HDC

Summary

HDC (histidine decarboxylase, HGNC:4855) is a protein-coding gene on chromosome 15q21.2, encoding Histidine decarboxylase (P19113). Catalyzes the biosynthesis of histamine from histidine.

This gene encodes a member of the group II decarboxylase family and forms a homodimer that converts L-histidine to histamine in a pyridoxal phosphate dependent manner. Histamine regulates several physiologic processes, including neurotransmission, gastric acid secretion,inflamation, and smooth muscle tone.

Source: NCBI Gene 3067 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Tourette syndrome (Limited, GenCC)
• GWAS associations: 2
• Clinical variants (ClinVar): 97 total — 2 pathogenic, 1 likely-pathogenic
• Druggable target: yes
• MANE Select transcript: NM_002112

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4855
Approved symbol	HDC
Name	histidine decarboxylase
Location	15q21.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000140287
Ensembl biotype	protein_coding
OMIM	142704
Entrez	3067

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 5 protein_coding, 4 retained_intron

ENST00000267845, ENST00000543581, ENST00000558679, ENST00000558761, ENST00000559190, ENST00000559683, ENST00000559816, ENST00000860523, ENST00000860524

RefSeq mRNA: 2 — MANE Select: NM_002112 NM_001306146, NM_002112

CCDS: CCDS10134, CCDS76754

Canonical transcript exons

ENST00000267845 — 12 exons

Exon	Start	End
ENSE00001120393	50252612	50252774
ENSE00001120399	50253600	50253666
ENSE00001120460	50265593	50265726
ENSE00003516239	50257425	50257547
ENSE00003519691	50258404	50258517
ENSE00003536407	50254130	50254273
ENSE00003542489	50241947	50243006
ENSE00003557592	50263235	50263407
ENSE00003591973	50254530	50254664
ENSE00003592649	50252430	50252520
ENSE00003602476	50248245	50248343
ENSE00003631171	50243143	50243244

Expression profiles

Bgee: expression breadth ubiquitous, 178 present calls, max score 93.78.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 7.1190 / max 1393.5210, expressed in 140 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
149855	6.5426	139
149858	0.5045	33
149854	0.0300	10
149857	0.0151	10
149856	0.0135	9
149853	0.0134	8

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
gall bladder	UBERON:0002110	93.78	gold quality
oocyte	CL:0000023	93.76	gold quality
secondary oocyte	CL:0000655	93.06	gold quality
cardia of stomach	UBERON:0001162	91.63	gold quality
body of stomach	UBERON:0001161	87.32	gold quality
fundus of stomach	UBERON:0001160	84.94	gold quality
stomach	UBERON:0000945	84.65	gold quality
corpus epididymis	UBERON:0004359	84.05	gold quality
lower esophagus mucosa	UBERON:0035834	83.48	gold quality
monocyte	CL:0000576	82.85	gold quality
mononuclear cell	CL:0000842	82.58	gold quality
rectum	UBERON:0001052	81.74	gold quality
leukocyte	CL:0000738	81.22	gold quality
upper lobe of left lung	UBERON:0008952	81.20	gold quality
lower esophagus muscularis layer	UBERON:0035833	80.13	gold quality
lower esophagus	UBERON:0013473	80.12	gold quality
right coronary artery	UBERON:0001625	80.08	gold quality
upper lobe of lung	UBERON:0008948	79.68	gold quality
skin of leg	UBERON:0001511	79.59	gold quality
hypothalamus	UBERON:0001898	79.48	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	79.16	gold quality
pylorus	UBERON:0001166	78.94	gold quality
cauda epididymis	UBERON:0004360	78.83	gold quality
smooth muscle tissue	UBERON:0001135	78.21	gold quality
vena cava	UBERON:0004087	77.83	gold quality
vermiform appendix	UBERON:0001154	77.40	gold quality
subcutaneous adipose tissue	UBERON:0002190	77.20	gold quality
caecum	UBERON:0001153	77.16	gold quality
skin of abdomen	UBERON:0001416	77.01	gold quality
zone of skin	UBERON:0000014	76.74	gold quality

Single-cell (SCXA)

Detected in 22 experiment(s), a significant marker in 22.

Experiment	Marker?	Max mean expression
E-MTAB-9801	yes	7207.42
E-MTAB-9067	yes	3328.39
E-GEOD-130473	yes	3116.29
E-MTAB-6678	yes	2582.62
E-MTAB-9221	yes	2364.08
E-MTAB-8221	yes	1337.44
E-MTAB-6505	yes	1102.24
E-MTAB-10042	yes	1056.98
E-CURD-55	yes	878.53
E-CURD-112	yes	820.99
E-MTAB-7407	yes	538.81
E-ANND-5	yes	532.77
E-HCAD-1	yes	40.56
E-CURD-88	yes	27.69
E-MTAB-8142	yes	16.70

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, CDX1, CEBPB, FOS, GATA4, GATA6, HDAC7, HIF1A, IRF6, JUN, KAT5, KLF2, KLF4, MAFK, NFE2, NR0B2, SP1, SREBF1, YY1, ZHX2

miRNA regulators (miRDB)

22 targeting HDC, 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-190A-3P	100.00	80.35	5520
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-498-3P	99.91	71.27	1114
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-580-3P	99.67	69.23	1841
HSA-MIR-670-5P	99.67	69.94	1565
HSA-MIR-4666B	99.64	68.69	1282
HSA-MIR-5689	99.50	71.26	1154
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-7849-3P	99.47	68.17	1224
HSA-MIR-5580-5P	99.38	66.96	1139
HSA-MIR-32-3P	99.36	68.20	2517
HSA-MIR-125A-5P	99.36	70.59	1640
HSA-MIR-125B-5P	99.36	70.36	1662
HSA-MIR-3085-3P	99.26	66.16	1490
HSA-MIR-3064-5P	99.26	66.13	1497
HSA-MIR-6504-5P	99.26	65.95	1487
HSA-MIR-211-3P	98.14	66.77	1052
HSA-MIR-4715-5P	97.62	67.47	506
HSA-MIR-12128	96.67	66.98	1471

Literature-anchored findings (GeneRIF, showing 33)

• the elevation of HDC expression during human monocytic differentiation (PMID:11556524)
• HDC expression is regulated by gastrin through a complex cis-acting element, which binds at least three distinct nuclear factors (PMID:12372397)
• Histidine decarboxylase promoter activity can be repressed by kruppel-like factor 4 (PMID:14670968)
• histidine decarboxylase mRNA is found in human vascular smooth muscle and endothelial cells (PMID:15167966)
• HDC and histamine content were significantly higher in the tumor specimens (PMID:15928846)
• Chronic urticaria expresses high levels of HDC as compared to normal foreskin, breast skin and cultured human keratinocytes. (PMID:16297195)
• HDC expression and histamine production are increased in the superficial kidney cortex zone during pregnancy (PMID:16760908)
• Defective levels found in normal placenta compared with pre-eclampsia labor. (PMID:16822545)
• Synthesis of histamine was found to be restricted to the basophil compartment of the CML clone and to depend on signaling through the PI3-kinase pathway. CML cells also expressed histamine receptors (PMID:16849647)
• HDC SNP’s are significantly associated with age at natural menopause in Caucasian women. (PMID:16919600)
• the apparent occurrence of an unusual TG 3’ splice site in intron 4 is discussed (PMID:17672918)
• Histamine decarboxylase expressed in endothelial cells of microvessels might play a role in regulating angiogenesis in esophageal squamous cell carcinomas. (PMID:19133005)
• HFR was regulated by HIF-1 activation. Depletion of HIF-1alpha prevents hypoxic induction of HDC in BMMCs. Hypoxia induces HDC expression by transcriptional mechanisms dependent upon HIF-1. (PMID:19266161)
• identification of a rare functional mutation in the HDC gene encoding L-histidine decarboxylase, the rate-limiting enzyme in histamine biosynthesis which points to its role in Tourette’s syndrome and tics (PMID:20445167)
• The histidine decarboxylase allele Glu644 in homozygosity increases the risk of developing rhinitis in the studied population (PMID:20608921)
• Studies provide lead compounds for inhibitors of ornithine decarboxylase and human histidine decarboxylase. (PMID:21454364)
• The novel concept that an autocrine loop, consisting of enhanced histamine synthesis by histidine decarboxylase, sustains cholangiocarcinoma growth is proposed. (PMID:21873469)
• It was shown that for serum and urine, HDC levels achieved sensitivities and specificities compatible to or even greater than those of established biomarkers for the diagnosis of intestinal mucosal injury in patients with acute intestinal obstruction. (PMID:21915437)
• Variants in the HDC gene may play little or no role in Tourette Syndrome susceptibility in Chinese Han population. (PMID:22095709)
• crystal of histidine decarboxylase belonged to space group C2, with unit-cell parameters a = 215.16, b = 112.72, c = 171.39 A, beta = 110.3 degrees (PMID:22684068)
• Structural study reveals that Ser-354 determines substrate specificity on human histidine decarboxylase. (PMID:22767596)
• Data indicate that histidine decarboxylase (HDC) is expressed by neutrophils. (PMID:23572231)
• Investigated variation across the HDC (histidine decarboxylase) gene for association with Tourette Syndrome. (PMID:23825391)
• HDC production in the stomach is associated with bile acid exposure and its related transcriptional regulation network of FXR, SHP, and CDX1. (PMID:24415870)
• The findings indicate that polymorphisms of HDC gene were significantly associated with breast cancer in Chinese Han population and may be novel diagnostic or therapeutic targets for breast cancer. (PMID:24835231)
• HDC rs17740607 polymorphism is at least a partial loss-of-function variant and acts as a protective factor against chronic heart failure (PMID:25846768)
• Human enterochromaffin-like cells appear to partially co-express VMAT-2 and HDC. Co-expression of VMAT-2 and HDC might be required for increased histamine production in patients with gastric neuroendocrine tumors. (PMID:26715806)
• a Possible Role for the Histidine Decarboxylase Gene in Tourette Syndrome in the Chinese Han Population (PMID:27529419)
• Human histidine decarboxylase (HDC) and dopa decarboxilase (DDC) are highly homologous enzymes responsible for the synthesis of biogenic amines (BA) like histamine, and serotonin and dopamine, respectively. This review summarizes the analogies and differences in their origin as well as their common pathophysiological scenarios. [review] (PMID:27769832)
• Study of the antitumour effects and the modulation of immune response by histamine in breast cancer. (PMID:31748740)
• Expression of histidine decarboxylase in melanocytes of the human skin. (PMID:33340761)
• Correlation between histidine decarboxylase expression of keratinocytes and visual analogue scale in patients with atopic dermatitis. (PMID:34140200)
• The Hdc GC box is critical for Hdc gene transcription and histamine-mediated anaphylaxis. (PMID:36804390)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	hdc	ENSDARG00000075454
mus_musculus	Hdc	ENSMUSG00000027360
rattus_norvegicus	Hdc	ENSRNOG00000010262
drosophila_melanogaster	Hdc	FBGN0005619
caenorhabditis_elegans		WBGENE00006409

Paralogs (7): GAD1 (ENSG00000128683), DDC (ENSG00000132437), GAD2 (ENSG00000136750), CSAD (ENSG00000139631), GADL1 (ENSG00000144644), SGPL1 (ENSG00000166224), PDXDC1 (ENSG00000179889)

Protein

Protein identifiers

Histidine decarboxylase — P19113 (reviewed: P19113)

All UniProt accessions (2): P19113, H0YLF0

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the biosynthesis of histamine from histidine.

Subunit / interactions. Homodimer.

Pathway. Amine and polyamine biosynthesis; histamine biosynthesis; histamine from L-histidine: step 1/1.

Similarity. Belongs to the group II decarboxylase family.

Isoforms (2)

UniProt ID	Names	Canonical?
P19113-1	1	yes
P19113-2	2

RefSeq proteins (2): NP_001293075, NP_002103* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002129	PyrdxlP-dep_de-COase	Domain
IPR010977	Aromatic_deC	Family
IPR015421	PyrdxlP-dep_Trfase_major	Homologous_superfamily
IPR015422	PyrdxlP-dep_Trfase_small	Homologous_superfamily
IPR015424	PyrdxlP-dep_Trfase	Homologous_superfamily
IPR021115	Pyridoxal-P_BS	Binding_site

Pfam: PF00282

Enzyme classification (BRENDA):

• EC 4.1.1.22 — histidine decarboxylase (BRENDA: 69 organisms, 43 substrates, 97 inhibitors, 39 Km, 9 kcat entries)

Substrate kinetics (BRENDA)

4 substrates with measured Km, best-characterized 4. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
L-HIS	0.078–35	22
L-HISTIDINE	0.09–100	13
1-METHYL-DL-HISTIDINE	5.8	1
3,4-DIHYDROXYPHENYLALANINE	0.13	1

Catalyzed reactions (Rhea), 1 shown:

• L-histidine + H(+) = histamine + CO2 (RHEA:20840)

UniProt features (58 total): helix 23, strand 14, turn 5, sequence variant 5, mutagenesis site 3, sequence conflict 3, binding site 2, chain 1, modified residue 1, splice variant 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
4E1O	X-RAY DIFFRACTION	1.8
7EIX	X-RAY DIFFRACTION	1.9
7EIW	X-RAY DIFFRACTION	2.1
7EIY	X-RAY DIFFRACTION	2.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P19113-F1	81.01	0.73

Functional residue map

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

Ligand- & substrate-binding residues (2): 81; 194

Post-translational modifications (1): 305

Mutagenesis-validated functional residues (3):

Position	Phenotype
305	loss of enzyme activity.
334	loss of enzyme activity.
354	strongly decreases affinity for histidine. strongly increases affinity for l-dopa and confers enzyme activity toward l-d

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-70921	Histidine catabolism

MSigDB gene sets: 183 (showing top): GOBP_PHENOL_CONTAINING_COMPOUND_METABOLIC_PROCESS, LEE_NEURAL_CREST_STEM_CELL_DN, GOBP_PHENOL_CONTAINING_COMPOUND_BIOSYNTHETIC_PROCESS, GOBP_ALPHA_AMINO_ACID_METABOLIC_PROCESS, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, KEGG_HISTIDINE_METABOLISM, FOSTER_TOLERANT_MACROPHAGE_UP, MARTINEZ_RB1_TARGETS_DN, RAMALHO_STEMNESS_DN, GOBP_AROMATIC_AMINO_ACID_METABOLIC_PROCESS, GOBP_ORGANIC_ACID_CATABOLIC_PROCESS, SCHAEFFER_PROSTATE_DEVELOPMENT_6HR_UP, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_DN, GOBP_ORGANIC_ACID_METABOLIC_PROCESS, GOBP_SMALL_MOLECULE_CATABOLIC_PROCESS

GO Biological Process (7): histamine biosynthetic process (GO:0001694), obsolete L-histidine metabolic process (GO:0006547), L-histidine catabolic process (GO:0006548), catecholamine biosynthetic process (GO:0042423), amino acid metabolic process (GO:0006520), carboxylic acid metabolic process (GO:0019752), biogenic amine biosynthetic process (GO:0042401)

GO Molecular Function (6): histidine decarboxylase activity (GO:0004398), pyridoxal phosphate binding (GO:0030170), protein binding (GO:0005515), lyase activity (GO:0016829), carbon-carbon lyase activity (GO:0016830), carboxy-lyase activity (GO:0016831)

GO Cellular Component (2): cytoplasm (GO:0005737), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Metabolism of amino acids and derivatives	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
biogenic amine biosynthetic process	2
cellular anatomical structure	2
histamine metabolic process	1
aromatic amino acid catabolic process	1
imidazole-containing compound catabolic process	1
L-amino acid catabolic process	1
proteinogenic amino acid catabolic process	1
catecholamine metabolic process	1
catechol-containing compound biosynthetic process	1
primary metabolic process	1
oxoacid metabolic process	1
biogenic amine metabolic process	1
amine biosynthetic process	1
carboxy-lyase activity	1
anion binding	1
vitamin B6 binding	1
binding	1
catalytic activity	1
lyase activity	1
carbon-carbon lyase activity	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

2414 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HDC	HRH1	P35367	798
HDC	HRH2	P25021	791
HDC	HRH3	Q9Y5N1	791
HDC	GAST	P01350	731
HDC	HRH4	Q9H3N8	729
HDC	SLITRK1	Q96PX8	725
HDC	IMMP2L	Q96T52	703
HDC	HNMT	P50135	675
HDC	SLITRK2	Q9H156	668
HDC	TBCD	Q9BTW9	652
HDC	AOC1	P19801	649
HDC	NPTX1	Q15818	648
HDC	SLC18A2	Q05940	609
HDC	HCRT	O43612	600
HDC	ODC1	P11926	574

IntAct

7 interactions, top by confidence:

A	B	Type	Score
HDC	DTX2	psi-mi:“MI:0915”(physical association)	0.560
DTX2	HDC	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (3): DTX2 (Two-hybrid), HDC (Affinity Capture-MS), HDC (Biochemical Activity)

ESM2 similar proteins: A0AA51Z3J4, A0PA85, A6QM00, B0B804, B0BC69, I1RV23, O84439, P14748, P16453, P18088, P19113, P20228, P23738, P34897, P48318, P48319, P48320, P48321, P48861, P49357, P49358, P50432, P54769, P54770, Q04792, Q05329, Q05683, Q06087, Q0VCA1, Q10104, Q16S21, Q28D99, Q3KLR8, Q3SZ20, Q4PRC2, Q5EA83, Q5IS68, Q5R7S7, Q6ZQY3, Q758F0

Diamond homologs: A0A2H5AIY0, A0A2H5AIY2, A0A2I6B3P0, A0AA51Z3J4, O82415, O88533, O96567, O96569, O96571, P05031, P14173, P16453, P17770, P18486, P19113, P20711, P22781, P23738, P27718, P34751, P48861, P54768, P54769, P54770, P54771, P80041, P81893, P93082, P93083, Q05733, Q06085, Q06086, Q06087, Q06088, Q0ZQX0, Q0ZS27, Q16S21, Q5EA83, Q6ZJK7, Q7XHL3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	1
Uncertain significance	70
Likely benign	10
Benign	4

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
14912	NM_002112.4(HDC):c.951G>A (p.Trp317Ter)	Pathogenic
4277990	NM_002112.4(HDC):c.1140+1G>C	Pathogenic
3067887	NM_002112.4(HDC):c.32-2A>G	Likely pathogenic

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

4373 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:50253651:C:A	G246W	0.999
15:50254653:A:C	S151R	0.999
15:50254653:A:T	S151R	0.999
15:50254655:T:G	S151R	0.999
15:50248321:C:G	R355P	0.998
15:50248323:G:C	S354R	0.998
15:50248323:G:T	S354R	0.998
15:50248325:T:G	S354R	0.998
15:50252467:A:G	L335P	0.998
15:50252613:A:G	W317R	0.998
15:50252613:A:T	W317R	0.998
15:50254252:C:G	A200P	0.998
15:50257539:G:C	S109R	0.998
15:50257539:G:T	S109R	0.998
15:50257541:T:G	S109R	0.998
15:50243210:A:T	V392D	0.997
15:50248285:C:G	R367P	0.997
15:50248298:A:G	W363R	0.997
15:50248298:A:T	W363R	0.997
15:50252623:A:C	C313W	0.997
15:50252669:G:A	S298F	0.997
15:50252670:A:G	S298P	0.997
15:50253650:C:A	G246V	0.997
15:50253650:C:T	G246E	0.997
15:50254620:C:A	R162S	0.997
15:50254620:C:G	R162S	0.997
15:50257522:A:G	L115P	0.997
15:50258406:A:G	W106R	0.997
15:50258406:A:T	W106R	0.997
15:50258447:C:T	G92E	0.997

dbSNP variants (sampled 300 via entrez): RS1000105151 (15:50246688 T>C), RS1000141474 (15:50246397 A>G), RS1000704339 (15:50248013 C>A,G,T), RS1000901051 (15:50254831 A>G), RS1000985258 (15:50266624 C>A), RS1001016637 (15:50266326 G>A,C,T), RS1001094803 (15:50241584 G>A,T), RS1001095615 (15:50259783 A>T), RS1001113772 (15:50260776 C>T), RS1001596044 (15:50255044 A>C), RS1001686184 (15:50249028 C>A), RS1001756955 (15:50255860 A>C), RS1001834310 (15:50243057 T>A,C), RS1001960685 (15:50256356 T>C), RS1002164063 (15:50249700 C>T)

Disease associations

OMIM: gene MIM:142704 | disease phenotypes: MIM:137580

GenCC curated gene-disease

Disease	Classification	Inheritance
Tourette syndrome	Limited	Autosomal dominant

Mondo (1): Tourette syndrome (MONDO:0007661)

Orphanet (1): NON RARE IN EUROPE: Tourette syndrome (Orphanet:856)

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST006482_14	Lung function (FEV1/FVC)	3.000000e-09
GCST90002379_67	Basophil count	5.000000e-13

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004713	FEV/FVC ratio
EFO:0005090	basophil count

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D005879	Tourette Syndrome	C10.228.140.079.898; C10.228.662.825.800; C10.574.500.850; C16.320.400.820; F03.625.992.850

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523192 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Decarboxylases

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Nickel	increases expression	3
Calcimycin	affects cotreatment, decreases reaction, increases activity, increases expression	2
Vorinostat	affects cotreatment, increases expression	2
Quercetin	decreases expression	2
Tetradecanoylphorbol Acetate	affects cotreatment, decreases reaction, increases activity, increases expression	2
Tretinoin	decreases expression	2
Valproic Acid	decreases expression, increases methylation	2
aristolochic acid I	increases expression	1
novichok	affects binding	1
mipafox	affects binding	1
triphenyl phosphate	affects expression	1
tabun	affects binding	1
O,O-diethyl O-3,5,6-trichloro-2-pyridyl phosphate	affects binding	1
VX-agent	affects binding	1
sodium arsenite	increases expression	1
perfluorooctanoic acid	decreases expression	1
alpha-fluoromethylhistidine	affects binding, decreases activity	1
atractylon	affects cotreatment, decreases reaction, increases activity, increases expression	1
phenylsaligenin cyclic phosphate	affects binding	1
histidine methyl ester	affects binding, decreases activity	1
phenyl di-n-pentylphosphinate	affects binding	1
di-n-butylphosphoric acid	affects expression	1
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	affects binding, decreases reaction, increases expression	1
tebuconazole	decreases expression	1
CGP 52608	affects binding, increases reaction	1
S-(N,N-diethylaminoethyl) isobutyl methylphosphothiolate	affects binding	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
nilotinib	decreases expression, affects binding, decreases reaction, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
pyeongwee-san extract	affects cotreatment, decreases reaction, increases activity, increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4477033	Binding	Inhibition of recombinant human HDC (1 to 512 residues) expressed in Escherichia coli BL21 (DE3) pLysS assessed as reduction in [14C]CO2 production from L-[U-14C]histidine at 10 uM relative to untreated control	Treatment of COPD, gastro-esophageal reflux disease (GERD), food allergies and other gastrointestinal conditions and disorders ameliorated by proper histamine management using a combination of histidine decarboxylase inhibitors, LRA drugs, anti-H1 and/or anti-H2 drugs

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00152750	PHASE4	UNKNOWN	Study of Clonidine on Sleep Architecture in Children With Tourette’s Syndrome (TS) and Comorbid ADHD
NCT00226824	PHASE4	TERMINATED	Safety Study of Galantamine in Tic Disorders
NCT00241176	PHASE4	COMPLETED	Open Label Trial of Aripiprazole in Children and Adolescents With Tourette’s Disorder
NCT00370838	PHASE4	COMPLETED	Comparison of Keppra and Clonidine in the Treatment of Tics
NCT01018056	PHASE4	COMPLETED	Developing New Treatments for Tourette Syndrome: Therapeutic Trials With Modulators of Glutamatergic Neurotransmission
NCT01547000	PHASE4	COMPLETED	Guanfacine in Children With Tic Disorders
NCT03239210	PHASE4	COMPLETED	Effects of Ondansetron in Obsessive-compulsive and Tic Disorders
NCT00004376	PHASE3	COMPLETED	Phase III Randomized, Double-Blind, Placebo-Controlled Study of Guanfacine for Tourette Syndrome and Attention Deficit Hyperactivity Disorder
NCT00206323	PHASE3	COMPLETED	A Randomized, Placebo-controlled, Tourette Syndrome Study.
NCT00206336	PHASE3	COMPLETED	An Open-label Study to Determine the Efficacy and Safety of Topiramate in the Treatment of Tourette Syndrome.
NCT00478842	PHASE3	COMPLETED	Pallidal Stimulation and Gilles de la Tourette Syndrome
NCT00681863	PHASE3	TERMINATED	Open-label Extension Study of Pramipexole in the Treatment of Children and Adolescents With Tourette Syndrome
NCT01501695	PHASE3	COMPLETED	Phase III Study of 5LGr to Treat Tic Disorder
NCT03087201	PHASE3	COMPLETED	CANNAbinoids in the Treatment of TICS (CANNA-TICS)
NCT03487783	PHASE3	COMPLETED	Aripiprazole Oral Solution in the Treatment of Children and Adolescents With Tourette’s Syndrome
NCT03567291	PHASE3	TERMINATED	Evaluation of Safety and Tolerability of Long-term TEV-50717 (Deutetrabenazine) for Treatment of Tourette Syndrome in Children and Adolescents
NCT03571256	PHASE3	COMPLETED	A Study to Test if TEV-50717 is Effective in Relieving Tics Associated With Tourette Syndrome (TS)
NCT06021522	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Evaluate Long-term Safety of Ecopipam Tablets in Children, Adolescents and Adults With Tourette’s Disorder
NCT00004393	PHASE2	COMPLETED	Phase II Double Blind Placebo Controlled Trial of Risperidone in Tourette Syndrome
NCT00004652	PHASE2	COMPLETED	Phase II Pilot Controlled Study of Short Vs Longer Term Pimozide (Orap) Therapy in Tourette Syndrome
NCT00231985	PHASE2	COMPLETED	Effectiveness of Behavior Therapy and Psychosocial Therapy for the Treatment of Tourette Syndrome and Chronic Tic Disorder
NCT00311909	PHASE2	COMPLETED	Thalamic Deep Brain Stimulation for Tourette Syndrome
NCT00529308	PHASE2	COMPLETED	Transcranial Magnetic Stimulation (TMS) for Individuals With Tourette’s Syndrome
NCT00558467	PHASE2	COMPLETED	Pramipexole Pilot Phase II Study in Children and Adolescents With Tourette Disorder According to DSM-IV Criteria
NCT01043549	PHASE2	TERMINATED	Repetitive Transcranial Magnetic Stimulation of the Posterior Parietal Cortex in Patients Suffering From Gilles de la Tourette Syndrome
NCT01133353	PHASE2	WITHDRAWN	A Study of the Effectiveness and Safety of Tetrabenazine MR in Pediatric Subjects With Tourette’s Syndrome
NCT01475383	PHASE2	WITHDRAWN	Study Evaluating The Safety And Efficacy Of PF-03654746 In Adult Subjects With Tourette’s Syndrome
NCT01647269	PHASE2	COMPLETED	A Trial of Bilateral Deep Brain Stimulation to the Globus Pallidus Internum in Tourette Syndrome
NCT01904773	PHASE2	COMPLETED	Safety, Tolerability, Pharmacokinetic, and Efficacy Study of AZD5213 in Adolescents With Tourette’s Disorder
NCT02102698	PHASE2	COMPLETED	Ecopipam Treatment of Tourette’s Syndrome in Subjects 7-17 Years
NCT02217007	PHASE2	WITHDRAWN	A Trial Evaluating the Efficacy, Safety, and Pharmacokinetics of SNC-102 in Subjects With Tourette Syndrome
NCT02247206	PHASE2	COMPLETED	VoIP Delivered Behavior Therapy for Tourette Syndrome
NCT02581865	PHASE2	COMPLETED	Safety and Efficacy Study of NBI-98854 in Adults With Tourette Syndrome
NCT02619084	PHASE2	COMPLETED	Subthalamic Stimulation in Tourette’s Syndrome
NCT02679079	PHASE2	COMPLETED	Safety and Efficacy Study of NBI-98854 in Children and Adolescents With Tourette Syndrome
NCT02879578	PHASE2	COMPLETED	Safety and Tolerability Study of NBI-98854 for the Treatment of Subjects With Tourette Syndrome
NCT03066193	PHASE2	COMPLETED	Efficacy of a Therapeutic Combination of Dronabinol and PEA for Tourette Syndrome
NCT03247244	PHASE2	TERMINATED	Safety and Efficacy of Cannabis in Tourette Syndrome
NCT03325010	PHASE2	COMPLETED	Safety, Tolerability, and Efficacy of NBI-98854 for the Treatment of Pediatric Subjects With Tourette Syndrome
NCT03444038	PHASE2	COMPLETED	Open-Label Safety and Tolerability Study of NBI-98854 for the Treatment of Pediatric Subjects With Tourette Syndrome