAG:A	donor_loss	0.9900
17:7580325:GAG:G	donor_gain	0.9900
17:7580326:AG:A	donor_loss	0.9900
17:7580327:GG:G	donor_loss	0.9900
17:7580328:GTA:G	donor_loss	0.9900
17:7580329:T:C	donor_loss	0.9900
17:7580334:C:G	donor_gain	0.9900
17:7580709:A:AG	acceptor_gain	0.9900
17:7580709:AG:A	acceptor_gain	0.9900
17:7580710:G:A	acceptor_loss	0.9900
17:7580710:G:GA	acceptor_gain	0.9900
17:7580710:GG:G	acceptor_gain	0.9900
17:7580710:GGA:G	acceptor_gain	0.9900
17:7580751:TG:T	donor_gain	0.9900
17:7580752:GG:G	donor_gain	0.9900
17:7580787:A:AG	donor_gain	0.9900
17:7580894:A:G	acceptor_loss	0.9900

AlphaMissense

2289 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:7580280:G:C	A174P	0.988
17:7580275:T:C	L172P	0.985
17:7580769:T:G	F249C	0.981
17:7580578:T:C	F227S	0.979
17:7580550:T:C	F218L	0.977
17:7580552:C:A	F218L	0.977
17:7580552:C:G	F218L	0.977
17:7580566:T:C	L223P	0.977
17:7580577:T:C	F227L	0.973
17:7580579:C:A	F227L	0.973
17:7580579:C:G	F227L	0.973
17:7580578:T:G	F227C	0.971
17:7581010:T:C	L292P	0.968
17:7580287:T:C	I176T	0.967
17:7580551:T:G	F218C	0.966
17:7580768:T:C	F249L	0.964
17:7580770:C:A	F249L	0.964
17:7580770:C:G	F249L	0.964
17:7580964:T:A	C277S	0.955
17:7580965:G:C	C277S	0.955
17:7580275:T:A	L172H	0.954
17:7580966:C:G	C277W	0.954
17:7580958:T:C	F275L	0.953
17:7580960:C:A	F275L	0.953
17:7580960:C:G	F275L	0.953
17:7579866:T:C	F36L	0.948
17:7579868:C:A	F36L	0.948
17:7579868:C:G	F36L	0.948
17:7580545:T:A	L216H	0.948
17:7580904:T:C	F257L	0.948

dbSNP variants (sampled 300 via entrez): RS1000205759 (17:7578715 A>C,G,T), RS1001624068 (17:7581246 T>C), RS1002739188 (17:7579174 A>G), RS1003335256 (17:7580323 G>A), RS1003391749 (17:7581638 A>C), RS1003599612 (17:7578763 C>T), RS1005323990 (17:7581825 G>A,C), RS1005724868 (17:7579593 C>G,T), RS1006130804 (17:7578950 A>G), RS1006462052 (17:7582294 T>C), RS1006802766 (17:7581321 C>A,G,T), RS1007434280 (17:7579195 C>G,T), RS1009144914 (17:7582580 T>C), RS1009330125 (17:7581873 C>A,T), RS1009692253 (17:7579509 A>G)

Disease associations

OMIM: gene MIM:153634 | disease phenotypes: MIM:612555

GenCC curated gene-disease

Mondo (1): breast-ovarian cancer, familial, susceptibility to, 2 (MONDO:0012933)

Orphanet (1): Hereditary breast and/or ovarian cancer syndrome (Orphanet:145)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST003264_225	Post bronchodilator FEV1/FVC ratio	4.000000e-06
GCST006288_282	Heel bone mineral density	8.000000e-10
GCST006288_350	Heel bone mineral density	5.000000e-08
GCST008568_7	IgA levels	1.000000e-06
GCST009602_83	Metabolic syndrome	3.000000e-08
GCST010002_119	Refractive error	3.000000e-22
GCST010703_158	Brain morphology (MOSTest)	3.000000e-09

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004713	FEV/FVC ratio
EFO:0009270	heel bone mineral density
EFO:0000195	metabolic syndrome
EFO:0004346	neuroimaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066517 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs9901675	CD68	3	0.00	1	methylphenidate
rs9901673	CD68		0.00	0

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.32	Kd	47.61	nM	CHEMBL5653589
7.32	ED50	47.61	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148030: Binding affinity to human CD68 incubated for 45 mins by Kinobead based pull down assay	kd	0.0476	uM

CTD chemical–gene interactions

80 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	increases abundance, decreases expression, increases expression, affects expression	4
sodium arsenite	increases abundance, increases expression, affects cotreatment	3
Tetradecanoylphorbol Acetate	increases expression	3
Cyclosporine	increases expression, decreases expression	3
Arsenic	increases abundance, increases expression, affects cotreatment	2
Lipopolysaccharides	affects cotreatment, affects expression, decreases reaction, increases expression	2
Methotrexate	decreases expression	2
Smoke	decreases expression, increases abundance, increases expression	2
Tretinoin	affects cotreatment, increases expression	2
Cadmium Chloride	decreases reaction, increases abundance, increases palmitoylation, increases expression	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
aristolochic acid I	increases expression	1
alternariol	increases expression	1
propionaldehyde	increases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
bisphenol A	affects expression	1
2,2’-methylenebis(4-methyl-6-tert-butylphenol)	affects response to substance, affects expression	1
sodium arsenate	increases abundance, increases expression	1
hydroxyhydroquinone	increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
beta-lapachone	increases expression	1
sulforaphane	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
butyraldehyde	increases expression	1
2-bromopalmitate	decreases reaction, increases abundance, increases palmitoylation	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
potassium chromate(VI)	increases expression	1
monobutyl phthalate	increases expression	1
ferrous chloride	increases expression	1
nickel sulfate	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651072	Binding	Binding affinity to human CD68 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.