HAL

Summary

HAL (histidine ammonia-lyase, HGNC:4806) is a protein-coding gene on chromosome 12q23.1, encoding Histidine ammonia-lyase (P42357).

Histidine ammonia-lyase is a cytosolic enzyme catalyzing the first reaction in histidine catabolism, the nonoxidative deamination of L-histidine to trans-urocanic acid. Histidine ammonia-lyase defects cause histidinemia which is characterized by increased histidine and histamine and decreased urocanic acid in body fluids. Several transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 3034 — RefSeq curated summary.

At a glance

• Gene–disease (curated): histidinemia (Moderate, GenCC)
• GWAS associations: 9
• Clinical variants (ClinVar): 212 total — 1 likely-pathogenic
• Phenotypes (HPO): 11
• Druggable target: yes
• MANE Select transcript: NM_002108

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4806
Approved symbol	HAL
Name	histidine ammonia-lyase
Location	12q23.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000084110
Ensembl biotype	protein_coding
OMIM	609457
Entrez	3034

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 19 protein_coding, 2 nonsense_mediated_decay, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000261208, ENST00000538703, ENST00000541929, ENST00000544080, ENST00000546579, ENST00000546999, ENST00000548636, ENST00000548808, ENST00000549376, ENST00000551562, ENST00000552509, ENST00000865986, ENST00000865987, ENST00000865988, ENST00000865989, ENST00000865990, ENST00000865991, ENST00000865992, ENST00000865993, ENST00000865994, ENST00000865995, ENST00000865996, ENST00000865997, ENST00000947597

RefSeq mRNA: 3 — MANE Select: NM_002108 NM_001258333, NM_001258334, NM_002108

CCDS: CCDS58264, CCDS58265, CCDS9058

Canonical transcript exons

ENST00000261208 — 21 exons

Exon	Start	End
ENSE00000817979	95993772	95993838
ENSE00001279054	95972662	95974372
ENSE00002219026	95996078	95996344
ENSE00003460264	95976429	95976498
ENSE00003480611	95994798	95994825
ENSE00003483402	95988193	95988240
ENSE00003511500	95993451	95993488
ENSE00003536775	95985908	95985966
ENSE00003541078	95986065	95986160
ENSE00003547724	95992680	95992805
ENSE00003556647	95994090	95994164
ENSE00003574240	95980798	95980863
ENSE00003578379	95995664	95995991
ENSE00003579942	95994933	95994993
ENSE00003582437	95977944	95978078
ENSE00003594738	95983911	95983991
ENSE00003608805	95993926	95993998
ENSE00003629942	95980556	95980721
ENSE00003631709	95976598	95976706
ENSE00003681233	95990393	95990532
ENSE00003685310	95987067	95987214

Expression profiles

Bgee: expression breadth ubiquitous, 181 present calls, max score 98.12.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 2.5343 / max 555.0205, expressed in 170 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
132759	0.9362	78
132762	0.9235	121
132760	0.2682	36
132761	0.2540	60
132757	0.0832	23
132758	0.0693	28

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	98.12	gold quality
penis	UBERON:0000989	97.30	gold quality
liver	UBERON:0002107	97.04	gold quality
upper leg skin	UBERON:0004262	96.75	gold quality
mammalian vulva	UBERON:0000997	95.22	gold quality
blood	UBERON:0000178	93.23	gold quality
oocyte	CL:0000023	89.39	gold quality
skin of leg	UBERON:0001511	89.29	gold quality
upper arm skin	UBERON:0004263	89.02	gold quality
zone of skin	UBERON:0000014	88.67	gold quality
monocyte	CL:0000576	88.62	gold quality
mononuclear cell	CL:0000842	88.17	gold quality
secondary oocyte	CL:0000655	88.12	gold quality
skin of abdomen	UBERON:0001416	88.12	gold quality
buccal mucosa cell	CL:0002336	87.84	gold quality
leukocyte	CL:0000738	87.81	gold quality
skin of hip	UBERON:0001554	87.44	gold quality
granulocyte	CL:0000094	84.13	gold quality
bone marrow	UBERON:0002371	81.23	gold quality
nipple	UBERON:0002030	78.84	gold quality
bone marrow cell	CL:0002092	78.29	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.10	gold quality
spleen	UBERON:0002106	76.91	gold quality
trabecular bone tissue	UBERON:0002483	76.46	gold quality
right lung	UBERON:0002167	74.70	gold quality
tongue squamous epithelium	UBERON:0006919	72.98	gold quality
pancreatic ductal cell	CL:0002079	72.65	silver quality
periodontal ligament	UBERON:0008266	72.61	gold quality
upper lobe of left lung	UBERON:0008952	71.98	gold quality
upper lobe of lung	UBERON:0008948	71.62	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	5.59

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): DNMT1, FOXO1, MAF

miRNA regulators (miRDB)

68 targeting HAL, 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-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-4525	99.94	64.38	675
HSA-MIR-5010-5P	99.94	64.11	705
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-8080	99.82	67.52	1342
HSA-MIR-4639-5P	99.81	67.37	1028
HSA-MIR-205-5P	99.81	70.05	1557
HSA-MIR-623	99.76	68.16	1170
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-4755-5P	99.71	70.34	2716
HSA-MIR-5006-3P	99.71	70.26	2728
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-518A-5P	99.70	69.01	2209
HSA-MIR-527	99.70	69.01	2209
HSA-MIR-6715B-5P	99.64	69.63	1420
HSA-MIR-6126	99.62	68.09	996
HSA-MIR-6073	99.60	70.36	793
HSA-MIR-4269	99.55	69.89	1373
HSA-MIR-4452	99.50	68.45	1493
HSA-MIR-548G-3P	99.48	68.67	2159
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-653-5P	99.46	67.35	1300
HSA-MIR-5589-3P	99.29	68.30	1443

Literature-anchored findings (GeneRIF, showing 6)

• This evidence supports that the Hal gene is turned on by glucocorticoids and by glucagon either via PKC or PKA, but prefers the PKA pathway. (PMID:15741241)
• This report describes the first mutations occurring in the coding region of the histidase structural gene in patients with histidinemia. (PMID:15806399)
• histidase is upregulated during keratinocyte differentiation and that all-trans retinoic acid but not UV irradiation modulates the expression level (PMID:18280705)
• Three LoF mutations in HAL were associated with increased histidine levels, which in turn were shown to be inversely related to the risk of CHD among both African Americans and European Americans. (PMID:25575548)
• In the analysis of the genotype tissue expression (GTEx) project datasets, HAL rs17676826 C and NOXRED1 rs8012548 G alleles were significantly associated with their mRNA expression levels in sun-exposed skin of the lower leg (P = 6.62 x 10(-6) and 1.37 x 10(-7) , respectively) and in sun-not-exposed suprapubic skin (P < .001 and 1.43 x 10(-8) , respectively). (PMID:31435991)
• The role of single nucleotide variant rs3819817 of the Histidine Ammonia-Lyase gene and 25-Hydroxyvitamin D on bone mineral density, adiposity markers, and skin pigmentation, in Mexican population. (PMID:36862244)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	hal	ENSDARG00000017444
mus_musculus	Hal	ENSMUSG00000020017
rattus_norvegicus	Hal	ENSRNOG00000004502
caenorhabditis_elegans		WBGENE00009813

Protein

Protein identifiers

Histidine ammonia-lyase — P42357 (reviewed: P42357)

All UniProt accessions (5): P42357, F8VNX0, F8W0V1, H0YHB0, Q4VB95

UniProt curated annotations — full annotation on UniProt →

Post-translational modifications. Contains an active site 4-methylidene-imidazol-5-one (MIO), which is formed autocatalytically by cyclization and dehydration of residues Ala-Ser-Gly.

Disease relevance. Histidinemia (HISTID) [MIM:235800] Autosomal recessive disease characterized by increased histidine and histamine as well as decreased urocanic acid in body fluids. The disease is caused by variants affecting the gene represented in this entry.

Pathway. Amino-acid degradation; L-histidine degradation into L-glutamate; N-formimidoyl-L-glutamate from L-histidine: step 1/3.

Similarity. Belongs to the PAL/histidase family.

Isoforms (3)

UniProt ID	Names	Canonical?
P42357-1	1	yes
P42357-2	2
P42357-3	3

RefSeq proteins (3): NP_001245262, NP_001245263, NP_002099* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001106	Aromatic_Lyase	Family
IPR005921	HutH	Family
IPR008948	L-Aspartase-like	Homologous_superfamily
IPR022313	Phe/His_NH3-lyase_AS	Active_site
IPR024083	Fumarase/histidase_N	Homologous_superfamily

Pfam: PF00221

Enzyme classification (BRENDA):

• EC 4.3.1.3 — histidine ammonia-lyase (BRENDA: 40 organisms, 24 substrates, 124 inhibitors, 35 Km, 5 kcat entries)

Substrate kinetics (BRENDA)

7 substrates with measured Km, best-characterized 7. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
L-HISTIDINE	0.038–20	24
4-FLUORO-DL-HISTIDINE	1.25–6.4	2
DL-HISTIDINE	2.7–10	2
UROCANATE	3–100	2
2-FLUOROHISTIDINE	20	1
4-FLUOROUROCANATE	5	1
NH3	8500	1

Catalyzed reactions (Rhea), 1 shown:

• L-histidine = trans-urocanate + NH4(+) (RHEA:21232)

UniProt features (15 total): modified residue 5, sequence variant 5, splice variant 2, chain 1, sequence conflict 1, cross-link 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P42357-F1	90.83	0.75

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 (6): 254, 396, 635, 637, 648, 253–255

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-70921	Histidine catabolism

MSigDB gene sets: 190 (showing top): JAEGER_METASTASIS_DN, GOBP_ALPHA_AMINO_ACID_METABOLIC_PROCESS, GOBP_GLUTAMATE_METABOLIC_PROCESS, GOBP_GLUTAMINE_FAMILY_AMINO_ACID_METABOLIC_PROCESS, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, LEE_LIVER_CANCER_CIPROFIBRATE_DN, GOBP_DICARBOXYLIC_ACID_METABOLIC_PROCESS, CADWELL_ATG16L1_TARGETS_DN, UEDA_PERIFERAL_CLOCK, KEGG_HISTIDINE_METABOLISM, HOWLIN_PUBERTAL_MAMMARY_GLAND, GOBP_AROMATIC_AMINO_ACID_METABOLIC_PROCESS, GOBP_AMIDE_METABOLIC_PROCESS, MODULE_294, GOBP_ORGANIC_ACID_CATABOLIC_PROCESS

GO Biological Process (4): L-histidine catabolic process (GO:0006548), obsolete L-histidine catabolic process to glutamate and formamide (GO:0019556), obsolete L-histidine catabolic process to glutamate and formate (GO:0019557), obsolete L-histidine metabolic process (GO:0006547)

GO Molecular Function (5): histidine ammonia-lyase activity (GO:0004397), catalytic activity (GO:0003824), protein binding (GO:0005515), lyase activity (GO:0016829), ammonia-lyase activity (GO:0016841)

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

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
cellular anatomical structure	2
aromatic amino acid catabolic process	1
imidazole-containing compound catabolic process	1
L-amino acid catabolic process	1
proteinogenic amino acid catabolic process	1
ammonia-lyase activity	1
molecular_function	1
binding	1
catalytic activity	1
carbon-nitrogen lyase activity	1
cytoplasm	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1912 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HAL	UROC1	Q96N76	984
HAL	PAH	P00439	746
HAL	AMDHD1	Q96NU7	709
HAL	DCN	P07585	648
HAL	FTCD	O95954	644
HAL	CYP2B6	P20813	572
HAL	PCGF2	P35227	549
HAL	SDS	P20132	526
HAL	OAT	P04181	519
HAL	GLUL	P15104	519
HAL	AASS	Q9UDR5	512
HAL	CYP11A1	P05108	498
HAL	LYVE1	Q9Y5Y7	496
HAL	PRODH	O43272	482
HAL	ZYG11A	Q6WRX3	467

IntAct

172 interactions, top by confidence:

A	B	Type	Score
FANCG	FANCA	psi-mi:“MI:0914”(association)	0.960
ANAPC5	CDC27	psi-mi:“MI:0914”(association)	0.810
TNIP1	NFKB1	psi-mi:“MI:0914”(association)	0.790
HEXIM2	AHCYL1	psi-mi:“MI:0914”(association)	0.740
LSMEM2	STX7	psi-mi:“MI:0914”(association)	0.740
POLR2L	RCCD1	psi-mi:“MI:0914”(association)	0.640
ALDH3A1	RCCD1	psi-mi:“MI:0914”(association)	0.640
PSMB1	PSMA7	psi-mi:“MI:0914”(association)	0.640
CFAP298	PEX7	psi-mi:“MI:0914”(association)	0.620
RPS19BP1	HAL	psi-mi:“MI:0915”(physical association)	0.560
ZSCAN12	A2ML1	psi-mi:“MI:0914”(association)	0.530
FTH1	A2ML1	psi-mi:“MI:0914”(association)	0.530
GMCL1	A2ML1	psi-mi:“MI:0914”(association)	0.530
TBC1D22B	A2ML1	psi-mi:“MI:0914”(association)	0.530
CCDC27	ALOX12B	psi-mi:“MI:0914”(association)	0.530
DPPA4	ALOX12B	psi-mi:“MI:0914”(association)	0.530
RAB9B	CHM	psi-mi:“MI:0914”(association)	0.530
DOCK10	HAL	psi-mi:“MI:0914”(association)	0.530
HAL	KCTD16	psi-mi:“MI:0914”(association)	0.530
NDUFS5	NDUFS4	psi-mi:“MI:0914”(association)	0.530
DTL	DNAJA2	psi-mi:“MI:0914”(association)	0.530
ZIC1	CTSV	psi-mi:“MI:0914”(association)	0.530

BioGRID (170): HAL (Affinity Capture-MS), HAL (Affinity Capture-MS), HAL (Affinity Capture-MS), HAL (Affinity Capture-MS), HAL (Affinity Capture-MS), HAL (Affinity Capture-MS), HAL (Affinity Capture-MS), HAL (Affinity Capture-MS), HAL (Affinity Capture-MS), HAL (Affinity Capture-MS), HAL (Affinity Capture-MS), HAL (Affinity Capture-MS), HAL (Affinity Capture-MS), HAL (Affinity Capture-MS), HAL (Affinity Capture-MS)

ESM2 similar proteins: A0A2H5AIW0, A0A2H5AIY6, A2X7F7, A7YWP4, O04058, O23865, O23924, O49835, O49836, O64963, P07218, P0DO55, P14166, P14717, P19142, P21213, P24481, P25872, P26600, P27991, P31425, P31426, P35492, P35510, P35511, P35513, P42357, P45724, P45726, P45727, P45728, P45729, P45730, P45731, P45732, P45733, P45734, P45735, Q01861, Q04593

Diamond homologs: A0RH39, A1AZX9, A2RGS5, A3CL24, A4IK90, A5INP9, A6QD47, A6TSX0, A6TXF8, A7GR00, A7YWP4, A7ZAE4, A8AZ70, A8G1S5, A8MF64, A8YYT1, A9GFW6, A9H863, A9VPT8, A9WHT8, B0RUX3, B1KP55, B2A3D9, B4UC43, B5ETN1, B5XIY2, B7HCD0, B7HKJ1, B7ISJ2, B7JI80, B8H2S1, B8J950, B9E7E0, B9IUH0, B9LLY0, C1CWB4, C1EN93, C3L982, C3P4M2, C5D4K1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	160
Likely benign	18
Benign	12

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
3775254	NM_002108.4(HAL):c.1520-5_1538del	Likely pathogenic

SpliceAI

2946 predictions. Top by Δscore:

Variant	Effect	Δscore
12:95974372:CCTGA:C	acceptor_loss	1.0000
12:95974373:C:CA	acceptor_loss	1.0000
12:95976594:TTA:T	donor_loss	1.0000
12:95976595:TACC:T	donor_loss	1.0000
12:95976596:A:AC	donor_gain	1.0000
12:95976597:C:CC	donor_gain	1.0000
12:95976597:CCTTA:C	donor_gain	1.0000
12:95976702:CAGCA:C	acceptor_gain	1.0000
12:95976703:AGCA:A	acceptor_gain	1.0000
12:95976704:GCA:G	acceptor_gain	1.0000
12:95976705:CA:C	acceptor_gain	1.0000
12:95976705:CAC:C	acceptor_gain	1.0000
12:95976706:AC:A	acceptor_loss	1.0000
12:95976707:C:CC	acceptor_gain	1.0000
12:95978079:C:CC	acceptor_gain	1.0000
12:95983918:T:C	donor_gain	1.0000
12:95985963:CTCT:C	acceptor_gain	1.0000
12:95985965:CT:C	acceptor_gain	1.0000
12:95985967:C:CC	acceptor_gain	1.0000
12:95986046:C:CA	donor_gain	1.0000
12:95987063:TGAC:T	donor_loss	1.0000
12:95987064:GACC:G	donor_loss	1.0000
12:95993836:CAA:C	acceptor_gain	1.0000
12:95993839:C:CC	acceptor_gain	1.0000
12:95993999:C:CC	acceptor_gain	1.0000
12:95994084:CCATA:C	donor_loss	1.0000
12:95994085:CATA:C	donor_loss	1.0000
12:95994086:ATAC:A	donor_loss	1.0000
12:95994087:TAC:T	donor_loss	1.0000
12:95994088:A:AG	donor_loss	1.0000

AlphaMissense

4264 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:95978010:C:G	D530H	0.999
12:95978011:C:A	E529D	0.999
12:95978011:C:G	E529D	0.999
12:95980591:C:T	G495E	0.999
12:95980819:G:C	F444L	0.999
12:95980819:G:T	F444L	0.999
12:95980821:A:G	F444L	0.999
12:95983914:A:C	N428K	0.999
12:95983914:A:T	N428K	0.999
12:95987196:C:A	G308W	0.999
12:95987197:A:C	N307K	0.999
12:95987197:A:T	N307K	0.999
12:95990478:A:G	L257P	0.999
12:95990482:C:G	D256H	0.999
12:95990486:A:C	S254R	0.999
12:95990486:A:T	S254R	0.999
12:95990488:T:G	S254R	0.999
12:95993463:A:G	S193P	0.999
12:95976610:C:G	R584P	0.998
12:95978008:G:C	D530E	0.998
12:95978008:G:T	D530E	0.998
12:95978009:T:A	D530V	0.998
12:95978009:T:G	D530A	0.998
12:95978012:T:A	E529V	0.998
12:95978023:G:C	S525R	0.998
12:95978023:G:T	S525R	0.998
12:95978025:T:G	S525R	0.998
12:95980592:C:A	G495W	0.998
12:95980620:G:C	F485L	0.998
12:95980620:G:T	F485L	0.998

dbSNP variants (sampled 300 via entrez): RS1000051158 (12:95987865 T>A,C), RS1000331925 (12:95975355 T>C), RS1000757570 (12:95993484 G>C), RS1000791110 (12:95987507 T>C), RS1000809826 (12:95993154 A>T), RS1000891160 (12:95987797 C>A), RS1000995060 (12:95981784 A>G), RS1001175634 (12:95988800 G>T), RS1001215171 (12:95996695 G>T), RS1001238574 (12:95987563 A>C), RS1001332172 (12:95983130 G>A), RS1001448133 (12:95982921 A>C,G), RS1001461636 (12:95993693 G>A,C,T), RS1001508705 (12:95984734 T>A), RS1001793303 (12:95985947 A>G)

Disease associations

OMIM: gene MIM:609457 | disease phenotypes: MIM:235800

GenCC curated gene-disease

Disease	Classification	Inheritance
histidinemia	Moderate	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
histidinemia	Limited	AR

Mondo (1): histidinemia (MONDO:0009345)

Orphanet (1): Histidinemia (Orphanet:2157)

HPO phenotypes

11 total (11 of 11 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000708	Atypical behavior
HP:0000752	Hyperactivity
HP:0001249	Intellectual disability
HP:0001328	Specific learning disability
HP:0002167	Abnormal speech pattern
HP:0002927	Histidinuria
HP:0010906	Hyperhistidinemia
HP:0011343	Moderate global developmental delay
HP:6000621	Elevated urinary N-tau-ribosylhistidine level

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST004726_6	Vitamin D levels	3.000000e-10
GCST008870_37	Keratinocyte cancer (MTAG)	1.000000e-08
GCST008871_17	Basal cell carcinoma	1.000000e-07
GCST009261_10	Pallidum volume	8.000000e-06
GCST009733_108	Urinary metabolite levels in chronic kidney disease	2.000000e-25
GCST010002_220	Refractive error	1.000000e-19
GCST010148_20	Cutaneous squamous cell carcinoma	4.000000e-08
GCST010304_74	Cutaneous malignant melanoma	2.000000e-10
GCST012020_370	Serum metabolite levels	8.000000e-27

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0010176	keratinocyte carcinoma
EFO:0005116	urinary metabolite measurement
EFO:1001927	cutaneous squamous cell carcinoma

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C538320	Histidinemia (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4003 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tetrachlorodibenzodioxin	decreases expression, increases expression, affects expression	6
Benzo(a)pyrene	decreases expression, decreases methylation, increases expression	3
Cyclosporine	decreases expression, increases expression	3
Acetaminophen	decreases expression, affects cotreatment, increases expression	2
Estradiol	decreases expression	2
aristolochic acid I	increases expression	1
sotorasib	affects cotreatment, increases expression	1
triphenyl phosphate	affects expression	1
sodium arsenate	decreases expression, increases abundance	1
terbufos	increases methylation	1
tris(2-butoxyethyl) phosphate	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
3,4,5,3’,4’-pentachlorobiphenyl	decreases expression	1
periodate-oxidized adenosine	affects expression	1
vanadyl sulfate	increases expression	1
pinosylvin	increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluoro-n-nonanoic acid	decreases expression	1
abrine	increases expression	1
trametinib	increases expression, affects cotreatment	1
(+)-JQ1 compound	increases expression	1
NVP-BKM120	affects cotreatment, increases expression	1
Arsenic Trioxide	increases expression	1
Air Pollutants, Occupational	decreases expression	1
Arsenic	decreases expression, increases abundance	1
Calcitriol	increases expression	1
Cisplatin	increases expression	1
Dietary Carbohydrates	affects cotreatment, increases expression	1
Fonofos	increases methylation	1
Methoxsalen	decreases activity	1

ChEMBL screening assays

12 unique, capped per target: 12 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL686687	Binding	The kinetic constant with the compound as substrate of S143A mutant enzyme was determined	Formation of the Michaelis complex without involvement of the prosthetic group dehydroalanine of histidine ammonialyase — Bioorg Med Chem Lett

Clinical trials (associated diseases)

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