ACKR2

Summary

ACKR2 (atypical chemokine receptor 2, HGNC:1565) is a protein-coding gene on chromosome 3p22.1, encoding Atypical chemokine receptor 2 (O00590). 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.

This gene encodes a beta chemokine receptor, which is predicted to be a seven transmembrane protein similar to G protein-coupled receptors. Chemokines and their receptor-mediated signal transduction are critical for the recruitment of effector immune cells to the inflammation site. This gene is expressed in a range of tissues and hemopoietic cells. The expression of this receptor in lymphatic endothelial cells and overexpression in vascular tumors suggested its function in chemokine-driven recirculation of leukocytes and possible chemokine effects on the development and growth of vascular tumors. This receptor appears to bind the majority of beta-chemokine family members; however, its specific function remains unknown. This gene is mapped to chromosome 3p21.3, a region that includes a cluster of chemokine receptor genes.

Source: NCBI Gene 1238 — RefSeq curated summary.

At a glance

• GWAS associations: 48 (top 2% of genes corpus-wide)
• Clinical variants (ClinVar): 118 total
• GTEx eGene: eQTL in 21 tissues, sQTL in 4 (q < 0.05)
• Constraint (gnomAD): pLI 0.12 (intermediate), LOEUF 1.93 (unconstrained)
• MANE Select transcript: NM_001296
• Notable: 118 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1565
Approved symbol	ACKR2
Name	atypical chemokine receptor 2
Location	3p22.1
Locus type	gene with protein product
Status	Approved
Aliases	CCR10, D6, CCR9
Ensembl gene	ENSG00000144648
Ensembl biotype	protein_coding
OMIM	602648
Entrez	1238

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 22 protein_coding, 5 protein_coding_CDS_not_defined

MANE Select: ENST00000422265

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 1, TSL 3: 3, TSL 4: 5

ENST00000422265, ENST00000442925, ENST00000460855, ENST00000463699, ENST00000480215, ENST00000492609, ENST00000493193, ENST00000494619, ENST00000497921, ENST00000498111, ENST00000565749, ENST00000865513, ENST00000865514, ENST00000865515, ENST00000865516, ENST00000865517, ENST00000865518, ENST00000865519, ENST00000865520, ENST00000865521, ENST00000865522, ENST00000865523, ENST00000865524, ENST00000913479, ENST00000947398, ENST00001115807, ENST00001131230

RefSeq mRNA: 1 — MANE Select: NM_001296 NM_001296

CCDS: CCDS2706

Canonical transcript exons

ENST00000422265 — 3 exons

Exon	Start	End
ENSE00003705950	42819631	42819711
ENSE00003841923	42809445	42809532
ENSE00003845476	42864466	42867286

Expression profiles

Bgee: expression breadth ubiquitous, 173 present calls, max score 80.53.

FANTOM5 (CAGE): breadth broad, TPM avg 1.5616 / max 259.6155, expressed in 212 samples.

Highest expression (Bgee): placenta, lobe of liver, male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, tibial nerve.

Genetic regulation across tissues (GTEx eQTL / sQTL)

ACKR2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 21 tissues and its splicing (sQTL) in 4 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 25 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Nerve Tibial	sqtl	8.8e-07	+0.32	3:42872353:T:C
Skin Sun Exposed Lower leg	eqtl	4.8e-06	+0.75	3:42875019:C:A
Brain Cortex	eqtl	3.0e-05	-0.44	3:42706056:G:A
Esophagus Mucosa	eqtl	1.1e-04	-0.20	3:42809057:G:A
Brain Hippocampus	eqtl	5.4e-04	-0.44	3:42758273:G:A
Brain Anterior cingulate cortex BA24	eqtl	9.1e-04	-0.38	3:42809057:G:A
Pituitary	eqtl	9.6e-04	-0.34	3:42758799:T:C
Brain Frontal Cortex BA9	eqtl	1.0e-03	-0.36	3:42691447:A:G
Brain Nucleus accumbens basal ganglia	eqtl	1.4e-03	-0.37	3:42868195:A:G
Skin Not Sun Exposed Suprapubic	eqtl	2.2e-03	+0.20	3:42873893:T:C
Nerve Tibial	eqtl	2.8e-03	+0.12	3:42838535:GACTGACCAT:G
Artery Tibial	eqtl	3.1e-03	+0.14	3:42827724:G:A
Brain Amygdala	eqtl	3.9e-03	-1.05	3:42768995:G:A
Thyroid	eqtl	3.9e-03	+0.16	3:42874386:C:T
Testis	sqtl	5.3e-03	-0.49	3:42816265:A:G
Brain Caudate basal ganglia	eqtl	6.0e-03	-0.31	3:42793445:C:A
Whole Blood	eqtl	7.2e-03	-0.59	3:42266332:G:A
Esophagus Muscularis	eqtl	9.2e-03	+0.29	3:42836230:G:A
Adipose Subcutaneous	eqtl	1.4e-02	+0.38	3:42811147:G:A
Muscle Skeletal	eqtl	1.6e-02	-0.46	3:42759843:T:TA

FANTOM5 promoters

10 alternative TSS:

Promoter ID	TPM avg	Samples expressed
36283	0.7772	74
36284	0.5950	42
36282	0.1566	35
36286	0.1514	69
36292	0.1423	1
36288	0.1301	42
36289	0.1203	61
36285	0.0365	18
36290	0.0294	7
36291	0.0178	6

Top tissues by expression

showing 100 of 285 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
placenta	UBERON:0001987	80.53	gold quality
right lobe of liver	UBERON:0001114	79.17	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.80	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	78.35	gold quality
tibial nerve	UBERON:0001323	75.58	gold quality
liver	UBERON:0002107	72.10	gold quality
sural nerve	UBERON:0015488	71.93	gold quality
subcutaneous adipose tissue	UBERON:0002190	71.58	gold quality
tibialis anterior	UBERON:0001385	71.51	silver quality
mucosa of transverse colon	UBERON:0004991	69.58	gold quality
left coronary artery	UBERON:0001626	68.84	gold quality
endothelial cell	CL:0000115	68.53	gold quality
omental fat pad	UBERON:0010414	68.46	gold quality
popliteal artery	UBERON:0002250	68.45	gold quality
tibial artery	UBERON:0007610	68.43	gold quality
peritoneum	UBERON:0002358	68.39	gold quality
right lobe of thyroid gland	UBERON:0001119	68.36	gold quality
left lobe of thyroid gland	UBERON:0001120	68.05	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	67.67	gold quality
amniotic fluid	UBERON:0000173	67.08	silver quality
coronary artery	UBERON:0001621	67.08	gold quality
lower esophagus muscularis layer	UBERON:0035833	67.07	gold quality
thyroid gland	UBERON:0002046	67.05	gold quality
rectum	UBERON:0001052	67.00	gold quality
adipose tissue of abdominal region	UBERON:0007808	66.99	gold quality
lower esophagus	UBERON:0013473	66.95	gold quality
colonic epithelium	UBERON:0000397	66.87	silver quality
C1 segment of cervical spinal cord	UBERON:0006469	66.60	gold quality
skin of leg	UBERON:0001511	66.51	gold quality
mucosa of stomach	UBERON:0001199	66.19	gold quality
right coronary artery	UBERON:0001625	66.16	gold quality
cervix squamous epithelium	UBERON:0006922	65.83	gold quality
skin of hip	UBERON:0001554	65.80	gold quality
ectocervix	UBERON:0012249	65.46	gold quality
right uterine tube	UBERON:0001302	65.44	gold quality
esophagus	UBERON:0001043	65.39	gold quality
minor salivary gland	UBERON:0001830	65.17	gold quality
left uterine tube	UBERON:0001303	64.98	gold quality
aorta	UBERON:0000947	64.78	gold quality
spinal cord	UBERON:0002240	64.41	gold quality
vagina	UBERON:0000996	64.30	gold quality
transverse colon	UBERON:0001157	64.17	gold quality
gall bladder	UBERON:0002110	64.14	gold quality
esophagus mucosa	UBERON:0002469	64.03	gold quality
adipose tissue	UBERON:0001013	63.68	gold quality
right atrium auricular region	UBERON:0006631	63.49	gold quality
upper lobe of left lung	UBERON:0008952	63.23	gold quality
calcaneal tendon	UBERON:0003701	63.04	gold quality
connective tissue	UBERON:0002384	63.01	gold quality
smooth muscle tissue	UBERON:0001135	62.86	gold quality
ileal mucosa	UBERON:0000331	62.83	silver quality
decidua	UBERON:0002450	62.52	silver quality
tonsil	UBERON:0002372	62.50	gold quality
hindlimb stylopod muscle	UBERON:0004252	62.50	gold quality
mouth mucosa	UBERON:0003729	62.39	gold quality
apex of heart	UBERON:0002098	62.33	gold quality
saliva-secreting gland	UBERON:0001044	62.30	gold quality
deltoid	UBERON:0001476	62.23	silver quality
cardiac atrium	UBERON:0002081	62.10	gold quality
upper lobe of lung	UBERON:0008948	61.46	gold quality
right lung	UBERON:0002167	61.45	gold quality
metanephros cortex	UBERON:0010533	61.36	gold quality
zone of skin	UBERON:0000014	61.31	gold quality
vermiform appendix	UBERON:0001154	61.25	gold quality
Brodmann (1909) area 10	UBERON:0013541	60.97	gold quality
fallopian tube	UBERON:0003889	60.90	gold quality
paraflocculus	UBERON:0005351	60.77	gold quality
left adrenal gland	UBERON:0001234	60.61	gold quality
skin of abdomen	UBERON:0001416	60.54	gold quality
lymph node	UBERON:0000029	60.50	gold quality
gastrocnemius	UBERON:0001388	60.37	gold quality
lower esophagus mucosa	UBERON:0035834	60.30	gold quality
thoracic aorta	UBERON:0001515	60.24	gold quality
heart	UBERON:0000948	60.15	gold quality
muscle of leg	UBERON:0001383	60.08	gold quality
ascending aorta	UBERON:0001496	60.06	gold quality
tendon	UBERON:0000043	59.96	gold quality
frontal pole	UBERON:0002795	59.96	gold quality
left adrenal gland cortex	UBERON:0035825	59.89	gold quality
middle frontal gyrus	UBERON:0002702	59.82	gold quality
cauda epididymis	UBERON:0004360	59.75	gold quality
adrenal gland	UBERON:0002369	59.74	gold quality
uterine cervix	UBERON:0000002	59.66	gold quality
endometrium epithelium	UBERON:0004811	59.36	gold quality
descending thoracic aorta	UBERON:0002345	59.28	gold quality
colon	UBERON:0001155	59.24	gold quality
heart left ventricle	UBERON:0002084	59.15	gold quality
body of stomach	UBERON:0001161	59.11	gold quality
islet of Langerhans	UBERON:0000006	58.86	gold quality
nasal cavity epithelium	UBERON:0005384	58.86	gold quality
right adrenal gland	UBERON:0001233	58.74	gold quality
large intestine	UBERON:0000059	58.72	gold quality
upper leg skin	UBERON:0004262	58.67	gold quality
muscle organ	UBERON:0001630	58.58	gold quality
cardiac ventricle	UBERON:0002082	58.57	gold quality
muscle layer of sigmoid colon	UBERON:0035805	58.44	gold quality
anatomical system	UBERON:0000467	58.41	gold quality
right adrenal gland cortex	UBERON:0035827	58.35	gold quality
stomach	UBERON:0000945	58.27	gold quality
intestine	UBERON:0000160	58.22	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-6678	yes	16.26
E-ANND-3	yes	7.64

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 209 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Thymus	tissue	120.8
Locus coeruleus	tissue	20.2
Pituitary gland	tissue	19.6
Placenta	tissue	15.0	high
Liver	tissue	8.8	not detected
Postcentral gyrus	tissue	8.3
Caudate putamen	tissue	7.9
Choroid plexus	tissue	7.2
Postcentral gyrus	tissue	6.9
Hippocampus	tissue	6.7	not detected
Nucleus accumbens	tissue	6.4
Cerebral cortex	tissue	6.4	low
Somatosensory cortex	tissue	6.4
Locus coeruleus	tissue	6.1
Hippocampus	tissue	6.1	low
Nucleus accumbens	tissue	5.9
Occipital cortex	tissue	5.6
Small intestine	tissue	5.3	not detected
Motor cortex	tissue	5.3
Putamen	tissue	5.0
Frontal cortex	tissue	4.8
Temporal cortex	tissue	4.4
Superior colliculi	tissue	4.3
Hippocampal formation	tissue	4.3
Entorhinal cortex	tissue	4.3
Substantia nigra	tissue	4.2
Prefrontal cortex	tissue	4.2
Retrosplenial and cingulate cortex	tissue	4.2
Adipose tissue	tissue	4.1	low
Thalamus	tissue	3.8
Duodenum	tissue	3.7	not detected
Adipose tissue	tissue	3.7	not detected
Basal ganglia	tissue	3.7	not detected
Retrosplenial cortex	tissue	3.7
Pons	tissue	3.6
Skeletal muscle	tissue	3.5	medium
Insular cortex	tissue	3.4
Superior colliculi	tissue	3.1
Medulla oblongata	tissue	3.1
Cerebellum	tissue	3.1	medium
Vagina	tissue	3.0	low
Midbrain	tissue	3.0
Superior colliculi	tissue	2.9
Spinal cord	tissue	2.9
Medulla oblongata	tissue	2.8
Spinal cord	tissue	2.7
Epididymis	tissue	2.6	not detected
Substantia nigra	tissue	2.6
Hypothalamus	tissue	2.5
Periaqueductal gray	tissue	2.5
Breast	tissue	2.3	low
Hippocampal formation	tissue	2.3
Entorhinal cortex	tissue	2.3
Amygdala	tissue	2.3
Ventral forebrain	tissue	2.3
Vagina	tissue	2.2	not detected
Fallopian tube	tissue	2.2	high
Corpus callosum	tissue	2.2
Olfactory bulb	tissue	2.2
Septum	tissue	2.2

Brain sub-regions (HPA Brain Atlas): detected in 569; highest nTPM — Arcuate nucleus (19.3), Median raphe nucleus (15.7), Nucleus ambiguus (14.1), Ventromedial nucleus (14.1), Piriform cortex (12.5).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting ACKR2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 87 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-7153-5P	99.94	68.89	1006
HSA-MIR-6744-5P	99.93	66.82	748
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-7978	99.86	66.90	856
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-383-3P	99.85	65.84	1359
HSA-MIR-1321	99.84	65.30	1811

Functional genomics

gnomAD constraint: pLI 0.118, LOEUF 1.93, missense Z 0.804 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000422265 — one region, missense o/e 0.96.

Literature-anchored findings (GeneRIF, showing 36)

• CCR10 is unlikely to be necessary for cutaneous homing of TH cells in the models studied here. CCR10 may instead play a role in the movement of specialized “effector” cutaneous TH cells to and/or within epidermal microenvironments. (PMID:12406880)
• In lymphatic vessels D6 acts as a nonsignaling decoy receptor and scavenger for inflammatory CC chemokines, by clearing them and preventing excessive diffusion via afferent lymphatics to lymph nodes. (PMID:12594248)
• CCR10 and its mucosal epithelial ligand CCL28 have roles in the migration of circulating IgA plasmablasts (PMID:12671049)
• D6 is constitutively internalized via a ligand-independent, phosphorylation-independent association with beta-arrestin. (PMID:15084596)
• We also propose that lymphatic endothelial cell-expressed D6 might have a distinct but complementary role in restricting inflammatory leukocyte access to the lymphatic vasculature. (PMID:16814608)
• demonstrate the importance of proinflammatory CC chemokines in de novo tumorigenesis and reveal chemokine sequestration by D6 to be a novel and effective method of tumor suppression (PMID:17607362)
• the heptahelical body of D6 on its own can engage the endocytotic machinery of HEK293 cells but that the C terminus is indispensable for scavenging because it prevents initial chemokine engagement of D6 from inhibiting subsequent chemokine uptake. (PMID:18201974)
• Emphasis on two new players involved in regulating inflammation at the maternal-fetal interface: the long pentraxin PTX3 and the decoy receptor for inflammatory chemokines D6. (PMID:18676013)
• D6 plays a negative role in the growth and metastasis of breast cancer. (PMID:18708360)
• D6 expression is GATA1 dependent (PMID:18714007)
• Genetic variations are associated with liver inflammation in chronic hepatitis C (PMID:18822328)
• Immunohistochemistry on lung lymph nodes from patients with pulmonary tuberculosis showed that D6 expression was prominent in lymphatic endothelial cells, while CD68-positive macrophages did not stain for D6. (PMID:19446728)
• D6 cooperates with CD26 in the negative regulation of CCL14 by the selective degradation of its biologically active isoform. (PMID:19632987)
• D6 protein is found predominantly inside human choriocarcinoma-derived cells with only a small fraction available on the cell surface at any one time, yet it can progressively remove extracellular chemokines, without apparent desensitization. (PMID:20147628)
• Chemokne D6 expression is higher in biopsies taken from more severe cardiac allograft rejection. (PMID:20404785)
• DARC and D6, the most studied members of this group of molecules, are reviewed. (PMID:21151196)
• CCL2 binding to primary adult human astrocytes is CCR2-independent and is likely to be mediated via the D6 decoy. (PMID:22226505)
• Chemokine decoy receptor D6 limits CC-chemokine-dependent pathogenic inflammation and is required for adequate cardiac remodeling after myocardial infarction. (PMID:22796582)
• D6 is expressed in AMs from patients with COPD, and its expression correlates with the degree of functional impairment and markers of immune activation. (PMID:22797410)
• These data demonstrate a novel role for D6 as a regulator of the transition from uninvolved to lesional skin in psoriasis. (PMID:22867710)
• We here summarize the knowledge available today on D6 structural and signaling properties and its essential role for the control of inflammatory cells traffic and proper development of the adaptive immune response. (PMID:22939232)
• co-expression of DARC, D6, and CCX-CKR significantly associated with higher survival in gastric cancer (PMID:23462454)
• D6, which is upregulated in both inflammatory and tumor contexts, is an essential regulator of inflammatory leukocyte interactions with lymphatic endothelial cells(LECs) and is required for immature/mature DC discrimination by LECs. (PMID:23479571)
• engagement of the ACR D6 by its ligands activates a beta-arrestin1-dependent, G protein-independent signaling pathway that results in the phosphorylation of the actin-binding protein cofilin through the Rac1-PAK1-LIMK1 cascade. (PMID:23633677)
• Data show that low decoy receptor D6 expression correlated to more invasive tumors and that tumor location influences D6 expression, which is lower in the more distal parts of the colon. (PMID:24013383)
• Data show the structural motifs in the atypical chemokine receptor 2 (ACKR2) are responsible for ligand binding, and suggest ACKR2-derived N-terminal peptides as being of potential therapeutic significance. (PMID:24644289)
• ACKR2 mediates chemokine scavenging by primary human trophoblasts. (PMID:25297873)
• Data indicates that D6 is concentrated on trophoblast cell membranes in pre-eclampsia, in line with higher circulating levels of D6-ligand chemokines, but its scavenging activity is affected by trophoblast cytoskeleton disarrangement. (PMID:27780270)
• ACKR2 is a molecular regulator play a role in inflammatory changes in patients with psoriasis. (PMID:28010760)
• ACKR2 is induced after traumatic brain injuries and has a significant impact on mortality and lesion development acutely following closed head injury. (PMID:29176798)
• Data suggest that MIRN146b and MIR10b directly bind 3’-untranslated region of ACKR2 and down-regulate expression of ACKR2 in keratinocytes and in lymphatic endothelial cells, respectively. (ACKR2 = atypical chemokine receptor 2) (PMID:29279330)
• Abnormal uterine inflammation in obstetric syndromes: molecular insights into the role of chemokine decoy receptor D6 and inflammasome NLRP3. (PMID:32030415)
• Expression of ACKR2 in placentas from different types of preeclampsia. (PMID:32056543)
• Biphasic Expression of Atypical Chemokine Receptor (ACKR) 2 and ACKR4 in Colorectal Neoplasms in Association with Histopathological Findings. (PMID:33374792)
• The Role of Atypical Chemokine Receptor D6 (ACKR2) in Physiological and Pathological Conditions; Friend, Foe, or Both? (PMID:35677043)
• Pan-cancer analysis of the prognostic significance of ACKR2 expression and the related genetic/epigenetic dysregulations. (PMID:37882761)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio		ENSDARG00000086314
mus_musculus	Ackr2	ENSMUSG00000044534
rattus_norvegicus	Ackr2	ENSRNOG00000019472

Paralogs (23): CCR6 (ENSG00000112486), CCRL2 (ENSG00000121797), CCR2 (ENSG00000121807), CXCR4 (ENSG00000121966), CCR7 (ENSG00000126353), ACKR4 (ENSG00000129048), ACKR3 (ENSG00000144476), RGR (ENSG00000148604), CXCR5 (ENSG00000160683), CCR5 (ENSG00000160791), CXCR1 (ENSG00000163464), CCR1 (ENSG00000163823), CX3CR1 (ENSG00000168329), CXCR6 (ENSG00000172215), XCR1 (ENSG00000173578), CCR9 (ENSG00000173585), CCR8 (ENSG00000179934), CXCR2 (ENSG00000180871), GALR2 (ENSG00000182687), CCR3 (ENSG00000183625), CCR4 (ENSG00000183813), CCR10 (ENSG00000184451), CXCR3 (ENSG00000186810)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1891697) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 2 distinct phenotype terms.

Mouse phenotype (MP)	Records
dermatitis	1
increased inflammatory response	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Trachypithecus phayrei	O97879	100.0%	Diamond
Pongo pygmaeus	O97881	100.0%	Diamond
Pan troglodytes	P56440	100.0%	Diamond
Pan paniscus	P60574	100.0%	Diamond
Lophocebus aterrimus	P61755	100.0%	Diamond
Pongo abelii	P61756	100.0%	Diamond
Semnopithecus entellus	P61757	100.0%	Diamond
Macaca mulatta	P61813	100.0%	Diamond
Macaca fascicularis	P61814	100.0%	Diamond
Macaca nemestrina	P61815	100.0%	Diamond
Papio anubis	P68269	100.0%	Diamond
Papio hamadryas	P68270	100.0%	Diamond
Cercocebus atys	O62743	99.7%	Diamond
Trachypithecus francoisi	O97878	99.7%	Diamond
Rhinopithecus bieti	O97880	99.7%	Diamond
Rhinopithecus avunculus	O97962	99.7%	Diamond
Macaca arctoides	O97975	99.7%	Diamond
Gorilla gorilla gorilla	P56439	99.7%	Diamond
Chlorocebus pygerythrus	Q8HZP3	99.7%	Diamond
Chlorocebus aethiops	Q95L01	99.7%	Diamond
Hylobates moloch	Q95NC0	99.7%	Diamond
Theropithecus gelada	Q95NC1	99.7%	Diamond
Symphalangus syndactylus	Q95NC5	99.7%	Diamond
Nasalis larvatus	Q95NC7	99.7%	Diamond
Colobus polykomos	Q95NC8	99.7%	Diamond
Cercocebus galeritus	Q9TV49	99.7%	Diamond
Pygathrix nemaeus	O97882	99.4%	Diamond
Nomascus leucogenys	O97883	99.4%	Diamond
Trachypithecus johnii	Q95NC6	99.4%	Diamond
Mandrillus sphinx	Q95ND1	99.4%	Diamond
Mandrillus leucophaeus	Q95ND2	99.4%	Diamond
Chlorocebus tantalus	Q95NE8	99.4%	Diamond
Allochrocebus solatus	Q9BGN6	99.4%	Diamond
Allochrocebus lhoesti	Q9XT76	99.4%	Diamond
Miopithecus talapoin	Q95NC3	99.1%	Diamond
Erythrocebus patas	Q95ND0	99.1%	Diamond
Chlorocebus sabaeus	Q9TV43	99.1%	Diamond
Cercopithecus cephus	Q9TV47	99.1%	Diamond
Cercopithecus nictitans	Q9TV45	98.6%	Diamond
Cercopithecus ascanius	Q9TV48	98.6%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
CCDC13-AS1	ncRNA	100874114
CCDC13	protein-coding	152206
CYP8B1	protein-coding	1582
HIGD1A	protein-coding	25994
CCDC13-AS2	ncRNA	729083
ZNF662	protein-coding	389114
KRABD1	protein-coding	100506243
KRABD1-AS1	ncRNA	100506275
HHATL-AS1	ncRNA	100874044
HHATL	protein-coding	57467
KLHL40	protein-coding	131377

Protein

Protein identifiers

Atypical chemokine receptor 2 — O00590 (reviewed: O00590)

Alternative names: C-C chemokine receptor D6, Chemokine receptor CCR-10, Chemokine receptor CCR-9, Chemokine-binding protein 2, Chemokine-binding protein D6

All UniProt accessions (5): O00590, V9GYB7, V9GYM0, V9GYX0, V9GZ70

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. Acts as a receptor for chemokines including CCL2, CCL3, CCL3L1, CCL4, CCL5, CCL7, CCL8, CCL11, CCL13, CCL17, CCL22, CCL23, CCL24, SCYA2/MCP-1, SCY3/MIP-1-alpha, SCYA5/RANTES and SCYA7/MCP-3. Upon active ligand stimulation, activates a beta-arrestin 1 (ARRB1)-dependent, G protein-independent signaling pathway that results in the phosphorylation of the actin-binding protein cofilin (CFL1) through a RAC1-PAK1-LIMK1 signaling pathway. Activation of this pathway results in up-regulation of ACKR2 from endosomal compartment to cell membrane, increasing its efficiency in chemokine uptake and degradation. By scavenging chemokines in tissues, on the surfaces of lymphatic vessels, and in placenta, plays an essential role in the resolution (termination) of the inflammatory response and in the regulation of adaptive immune responses. Plays a major role in the immune silencing of macrophages during the resolution of inflammation. Acts as a regulator of inflammatory leukocyte interactions with lymphatic endothelial cells (LECs) and is required for immature/mature dendritic cells discrimination by LECs.

Subcellular location. Early endosome. Recycling endosome. Cell membrane.

Tissue specificity. Found in endothelial cells lining afferent lymphatics in dermis and lymph nodes. Also found in lymph nodes subcapsular and medullary sinuses, tonsillar lymphatic sinuses and lymphatics in mucosa and submucosa of small and large intestine and appendix. Also found in some malignant vascular tumors. Expressed at high levels in Kaposi sarcoma-related pathologies. Expressed on apoptotic neutrophils (at protein level). Expressed primarily in placenta and fetal liver, and found at very low levels in the lung and lymph node.

Post-translational modifications. Phosphorylated on serine residues in the C-terminal cytoplasmic tail.

Domain organisation. The C-terminal cytoplasmic tail controls its phosphorylation, stability, intracellular trafficking itinerary, and chemokine scavenging properties.

Induction. By interleukin-6 and interferon-gamma.

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

RefSeq proteins (1): NP_001287* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR000355	Chemokine_rcpt	Family
IPR001277	CXCR4/ACKR2	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain
IPR050119	CCR1-9-like	Family

Pfam: PF00001

UniProt features (38 total): topological domain 8, modified residue 8, transmembrane region 7, sequence variant 4, sequence conflict 3, region of interest 2, chain 1, short sequence motif 1, compositionally biased region 1, glycosylation site 1, disulfide bond 1, strand 1

Structure

Experimental structures (PDB)

3 structures by resolution:

PDB	Title	Method	Resolution (Å)
8J8V	Structure of beta-arrestin2 in complex with D6Rpp (Local Refine)	ELECTRON MICROSCOPY	3.22
8GO9	Structure of beta-arrestin2 in complex with a phosphopeptide corresponding to the human …	ELECTRON MICROSCOPY	3.35
8J8Z	Structure of beta-arrestin1 in complex with D6Rpp	ELECTRON MICROSCOPY	3.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O00590-F1	80.89	0.51

Antibody-complex structures (SAbDab)

3 antibodies co-crystallized with this protein: 8GO9, 8J8V, 8J8Z

Human Protein Atlas

Protein class: Transporters, G-protein coupled receptors, GPCRs excl olfactory receptors, Chemokines and chemotactic factors receptors, Predicted membrane proteins, GPCRHMM predicted membrane proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cytosol; vesicles; nucleoplasm

Antibody reliability (HPA): IH enhanced · IF supported

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 (8)

Type	Positions
Phosphothreonine	339, 354
Phosphoserine	343, 345, 346, 348, 350, 351

Disulfide bonds (1)

Type	Positions
Disulfide bond	117–195

Glycosylation sites (1)

Type	Positions
N-linked (glcnac…) asparagine	19

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 6; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

6 pathways:

ID	Pathway	Evidence
R-HSA-380108	Chemokine receptors bind chemokines	curated
R-HSA-373076	Class A/1 (Rhodopsin-like receptors)	—
R-HSA-500792	GPCR ligand binding	—
R-HSA-375276	Peptide ligand-binding receptors	—
R-HSA-162582	Signal Transduction	—
R-HSA-372790	Signaling by GPCR	—

MSigDB gene sets: 479 (showing top): AHRARNT_01, MORF_RAGE, GOBP_CELL_CHEMOTAXIS, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_PEPTIDE, MODULE_45, MODULE_64, GOCC_CELL_SURFACE, HSIAO_HOUSEKEEPING_GENES, GAURNIER_PSMD4_TARGETS, MODULE_16, GGGTGGRR_PAX4_03, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_UP, GCM_PRKCG, GOBP_TAXIS

GO Biological Process (10): inflammatory response (GO:0006954), immune response (GO:0006955), positive regulation of cytosolic calcium ion concentration (GO:0007204), calcium-mediated signaling (GO:0019722), intracellular signal transduction (GO:0035556), cell chemotaxis (GO:0060326), chemotaxis (GO:0006935), signal transduction (GO:0007165), G protein-coupled receptor signaling pathway (GO:0007186), chemokine-mediated signaling pathway (GO:0070098)

GO Molecular Function (6): chemokine receptor activity (GO:0004950), C-C chemokine receptor activity (GO:0016493), C-C chemokine binding (GO:0019957), receptor decoy activity (GO:0140319), G protein-coupled receptor activity (GO:0004930), protein binding (GO:0005515)

GO Cellular Component (7): early endosome (GO:0005769), cytosol (GO:0005829), actin filament (GO:0005884), plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), recycling endosome (GO:0055037), membrane (GO:0016020)

Reactome top-level categories

5 top-level categories:

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

GO top-level categories

40 GO namespaces:

Category	Terms
signal transduction	2
G protein-coupled receptor signaling pathway	2
chemokine binding	2
endosome	2
cellular anatomical structure	2
defense response	1
immune system process	1
response to stimulus	1
regulation of biological quality	1
intracellular signaling cassette	1
intracellular anatomical structure	1
chemotaxis	1
cell migration	1
cellular response to chemical stimulus	1
response to chemical	1
taxis	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
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
molecular sequestering activity	1
transmembrane signaling receptor activity	1
binding	1
cytoplasm	1
actin cytoskeleton	1
polymeric cytoskeletal fiber	1
membrane	1
cell periphery	1
plasma membrane	1
cell surface	1
side of membrane	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 5 of 23 annotations. The rest are phylogenetic / computational / electronic (IEA).

5 experimentally-supported GO terms:

GO term	NS	Evidence
actin filament	CC	direct assay
cytosol	CC	direct assay
plasma membrane	CC	direct assay
chemokine receptor activity	MF	direct assay
receptor decoy activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 1,622 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ACKR2	CCL25	O15444	958
ACKR2	CCL27	Q9Y4X3	891
ACKR2	MADCAM1	Q13477	854
ACKR2	CD8A	P01732	821
ACKR2	CCL21	O00585	799
ACKR2	CXCL12	P48061	765
ACKR2	CCL5	P13501	743
ACKR2	CD4	P01730	719
ACKR2	ITGAE	P38570	717
ACKR2	CCL28	Q9NRJ3	714
ACKR2	CCL3	P10147	695
ACKR2	CXCL13	O43927	678
ACKR2	CXCL11	O14625	677
ACKR2	CCL4	P13236	674
ACKR2	SELPLG	Q14242	662

IntAct

Human interaction partners of ACKR2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

10 partners by confidence:

Partner	Interaction type	MIscore	Records
EFNA5	physical association	0.560	3
GJA8	physical association	0.560	3
MS4A1	physical association	0.560	3
NIPAL4	physical association	0.560	3
SACM1L	physical association	0.560	3
SLC13A4	physical association	0.560	3
TMEM167B	physical association	0.560	3
CDK18	physical association	0.400	2
CREB3	physical association	0.370	1
TMEM223	association	0.350	1

BioGRID (83 interactions; top human partners by supporting records): CDK18 (Affinity Capture-MS; 2 records), ACAD9 (Affinity Capture-MS), APOB (Affinity Capture-MS), APP (Reconstituted Complex), ARL6IP5 (Affinity Capture-MS), ATP12A (Affinity Capture-MS), ATP2B4 (Affinity Capture-MS), ATP9A (Affinity Capture-MS), ATPIF1 (Affinity Capture-MS), C10orf35 (Affinity Capture-MS), CAV2 (Affinity Capture-MS), CCL13 (Reconstituted Complex), CCL14 (Reconstituted Complex), CCL5 (Reconstituted Complex), CCL7 (Reconstituted Complex)

Ligand–receptor pairs (CellPhoneDB) (11)

Curated ligand–receptor partners (cell-cell communication), distinct from the protein–protein interactions above.

11 ligand–receptor pairs:

Partner	This gene’s role	Signaling class
CCL14	receptor	Signaling by Chemokines
CCL2	receptor	Signaling by Chemokines
CCR9		Signaling by Chemokines
CCL4	receptor	Signaling by Chemokines
CCL3	receptor	Signaling by Chemokines
CCR10		Signaling by Chemokines
CCL11	receptor	Signaling by Chemokines
CCL5	receptor	Signaling by Chemokines
CCL13	receptor	Signaling by Chemokines
CCL8	receptor	Signaling by Chemokines
CCL7	receptor	Signaling by Chemokines

Disease & clinical

Genetic variants

Variant evidence for ACKR2: 118 ClinVar records (0 pathogenic / likely pathogenic); 48 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	102
Likely benign	3
Benign	4

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 24 predictions of 499):

Position(s)	Effect	Δscore	Sites
17:42680618–42680619	acceptor_loss	1.0000	2
3:45900808–45900809	acceptor_loss	1.0000	6
17:42680618–42680619	acceptor_loss	0.9900	3
3:42809530	donor_gain	0.9900
3:42809533–42809534	donor_loss	0.9900	5
3:45886656	donor_loss	0.9900	3
3:45901099	acceptor_gain	0.9900
17:42680629	acceptor_gain	0.9800
3:45886657	donor_loss	0.9800
3:45897648	donor_gain	0.9800

AlphaMissense

403 missense substitutions predicted likely pathogenic (of 2,535 scored), across 146 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
C117	7	0.911	0.952
C195	7	0.903	0.943
C36	7	0.901	0.960
C284	7	0.870	0.912
W110	7	0.839	0.968
F219	7	0.816	0.941
F112	7	0.807	0.910
F199	7	0.793	0.934
F182	7	0.758	0.857
F101	6	0.768	0.854
P265	6	0.761	0.916
P222	6	0.755	0.946
F95	6	0.746	0.811
N64	6	0.720	0.909
G113	6	0.708	0.859
D291	6	0.701	0.749
W169	5	0.848	0.969
G218	5	0.846	0.934
F44	5	0.845	0.907
Y143	5	0.811	0.917

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

1 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	unfavorable	0.00023

Disease associations

OMIM: gene MIM:602648 | disease phenotypes:

GWAS associations

showing 30 of 48 associations:

Study	Trait	p-value
GCST90002393_425	Monocyte count	2e-218
GCST90002394_503	Monocyte percentage of white cells	4e-192
GCST004625_166	Monocyte count	7e-121
GCST004609_33	Monocyte percentage of white cells	1e-97
GCST90002393_424	Monocyte count	1e-87
GCST011913_3	Thymus and reactivation regulated chemokine levels	2e-82
GCST004608_70	Granulocyte percentage of myeloid white cells	1e-65
GCST004625_165	Monocyte count	4e-65
GCST004460_22	Eotaxin levels	2e-46
GCST90002394_502	Monocyte percentage of white cells	4e-45
GCST004609_32	Monocyte percentage of white cells	8e-38
GCST90002381_54	Eosinophil count	9e-32
GCST90002382_70	Eosinophil percentage of white cells	2e-26
GCST90002407_288	White blood cell count	2e-24
GCST90002398_464	Neutrophil count	2e-23
GCST004606_18	Eosinophil count	5e-21
GCST004438_29	Monocyte chemoattractant protein-1 levels	9e-20
GCST004624_68	Sum eosinophil basophil counts	2e-19
GCST004608_69	Granulocyte percentage of myeloid white cells	5e-19
GCST002665_5	Cerebrospinal fluid levels of Alzheimer’s disease-related proteins	4e-18
GCST004626_93	Myeloid white cell count	6e-18
GCST000612_32	Celiac disease	3e-17
GCST90013406_86	Liver enzyme levels (alkaline phosphatase)	6e-17
GCST90002389_147	Lymphocyte percentage of white cells	1e-15
GCST90002381_53	Eosinophil count	6e-15
GCST004610_132	White blood cell count	2e-14
GCST005977_29	Monocyte count	2e-14
GCST004600_187	Eosinophil percentage of white cells	9e-14
GCST004617_156	Eosinophil percentage of granulocytes	9e-14
GCST004626_94	Myeloid white cell count	6e-13

EFO canonical traits (from GWAS)

18 canonical traits:

EFO ID	Trait name
EFO:0005188	CCL11 measurement
EFO:0005091	monocyte count
EFO:0006514	Alzheimer’s disease biomarker measurement
EFO:0008122	eotaxin measurement
EFO:0007991	eosinophil percentage of leukocytes
EFO:0004842	eosinophil count
EFO:0007997	granulocyte percentage of myeloid white cells
EFO:0007989	monocyte percentage of leukocytes
EFO:0004833	neutrophil count
EFO:0007987	granulocyte count
EFO:0007996	eosinophil percentage of granulocytes
EFO:0005090	basophil count
EFO:0007994	neutrophil percentage of granulocytes
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0004747	protein measurement
EFO:0007959	fetal genotype effect measurement
EFO:0008236	monokine induced by gamma interferon measurement
EFO:0004533	alkaline phosphatase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4105988 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — Chemokine receptors

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, decreases methylation	2
Benzo(a)pyrene	decreases expression, increases methylation, affects methylation	2
GSK-J4	decreases expression	1
dicrotophos	increases expression	1
cobalt oxide	increases expression	1
CGP 52608	affects binding, increases reaction	1
Acetaminophen	decreases expression	1
Allergens	affects cotreatment, increases expression	1
Arsenic	affects methylation	1
Vehicle Emissions	affects cotreatment, increases expression	1
Cadmium	decreases expression, increases abundance	1
Diethylhexyl Phthalate	increases expression	1
Diethylstilbestrol	decreases expression	1
Lead	increases expression	1
Silicon Dioxide	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Zearalenone	decreases expression	1
Cadmium Chloride	decreases expression, increases abundance	1
Okadaic Acid	decreases expression	1
Lactic Acid	decreases expression	1
Genistein	decreases expression	1
S-Nitrosoglutathione	increases 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
CHEMBL4037559	Binding	Agonist activity at CCR10 (unknown origin)	Discovery of Novel 1-Cyclopentenyl-3-phenylureas as Selective, Brain Penetrant, and Orally Bioavailable CXCR2 Antagonists. — *J Med Chem*
CHEMBL5579101	Functional	Agonist activity at human ACKR2 transfected in HEK293T cells co-expressing LgBiT-fused SmBiT-beta-arrestin assessed as beta-arrestin recruitment by bioluminescence based NanoBiT assay	Novel Small-Molecule Atypical Chemokine Receptor 3 Agonists: Design, Synthesis, and Pharmacological Evaluation for Antiplatelet Therapy. — *J Med Chem*

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

50 trials:

NCT	Phase	Status	Title
NCT02343562	Phase 4	UNKNOWN	Probiotics for Prophylaxis of Postoperative Hirschsprungs Associated Enterocolitis
NCT07186647	Phase 4	COMPLETED	Laparoscopic-Assisted Transanal Pull-Through for Hirschsprung Disease in Pediatric:Short and Intermediate Outcomes of Two Different Techniques
NCT04904081	Phase 3	UNKNOWN	Feasibility of Use of Indocyanine Green in Pediatric Colorectal Surgery
NCT00630838	Phase 2	COMPLETED	Probiotic Prophylaxis of Hirschprung’s Disease Associated Enterocolitis (HAEC)
NCT01985646	Early Phase 1	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
NCT06874686	Not specified	COMPLETED	Minimally Invasive Surgical Intervention for Hirschsprung’s Disease in Pediatric Patients
NCT06880666	Not specified	COMPLETED	Minimally Invasive Surgical Intervention for Hirschsprung Disease
NCT07098494	Not specified	COMPLETED	Probiotics and Post-Pullthrough Hirschsprung’s Disease-Associated Enterocolitis
NCT07156981	Not specified	NOT_YET_RECRUITING	Effects of Physiotherapy in Children With Hirschsprung’s Disease
NCT07343622	Not specified	NOT_YET_RECRUITING	Robot/Laparoscopic-Assisted Transanal Transection Duhamel Versus Modified Soave Pull-Through for TCA
NCT07468565	Not specified	NOT_YET_RECRUITING	Surgical Approach for the Treatment of Hirschsprung Disease Using the Swenson Technique (SMILES)
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