ACKR1

Summary

ACKR1 (atypical chemokine receptor 1 (Duffy blood group), HGNC:4035) is a protein-coding gene on chromosome 1q23.2, encoding Atypical chemokine receptor 1 (Q16570). Atypical chemokine receptor that controls chemokine levels and localization via high-affinity chemokine binding that is uncoupled from classic ligand-driven signal transduction cascades, resulting instead in chemokine sequestration, degradation, or transcytosis.

The protein encoded by this gene is a glycosylated membrane protein and a non-specific receptor for several chemokines. The encoded protein is the receptor for the human malarial parasites Plasmodium vivax and Plasmodium knowlesi. Polymorphisms in this gene are the basis of the Duffy blood group system. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 2532 — RefSeq curated summary.

At a glance

• GWAS associations: 74
• Clinical variants (ClinVar): 62 total — 4 pathogenic, 1 likely-pathogenic
• Druggable target: yes
• MANE Select transcript: NM_002036

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4035
Approved symbol	ACKR1
Name	atypical chemokine receptor 1 (Duffy blood group)
Location	1q23.2
Locus type	gene with protein product
Status	Approved
Aliases	CCBP1, GPD, Dfy, CD234
Ensembl gene	ENSG00000213088
Ensembl biotype	protein_coding
OMIM	613665
Entrez	2532

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 7 protein_coding, 1 retained_intron

ENST00000368121, ENST00000368122, ENST00000435307, ENST00000714112, ENST00000851528, ENST00000960790, ENST00000960791, ENST00000960792

RefSeq mRNA: 2 — MANE Select: NM_002036 NM_001122951, NM_002036

CCDS: CCDS1183, CCDS44252

Canonical transcript exons

ENST00000368122 — 2 exons

Exon	Start	End
ENSE00001446363	159205461	159206500
ENSE00001777134	159204875	159204980

Expression profiles

Bgee: expression breadth ubiquitous, 241 present calls, max score 99.31.

FANTOM5 (CAGE): breadth broad, TPM avg 3.8420 / max 328.0608, expressed in 241 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
5963	3.0780	221
5959	0.2867	101
5960	0.1814	84
5958	0.1137	66
5962	0.0746	48
5957	0.0485	24
5961	0.0343	13
5966	0.0249	13

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
vena cava	UBERON:0004087	99.31	gold quality
left uterine tube	UBERON:0001303	98.92	gold quality
mucosa of stomach	UBERON:0001199	98.85	gold quality
subcutaneous adipose tissue	UBERON:0002190	98.46	gold quality
pericardium	UBERON:0002407	98.28	gold quality
tibial nerve	UBERON:0001323	98.20	gold quality
omental fat pad	UBERON:0010414	98.19	gold quality
peritoneum	UBERON:0002358	98.16	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	98.13	gold quality
adipose tissue of abdominal region	UBERON:0007808	97.58	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	97.25	gold quality
lower esophagus muscularis layer	UBERON:0035833	97.16	gold quality
lower esophagus	UBERON:0013473	97.05	gold quality
ectocervix	UBERON:0012249	96.89	gold quality
coronary artery	UBERON:0001621	96.84	gold quality
endocervix	UBERON:0000458	96.81	gold quality
left coronary artery	UBERON:0001626	96.76	gold quality
cerebellar hemisphere	UBERON:0002245	96.53	gold quality
cerebellar cortex	UBERON:0002129	96.42	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.35	gold quality
body of uterus	UBERON:0009853	96.33	gold quality
right coronary artery	UBERON:0001625	96.30	gold quality
gall bladder	UBERON:0002110	96.08	gold quality
saphenous vein	UBERON:0007318	96.02	gold quality
upper lobe of left lung	UBERON:0008952	95.97	gold quality
nipple	UBERON:0002030	95.94	gold quality
skin of leg	UBERON:0001511	95.85	gold quality
layer of synovial tissue	UBERON:0007616	95.79	gold quality
fundus of stomach	UBERON:0001160	95.72	gold quality
superficial temporal artery	UBERON:0001614	95.59	gold quality

Single-cell (SCXA)

Detected in 17 experiment(s), a significant marker in 16.

Experiment	Marker?	Max mean expression
E-MTAB-10137	yes	11315.00
E-CURD-126	yes	5426.29
E-HCAD-11	yes	4060.17
E-MTAB-6308	yes	3842.39
E-MTAB-8322	yes	3500.31
E-HCAD-15	yes	3379.48
E-MTAB-10287	yes	3163.57
E-GEOD-135922	yes	2794.43
E-MTAB-9841	yes	2683.81
E-MTAB-8410	yes	2239.00
E-CURD-46	yes	1976.53
E-HCAD-1	yes	50.32
E-MTAB-6701	yes	32.02
E-GEOD-130148	yes	5.91
E-MTAB-9067	yes	4.05

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): DBP, GATA2, SP1

Literature-anchored findings (GeneRIF, showing 40)

• facilitates an early step in transcriptional elongation by Pol II (PMID:15728673)
• promotes early elongation and counteracts Polycomb group repression by recruiting the ASH1 and TRX histone methyltransferases to chromatin (PMID:18846226)
• KIS is a key transcriptional regulator of genes that function in the CRY signaling cascade, and thus it plays an important role in the synchronization of circadian rhythms with the dayrationight cycle. (PMID:20041201)
• analysis of this disease model can complement and expand upon the existing studies for this disease, allowing a better understanding of the role of kismet in neural developmental, and Chd7 in CS pathogenesis (PMID:20716578)
• the evolutionary conservation of Kismet/CHD8 function in negatively controlling hedgehog expression. (PMID:21146514)
• KIS promotes transcription elongation and counteracts Polycomb group repression via distinct mechanisms. KIS antagonizes Polycomb group repression by facilitating ASH1-dependent H3K36 dimethylation. (PMID:24004944)
• Kis is important for motor neuron synaptic morphology, the localization and clustering of postsynaptic glutamate receptors, larval motor behavior, and synaptic transmission. (PMID:25412171)
• The CHD Protein, Kismet, is Important for the Recycling of Synaptic Vesicles during Endocytosis. (PMID:31852969)
• The Duffy promoter polymorphism was not disproportionately represented in persons with HIVAN (HIV nepthropathy) calling into question any significant role in the pathogenesis of HIVAN. (PMID:11730271)
• signature of directional selection on FY*O in sub-Saharan Africa; understanding the extent to which natural selection has also played a role in the extreme geographic differentiation of the other derived allele at this locus, FY*A (PMID:11753822)
• Duffy antigen may play a role at local level by binding locally produced chemokines in psoriasis vulgaris (PMID:12160521)
• Vascular endothelial cells may induce Duffy protein to regulate leukocytes and/or chemokine trafficking (PMID:12697152)
• Duffy antigen has a role in enhancing leukocyte recruitment to sites of inflammation by facilitating movement of chemokines across the endothelium. (PMID:12734373)
• The expression of DARC in the context of NSCLC tumors may act as a chemokine decoy receptor and interferes with normal tumor growth and chemokine-induced tumor neovascularization. (PMID:15214968)
• susceptibility of African American recipients to acute rejection and to delayed allograft function was not associated with DARC alleles or genotype in kidney transplantation. (PMID:15327416)
• human Duffy antigen binds selected inflammatory, but not homeostatic, chemokines and that this binding pattern is reflected by endothelial cells within inflamed and non-inflamed tissue (PMID:15358176)
• Forty Caucasian and 130 donors of African ancestry were serologically Fy(b-); among these, the majority of the donors of African ancestry had FY*B with the GATA SNP, while the majority of Caucasians typing Fy(b-) had FY*B with 265 T/298 A SNPs. (PMID:15569072)
• crystal structure of the P. knowlesi DBL domain (Pkalpha-DBL), which binds to DARC (Duffy antigen receptor for chemokines) during invasion of human erythrocytes (PMID:16372020)
• DARC is involved in accumulation of extravascular chemokines in endothelial cella[review] (PMID:17073738)
• Seven DARC glycosylation variants were obtained & expressed in human K562 cells. three canonical sites are used for sugar attachment. (PMID:17382291)
• There is a genetic association between Darc gene polymorphism and bone mineral density in humans. (PMID:17416748)
• Anti-Fy(a) has the potential to lead to significant fetal hemolysis. AntiFy(a)guidelines developed are appropriate for ensitization are appropriate for pregnancies complicated by anti-Fy(a) alloimmunization (PMID:17880612)
• DARC on endothelial cells attenuated the angiogenic activity by causing senescence (PMID:17955335)
• These results suggest a novel mechanism by which DARC could modulate inflammatory responses to chemokines in vivo. (PMID:18230715)
• FY- status was strongly associated with chronic organ damage and proteinuria in sickle cell anemia (PMID:18248572)
• DARC influences HIV/AIDS susceptibility by mediating trans-infection of HIV-1 and by affecting both chemokine-HIV interactions and chemokine-driven inflammation. (PMID:18621010)
• Susceptibility to asthma and atopy among certain populations of African descent is influenced by a functional polymorphism in the gene encoding Duffy antigen/receptor for chemokines (PMID:18827265)
• Genetic polymorphisms in Duffy genes are not associated with malaria resistance in patients from Baixo Amazonas region, Brazil (PMID:19048480)
• DARC internalized chemokines but did not effectively scavenge them. (PMID:19060902)
• Loss of red cell chemokine scavenging promotes transfusion-related lung inflammation (PMID:19064726)
• Polymorphism in DARC is predictive of low neutrophil count in African Americans. (PMID:19180233)
• Multiple myeloma patients show a variation in the phenotype of DARC protein. (PMID:19206111)
• Interest in DARC has risen as it has become a potential explanation for some of the differences in prognosis and presentation seen in those with African genealogy in diseases of inflammation and malignancy–REVIEW (PMID:19290478)
• DARC genotype is not associated with the progression of AIDS or risk for HIV acquisition. (PMID:19454339)
• Expression of DARC has no effect on HIV-1 acquisition or progression to AIDS in African Americans. (PMID:19454340)
• Lack of DARC has no influence on HIV disease progression in African population. (PMID:19454341)
• Polymorphisms of DARC has minimal impact on HIV disease progression. (PMID:19454342)
• The interaction between DARC genotype and the cellular milieu defined by WBC counts may influence HIV disease course. (PMID:19620399)
• The Duffy antigen only minimally alters the pharmacokinetics of rhMCP-1 for doses up to 2 microg/kg. (PMID:19822078)
• increased expression is associated with ovalocytosis in Southeast Asia (PMID:19927622)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ackr1	ENSMUSG00000037872
rattus_norvegicus	Ackr1	ENSRNOG00000069330

Protein

Protein identifiers

Atypical chemokine receptor 1 — Q16570 (reviewed: Q16570)

Alternative names: Duffy antigen receptor for chemokines, Duffy antigen/chemokine receptor, Duffy blood group antigen, Fy glycoprotein, Glycoprotein D, Plasmodium vivax receptor

All UniProt accessions (4): A0AAQ5BHJ4, Q16570, Q5Y7A1, Q5Y7A2

UniProt curated annotations — full annotation on UniProt →

Function. Atypical chemokine receptor that controls chemokine levels and localization via high-affinity chemokine binding that is uncoupled from classic ligand-driven signal transduction cascades, resulting instead in chemokine sequestration, degradation, or transcytosis. Also known as interceptor (internalizing receptor) or chemokine-scavenging receptor or chemokine decoy receptor. Has a promiscuous chemokine-binding profile, interacting with inflammatory chemokines of both the CXC and the CC subfamilies but not with homeostatic chemokines. Acts as a receptor for chemokines including CCL2, CCL5, CCL7, CCL11, CCL13, CCL14, CCL17, CXCL5, CXCL6, IL8/CXCL8, CXCL11, GRO, RANTES, MCP-1 and TARC. May regulate chemokine bioavailability and, consequently, leukocyte recruitment through two distinct mechanisms: when expressed in endothelial cells, it sustains the abluminal to luminal transcytosis of tissue-derived chemokines and their subsequent presentation to circulating leukocytes; when expressed in erythrocytes, serves as blood reservoir of cognate chemokines but also as a chemokine sink, buffering potential surges in plasma chemokine levels. (Microbial infection) Acts as a receptor for the malaria parasite Plasmodium vivax. (Microbial infection) Acts as a receptor for the malaria parasite Plasmodium knowlesi.

Subunit / interactions. (Microbial infection) Interacts (via N-terminal extracellular domain) with Plasmodium vivax Duffy receptor (DBP) (via PvRII region). (Microbial infection) Interacts (via N-terminal extracellular domain) with Plasmodium knowlesi Duffy receptor alpha form (DBPalpha) (via region II).

Subcellular location. Early endosome. Recycling endosome. Membrane.

Tissue specificity. Found in adult kidney, adult spleen, bone marrow and fetal liver. In particular, it is expressed along postcapillary venules throughout the body, except in the adult liver. Erythroid cells and postcapillary venule endothelium are the principle tissues expressing duffy. Fy(-A-B) individuals do not express duffy in the bone marrow, however they do, in postcapillary venule endothelium.

Post-translational modifications. Sulfation at Tyr-41 facilitates interaction with MGSA/CXCL1, RANTES/CCL5 and MCP-1/CCL2 but not IL8/CXCL8. Sulfation at Tyr-30 facilitates interaction with IL8/CXCL8. (Microbial infection) Sulfation at Tyr-41 facilitates interaction with Plasmodium vivax Duffy receptor (DBP). Sulfation at Tyr-30/Tyr-41 and Tyr-41 alone increases binding affinity of Plasmodium vivax parasites and likely promotes invasion of red blood cells. (Microbial infection) Sulfation at Tyr-41 facilitates interaction with Plasmodium knowlesi Duffy receptor alpha form (DBPalpha). Sulfation at Tyr-30/Tyr-41 and Tyr-41 alone increases binding affinity of Plasmodium knowlesi parasites and likely promotes invasion of red blood cells.

Polymorphism. DARC is responsible for the Duffy blood group system (FY) [MIM:110700]. The molecular basis of the Fy(A)=Fy1/Fy(B)=Fy2 blood group antigens is a single variation in position 42; Gly-42 corresponds to Fy(A) and Asp-42 to Fy(B). Individuals that do not produce the Duffy antigen (FY(A-B-)) are more resistant to infection by the malarial parasite Plasmodium vivax. This allele is found predominantly in population of African origin [MIM:611162]. Genetic variations in DARC define the white blood cell count quantitative trait locus 1 (WBCQ1) [MIM:611862]. Peripheral white blood cell count (WBC) is a common clinical measurement, used to determine evidence of acute inflammation or infection. Peripheral WBC is the sum of several cell types including neutrophils and lymphocytes, which are the most common types of WBC, as well as less common cell types such as eosinophils, basophils, and monocytes. Elevated WBC has been associated with risk of coronary heart disease, cancer, and all-cause mortality. White blood cell levels have widespread clinical applications including assessment of patients undergoing chemotherapy and evaluation of infection.

Miscellaneous. A subset of erythroblasts from genotypically Duffy-negative individuals transiently expresses ACKR1 during terminal erythroid differentiation and P.vivax merozoites can invade these ACKR1-expressing Duffy-negative erythroblasts.

Similarity. Belongs to the G-protein coupled receptor 1 family. Atypical chemokine receptor subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q16570-1	2	yes
Q16570-2	1

RefSeq proteins (2): NP_001116423, NP_002027* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005384	Duffy_chemokine_rcpt	Family

UniProt features (54 total): mutagenesis site 23, topological domain 8, transmembrane region 7, sequence variant 5, modified residue 2, glycosylation site 2, disulfide bond 2, chain 1, region of interest 1, splice variant 1, helix 1, strand 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
7P93	X-RAY DIFFRACTION	1.55
4NUU	X-RAY DIFFRACTION	1.95
8A44	X-RAY DIFFRACTION	2.49
4NUV	X-RAY DIFFRACTION	2.6
8JPS	ELECTRON MICROSCOPY	3.65
8YNF	ELECTRON MICROSCOPY	3.65

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q16570-F1	78.25	0.46

Antibody-complex structures (SAbDab): 1 — 8A44

Functional residue map

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

Post-translational modifications (2): 30, 41

Disulfide bonds (2): 51–276, 129–195

Glycosylation sites (2): 16, 33

Mutagenesis-validated functional residues (23):

Position	Phenotype
9	does not affect interaction with plasmodium vivax duffy receptor (dbp).
10	does not affect interaction with plasmodium vivax duffy receptor (dbp).
11	does not affect interaction with plasmodium vivax duffy receptor (dbp).
12	does not affect interaction with plasmodium vivax duffy receptor (dbp).
13	does not affect interaction with plasmodium vivax duffy receptor (dbp).
15	does not affect interaction with plasmodium vivax duffy receptor (dbp).
16	does not affect interaction with plasmodium vivax duffy receptor (dbp).
17	does not affect interaction with plasmodium vivax duffy receptor (dbp).
18	does not affect interaction with plasmodium vivax duffy receptor (dbp).
19	modulates the affinity of the interaction with plasmodium vivax duffy receptor (dbp).
20	significantly reduces binding with plasmodium vivax duffy receptor (dbp).
21	significantly reduces binding with plasmodium vivax duffy receptor (dbp).
22	significantly reduces binding with plasmodium vivax duffy receptor (dbp).
23	modulates the affinity of the interaction with plasmodium vivax duffy receptor (dbp).
24	significantly reduces binding with plasmodium vivax duffy receptor (dbp).
25	significantly reduces binding with plasmodium vivax duffy receptor (dbp).
26	significantly reduces binding with plasmodium vivax duffy receptor (dbp).
27	does not affect interaction with plasmodium vivax duffy receptor (dbp).
28	does not affect interaction with plasmodium vivax duffy receptor (dbp).
29	does not affect interaction with plasmodium vivax duffy receptor (dbp).
30	does not affect interaction with plasmodium vivax duffy receptor (dbp).
30	abolishes sulfation. reduces binding with il8/cxcl8.
41	abolishes sulfation. reduces binding with mgsa/cxcl1, rantes/ccl5 and mcp-1/ccl2. reduces binding with plasmodium vivax

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-375276	Peptide ligand-binding receptors
R-HSA-162582	Signal Transduction
R-HSA-372790	Signaling by GPCR
R-HSA-373076	Class A/1 (Rhodopsin-like receptors)
R-HSA-500792	GPCR ligand binding

MSigDB gene sets: 177 (showing top): MCLACHLAN_DENTAL_CARIES_UP, MODULE_255, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_PEPTIDE, MODULE_64, MODULE_317, HSIAO_HOUSEKEEPING_GENES, SMID_BREAST_CANCER_RELAPSE_IN_LUNG_DN, MORF_RAD51L3, MODULE_118, PICCALUGA_ANGIOIMMUNOBLASTIC_LYMPHOMA_UP, REACTOME_PEPTIDE_LIGAND_BINDING_RECEPTORS, MODULE_289, MARTINEZ_RB1_TARGETS_DN, GATA6_01

GO Biological Process (5): defense response (GO:0006952), inflammatory response (GO:0006954), chemokine-mediated signaling pathway (GO:0070098), signal transduction (GO:0007165), G protein-coupled receptor signaling pathway (GO:0007186)

GO Molecular Function (6): transmembrane signaling receptor activity (GO:0004888), G protein-coupled receptor activity (GO:0004930), C-C chemokine binding (GO:0019957), signaling receptor activity (GO:0038023), protein binding (GO:0005515), chemokine binding (GO:0019956)

GO Cellular Component (5): early endosome (GO:0005769), plasma membrane (GO:0005886), recycling endosome (GO:0055037), endosome (GO:0005768), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Class A/1 (Rhodopsin-like receptors)	1
Signal Transduction	1
GPCR ligand binding	1
Signaling by GPCR	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
G protein-coupled receptor signaling pathway	2
endosome	2
response to stress	1
defense response	1
cytokine-mediated signaling pathway	1
cellular response to chemokine	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
G protein-coupled receptor activity	1
signal transduction	1
signaling receptor activity	1
transmembrane signaling receptor activity	1
chemokine binding	1
molecular transducer activity	1
binding	1
cytokine binding	1
membrane	1
cell periphery	1
endomembrane system	1
cytoplasmic vesicle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1308 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ACKR1	TNFRSF14	Q92956	998
ACKR1	NECTIN1	Q15223	994
ACKR1	CCL2	P13500	993
ACKR1	CCL5	P13501	993
ACKR1	CXCL8	P10145	990
ACKR1	CXCL1	P09341	988
ACKR1	NECTIN2	Q92692	986
ACKR1	CD82	P27701	973
ACKR1	CXCL5	P42830	897
ACKR1	TNFSF14	O43557	884
ACKR1	GYPC	P04921	856
ACKR1	PPBP	P02775	834
ACKR1	FYB1	O15117	807
ACKR1	HS3ST5	Q8IZT8	790
ACKR1	BTLA	Q7Z6A9	788

IntAct

2 interactions, top by confidence:

A	B	Type	Score
ACKR1		psi-mi:“MI:0915”(physical association)	0.370

BioGRID (3): ACKR1 (Two-hybrid), ACKR1 (Reconstituted Complex), ACKR1 (Reconstituted Complex)

ESM2 similar proteins: A0A0R4IM31, A0A0R4IP11, E9QJ73, F8VQN3, O00270, O00421, O15218, O35457, O97663, P31392, P32302, P34997, P43142, P49685, Q04683, Q0II78, Q0VDU3, Q149R9, Q16570, Q3ZC80, Q67ES2, Q6XKD3, Q75ZH0, Q7TMA4, Q7TQA9, Q7TQP4, Q7TSN5, Q7TSN6, Q863H8, Q8BZR0, Q8TDV2, Q95LF2, Q95LF3, Q95LF4, Q95LF5, Q95LF7, Q95LF9, Q95LG5, Q96CH1, Q96G91

Diamond homologs: Q16570, Q863H8, Q95LF2, Q95LF3, Q95LF4, Q95LF5, Q95LF7, Q95LF9, Q95LG5, Q9GLX0, Q9QUI6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	1
Uncertain significance	42
Likely benign	5
Benign	3

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
18395	NM_002036.3(ACKR1):c.-67T>C	Pathogenic
18397	NM_002036.4(ACKR1):c.286_299del (p.Trp96fs)	Pathogenic
58109	GRCh38/hg38 1q23.1-25.1(chr1:157747246-176021247)x3	Pathogenic
688082	GRCh37/hg19 1q23.1-24.2(chr1:157321299-167391423)x1	Pathogenic
3242278	GRCh37/hg19 1q22-23.2(chr1:155709113-159191078)x3	Likely pathogenic

SpliceAI

426 predictions. Top by Δscore:

Variant	Effect	Δscore
1:159204896:T:A	acceptor_gain	0.9900
1:159205446:G:A	acceptor_gain	0.9800
1:159204979:GG:G	donor_gain	0.9700
1:159204980:GG:G	donor_gain	0.9700
1:159205457:CCAGG:C	acceptor_loss	0.9700
1:159205458:CAG:C	acceptor_loss	0.9700
1:159205459:A:AG	acceptor_gain	0.9700
1:159205460:G:A	acceptor_loss	0.9700
1:159205460:G:GG	acceptor_gain	0.9700
1:159205459:AGGCG:A	acceptor_gain	0.9600
1:159205460:GGC:G	acceptor_gain	0.9600
1:159205460:GGCGG:G	acceptor_gain	0.9600
1:159204897:G:A	acceptor_gain	0.9500
1:159204977:CAGG:C	donor_gain	0.9500
1:159205459:AGGC:A	acceptor_gain	0.9500
1:159205460:GGCG:G	acceptor_gain	0.9500
1:159204981:G:GG	donor_gain	0.9400
1:159204900:A:AG	acceptor_gain	0.9300
1:159204901:G:GG	acceptor_gain	0.9300
1:159204978:AGG:A	donor_gain	0.9300
1:159204979:GGG:G	donor_gain	0.9300
1:159204979:GGGTG:G	donor_loss	0.9000
1:159204981:G:GA	donor_loss	0.9000
1:159204982:TGAG:T	donor_loss	0.9000
1:159204983:GAG:G	donor_loss	0.9000
1:159204892:ATCTT:A	acceptor_gain	0.8900
1:159204984:AG:A	donor_loss	0.8800
1:159204976:ACAGG:A	donor_gain	0.8600
1:159204897:GGAA:G	acceptor_loss	0.8400
1:159204898:GAAGC:G	acceptor_loss	0.8400

AlphaMissense

2125 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:159205644:A:C	S69R	0.991
1:159205646:T:A	S69R	0.991
1:159205646:T:G	S69R	0.991
1:159205767:A:C	S110R	0.990
1:159205769:C:A	S110R	0.990
1:159205769:C:G	S110R	0.990
1:159205590:T:A	C51S	0.979
1:159205591:G:C	C51S	0.979
1:159205665:A:C	S76R	0.978
1:159205667:C:A	S76R	0.978
1:159205667:C:G	S76R	0.978
1:159205755:A:C	S106R	0.975
1:159205757:T:A	S106R	0.975
1:159205757:T:G	S106R	0.975
1:159206196:T:A	W253R	0.975
1:159206196:T:C	W253R	0.975
1:159205653:G:C	G72R	0.970
1:159206184:T:A	W249R	0.970
1:159206184:T:C	W249R	0.970
1:159205590:T:C	C51R	0.969
1:159205591:G:A	C51Y	0.967
1:159205959:T:A	W174R	0.967
1:159205959:T:C	W174R	0.967
1:159206199:T:A	W254R	0.966
1:159206199:T:C	W254R	0.966
1:159205764:T:C	F109L	0.959
1:159205766:C:A	F109L	0.959
1:159205766:C:G	F109L	0.959
1:159206265:T:C	C276R	0.956
1:159205592:C:G	C51W	0.954

dbSNP variants (sampled 300 via entrez): RS1000157237 (1:159203016 T>G), RS1000192024 (1:159206348 C>T), RS1000194263 (1:159203818 G>A), RS1000373017 (1:159203238 T>C), RS1000488956 (1:159204257 C>T), RS1002177776 (1:159205639 TCA>T), RS1002437787 (1:159205891 C>A,G,T), RS1004711541 (1:159203660 G>A), RS1004817822 (1:159206929 G>A), RS1006397896 (1:159205189 C>T), RS1006484993 (1:159205701 T>C,G), RS1006530758 (1:159203418 T>C), RS1006720455 (1:159206390 C>A,T), RS1007148900 (1:159203244 G>T), RS1007541826 (1:159204756 C>T)

Disease associations

OMIM: gene MIM:613665 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

74 associations (top):

Study	Trait	p-value
GCST001059_13	Neutrophil count	1.000000e-08
GCST001302_1	White blood cell count	7.000000e-55
GCST001302_3	White blood cell count	5.000000e-24
GCST001316_6	IgE levels	2.000000e-11
GCST001385_2	Inflammatory biomarkers	4.000000e-51
GCST001385_5	Inflammatory biomarkers	2.000000e-11
GCST001584_1	Lean body mass and age at menarche (combined)	7.000000e-07
GCST001650_1	C-reactive protein	1.000000e-37
GCST001650_11	C-reactive protein	3.000000e-10
GCST001650_8	C-reactive protein	4.000000e-73
GCST001691_5	Monocyte chemoattractant protein-1 levels	1.000000e-21
GCST001762_307	Obesity-related traits	1.000000e-21
GCST001779_1	Hematology traits	2.000000e-23
GCST001779_8	Hematology traits	5.000000e-47
GCST002556_1	White blood cell count	7.000000e-69
GCST002556_9	White blood cell count	1.000000e-149
GCST002743_2	Neutrophil count in HIV-infection	3.000000e-17
GCST004126_1	White blood cell count	6.000000e-56
GCST004128_1	White blood cell count (neutrophil)	6.000000e-65
GCST004129_3	White blood cell count (monocyte)	8.000000e-18
GCST004438_19	Monocyte chemoattractant protein-1 levels	1.000000e-44
GCST004457_11	Growth-regulated protein alpha levels	1.000000e-55
GCST004460_25	Eotaxin levels	1.000000e-26
GCST004610_32	White blood cell count	3.000000e-23
GCST004613_1	Sum neutrophil eosinophil counts	9.000000e-30
GCST004613_55	Sum neutrophil eosinophil counts	2.000000e-12
GCST004613_56	Sum neutrophil eosinophil counts	2.000000e-10
GCST004614_116	Granulocyte count	4.000000e-12
GCST004614_117	Granulocyte count	1.000000e-10
GCST004614_118	Granulocyte count	9.000000e-29

EFO canonical traits (16, from GWAS)

EFO ID	Trait name
EFO:0004833	neutrophil count
EFO:0004458	C-reactive protein measurement
EFO:0004341	body fat distribution
EFO:0004703	age at menarche
EFO:0005091	monocyte count
EFO:0008146	growth-regulated alpha protein measurement
EFO:0008122	eotaxin measurement
EFO:0004842	eosinophil count
EFO:0007987	granulocyte count
EFO:0005090	basophil count
EFO:0007992	basophil percentage of leukocytes
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0007990	neutrophil percentage of leukocytes
EFO:0007995	basophil percentage of granulocytes
EFO:0007959	fetal genotype effect measurement
EFO:0007989	monocyte percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2321626 (SINGLE PROTEIN)

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2814778	ACKR1		0.00	0

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: gpcr — Chemokine receptors

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression	4
Cadmium Chloride	decreases expression, increases expression	3
methacrylaldehyde	affects cotreatment, increases expression, increases abundance	2
Acrolein	affects cotreatment, increases expression, increases abundance	2
Air Pollutants	affects cotreatment, increases abundance, increases expression, decreases expression	2
Formaldehyde	increases expression	2
Ozone	affects cotreatment, increases expression, increases abundance	2
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	decreases expression, affects cotreatment	1
Resveratrol	affects cotreatment, decreases expression	1
Arsenic Trioxide	decreases expression	1
Vorinostat	decreases expression, affects cotreatment	1
Vehicle Emissions	decreases expression, increases abundance	1
Diethylhexyl Phthalate	decreases expression	1
Folic Acid	decreases expression	1
Hydrocortisone	increases expression, decreases reaction	1
Ivermectin	decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Rotenone	decreases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	decreases expression	1
Vitallium	increases expression	1
Mifepristone	decreases reaction, increases expression	1
Medroxyprogesterone Acetate	increases expression	1
Antirheumatic Agents	decreases expression	1
Thapsigargin	increases expression	1
Okadaic Acid	decreases expression	1
Particulate Matter	increases abundance, decreases expression	1

ChEMBL screening assays

3 unique, capped per target: 2 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2328017	Binding	Antagonist activity at Duffy (unknown origin) assessed as inhibition of chemotaxis at 10 uM	1-(4-Phenylpiperazin-1-yl)-2-(1H-pyrazol-1-yl)ethanones as novel CCR1 antagonists. — Bioorg Med Chem Lett
CHEMBL2328506	Functional	Antagonist activity at Duffy (unknown origin) assessed as inhibition of calcium flux at 10 uM	1-(4-Phenylpiperazin-1-yl)-2-(1H-pyrazol-1-yl)ethanones as novel CCR1 antagonists. — Bioorg Med Chem Lett

Cellosaurus cell lines

4 cell lines: 3 transformed cell line, 1 spontaneously immortalized cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_C0X9	BEL-A ACKR1 KO	Transformed cell line	Sex unspecified
CVCL_C0XH	BEL-A 4x KO	Transformed cell line	Sex unspecified
CVCL_C0XI	BEL-A 5x KO	Transformed cell line	Sex unspecified
CVCL_KW84	PathHunter CHO-K1 DARC beta-arrestin	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

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