CCR9

Summary

CCR9 (C-C motif chemokine receptor 9, HGNC:1610) is a protein-coding gene on chromosome 3p21.31, encoding C-C chemokine receptor type 9 (P51686). Receptor for chemokine SCYA25/TECK.

The protein encoded by this gene is a G protein-coupled receptor with seven transmembrane domains that belongs to the beta chemokine receptor family. Chemokines and their receptors are key regulators of thymocyte migration and maturation in normal and inflammation conditions. This gene is differentially expressed in T lymphocytes of the small intestine and colon, and its interaction with chemokine 25 contributes to intestinal intra-epithelial lymphocyte homing to the small intestine. This suggests a role for this gene in directing immune responses to different segments of the gastrointestinal tract. This gene and its exclusive ligand, chemokine 25, are overexpressed in a variety of malignant tumors and are closely associated with tumor proliferation, apoptosis, invasion, migration and drug resistance. This gene maps to the chemokine receptor gene cluster. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 10803 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 61 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_031200

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1610
Approved symbol	CCR9
Name	C-C motif chemokine receptor 9
Location	3p21.31
Locus type	gene with protein product
Status	Approved
Aliases	GPR-9-6, CDw199
Ensembl gene	ENSG00000173585
Ensembl biotype	protein_coding
OMIM	604738
Entrez	10803

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 6 protein_coding, 1 retained_intron

ENST00000357632, ENST00000395963, ENST00000422395, ENST00000463197, ENST00000706789, ENST00000902118, ENST00000959606

RefSeq mRNA: 5 — MANE Select: NM_031200 NM_001256369, NM_001386447, NM_001386448, NM_006641, NM_031200

CCDS: CCDS2732, CCDS2733

Canonical transcript exons

ENST00000357632 — 3 exons

Exon	Start	End
ENSE00003587279	45900810	45903174
ENSE00003627693	45894906	45894954
ENSE00003841903	45886543	45886655

Expression profiles

Bgee: expression breadth ubiquitous, 106 present calls, max score 93.19.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.6415 / max 427.3848, expressed in 67 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
36395	0.4140	59
36394	0.1409	26
36396	0.0579	18
202741	0.0287	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
thymus	UBERON:0002370	93.19	gold quality
duodenum	UBERON:0002114	72.52	gold quality
small intestine Peyer’s patch	UBERON:0003454	67.95	gold quality
small intestine	UBERON:0002108	67.69	gold quality
granulocyte	CL:0000094	66.31	gold quality
sural nerve	UBERON:0015488	64.60	gold quality
vermiform appendix	UBERON:0001154	62.25	gold quality
vastus lateralis	UBERON:0001379	60.30	gold quality
quadriceps femoris	UBERON:0001377	60.14	gold quality
bone marrow cell	CL:0002092	59.89	silver quality
blood	UBERON:0000178	59.14	gold quality
trachea	UBERON:0003126	59.07	gold quality
dorsal plus ventral thalamus	UBERON:0001897	59.03	gold quality
dorsal root ganglion	UBERON:0000044	58.67	gold quality
bone marrow	UBERON:0002371	58.30	gold quality
epithelium of bronchus	UBERON:0002031	58.19	gold quality
layer of synovial tissue	UBERON:0007616	57.91	gold quality
spleen	UBERON:0002106	57.85	gold quality
mucosa of transverse colon	UBERON:0004991	57.82	gold quality
cerebellar vermis	UBERON:0004720	57.59	gold quality
leukocyte	CL:0000738	57.27	gold quality
monocyte	CL:0000576	56.06	gold quality
metanephric glomerulus	UBERON:0004736	55.97	gold quality
colonic epithelium	UBERON:0000397	54.33	silver quality
lymph node	UBERON:0000029	53.84	gold quality
skeletal muscle tissue	UBERON:0001134	53.09	gold quality
mucosa of stomach	UBERON:0001199	52.46	gold quality
muscle tissue	UBERON:0002385	51.90	gold quality
gall bladder	UBERON:0002110	51.76	gold quality
apex of heart	UBERON:0002098	51.62	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.42

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): BATF, HAND1, NFATC1, NFATC2, RARA

miRNA regulators (miRDB)

65 targeting CCR9, 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-4455	100.00	65.48	1587
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-7153-5P	99.94	68.89	1006
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-466	99.67	70.85	2863

Literature-anchored findings (GeneRIF, showing 40)

• A subset of CCR9+ T cells from normal donors has characteristics of mucosal T cells in terms of activated phenotype, proliferative response to anti-CD2 stimulation, a Th1 or Tr1 cytokine profile, and support for Ig production by cocultured B cells. (PMID:12816994)
• CCR9 selectively induced T-ALL CD4+ T-cell chemotaxis and adhesion. (PMID:14559839)
• High Expression of CCR9 is associated with prostate cancer cell migration and invasion (PMID:15623660)
• involved in the pathogenesis of lymphatic filarial disease (PMID:15717282)
• CCR9 overexpression is associated with Adult T-cell leukemia cells infiltrating gastrointestinal tract (PMID:17205512)
• CCR9 expression is reduced on epithelial and lamina propria T cells in untreated celiac disease. Down-regulation of CCR9 persists in intraepithelial T cells from well-treated patients. Possible ongoing immune activation preferentially within epithelium. (PMID:17570212)
• CCR9 is expressed on human melanoma cells and participates in the enhanced motility of melanoma cells and is likely a “homing receptor” for melanoma to the small bowel. (PMID:18245518)
• Functionally active CCR9 on melanoma cells facilitates metastasis to the small intestine which may explain high incidence of metastis to the small intestine. (PMID:18245522)
• more active homing of CCR9-926AG T cells to Peyer’s patches may produce changes in Ag presentation and result in increased incidence of skin graft vs. host disease. (PMID:19525985)
• Results demonstrate enhanced pancreatic intraepithelial neoplasia and pancreatic cancer cell proliferation with activation of CCR9 by its selective ligand CCL25 (PMID:19756884)
• Studies indicate that D6 chemokine receptor(CCR-9) may act as scavenging decoys and are involved in clearance of chemokines. (PMID:20036838)
• over-expressed TECK interacts with CCR9 on the endometrial stromal cells in the endometriotic milieu, which may contribute to the onset and progression of endometriosis. (PMID:20081876)
• CCR9 expression by monocytes is increased in rheumatoid arthritis (PMID:20738854)
• TLR2 ligands induce CCR9 and CCR10 expression by circulating B-cells and increase their chemotaxis. TLR2 stimulation also induced J chain and IgA production demonstrating the induction of mucosal-like antibody secreting cells. (PMID:20947433)
• The high fraction of circulating IgA+ and IgG+ B cells expressing CCR9 and CCR10 in the first months of life indicates activation of naive B cells in the gut, coinciding with bacterial colonization. (PMID:21075690)
• CCL25 enhanced the expression of MMP-1, -9, -11 and -13 active proteins by BrCa cells in a CCR9-dependent fashion. (PMID:21344163)
• CCR9+ Th cells are a subset of IL-21-producing T helper cells that influence regional specification of autoimmune diseases that affect accessory organs of the digestive system (PMID:21511186)
• We provide the first evidence that CCR9 and its natural ligand CCL25 are highly expressed by ovarian cancer tissue and their expression correlates with histological subtypes. (PMID:21637913)
• Notch1 regulates chemotaxis and proliferation by controlling the CC-chemokine receptors 5 and 9 in T cell acute lymphoblastic leukaemia. (PMID:21984373)
• Data suggest that P-glycoprotein associate with the F-actin cytoskeleton through ezrin/radixin/moesin (ERM) in CCR9/CCL25 induced multidrug resistance of acute T-lymphocytic leukemia (T-ALL) cells. (PMID:23326330)
• results suggest that CCR9 can act as a novel prognostic marker and therapeutic target for hepatocellular carcinoma (PMID:24481516)
• Only rotavirus specific CD4 T cells expressed intestinal homing receptors alpha4beta7 and CCR9. (PMID:24606696)
• CCR9 expression is elevated in the nodal lymphomas of patients with GI involvement (PMID:24828696)
• The results show the potential of the 91R monoclonal antibody as a therapeutic agent for treatment of CCR9-expressing tumors. (PMID:24870448)
• High CCR9 expression is associated with the pathogenesis of ulcerative colitis. (PMID:24936795)
• Expression of CCR9 and CCL25, the only natural ligand of CCR9, was significantly higher (p<0.0001) in NSCLC tissues and serum respectively, compared to their respective controls. (PMID:25296976)
• CCR9-CCL25 interaction promoted proliferation and suppressed apoptosis of non-small cell lung cancer cells by activating the PI3K/Akt pathway. (PMID:25691296)
• activation of Notch1 has a dominant-negative effect on Ccr9 transcription and that Notch1 and E proteins control the dynamic expression of Ccr9 during T cell development. (PMID:25710912)
• We also show that primary tumors can be modeled in immunocompetent mice by microinjecting CCR9-expressing cancer cell lines into early-stage mouse blastocysts, which induces central immune tolerance (PMID:26006007)
• CCR9 could be beneficial in predicting lymph node metastasis, and it might act as a novel prognostic biomarker for lung adenocarcinoma. (PMID:26168791)
• CCR9 mRNA and protein levels were significantly increased in the nasopharyngeal carcinoma group compared with the control group. (PMID:26279399)
• CCR9 and Integrin-beta7 expression has a differential effect on graft fate during acute graft-versus-host disease (GVHD) of the liver depending on the GVHD target tissue. (PMID:26348893)
• Results indicated that the expression levels of CCR9 in lesional skin may be a useful biologic marker of the clinical efficacy of infliximab therapy in psoriasis patients. (PMID:26507968)
• this study showed that CCR7 are overexpressed in CD4(-) CD8(-) thymocytes of myasthenia gravis patients. (PMID:26616645)
• Studies indicate important roles played by chemokine ligand 25 (CCL25)/chemokine receptor 9 (CCR9) in tumorigenesis, tumor chemoresistance and metastasis. (PMID:26879872)
• that CCL25/CCR9 signal may provide cancer cells with chemotactic abilities through influencing several epithelial-mesenchymal transitionmarkers (PMID:27008282)
• There were significantly increased CCR9 protein levels in failing human hearts. (PMID:27146447)
• It plays a pathogenic role in liver diseases and it will be a therapeutic target of the diseases. (PMID:27795503)
• Xray crystal structure of the CCR9 receptor in complex with vercirnon at 2.8 A resolution (PMID:27926729)
• our observations of increased circulating CCR9+ IL-17+ Treg cells and its inverse correlation with the severity of intestinal tissue injury in NEC are novel (PMID:31129099)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ccr9a	ENSDARG00000055186
danio_rerio	ccr9b	ENSDARG00000099738
mus_musculus	Ccr9	ENSMUSG00000029530
rattus_norvegicus	Ccr9	ENSRNOG00000006311

Paralogs (23): CCR6 (ENSG00000112486), CCRL2 (ENSG00000121797), CCR2 (ENSG00000121807), CXCR4 (ENSG00000121966), CCR7 (ENSG00000126353), ACKR4 (ENSG00000129048), ACKR3 (ENSG00000144476), ACKR2 (ENSG00000144648), RGR (ENSG00000148604), CXCR5 (ENSG00000160683), CCR5 (ENSG00000160791), CXCR1 (ENSG00000163464), CCR1 (ENSG00000163823), CX3CR1 (ENSG00000168329), CXCR6 (ENSG00000172215), XCR1 (ENSG00000173578), CCR8 (ENSG00000179934), CXCR2 (ENSG00000180871), GALR2 (ENSG00000182687), CCR3 (ENSG00000183625), CCR4 (ENSG00000183813), CCR10 (ENSG00000184451), CXCR3 (ENSG00000186810)

Protein

Protein identifiers

C-C chemokine receptor type 9 — P51686 (reviewed: P51686)

Alternative names: G-protein coupled receptor 28, GPR-9-6

All UniProt accessions (2): P51686, C9JWC0

UniProt curated annotations — full annotation on UniProt →

Function. Receptor for chemokine SCYA25/TECK. Subsequently transduces a signal by increasing the intracellular calcium ions level. (Microbial infection) Alternative coreceptor with CD4 for HIV-1 infection.

Subcellular location. Cell membrane.

Tissue specificity. Highly expressed in the thymus and low in lymph nodes and spleen.

Miscellaneous. EC50 of SCYA25/TECK for isoform 1 is lower than for isoform 2.

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

Isoforms (2)

UniProt ID	Names	Canonical?
P51686-1	1, CCR9A	yes
P51686-2	2, CCR9B

RefSeq proteins (5): NP_001243298, NP_001373376, NP_001373377, NP_006632, NP_112477* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR000355	Chemokine_rcpt	Family
IPR004069	Chemokine_CCR9	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain
IPR050119	CCR1-9-like	Family

Pfam: PF00001

UniProt features (38 total): helix 16, topological domain 8, transmembrane region 7, disulfide bond 2, sequence variant 2, chain 1, glycosylation site 1, splice variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
5LWE	X-RAY DIFFRACTION	2.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P51686-F1	83.69	0.45

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): 38–289, 119–198

Glycosylation sites (1): 32

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-380108	Chemokine receptors bind chemokines
R-HSA-418594	G alpha (i) signalling events
R-HSA-162582	Signal Transduction
R-HSA-372790	Signaling by GPCR
R-HSA-373076	Class A/1 (Rhodopsin-like receptors)
R-HSA-375276	Peptide ligand-binding receptors
R-HSA-388396	GPCR downstream signalling
R-HSA-500792	GPCR ligand binding

MSigDB gene sets: 242 (showing top): GOBP_CELL_CHEMOTAXIS, GOBP_RESPONSE_TO_PEPTIDE, MODULE_64, GOCC_CELL_SURFACE, HSIAO_HOUSEKEEPING_GENES, GGGTGGRR_PAX4_03, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_UP, GCM_PRKCG, GOBP_TAXIS, REACTOME_PEPTIDE_LIGAND_BINDING_RECEPTORS, YGACNNYACAR_UNKNOWN, GCM_RING1, OSWALD_HEMATOPOIETIC_STEM_CELL_IN_COLLAGEN_GEL_UP, MODULE_75, SU_THYMUS

GO Biological Process (10): CD8-positive, gamma-delta intraepithelial T cell differentiation (GO:0002305), chemotaxis (GO:0006935), immune response (GO:0006955), cellular defense response (GO:0006968), G protein-coupled receptor signaling pathway (GO:0007186), positive regulation of cytosolic calcium ion concentration (GO:0007204), calcium-mediated signaling (GO:0019722), cell chemotaxis (GO:0060326), signal transduction (GO:0007165), chemokine-mediated signaling pathway (GO:0070098)

GO Molecular Function (4): chemokine receptor activity (GO:0004950), C-C chemokine receptor activity (GO:0016493), C-C chemokine binding (GO:0019957), G protein-coupled receptor activity (GO:0004930)

GO Cellular Component (4): plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), cell surface (GO:0009986), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Signaling by GPCR	2
Peptide ligand-binding receptors	1
GPCR downstream signalling	1
Signal Transduction	1
GPCR ligand binding	1
Class A/1 (Rhodopsin-like receptors)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
G protein-coupled receptor signaling pathway	2
chemokine binding	2
cellular anatomical structure	2
gamma-delta intraepithelial T cell differentiation	1
response to chemical	1
taxis	1
immune system process	1
response to stimulus	1
defense response	1
G protein-coupled receptor activity	1
signal transduction	1
regulation of biological quality	1
intracellular signaling cassette	1
chemotaxis	1
cell migration	1
cellular response to chemical stimulus	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
cytokine-mediated signaling pathway	1
cellular response to chemokine	1
G protein-coupled chemoattractant receptor activity	1
cytokine receptor activity	1
chemokine-mediated signaling pathway	1
chemokine receptor activity	1
C-C chemokine binding	1
transmembrane signaling receptor activity	1
membrane	1
cell periphery	1
plasma membrane	1
cell surface	1
side of membrane	1

Protein interactions and networks

STRING

1440 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CCR9	CCL25	O15444	999
CCR9	MADCAM1	Q13477	994
CCR9	CCL21	O00585	957
CCR9	CCL19	Q99731	904
CCR9	CCL3	P10147	855
CCR9	CD8A	P01732	804
CCR9	CD4	P01730	790
CCR9	CXCL12	P48061	770
CCR9	CCL27	Q9Y4X3	761
CCR9	CCR5	P51681	747
CCR9	ITGB7	P26010	746
CCR9	CCR1	P32246	734
CCR9	ITGA4	P13612	726
CCR9	ITGAE	P38570	712
CCR9	SELPLG	Q14242	703

IntAct

20 interactions, top by confidence:

A	B	Type	Score
DGAT1	CCR9	psi-mi:“MI:0915”(physical association)	0.550
NEU1	CCR9	psi-mi:“MI:0915”(physical association)	0.370
RHBDD2	CCR9	psi-mi:“MI:0915”(physical association)	0.370
TMC6	CCR9	psi-mi:“MI:0915”(physical association)	0.370
SPNS1	CCR9	psi-mi:“MI:0915”(physical association)	0.370
ADGRG1	CCR9	psi-mi:“MI:0915”(physical association)	0.370
CD81	CCR9	psi-mi:“MI:0915”(physical association)	0.370
TSPAN7	CCR9	psi-mi:“MI:0915”(physical association)	0.370
YWHAE	CCR9	psi-mi:“MI:0915”(physical association)	0.370
KDELR1	CCR9	psi-mi:“MI:0915”(physical association)	0.370
AIG1	CCR9	psi-mi:“MI:0915”(physical association)	0.370
TRPM4	CCR9	psi-mi:“MI:0915”(physical association)	0.370
TTYH1	CCR9	psi-mi:“MI:0915”(physical association)	0.370
OSTC	CCR9	psi-mi:“MI:0915”(physical association)	0.370
SAP130	CCR9	psi-mi:“MI:0915”(physical association)	0.370
SCAMP4	CCR9	psi-mi:“MI:0915”(physical association)	0.370
G6PC3	CCR9	psi-mi:“MI:0915”(physical association)	0.370
HLA-A	CCR9	psi-mi:“MI:0915”(physical association)	0.370
CCR9	ABCC4	psi-mi:“MI:0914”(association)	0.350

BioGRID (19): NEU1 (Two-hybrid), RHBDD2 (Two-hybrid), TMC6 (Two-hybrid), SPNS1 (Two-hybrid), GPR56 (Two-hybrid), CD81 (Two-hybrid), TSPAN7 (Two-hybrid), YWHAE (Two-hybrid), KDELR1 (Two-hybrid), DGAT1 (Two-hybrid), AIG1 (Two-hybrid), TRPM4 (Two-hybrid), TTYH1 (Two-hybrid), OSTC (Two-hybrid), SAP130 (Two-hybrid)

ESM2 similar proteins: A0T2N3, F7EQ49, O08878, O70526, O88410, O88855, P30411, P46093, P46663, P48146, P49220, P49681, P49682, P49684, P50132, P51680, P51686, P56484, P79960, P97583, Q15722, Q1JQB3, Q1WLP9, Q28642, Q2TAD5, Q3BCU0, Q3T181, Q4KLH9, Q4VA82, Q56UD9, Q5KSK8, Q5MD61, Q61125, Q7SZP9, Q867B2, Q8BMP4, Q8BUD0, Q8HZN9, Q8HZP1, Q8HZP2

Diamond homologs: A0T2N3, A6QNL7, F5HDK1, F5HF62, F7EQ49, O00590, O08565, O08707, O08878, O09027, O54689, O54814, O55193, O62747, O88410, O97571, O97665, P09703, P0C7U4, P11613, P21109, P25024, P25025, P32246, P32248, P32302, P34997, P35343, P35344, P35351, P35374, P35407, P35411, P41597, P46092, P46094, P47774, P49238, P49682, P50052

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
CCL25	up-regulates	CCR9	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	53
Likely benign	1
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

2467 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:45901209:A:C	S141R	0.997
3:45901211:C:A	S141R	0.997
3:45901211:C:G	S141R	0.997
3:45901124:G:C	W112C	0.996
3:45901124:G:T	W112C	0.996
3:45900972:G:C	G62R	0.994
3:45901122:T:A	W112R	0.993
3:45901122:T:C	W112R	0.993
3:45901143:T:A	C119S	0.993
3:45901144:G:C	C119S	0.993
3:45901380:T:A	C198S	0.992
3:45901381:G:C	C198S	0.992
3:45901758:T:C	F324L	0.992
3:45901760:C:A	F324L	0.992
3:45901760:C:G	F324L	0.992
3:45900973:G:A	G62D	0.991
3:45900986:C:A	N66K	0.991
3:45900986:C:G	N66K	0.991
3:45901069:A:C	D94A	0.991
3:45901719:T:C	C311R	0.991
3:45901182:A:C	S132R	0.990
3:45901184:C:A	S132R	0.990
3:45901184:C:G	S132R	0.990
3:45901381:G:A	C198Y	0.990
3:45901575:T:C	F263L	0.990
3:45901577:T:A	F263L	0.990
3:45901577:T:G	F263L	0.990
3:45901716:A:C	S310R	0.990
3:45901718:T:A	S310R	0.990
3:45901718:T:G	S310R	0.990

dbSNP variants (sampled 300 via entrez): RS1000247122 (3:45889107 A>G), RS1000298349 (3:45902442 C>T), RS1001108102 (3:45891037 G>A,C,T), RS1001275860 (3:45890817 T>A), RS1001288822 (3:45890461 A>G), RS1001361791 (3:45897739 C>A), RS1001491953 (3:45896981 T>C,G), RS1001615056 (3:45903618 C>T), RS1001839341 (3:45897263 C>A,G,T), RS1002138119 (3:45885096 A>G), RS1002283295 (3:45892463 A>G), RS1002440591 (3:45898629 C>G), RS1002447733 (3:45897433 G>A,C), RS1002469175 (3:45884907 T>C), RS1003297147 (3:45895956 G>A)

Disease associations

OMIM: gene MIM:604738 | disease phenotypes: MIM:615994, MIM:142623

GenCC curated gene-disease

Mondo (2): Bardet-Biedl syndrome 17 (MONDO:0014445), Hirschsprung disease, susceptibility to, 1 (MONDO:0007723)

Orphanet (2): Bardet-Biedl syndrome (Orphanet:110), Hirschsprung disease (Orphanet:388)

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST000612_32	Celiac disease	3.000000e-17
GCST90000255_22	Severe COVID-19 infection with respiratory failure (analysis I)	1.000000e-10
GCST90000256_1	Severe COVID-19 infection with respiratory failure (analysis II)	9.000000e-12
GCST90013406_86	Liver enzyme levels (alkaline phosphatase)	6.000000e-17

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004533	alkaline phosphatase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5815 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 349 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL2178578	VERCIRNON	3	349

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — Chemokine receptors

Most potent curated ligand interactions (2 total), top 2:

Ligand	Action	Affinity	Parameter
vercirnon	Antagonist	8.22	pIC50
compound 24 [PMID: 26987013 ]	Antagonist	8.22	pKi

Binding affinities (BindingDB)

122 measured of 122 human assays (122 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
4-tert-butyl-N-[7-chloro-2-(2-methoxy-3-pyridinyl)-1,3-dioxoisoindol-4-yl]benzenesulfonamide	KI	3 nM	US-9969687: Compounds useful as CCR9 modulators
4-tert-butyl-N-[7-chloro-2-(2-cyanothiophen-3-yl)-1,3-dioxoisoindol-4-yl]benzenesulfonamide	KI	3 nM	US-9969687: Compounds useful as CCR9 modulators
4-tert-butyl-N-[7-chloro-2-(3-methyl-4-pyridinyl)-1,3-dioxoisoindol-4-yl]benzenesulfonamide	KI	3 nM	US-9969687: Compounds useful as CCR9 modulators
4-tert-butyl-N-[7-chloro-1,3-dioxo-2-(2-oxo-3H-pyridin-3-yl)isoindol-4-yl]benzenesulfonamide	KI	4 nM	US-9969687: Compounds useful as CCR9 modulators
4-tert-butyl-N-[7-chloro-2-(2-methoxy-1-oxidopyridin-1-ium-3-yl)-1,3-dioxoisoindol-4-yl]benzenesulfonamide	KI	6 nM	US-9969687: Compounds useful as CCR9 modulators
4-tert-butyl-N-[7-chloro-2-(2,6-dimethyl-3-pyridinyl)-1,3-dioxoisoindol-4-yl]benzenesulfonamide	KI	6 nM	US-9969687: Compounds useful as CCR9 modulators
4-tert-butyl-N-[7-chloro-2-(6-methyl-2-pyridinyl)-1,3-dioxoisoindol-4-yl]benzenesulfonamide	KI	6 nM	US-9969687: Compounds useful as CCR9 modulators
4-tert-butyl-N-[7-chloro-2-(2,6-dimethoxy-3-pyridinyl)-1,3-dioxoisoindol-4-yl]benzenesulfonamide	KI	6 nM	US-9969687: Compounds useful as CCR9 modulators
4-tert-butyl-N-[7-chloro-2-[(3-fluoro-1-oxidopyridin-1-ium-2-yl)methyl]-1,3-dioxoisoindol-4-yl]benzenesulfonamide	KI	7 nM	US-9969687: Compounds useful as CCR9 modulators
4-tert-butyl-N-[7-chloro-2-(2-methoxy-4-methyl-3-pyridinyl)-1,3-dioxoisoindol-4-yl]benzenesulfonamide	KI	9 nM	US-9969687: Compounds useful as CCR9 modulators
4-tert-butyl-N-[7-chloro-2-[(1-oxidopyridin-1-ium-2-yl)methyl]-1,3-dioxoisoindol-4-yl]benzenesulfonamide	KI	10 nM	US-9969687: Compounds useful as CCR9 modulators
3-[4-[(4-tert-butylphenyl)sulfonylamino]-7-chloro-1,3-dioxoisoindol-2-yl]pyridine-2-carboxylic acid	KI	10 nM	US-9969687: Compounds useful as CCR9 modulators
4-tert-butyl-N-[7-chloro-2-(2-methoxy-5-methyl-3-pyridinyl)-1,3-dioxoisoindol-4-yl]benzenesulfonamide	KI	11 nM	US-9969687: Compounds useful as CCR9 modulators
4-tert-butyl-N-[7-chloro-2-(2-methyl-3-pyridinyl)-1,3-dioxoisoindol-4-yl]benzenesulfonamide	KI	12 nM	US-9969687: Compounds useful as CCR9 modulators
4-tert-butyl-N-[7-chloro-2-(3-methylimidazol-4-yl)-1,3-dioxoisoindol-4-yl]benzenesulfonamide	KI	12 nM	US-9969687: Compounds useful as CCR9 modulators
4-tert-butyl-N-(7-chloro-1,3-dioxo-2-pyridin-2-ylisoindol-4-yl)benzenesulfonamide	KI	12 nM	US-9969687: Compounds useful as CCR9 modulators
4-tert-butyl-N-[7-chloro-1,3-dioxo-2-[(2-oxo-3H-pyridin-3-yl)methyl]isoindol-4-yl]benzenesulfonamide	KI	12 nM	US-9969687: Compounds useful as CCR9 modulators
4-tert-butyl-N-[7-chloro-2-(2-methyl-1-oxidopyridin-1-ium-3-yl)-1,3-dioxoisoindol-4-yl]benzenesulfonamide	KI	13 nM	US-9969687: Compounds useful as CCR9 modulators
4-tert-butyl-N-[7-chloro-2-(6-methoxy-2-methyl-3-pyridinyl)-1,3-dioxoisoindol-4-yl]benzenesulfonamide	KI	13 nM	US-9969687: Compounds useful as CCR9 modulators
ethyl 3-[4-[(4-tert-butylphenyl)sulfonylamino]-7-chloro-1,3-dioxoisoindol-2-yl]pyridine-2-carboxylate	KI	14 nM	US-9969687: Compounds useful as CCR9 modulators
ethyl 3-[4-[(4-tert-butylphenyl)sulfonylamino]-7-chloro-1,3-dioxoisoindol-2-yl]-1-oxidopyridin-1-ium-2-carboxylate	KI	14 nM	US-9969687: Compounds useful as CCR9 modulators
methyl 5-[4-[(4-tert-butylphenyl)sulfonylamino]-7-chloro-1,3-dioxoisoindol-2-yl]-1-methylpyrazole-3-carboxylate	KI	15 nM	US-9969687: Compounds useful as CCR9 modulators
4-tert-butyl-N-[7-chloro-2-[(4-methyl-3-pyridinyl)methyl]-1,3-dioxoisoindol-4-yl]benzenesulfonamide	KI	16 nM	US-9969687: Compounds useful as CCR9 modulators
methyl 3-[4-[(4-tert-butylphenyl)sulfonylamino]-7-chloro-1,3-dioxoisoindol-2-yl]-1-methylpyrazole-5-carboxylate	KI	16 nM	US-9969687: Compounds useful as CCR9 modulators
4-tert-butyl-N-[7-chloro-1,3-dioxo-2-(pyridin-4-ylmethyl)isoindol-4-yl]benzenesulfonamide	KI	17 nM	US-9969687: Compounds useful as CCR9 modulators
4-tert-butyl-N-[7-cyano-2-(5-methoxy-3-pyridinyl)-1,3-dioxoisoindol-4-yl]benzenesulfonamide	KI	17 nM	US-9969687: Compounds useful as CCR9 modulators
4-tert-butyl-N-[7-cyano-1,3-dioxo-2-(pyridin-2-ylmethyl)isoindol-4-yl]benzenesulfonamide	KI	17 nM	US-9969687: Compounds useful as CCR9 modulators
4-tert-butyl-N-[7-chloro-2-(2-cyano-5-methyl-3-pyridinyl)-1,3-dioxoisoindol-4-yl]benzenesulfonamide	KI	18 nM	US-9969687: Compounds useful as CCR9 modulators
4-tert-butyl-N-(7-chloro-1,3-dioxo-2-pyridin-4-ylisoindol-4-yl)benzenesulfonamide	KI	18 nM	US-9969687: Compounds useful as CCR9 modulators
4-tert-butyl-N-[7-chloro-2-[(4,6-dimethyl-2-oxo-3H-pyridin-3-yl)methyl]-1,3-dioxoisoindol-4-yl]benzenesulfonamide	KI	20 nM	US-9969687: Compounds useful as CCR9 modulators
4-tert-butyl-N-[7-chloro-2-[(1-methylpyrazol-3-yl)methyl]-1,3-dioxoisoindol-4-yl]benzenesulfonamide	KI	21 nM	US-9969687: Compounds useful as CCR9 modulators
4-tert-butyl-N-[7-chloro-2-(6-methyl-1-oxidopyridin-1-ium-2-yl)-1,3-dioxoisoindol-4-yl]benzenesulfonamide	KI	21 nM	US-9969687: Compounds useful as CCR9 modulators
4-tert-butyl-N-[7-chloro-2-(4-ethyl-5-methoxy-3-pyridinyl)-1,3-dioxoisoindol-4-yl]benzenesulfonamide	KI	21 nM	US-9969687: Compounds useful as CCR9 modulators
4-tert-butyl-N-[7-chloro-2-(5-methoxy-6-methyl-2-pyridinyl)-1,3-dioxoisoindol-4-yl]benzenesulfonamide	KI	22 nM	US-9969687: Compounds useful as CCR9 modulators
4-tert-butyl-N-[7-chloro-2-(2-methylpyrazol-3-yl)-1,3-dioxoisoindol-4-yl]benzenesulfonamide	KI	23 nM	US-9969687: Compounds useful as CCR9 modulators
4-tert-butyl-N-[7-chloro-2-(4-methyl-3-pyridinyl)-1,3-dioxoisoindol-4-yl]benzenesulfonamide	KI	23 nM	US-9969687: Compounds useful as CCR9 modulators
4-tert-butyl-N-[7-chloro-2-[(4-methyl-1-oxidopyridin-1-ium-3-yl)methyl]-1,3-dioxoisoindol-4-yl]benzenesulfonamide	KI	23 nM	US-9969687: Compounds useful as CCR9 modulators
4-tert-butyl-N-[7-chloro-2-(5-methyl-2-pyridinyl)-1,3-dioxoisoindol-4-yl]benzenesulfonamide	KI	23 nM	US-9969687: Compounds useful as CCR9 modulators
4-tert-butyl-N-[7-chloro-2-[(3-fluoro-2-pyridinyl)methyl]-1,3-dioxoisoindol-4-yl]benzenesulfonamide	KI	23 nM	US-9969687: Compounds useful as CCR9 modulators
4-tert-butyl-N-[7-chloro-2-(1-methyl-6-oxo-3-pyridinyl)-1,3-dioxoisoindol-4-yl]benzenesulfonamide	KI	23 nM	US-9969687: Compounds useful as CCR9 modulators
3-[4-[(4-tert-butylphenyl)sulfonylamino]-7-chloro-1,3-dioxoisoindol-2-yl]thiophene-2-carboxylic acid	KI	23 nM	US-9969687: Compounds useful as CCR9 modulators
4-tert-butyl-N-(7-chloro-1,3-dioxo-2-pyrazin-2-ylisoindol-4-yl)benzenesulfonamide	KI	24 nM	US-9969687: Compounds useful as CCR9 modulators
4-tert-butyl-N-[7-chloro-2-(2,5-dimethyl-3-pyridinyl)-1,3-dioxoisoindol-4-yl]benzenesulfonamide	KI	25 nM	US-9969687: Compounds useful as CCR9 modulators
4-tert-butyl-N-[7-chloro-2-(4-ethyl-5-methoxy-1-oxidopyridin-1-ium-3-yl)-1,3-dioxoisoindol-4-yl]benzenesulfonamide	KI	25 nM	US-9969687: Compounds useful as CCR9 modulators
4-tert-butyl-N-[7-chloro-2-(2-fluoro-3-pyridinyl)-1,3-dioxoisoindol-4-yl]benzenesulfonamide	KI	26 nM	US-9969687: Compounds useful as CCR9 modulators
4-tert-butyl-N-[7-chloro-1,3-dioxo-2-(pyridin-3-ylmethyl)isoindol-4-yl]benzenesulfonamide	KI	27 nM	US-9969687: Compounds useful as CCR9 modulators
4-tert-butyl-N-[7-chloro-2-(3-methyl-1-oxidopyridin-1-ium-4-yl)-1,3-dioxoisoindol-4-yl]benzenesulfonamide	KI	29 nM	US-9969687: Compounds useful as CCR9 modulators
4-tert-butyl-N-[7-chloro-1,3-dioxo-2-(pyrimidin-2-ylmethyl)isoindol-4-yl]benzenesulfonamide	KI	30 nM	US-9969687: Compounds useful as CCR9 modulators
4-tert-butyl-N-[7-chloro-2-(5-fluoro-2-pyridinyl)-1,3-dioxoisoindol-4-yl]benzenesulfonamide	KI	30 nM	US-9969687: Compounds useful as CCR9 modulators
4-tert-butyl-N-[7-chloro-2-(2,6-dimethyl-1-oxidopyridin-1-ium-3-yl)-1,3-dioxoisoindol-4-yl]benzenesulfonamide	KI	32 nM	US-9969687: Compounds useful as CCR9 modulators

ChEMBL bioactivities

399 potent at pChembl≥5 of 400 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.52	IC50	0.3	nM	CHEMBL3604484
9.30	Ki	0.5012	nM	CHEMBL6170963
9.28	Ki	0.53	nM	CHEMBL6170963
8.96	Ki	1.1	nM	VERCIRNON
8.82	IC50	1.5	nM	CHEMBL3814804
8.70	Ki	2	nM	CHEMBL3799487
8.66	Ki	2.188	nM	VERCIRNON
8.62	Ki	2.4	nM	VERCIRNON
8.59	IC50	2.6	nM	VERCIRNON
8.55	IC50	2.8	nM	VERCIRNON
8.52	Ki	3	nM	CHEMBL3799487
8.52	Ki	3	nM	CHEMBL3799229
8.52	Ki	3	nM	CHEMBL3800062
8.52	Ki	3	nM	CHEMBL5956921
8.52	Ki	3	nM	CHEMBL3798484
8.49	IC50	3.2	nM	CHEMBL3604486
8.49	IC50	3.2	nM	CHEMBL3604485
8.43	Ki	3.7	nM	VERCIRNON
8.42	IC50	3.8	nM	CHEMBL3604487
8.40	IC50	4	nM	CHEMBL3604489
8.40	Ki	4	nM	CHEMBL3798368
8.40	Ki	4	nM	CHEMBL5770499
8.30	Ki	5	nM	CHEMBL3799111
8.30	Ki	5	nM	CHEMBL3798186
8.30	IC50	5	nM	VERCIRNON
8.22	IC50	6	nM	VERCIRNON
8.22	IC50	6	nM	CHEMBL3604496
8.22	Ki	6	nM	CHEMBL3799111
8.22	Ki	6	nM	CHEMBL3798186
8.22	Ki	6	nM	CHEMBL3798368
8.22	Ki	6	nM	CHEMBL3798178
8.22	Ki	6	nM	CHEMBL3798484
8.22	Ki	6	nM	CHEMBL3798612
8.22	Ki	6	nM	CHEMBL3797271
8.22	Ki	6	nM	CHEMBL3798193
8.15	Ki	7	nM	CHEMBL3799829
8.15	Ki	7	nM	CHEMBL3799853
8.15	Ki	7	nM	CHEMBL5787355
8.10	Ki	8	nM	CHEMBL3800135
8.10	Ki	8	nM	CHEMBL3798193
8.10	IC50	8	nM	CHEMBL3814136
8.06	IC50	8.7	nM	CHEMBL3604483
8.05	IC50	9	nM	CHEMBL3604493
8.05	Ki	9	nM	CHEMBL3798612
8.05	Ki	9	nM	CHEMBL3800270
8.05	Ki	9	nM	CHEMBL3798723
8.00	IC50	10	nM	VERCIRNON
8.00	Ki	10	nM	VERCIRNON
8.00	Ki	10	nM	CHEMBL3798178
8.00	Ki	10	nM	CHEMBL3797882

PubChem BioAssay actives

176 with measured affinity, of 193 total; 50 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-tert-butyl-N-(4-chloro-2-pyrimidin-2-ylphenyl)benzenesulfonamide	1239784: Antagonist activity at CCR9 receptor (unknown origin) assessed as inhibition of TECK-induced calcium mobilization incubated for 10 mins prior to TECK induction	ic50	0.0003	uM
4-tert-butyl-N-[4-chloro-2-(1-oxidopyridin-1-ium-4-carbonyl)phenyl]benzenesulfonamide	1296738: Antagonist activity at CCR9 receptor in human MOLT4 cells assessed as inhibition of CCL25-induced increase in intracellular calcium level preincubated for 1 hr followed CCL25 addition by FLIPR assay	ki	0.0011	uM
1-[(4-tert-butylphenyl)methyl]-6-chloropyrrolo[3,2-c]pyridine-2-carboxylic acid	1306155: Antagonist activity at CCR9 (unknown origin) assessed as inhibition of TECK-stimulated calcium mobilization preincubated for 10 mins followed by agonist addition measured for 90 sec by fluo-8 dye-based FLIPR assay	ic50	0.0015	uM
4-tert-butyl-N-[7-chloro-2-(4-methoxy-3-pyridinyl)-1,3-dioxoisoindol-4-yl]benzenesulfonamide	1296738: Antagonist activity at CCR9 receptor in human MOLT4 cells assessed as inhibition of CCL25-induced increase in intracellular calcium level preincubated for 1 hr followed CCL25 addition by FLIPR assay	ki	0.0020	uM
4-tert-butyl-N-[7-chloro-2-(2-methyl-3-pyridinyl)-1,3-dioxoisoindol-4-yl]benzenesulfonamide	1296738: Antagonist activity at CCR9 receptor in human MOLT4 cells assessed as inhibition of CCL25-induced increase in intracellular calcium level preincubated for 1 hr followed CCL25 addition by FLIPR assay	ki	0.0030	uM
4-tert-butyl-N-[7-chloro-2-(2-methoxy-3-pyridinyl)-1,3-dioxoisoindol-4-yl]benzenesulfonamide	1296738: Antagonist activity at CCR9 receptor in human MOLT4 cells assessed as inhibition of CCL25-induced increase in intracellular calcium level preincubated for 1 hr followed CCL25 addition by FLIPR assay	ki	0.0030	uM
N-[2-(5-aminopyrimidin-4-yl)-4-chlorophenyl]-4-tert-butylbenzenesulfonamide	1239784: Antagonist activity at CCR9 receptor (unknown origin) assessed as inhibition of TECK-induced calcium mobilization incubated for 10 mins prior to TECK induction	ic50	0.0032	uM
N-[2-(3-aminopyrazin-2-yl)-4-chlorophenyl]-4-tert-butylbenzenesulfonamide	1239784: Antagonist activity at CCR9 receptor (unknown origin) assessed as inhibition of TECK-induced calcium mobilization incubated for 10 mins prior to TECK induction	ic50	0.0032	uM
N-[2-(4-aminopyridazin-3-yl)-4-chlorophenyl]-4-tert-butylbenzenesulfonamide	1239784: Antagonist activity at CCR9 receptor (unknown origin) assessed as inhibition of TECK-induced calcium mobilization incubated for 10 mins prior to TECK induction	ic50	0.0038	uM
N-[2-(2-amino-5-hydroxypyrimidin-4-yl)-4-chlorophenyl]-4-tert-butylbenzenesulfonamide	1239784: Antagonist activity at CCR9 receptor (unknown origin) assessed as inhibition of TECK-induced calcium mobilization incubated for 10 mins prior to TECK induction	ic50	0.0040	uM
4-tert-butyl-N-[7-chloro-2-(2-methoxy-1-oxidopyridin-1-ium-3-yl)-1,3-dioxoisoindol-4-yl]benzenesulfonamide	1296738: Antagonist activity at CCR9 receptor in human MOLT4 cells assessed as inhibition of CCL25-induced increase in intracellular calcium level preincubated for 1 hr followed CCL25 addition by FLIPR assay	ki	0.0040	uM
4-tert-butyl-N-[7-chloro-2-(2,6-dimethyl-3-pyridinyl)-1,3-dioxoisoindol-4-yl]benzenesulfonamide	1296738: Antagonist activity at CCR9 receptor in human MOLT4 cells assessed as inhibition of CCL25-induced increase in intracellular calcium level preincubated for 1 hr followed CCL25 addition by FLIPR assay	ki	0.0050	uM
4-tert-butyl-N-[7-chloro-2-(6-methyl-2-pyridinyl)-1,3-dioxoisoindol-4-yl]benzenesulfonamide	1296738: Antagonist activity at CCR9 receptor in human MOLT4 cells assessed as inhibition of CCL25-induced increase in intracellular calcium level preincubated for 1 hr followed CCL25 addition by FLIPR assay	ki	0.0050	uM
4-tert-butyl-N-[7-chloro-2-(2-methyl-1-oxidopyridin-1-ium-3-yl)-1,3-dioxoisoindol-4-yl]benzenesulfonamide	1296738: Antagonist activity at CCR9 receptor in human MOLT4 cells assessed as inhibition of CCL25-induced increase in intracellular calcium level preincubated for 1 hr followed CCL25 addition by FLIPR assay	ki	0.0060	uM
4-tert-butyl-N-(7-chloro-1,3-dioxo-2-pyridin-2-ylisoindol-4-yl)benzenesulfonamide	1296738: Antagonist activity at CCR9 receptor in human MOLT4 cells assessed as inhibition of CCL25-induced increase in intracellular calcium level preincubated for 1 hr followed CCL25 addition by FLIPR assay	ki	0.0060	uM
4-tert-butyl-N-[7-chloro-2-(3-methyl-4-pyridinyl)-1,3-dioxoisoindol-4-yl]benzenesulfonamide	1296738: Antagonist activity at CCR9 receptor in human MOLT4 cells assessed as inhibition of CCL25-induced increase in intracellular calcium level preincubated for 1 hr followed CCL25 addition by FLIPR assay	ki	0.0060	uM
4-tert-butyl-N-[4-chloro-2-(6-ethyl-5-hydroxypyrimidin-4-yl)phenyl]benzenesulfonamide	1239784: Antagonist activity at CCR9 receptor (unknown origin) assessed as inhibition of TECK-induced calcium mobilization incubated for 10 mins prior to TECK induction	ic50	0.0060	uM
4-tert-butyl-N-[7-chloro-2-[(1-oxidopyridin-1-ium-2-yl)methyl]-1,3-dioxoisoindol-4-yl]benzenesulfonamide	1296738: Antagonist activity at CCR9 receptor in human MOLT4 cells assessed as inhibition of CCL25-induced increase in intracellular calcium level preincubated for 1 hr followed CCL25 addition by FLIPR assay	ki	0.0060	uM
4-tert-butyl-N-[7-chloro-2-(4-methyl-3-pyridinyl)-1,3-dioxoisoindol-4-yl]benzenesulfonamide	1296738: Antagonist activity at CCR9 receptor in human MOLT4 cells assessed as inhibition of CCL25-induced increase in intracellular calcium level preincubated for 1 hr followed CCL25 addition by FLIPR assay	ki	0.0070	uM
4-tert-butyl-N-[7-chloro-2-(2-fluoro-3-pyridinyl)-1,3-dioxoisoindol-4-yl]benzenesulfonamide	1296738: Antagonist activity at CCR9 receptor in human MOLT4 cells assessed as inhibition of CCL25-induced increase in intracellular calcium level preincubated for 1 hr followed CCL25 addition by FLIPR assay	ki	0.0070	uM
4-tert-butyl-N-[7-chloro-1,3-dioxo-2-(pyridin-4-ylmethyl)isoindol-4-yl]benzenesulfonamide	1296738: Antagonist activity at CCR9 receptor in human MOLT4 cells assessed as inhibition of CCL25-induced increase in intracellular calcium level preincubated for 1 hr followed CCL25 addition by FLIPR assay	ki	0.0080	uM
4-tert-butyl-N-[7-chloro-2-(2,6-dimethoxy-3-pyridinyl)-1,3-dioxoisoindol-4-yl]benzenesulfonamide	1296738: Antagonist activity at CCR9 receptor in human MOLT4 cells assessed as inhibition of CCL25-induced increase in intracellular calcium level preincubated for 1 hr followed CCL25 addition by FLIPR assay	ki	0.0080	uM
1-[(4-tert-butylphenyl)methyl]-6-cyanoindole-2-carboxylic acid	1306155: Antagonist activity at CCR9 (unknown origin) assessed as inhibition of TECK-stimulated calcium mobilization preincubated for 10 mins followed by agonist addition measured for 90 sec by fluo-8 dye-based FLIPR assay	ic50	0.0080	uM
4-tert-butyl-N-[4-chloro-2-[3-hydroxy-4-(hydroxymethyl)-2-pyridinyl]phenyl]benzenesulfonamide	1239784: Antagonist activity at CCR9 receptor (unknown origin) assessed as inhibition of TECK-induced calcium mobilization incubated for 10 mins prior to TECK induction	ic50	0.0087	uM
4-tert-butyl-N-[7-chloro-2-(4-ethoxy-3-pyridinyl)-1,3-dioxoisoindol-4-yl]benzenesulfonamide	1296738: Antagonist activity at CCR9 receptor in human MOLT4 cells assessed as inhibition of CCL25-induced increase in intracellular calcium level preincubated for 1 hr followed CCL25 addition by FLIPR assay	ki	0.0090	uM
4-tert-butyl-N-[4-chloro-2-[6-(dimethylamino)-5-hydroxypyrimidin-4-yl]phenyl]benzenesulfonamide	1239784: Antagonist activity at CCR9 receptor (unknown origin) assessed as inhibition of TECK-induced calcium mobilization incubated for 10 mins prior to TECK induction	ic50	0.0090	uM
methyl 3-[(1R)-1-(3,4-difluorophenyl)propyl]-5-(1,2-oxazol-5-yl)-2-sulfanylidene-1H-imidazole-4-carboxylate	1957049: Inhibition of human CCR9 in recombinant MCP-1-induced calcium mobilization in THP-1 cells	ic50	0.0100	uM
4-tert-butyl-N-[7-chloro-2-(5-fluoro-2-pyridinyl)-1,3-dioxoisoindol-4-yl]benzenesulfonamide	1296738: Antagonist activity at CCR9 receptor in human MOLT4 cells assessed as inhibition of CCL25-induced increase in intracellular calcium level preincubated for 1 hr followed CCL25 addition by FLIPR assay	ki	0.0100	uM
4-tert-butyl-N-[7-chloro-2-(2,5-dimethyl-3-pyridinyl)-1,3-dioxoisoindol-4-yl]benzenesulfonamide	1296738: Antagonist activity at CCR9 receptor in human MOLT4 cells assessed as inhibition of CCL25-induced increase in intracellular calcium level preincubated for 1 hr followed CCL25 addition by FLIPR assay	ki	0.0110	uM
4-tert-butyl-N-(7-chloro-1,3-dioxo-2-pyridin-4-ylisoindol-4-yl)benzenesulfonamide	1296738: Antagonist activity at CCR9 receptor in human MOLT4 cells assessed as inhibition of CCL25-induced increase in intracellular calcium level preincubated for 1 hr followed CCL25 addition by FLIPR assay	ki	0.0110	uM
4-tert-butyl-N-[4-chloro-2-(5-hydroxypyrimidin-4-yl)phenyl]benzenesulfonamide	1239784: Antagonist activity at CCR9 receptor (unknown origin) assessed as inhibition of TECK-induced calcium mobilization incubated for 10 mins prior to TECK induction	ic50	0.0110	uM
4-tert-butyl-N-[4-chloro-2-[5-hydroxy-6-(hydroxymethyl)pyrimidin-4-yl]phenyl]benzenesulfonamide	1239784: Antagonist activity at CCR9 receptor (unknown origin) assessed as inhibition of TECK-induced calcium mobilization incubated for 10 mins prior to TECK induction	ic50	0.0110	uM
4-tert-butyl-N-[7-chloro-2-[(4-methyl-1-oxidopyridin-1-ium-3-yl)methyl]-1,3-dioxoisoindol-4-yl]benzenesulfonamide	1296738: Antagonist activity at CCR9 receptor in human MOLT4 cells assessed as inhibition of CCL25-induced increase in intracellular calcium level preincubated for 1 hr followed CCL25 addition by FLIPR assay	ki	0.0120	uM
4-tert-butyl-N-[7-chloro-2-[(1-oxidopyridin-1-ium-3-yl)methyl]-1,3-dioxoisoindol-4-yl]benzenesulfonamide	1296738: Antagonist activity at CCR9 receptor in human MOLT4 cells assessed as inhibition of CCL25-induced increase in intracellular calcium level preincubated for 1 hr followed CCL25 addition by FLIPR assay	ki	0.0130	uM
4-tert-butyl-N-[7-chloro-2-[(3-fluoro-2-pyridinyl)methyl]-1,3-dioxoisoindol-4-yl]benzenesulfonamide	1296738: Antagonist activity at CCR9 receptor in human MOLT4 cells assessed as inhibition of CCL25-induced increase in intracellular calcium level preincubated for 1 hr followed CCL25 addition by FLIPR assay	ki	0.0130	uM
4-tert-butyl-N-[7-chloro-2-[(5-methyl-1-oxidopyridin-1-ium-2-yl)methyl]-1,3-dioxoisoindol-4-yl]benzenesulfonamide	1296738: Antagonist activity at CCR9 receptor in human MOLT4 cells assessed as inhibition of CCL25-induced increase in intracellular calcium level preincubated for 1 hr followed CCL25 addition by FLIPR assay	ki	0.0130	uM
4-tert-butyl-N-[7-chloro-2-(6-methoxy-2-methyl-3-pyridinyl)-1,3-dioxoisoindol-4-yl]benzenesulfonamide	1296738: Antagonist activity at CCR9 receptor in human MOLT4 cells assessed as inhibition of CCL25-induced increase in intracellular calcium level preincubated for 1 hr followed CCL25 addition by FLIPR assay	ki	0.0140	uM
N-[2-(6-amino-5-hydroxypyrimidin-4-yl)-4-chlorophenyl]-4-tert-butylbenzenesulfonamide	1239784: Antagonist activity at CCR9 receptor (unknown origin) assessed as inhibition of TECK-induced calcium mobilization incubated for 10 mins prior to TECK induction	ic50	0.0140	uM
4-tert-butyl-N-[7-chloro-2-(1-oxidopyridin-1-ium-3-yl)-1,3-dioxoisoindol-4-yl]benzenesulfonamide	1296738: Antagonist activity at CCR9 receptor in human MOLT4 cells assessed as inhibition of CCL25-induced increase in intracellular calcium level preincubated for 1 hr followed CCL25 addition by FLIPR assay	ki	0.0160	uM
4-tert-butyl-N-[7-chloro-2-(2-methoxy-5-methyl-3-pyridinyl)-1,3-dioxoisoindol-4-yl]benzenesulfonamide	1296738: Antagonist activity at CCR9 receptor in human MOLT4 cells assessed as inhibition of CCL25-induced increase in intracellular calcium level preincubated for 1 hr followed CCL25 addition by FLIPR assay	ki	0.0160	uM
4-tert-butyl-N-[7-chloro-2-(5-methoxy-6-methyl-2-pyridinyl)-1,3-dioxoisoindol-4-yl]benzenesulfonamide	1296738: Antagonist activity at CCR9 receptor in human MOLT4 cells assessed as inhibition of CCL25-induced increase in intracellular calcium level preincubated for 1 hr followed CCL25 addition by FLIPR assay	ki	0.0160	uM
4-tert-butyl-N-[7-chloro-2-(2-cyano-5-methyl-3-pyridinyl)-1,3-dioxoisoindol-4-yl]benzenesulfonamide	1296738: Antagonist activity at CCR9 receptor in human MOLT4 cells assessed as inhibition of CCL25-induced increase in intracellular calcium level preincubated for 1 hr followed CCL25 addition by FLIPR assay	ki	0.0180	uM
4-tert-butyl-N-[7-chloro-2-(5-methoxy-4-methyl-3-pyridinyl)-1,3-dioxoisoindol-4-yl]benzenesulfonamide	1296738: Antagonist activity at CCR9 receptor in human MOLT4 cells assessed as inhibition of CCL25-induced increase in intracellular calcium level preincubated for 1 hr followed CCL25 addition by FLIPR assay	ki	0.0180	uM
4-tert-butyl-N-[7-cyano-1,3-dioxo-2-(pyridin-3-ylmethyl)isoindol-4-yl]benzenesulfonamide	1296738: Antagonist activity at CCR9 receptor in human MOLT4 cells assessed as inhibition of CCL25-induced increase in intracellular calcium level preincubated for 1 hr followed CCL25 addition by FLIPR assay	ki	0.0190	uM
4-tert-butyl-N-[7-chloro-2-(6-methyl-3-pyridinyl)-1,3-dioxoisoindol-4-yl]benzenesulfonamide	1296738: Antagonist activity at CCR9 receptor in human MOLT4 cells assessed as inhibition of CCL25-induced increase in intracellular calcium level preincubated for 1 hr followed CCL25 addition by FLIPR assay	ki	0.0190	uM
4-tert-butyl-N-[7-chloro-2-(6-fluoro-3-pyridinyl)-1,3-dioxoisoindol-4-yl]benzenesulfonamide	1296738: Antagonist activity at CCR9 receptor in human MOLT4 cells assessed as inhibition of CCL25-induced increase in intracellular calcium level preincubated for 1 hr followed CCL25 addition by FLIPR assay	ki	0.0190	uM
4-tert-butyl-N-[7-chloro-1,3-dioxo-2-(pyridin-2-ylmethyl)isoindol-4-yl]benzenesulfonamide	1296738: Antagonist activity at CCR9 receptor in human MOLT4 cells assessed as inhibition of CCL25-induced increase in intracellular calcium level preincubated for 1 hr followed CCL25 addition by FLIPR assay	ki	0.0200	uM
1-[(4-tert-butylphenyl)methyl]-6-chloropyrrolo[3,2-b]pyridine-2-carboxylic acid	1306155: Antagonist activity at CCR9 (unknown origin) assessed as inhibition of TECK-stimulated calcium mobilization preincubated for 10 mins followed by agonist addition measured for 90 sec by fluo-8 dye-based FLIPR assay	ic50	0.0200	uM
4-tert-butyl-N-[7-chloro-2-(5-methyl-2-pyridinyl)-1,3-dioxoisoindol-4-yl]benzenesulfonamide	1296738: Antagonist activity at CCR9 receptor in human MOLT4 cells assessed as inhibition of CCL25-induced increase in intracellular calcium level preincubated for 1 hr followed CCL25 addition by FLIPR assay	ki	0.0210	uM
4-tert-butyl-N-[7-chloro-1,3-dioxo-2-(pyridin-3-ylmethyl)isoindol-4-yl]benzenesulfonamide	1296738: Antagonist activity at CCR9 receptor in human MOLT4 cells assessed as inhibition of CCL25-induced increase in intracellular calcium level preincubated for 1 hr followed CCL25 addition by FLIPR assay	ki	0.0220	uM

CTD chemical–gene interactions

8 total (human), top 8 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
quercitrin	decreases expression	1
Amiodarone	increases expression	1
Benzo(a)pyrene	increases expression	1
Calcium	affects abundance	1
Ozone	increases expression	1
Zinc	increases expression	1
Aflatoxin B1	increases methylation	1
Okadaic Acid	decreases expression	1

ChEMBL screening assays

30 unique, capped per target: 17 binding, 13 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2184856	Functional	Antagonist activity at CCR9 assessed as inhibition of CCL25-induced chemotaxis by cell based assay	Chemokine receptor antagonists. — J Med Chem
CHEMBL2184877	Binding	Binding affinity to CCR9	Chemokine receptor antagonists. — J Med Chem

Cellosaurus cell lines

5 cell lines: 3 cancer cell line, 2 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B8CS	Abcam HCT 116 CCR9 KO	Cancer cell line	Male
CVCL_B9F0	Abcam A-549 CCR9 KO	Cancer cell line	Male
CVCL_D2E6	Abcam MCF-7 CCR9 KO	Cancer cell line	Female
CVCL_D2SF	CHO/hCCR9	Spontaneously immortalized cell line	Female
CVCL_KW63	PathHunter CHO-K1 CCR9 beta-arrestin	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02343562	PHASE4	UNKNOWN	Probiotics for Prophylaxis of Postoperative Hirschsprungs Associated Enterocolitis
NCT07186647	PHASE4	COMPLETED	Laparoscopic-Assisted Transanal Pull-Through for Hirschsprung Disease in Pediatric:Short and Intermediate Outcomes of Two Different Techniques
NCT04904081	PHASE3	UNKNOWN	Feasibility of Use of Indocyanine Green in Pediatric Colorectal Surgery
NCT00630838	PHASE2	COMPLETED	Probiotic Prophylaxis of Hirschprung’s Disease Associated Enterocolitis (HAEC)
NCT01985646	EARLY_PHASE1	COMPLETED	A Trial on Conservative Treatment for Infants’ Hirschsprung Disease
NCT00478712	Not specified	RECRUITING	Hirschsprung Disease Genetic Study
NCT01515501	Not specified	COMPLETED	Endoscopic Mucosal Resection for the Diagnosis of a-Ganglionosis, a Controlled Prospective Trial (EDGE Trial)
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT01927809	Not specified	UNKNOWN	Genetic Mosaicism in Hirschsprung’s Disease
NCT02193685	Not specified	UNKNOWN	Identification Genetic, Immunologic and Microbial Markers of Hirschsprung Associated Enterocolitis in Children With Hirschsprung Disease
NCT02216994	Not specified	UNKNOWN	A New Scoring System Improves Diagnostic Accuracy of Intestinal Dysganglionosis –a Prospective Study
NCT02296008	Not specified	COMPLETED	3D High Resolution Anorectal Manometry in Children After Surgery for Anorectal Disorders
NCT02776176	Not specified	UNKNOWN	Enhanced Recovery After Surgery In Hirschsprung Disease
NCT02857205	Not specified	COMPLETED	MICROPRUNG : Intestinal Microbiota Analysis in Patients With or Without Hirschsprung’s Associated EnteroColitis
NCT03269812	Not specified	UNKNOWN	Laparoscopic Assisted Pull-through Versus Other Surgical Procedures for Treatment of Hirschsprung Disease
NCT03666767	Not specified	COMPLETED	Management and Outcomes of Congenital Anomalies in Low-, Middle- and High-Income Countries
NCT04020939	Not specified	COMPLETED	The Role of Indocyanine Green Angiography Fluorescence on Intestinal Resections in Pediatric Surgery.
NCT04106947	Not specified	UNKNOWN	Transition of Care for Patients With Hirschsprung Disease and Anorectal Malformations
NCT04149093	Not specified	UNKNOWN	The Association Between Calretinin and the Function of Ganglion Cells in Hirschsprung Disease
NCT04150120	Not specified	COMPLETED	eHealth as an Aid for Facilitating and Supporting Self-management in Families With Long-term Childhood Illness
NCT04213976	Not specified	UNKNOWN	Ostomy in Continuity or Conventional Ileostomy: a Retrospective Multicentric Analysis
NCT04476225	Not specified	COMPLETED	Induced Pluripotent Stem Cells for Disease Research
NCT04598841	Not specified	COMPLETED	Nutrition Support for Hirschsprung Disease
NCT04622410	Not specified	RECRUITING	Registry for Hirschsprung Disease of the BELAPS
NCT04624334	Not specified	TERMINATED	Non-invasive Assessment of Colonic Motility
NCT04730128	Not specified	COMPLETED	Translation and Validation of a Disease-specific Questionnaire for Hirschsprung’s Disease in Danish Patients
NCT04837963	Not specified	COMPLETED	Does Hirschsprung Disease Increase the Risk of Febrile Urinary Tract Infection in Children
NCT04957667	Not specified	COMPLETED	Scintigraphic Defecography for Evaluation of Functional Outcome in an Adult Hirschsprung Population
NCT05038345	Not specified	TERMINATED	Hirschsprung Disease Trends in the United States: Analysis of the National Inpatient Sample
NCT05044741	Not specified	COMPLETED	Risk Factors of Perforated HSCR in Neonates
NCT05293353	Not specified	UNKNOWN	Neokare Safety and Tolerability Assessment in Neonates With GI Problems
NCT05307419	Not specified	UNKNOWN	Full Thickness vs. Rectal Suction Biopsy in the Diagnosis of Hirschsprungs Disease
NCT05450991	Not specified	RECRUITING	Long-term Qualitative and Quantitative Outcomes of Children With Hirschsprung’s Disease and Anorectal Malformations
NCT05655845	Not specified	UNKNOWN	Risk Factors for Bowel Dysfunction at Preschool and Early Childhood Age in Children With Hirschsprung Disease
NCT06072976	Not specified	RECRUITING	The Influence of Feeding Source on the Gut Microbiome and Time to Full Feeds in Neonates With Congenital Gastrointestinal Pathologies
NCT06197061	Not specified	UNKNOWN	Comparison of Robot-assisted With Laparoscopic-assisted Modified Soave Procedure for Classical Hirschsprung Disease
NCT06573723	Not specified	RECRUITING	Institutional Registry of Rare Diseases
NCT06590142	Not specified	RECRUITING	Hirschsprung’s Advances; Working Towards Autologous tIssue therapIes
NCT06592534	Not specified	NOT_YET_RECRUITING	Babies With Enterocolitis - A Study of Faecal Calprotectin in Hirschsprung Disease (The BEACH Study)
NCT06650683	Not specified	RECRUITING	Impact of Providing Nursing Support on Parental Stress Related to Preoperative Care of a Newborn with Hirschsprung’s Disease