ALKBH1

Summary

ALKBH1 (alkB homolog 1, histone H2A dioxygenase, HGNC:17911) is a protein-coding gene on chromosome 14q24.3, encoding Nucleic acid dioxygenase ALKBH1 (Q13686). Dioxygenase that acts on nucleic acids, such as DNA and tRNA.

This gene encodes a homolog to the E. coli alkB gene product. The E. coli alkB protein is part of the adaptive response mechanism of DNA alkylation damage repair. It is involved in damage reversal by oxidative demethylation of 1-methyladenine and 3-methylcytosine.

Source: NCBI Gene 8846 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 57 total
• Druggable target: yes
• MANE Select transcript: NM_006020

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17911
Approved symbol	ALKBH1
Name	alkB homolog 1, histone H2A dioxygenase
Location	14q24.3
Locus type	gene with protein product
Status	Approved
Aliases	hABH, alkB, ABH
Ensembl gene	ENSG00000100601
Ensembl biotype	protein_coding
OMIM	605345
Entrez	8846

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 4 protein_coding, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000216489, ENST00000554097, ENST00000555100, ENST00000557057, ENST00000856894, ENST00000856895, ENST00000856896

RefSeq mRNA: 1 — MANE Select: NM_006020 NM_006020

CCDS: CCDS32127

Canonical transcript exons

ENST00000216489 — 6 exons

Exon	Start	End
ENSE00000808492	77704369	77704477
ENSE00001158423	77672404	77674241
ENSE00002526080	77707822	77708023
ENSE00003501690	77675656	77675849
ENSE00003562374	77694738	77694900
ENSE00003641188	77679880	77679970

Expression profiles

Bgee: expression breadth ubiquitous, 273 present calls, max score 96.44.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.4117 / max 49.2911, expressed in 1766 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
144246	6.4117	1766

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	96.44	gold quality
secondary oocyte	CL:0000655	94.92	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.85	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.36	gold quality
endothelial cell	CL:0000115	85.45	silver quality
heart right ventricle	UBERON:0002080	84.46	gold quality
cartilage tissue	UBERON:0002418	84.24	gold quality
adult organism	UBERON:0007023	84.15	gold quality
cervix squamous epithelium	UBERON:0006922	84.03	silver quality
jejunal mucosa	UBERON:0000399	83.80	gold quality
gastrocnemius	UBERON:0001388	83.61	gold quality
embryo	UBERON:0000922	83.45	gold quality
muscle of leg	UBERON:0001383	83.22	gold quality
ventricular zone	UBERON:0003053	82.93	gold quality
ganglionic eminence	UBERON:0004023	82.85	gold quality
mucosa of urinary bladder	UBERON:0001259	82.41	silver quality
hindlimb stylopod muscle	UBERON:0004252	81.73	gold quality
muscle organ	UBERON:0001630	81.70	gold quality
decidua	UBERON:0002450	81.63	silver quality
mucosa of transverse colon	UBERON:0004991	81.46	gold quality
heart left ventricle	UBERON:0002084	81.45	gold quality
cardiac ventricle	UBERON:0002082	81.41	gold quality
cauda epididymis	UBERON:0004360	81.20	gold quality
biceps brachii	UBERON:0001507	81.12	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	81.04	gold quality
granulocyte	CL:0000094	80.93	gold quality
apex of heart	UBERON:0002098	80.89	gold quality
palpebral conjunctiva	UBERON:0001812	80.87	gold quality
corpus epididymis	UBERON:0004359	80.77	gold quality
diaphragm	UBERON:0001103	80.75	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.31

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): EOMES

miRNA regulators (miRDB)

99 targeting ALKBH1, 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-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
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-6873-3P	100.00	71.42	2626
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-23B-5P	99.98	66.07	587
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-23A-5P	99.94	65.39	468
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-4302	99.89	67.94	1187
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-202-3P	99.84	71.41	1290
HSA-MIR-130B-5P	99.83	68.50	1888

Literature-anchored findings (GeneRIF, showing 30)

• AlkB homologues, hABH2 and hABH3, also are oxidative DNA demethylases; AlkB and hABH3, but not hABH2, also repair RNA (PMID:12594517)
• hABH1 is a functional mitochondrial AlkB homolog that repairs 3-methylcytosine in single-stranded DNA and RNA. (PMID:18603530)
• show that ABH1 unexpectedly has a second activity, cleaving DNA at abasic (AP) sites such as those arising spontaneously from alkylation-dependent depurination reactions. (PMID:19959401)
• Homology modeling and different tertiary structure based study were performed on human AlkB homolog hABH1. (PMID:21956739)
• Primary and secondary lysine residues of ALKBH1 are involved in lyase reactions and form a covalent adduct with the 5’DNA product, demonstrating two plausible chemical mechanisms to account for the covalent attachment. (PMID:23577621)
• ALKBH1’s role in class switch recombination and abasic site cleavage during base excision repair (PMID:23825659)
• AlkB has a wide variety of substrates, including monoalkyl and exocyclic bridged adducts. (Review) (PMID:26152727)
• The authors identify ALKBH1/ABH1 as the dioxygenase responsible for oxidising m(5)C34 of mt-tRNA(M)(et) to generate an f(5)C34 modification. (PMID:27497299)
• The ALKBH1-catalyzed demethylation of the target tRNAs results in attenuated translation initiation and decreased usage of tRNAs in protein synthesis. (PMID:27745969)
• The authors postulate that the very low 6-methyl adenine oxygenase activity associated with ALKBH1 is unlikely to represent the major function of the enzyme in the cell, while the cellular role of the lyase activity (including its subsequent covalent attachment to DNA) remains uncertain. (PMID:28290676)
• Nuclear and mitochondrial ALKBH1 play distinct roles in tRNA modification. (PMID:28472312)
• Localization and subcellular fractionation studies with the endogenous protein in two cell strains confirm that ALKBH1 is primarily in the mitochondria. (PMID:29097205)
• The abundance of 6mA was significantly lower in cancers, accompanied by decreased N6AMT1 and increased ALKBH1 levels, and downregulation of 6mA modification levels promoted tumorigenesis. Collectively, Results demonstrate that DNA 6mA modification is extensively present in human cells and the decrease of genomic DNA 6mA promotes human tumorigenesis. (PMID:30017583)
• This study characterized ALKBH1 to be a mitochondrial-localized protein with N6-methyldeoxyadenosine demethylation activity. Loss of ALKBH1 also disrupted mitochondrial OXPHOS function. (PMID:30412255)
• Aberrantly high mRNA expression of demethylase genes, FTO and ALKBH1, was markedly associated with poor prognosis in gastric cancer. (PMID:30637548)
• Data show that the three DNA repair enzymes ALKBH2, ALKBH3, and AlkB are not only able to repair DNA adducts, but also can edit the epigenetic modification and generate the corresponding oxidative derivatives. (PMID:31114894)
• AlkB homologue 1 (ALKBH1) was capable of demethylating m(3)C in mRNA of mammalian cells in vitro. Overexpression and knockdown of ALKBH1 in cultured human cells can induce decrease and increase of the level of m(3)C in mRNA, respectively, revealing the eraser enzyme property of ALKBH1 on m(3)C in mRNA. (PMID:31188562)
• Downregulation of Alkbh1 impacts cell growth in HeLa cells and delays development in Caenorhabditis elegans, where the mitochondrial role of Alkbh1 seems to be conserved. (PMID:31434717)
• Structural basis of nucleic acid recognition and 6mA demethylation by human ALKBH1. (PMID:32051559)
• MiRNA-339-5p suppresses the malignant development of gastric cancer via targeting ALKBH1. (PMID:32380054)
• ALKBH1 deficiency leads to loss of homeostasis in human diploid somatic cells. (PMID:32661925)
• ALKBH1 promotes lung cancer by regulating m6A RNA demethylation. (PMID:33068553)
• A positive feedback loop between AlkB homolog 5 and miR-193a-3p promotes growth and metastasis in esophageal squamous cell carcinoma. (PMID:33231844)
• ALKBH1-demethylated DNA N6-methyladenine modification triggers vascular calcification via osteogenic reprogramming in chronic kidney disease. (PMID:34003800)
• Demethyltransferase AlkBH1 substrate diversity and relationship to human diseases. (PMID:34046849)
• DNA demethylase ALKBH1 promotes adipogenic differentiation via regulation of HIF-1 signaling. (PMID:34922943)
• Evaluating the Potential for ABO-incompatible Islet Transplantation: Expression of ABH Antigens on Human Pancreata, Isolated Islets, and Embryonic Stem Cell-derived Islets. (PMID:36228319)
• ALKBH1 contributes to renal cell carcinoma progression by reducing N6-methyladenine of GPR137. (PMID:36920340)
• DNA 6mA demethylase ALKBH1 regulates DDX18 expression to promote proliferation of human head and neck squamous cell carcinoma. (PMID:36976498)
• The N[6]-methyladenine DNA demethylase ALKBH1 promotes gastric carcinogenesis by disrupting NRF1 binding capacity. (PMID:36989111)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	alkbh1	ENSDARG00000071164
mus_musculus	Alkbh1	ENSMUSG00000079036
rattus_norvegicus	Alkbh1	ENSRNOG00000012264
drosophila_melanogaster	AlkB	FBGN0065035
caenorhabditis_elegans		WBGENE00021783

Protein

Protein identifiers

Nucleic acid dioxygenase ALKBH1 — Q13686 (reviewed: Q13686)

Alternative names: Alkylated DNA repair protein alkB homolog 1, Alpha-ketoglutarate-dependent dioxygenase ABH1, DNA 6mA demethylase, DNA N6-methyl adenine demethylase ALKBH1, DNA lyase ABH1, DNA oxidative demethylase ALKBH1, mRNA N(3)-methylcytidine demethylase

All UniProt accessions (3): Q13686, G3V4M4, H0YJF3

UniProt curated annotations — full annotation on UniProt →

Function. Dioxygenase that acts on nucleic acids, such as DNA and tRNA. Requires molecular oxygen, alpha-ketoglutarate and iron. A number of activities have been described for this dioxygenase, but recent results suggest that it mainly acts on tRNAs and mediates their demethylation or oxidation depending on the context and subcellular compartment. Mainly acts as a tRNA demethylase by removing N(1)-methyladenine from various tRNAs, with a preference for N(1)-methyladenine at position 58 (m1A58) present on a stem loop structure of tRNAs. Acts as a regulator of translation initiation and elongation in response to glucose deprivation: regulates both translation initiation, by mediating demethylation of tRNA(Met), and translation elongation, N(1)-methyladenine-containing tRNAs being preferentially recruited to polysomes to promote translation elongation. In mitochondrion, specifically interacts with mt-tRNA(Met) and mediates oxidation of mt-tRNA(Met) methylated at cytosine(34) to form 5-formylcytosine (f(5)c) at this position. mt-tRNA(Met) containing the f(5)c modification at the wobble position enables recognition of the AUA codon in addition to the AUG codon, expanding codon recognition in mitochondrial translation. Specifically demethylates DNA methylated on the 6th position of adenine (N(6)-methyladenosine) DNA. N(6)-methyladenosine (m6A) DNA is present at some L1 elements in embryonic stem cells and probably promotes their silencing. Demethylates mRNAs containing N(3)-methylcytidine modification. Also able to repair alkylated single-stranded DNA by oxidative demethylation, but with low activity. Also has DNA lyase activity and introduces double-stranded breaks at abasic sites: cleaves both single-stranded DNA and double-stranded DNA at abasic sites, with the greatest activity towards double-stranded DNA with two abasic sites. DNA lyase activity does not require alpha-ketoglutarate and iron and leads to the formation of an irreversible covalent protein-DNA adduct with the 5’ DNA product. DNA lyase activity is not required during base excision repair and class switch recombination of the immunoglobulin heavy chain during B lymphocyte activation. May play a role in placental trophoblast lineage differentiation.

Subunit / interactions. Monomer. Interacts with DNAJB6.

Subcellular location. Nucleus. Mitochondrion.

Tissue specificity. Ubiquitous.

Cofactor. Binds 1 Fe(2+) ion per subunit.

Similarity. Belongs to the alkB family.

RefSeq proteins (1): NP_006011* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004574	Alkb	Family
IPR005123	Oxoglu/Fe-dep_dioxygenase_dom	Domain
IPR027450	AlkB-like	Domain
IPR037151	AlkB-like_sf	Homologous_superfamily

Pfam: PF13532

Enzyme classification (BRENDA):

• EC 1.14.11.51 — DNA N6-methyladenine demethylase (BRENDA: 5 organisms, 3 substrates, 1 inhibitors, 0 Km, 0 kcat entries)

Catalyzed reactions (Rhea), 7 shown:

• a methylated nucleobase within DNA + 2-oxoglutarate + O2 = a nucleobase within DNA + formaldehyde + succinate + CO2 (RHEA:30299)
• an N(6)-methyl-2’-deoxyadenosine in DNA + 2-oxoglutarate + O2 = a 2’-deoxyadenosine in DNA + formaldehyde + succinate + CO2 (RHEA:49524)
• 5-methylcytidine(34) in mitochondrial tRNA(Met) + 2 2-oxoglutarate + 2 O2 = 5-formylcytidine(34) in mitochondrial tRNA(Met) + 2 succinate + 2 CO2 + H2O (RHEA:54144)
• an N(1)-methyladenosine in tRNA + 2-oxoglutarate + O2 = an adenosine in tRNA + formaldehyde + succinate + CO2 (RHEA:54576)
• an N(3)-methylcytidine in mRNA + 2-oxoglutarate + O2 = a cytidine in mRNA + formaldehyde + succinate + CO2 (RHEA:60920)
• 2’-deoxyribonucleotide-(2’-deoxyribose 5’-phosphate)-2’-deoxyribonucleotide-DNA = a 3’-end 2’-deoxyribonucleotide-(2,3-dehydro-2,3-deoxyribose 5’-phosphate)-DNA + a 5’-end 5’-phospho-2’-deoxyribonucleoside-DNA + H(+) (RHEA:66592)
• N(1)-methyladenosine(58) in tRNA + 2-oxoglutarate + O2 = adenosine(58) in tRNA + formaldehyde + succinate + CO2 (RHEA:79019)

UniProt features (91 total): mutagenesis site 37, strand 19, helix 14, binding site 8, sequence conflict 3, turn 3, site 2, sequence variant 2, chain 1, domain 1, region of interest 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
6IE3	X-RAY DIFFRACTION	1.97
8K62	X-RAY DIFFRACTION	1.99
6IE2	X-RAY DIFFRACTION	2.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13686-F1	86.47	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.

Catalytic / active sites (2): 133 (primary catalytic residue forming the imine linkage with dna); 133 (secondary catalytic residue forming the imine linkage with dna)

Ligand- & substrate-binding residues (8): 338–344; 144; 175–177; 220–222; 231; 233; 233; 287

Mutagenesis-validated functional residues (37):

Position	Phenotype
3	does not affect dna lyase activity.
25	moderate decrease in dna lyase activity. reduced dna lyase activity; when associated with a-133.
55	does not affect dna lyase activity.
61	does not affect dna lyase activity.
64	does not affect dna lyase activity.
87	does not affect dna lyase activity.
94	does not affect dna lyase activity.
113	does not affect dna lyase activity.
116	does not affect dna lyase activity.
118	does not affect dna lyase activity.
120	does not affect dna lyase activity.
125	does not affect dna lyase activity.
129	does not affect dna lyase activity.
133	reduced dna lyase activity. slightly more reduced dna lyase activity; when associated with a-25. strongly reduced activi
134	does not affect dna lyase activity.
137	does not affect dna lyase activity.
148	does not affect dna lyase activity.
154	does not affect dna lyase activity. strongly reduced activity; when associated with a-133.
158	does not affect dna lyase activity.
167	does not affect dna lyase activity.
182	does not affect dna lyase activity.
183	does not affect dna lyase activity.
218	reduces fe2og dioxygenase activity by 50%.
231–233	loss of catalytic activity. abolishes ability to regulate translation in respose to glucose deprivation.
231	near loss of fe2og dioxygenase activity. no effect on dna lyase activity.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 186 (showing top): GOBP_NEGATIVE_REGULATION_OF_NEURON_APOPTOTIC_PROCESS, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOMF_ENDONUCLEASE_ACTIVITY, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_PAIRED_DONORS_WITH_INCORPORATION_OR_REDUCTION_OF_MOLECULAR_OXYGEN, GOMF_NUCLEASE_ACTIVITY, GOBP_TRNA_METABOLIC_PROCESS, GOBP_GROWTH, GOBP_MITOCHONDRIAL_TRANSLATION, GOBP_OXIDATIVE_DEMETHYLATION, GOBP_REGULATION_OF_TRANSLATIONAL_ELONGATION, GOBP_TRANSLATIONAL_INITIATION, GOBP_NEUROGENESIS, BROWNE_HCMV_INFECTION_16HR_UP, KAUFFMANN_DNA_REPAIR_GENES, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP

GO Biological Process (20): in utero embryonic development (GO:0001701), neuron migration (GO:0001764), placenta development (GO:0001890), tRNA wobble cytosine modification (GO:0002101), DNA repair (GO:0006281), regulation of translational initiation (GO:0006446), regulation of translational elongation (GO:0006448), neuron projection development (GO:0031175), oxidative RNA demethylation (GO:0035513), RNA repair (GO:0042245), negative regulation of neuron apoptotic process (GO:0043524), developmental growth (GO:0048589), regulation of mitochondrial translation (GO:0070129), positive regulation of gene expression, epigenetic (GO:0141137), regulation of translational initiation by tRNA modification (GO:1990983), regulation of translation (GO:0006417), DNA damage response (GO:0006974), regulation of gene expression (GO:0010468), cell differentiation (GO:0030154), positive chemotaxis (GO:0050918)

GO Molecular Function (15): tRNA binding (GO:0000049), ferrous iron binding (GO:0008198), 2-oxoglutarate-dependent dioxygenase activity (GO:0016706), oxidative RNA demethylase activity (GO:0035515), broad specificity oxidative DNA demethylase activity (GO:0035516), chemoattractant activity (GO:0042056), class I DNA-(apurinic or apyrimidinic site) endonuclease activity (GO:0140078), DNA N6-methyladenine demethylase activity (GO:0141131), 2-oxoglutarate-dependent tRNA 5-methylcytidine formyltransferase activity (GO:0160290), tRNA demethylase activity (GO:1990984), catalytic activity (GO:0003824), oxidoreductase activity (GO:0016491), lyase activity (GO:0016829), metal ion binding (GO:0046872), dioxygenase activity (GO:0051213)

GO Cellular Component (7): euchromatin (GO:0000791), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759), endoplasmic reticulum (GO:0005783)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
2-oxoglutarate-dependent dioxygenase activity	4
regulation of translation	3
intracellular membrane-bounded organelle	3
DNA demethylase activity	2
catalytic activity, acting on a tRNA	2
catalytic activity	2
cellular anatomical structure	2
cytoplasm	2
chordate embryonic development	1
cell migration	1
generation of neurons	1
animal organ development	1
tRNA wobble base modification	1
DNA metabolic process	1
DNA damage response	1
translational initiation	1
translational elongation	1
neuron development	1
plasma membrane bounded cell projection organization	1
RNA modification	1
oxidative demethylation	1
RNA metabolic process	1
negative regulation of apoptotic process	1
regulation of neuron apoptotic process	1
neuron apoptotic process	1
developmental process	1
growth	1
mitochondrial translation	1
regulation of mitochondrial gene expression	1
positive regulation of gene expression	1
epigenetic regulation of gene expression	1
tRNA modification	1
regulation of translational initiation	1
translation	1
post-transcriptional regulation of gene expression	1
regulation of protein metabolic process	1
cellular response to stress	1
gene expression	1
regulation of macromolecule biosynthetic process	1
cellular developmental process	1

Protein interactions and networks

STRING

1382 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ALKBH1	ALKBH3	Q96Q83	990
ALKBH1	ALKBH2	Q6NS38	987
ALKBH1	ALKBH5	Q6P6C2	980
ALKBH1	JMJD4	Q9H9V9	965
ALKBH1	FTO	Q9C0B1	959
ALKBH1	ALKBH6	Q3KRA9	953
ALKBH1	ALKBH4	Q9NXW9	953
ALKBH1	ALKBH8	Q96BT7	950
ALKBH1	ALKBH7	Q9BT30	946
ALKBH1	METTL3	Q86U44	849
ALKBH1	METTL14	Q9HCE5	844
ALKBH1	WTAP	Q15007	839
ALKBH1	YTHDC1	Q96MU7	804
ALKBH1	YTHDF1	Q9BYJ9	794
ALKBH1	YTHDF2	Q9Y5A9	790

IntAct

3 interactions, top by confidence:

A	B	Type	Score
ALKBH1	Dnajb6	psi-mi:“MI:0915”(physical association)	0.370
RAB20	BCL10	psi-mi:“MI:0914”(association)	0.350

BioGRID (8): ALKBH1 (Affinity Capture-MS), ALKBH1 (Affinity Capture-MS), ALKBH1 (Affinity Capture-MS), ALKBH1 (Proximity Label-MS), ALKBH1 (Negative Genetic), ALKBH1 (Affinity Capture-RNA), DNAJB6 (Affinity Capture-Western), ALKBH1 (Affinity Capture-Western)

ESM2 similar proteins: A0A084API4, A0A098E171, A0A179H324, A0A2Z4HQ03, A0A9P4XUZ4, A4RHU9, A6YRN9, B2KWI2, B6HLP7, C0HMB1, G4MZ21, K0E678, O13767, O60066, O60993, P0CB42, P0CQ68, P40032, Q03305, Q05531, Q12415, Q13686, Q15FB7, Q2H0G2, Q2U6Q1, Q32L00, Q4I1M9, Q4IQK7, Q4W9F7, Q4WED9, Q4WF55, Q54N08, Q58DM4, Q5AY37, Q5B5P1, Q5XIC8, Q6C423, Q6C7U7, Q6C9E7, Q6C9T3

Diamond homologs: A0A9P4XUZ4, B1PS76, B8GWW6, F4JFR7, F4KAV2, P05050, P0CAT7, P0CB42, P37462, Q13686, Q54N08, Q9LJH2, Q9SA98, G4MZ21, O60066

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	51
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1200 predictions. Top by Δscore:

Variant	Effect	Δscore
14:77675859:A:AC	acceptor_gain	1.0000
14:77675859:A:C	acceptor_gain	1.0000
14:77679883:A:AC	donor_gain	1.0000
14:77679883:ACTGT:A	donor_gain	1.0000
14:77679884:C:CC	donor_gain	1.0000
14:77679884:CTGTC:C	donor_gain	1.0000
14:77679909:CGG:C	donor_gain	1.0000
14:77707816:CTGTA:C	donor_loss	1.0000
14:77707817:TGTA:T	donor_loss	1.0000
14:77707818:GTACC:G	donor_loss	1.0000
14:77707819:TACC:T	donor_loss	1.0000
14:77707820:A:AT	donor_loss	1.0000
14:77707821:C:G	donor_loss	1.0000
14:77674237:CAAAG:C	acceptor_gain	0.9900
14:77674239:AAG:A	acceptor_gain	0.9900
14:77674240:AG:A	acceptor_gain	0.9900
14:77674242:C:CA	acceptor_loss	0.9900
14:77674242:C:CC	acceptor_gain	0.9900
14:77675652:TCAC:T	donor_loss	0.9900
14:77675654:ACCTG:A	donor_loss	0.9900
14:77675793:CT:C	acceptor_gain	0.9900
14:77675795:C:CC	acceptor_gain	0.9900
14:77675795:C:G	acceptor_gain	0.9900
14:77675808:C:T	acceptor_gain	0.9900
14:77675813:C:CT	acceptor_gain	0.9900
14:77675861:G:GC	acceptor_gain	0.9900
14:77679879:CCTTA:C	donor_gain	0.9900
14:77679884:CTGT:C	donor_gain	0.9900
14:77679969:ACC:A	acceptor_loss	0.9900
14:77679971:C:A	acceptor_loss	0.9900

AlphaMissense

2559 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:77679889:C:A	W179C	0.998
14:77679889:C:G	W179C	0.998
14:77679918:A:G	W170R	0.998
14:77679918:A:T	W170R	0.998
14:77679891:A:G	W179R	0.996
14:77679891:A:T	W179R	0.996
14:77679916:C:A	W170C	0.996
14:77679916:C:G	W170C	0.996
14:77674123:G:C	H287D	0.995
14:77674236:C:T	G249E	0.995
14:77675698:T:A	D233V	0.995
14:77675736:A:C	N220K	0.995
14:77675736:A:T	N220K	0.995
14:77675846:A:G	Y184H	0.995
14:77679905:C:A	G174V	0.995
14:77704399:A:G	W88R	0.995
14:77704399:A:T	W88R	0.995
14:77675698:T:G	D233A	0.994
14:77675705:G:C	H231D	0.994
14:77675750:C:G	A216P	0.994
14:77679906:C:G	G174R	0.994
14:77694803:G:C	N130K	0.994
14:77694803:G:T	N130K	0.994
14:77673966:A:T	V339D	0.993
14:77673970:G:T	R338S	0.993
14:77674220:A:C	F254L	0.993
14:77674220:A:T	F254L	0.993
14:77674222:A:G	F254L	0.993
14:77674236:C:A	G249V	0.993
14:77679905:C:T	G174D	0.993

dbSNP variants (sampled 300 via entrez): RS1000010125 (14:77692826 T>A), RS1000080234 (14:77702947 G>T), RS1000088072 (14:77694797 G>C), RS1000248939 (14:77692647 C>A,T), RS1000454027 (14:77697658 G>A), RS1000510216 (14:77703362 C>G,T), RS1000639945 (14:77698760 T>C), RS1000680699 (14:77700349 AGTTGATTAATC>A), RS1000833032 (14:77697927 C>T), RS1000962399 (14:77681554 C>T), RS1001067737 (14:77708835 G>A), RS1001147660 (14:77687378 G>T), RS1001216199 (14:77696207 G>A), RS1001389470 (14:77676983 C>A,T), RS1001394774 (14:77690800 A>C,G)

Disease associations

OMIM: gene MIM:605345 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST001629_5	Response to platinum-based chemotherapy in non-small-cell lung cancer	4.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5169151 (SINGLE PROTEIN)

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

ChEMBL bioactivities

47 potent at pChembl≥5 of 49 total, top 47 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.51	IC50	31	nM	CHEMBL5594860
7.35	IC50	45	nM	CHEMBL5592755
7.34	IC50	46	nM	CHEMBL5589846
7.31	IC50	49	nM	CHEMBL5595130
7.24	IC50	57	nM	CHEMBL5595043
7.20	IC50	63	nM	CHEMBL5591751
7.18	IC50	66	nM	CHEMBL5592290
7.16	IC50	69	nM	CHEMBL5594481
7.12	IC50	75	nM	CHEMBL5593984
7.12	IC50	76	nM	CHEMBL5593555
7.10	IC50	80	nM	CHEMBL5593030
7.09	IC50	82	nM	CHEMBL5595752
7.09	IC50	82	nM	CHEMBL5591739
7.04	IC50	91	nM	CHEMBL5595276
7.01	IC50	98	nM	CHEMBL5594280
7.01	IC50	98	nM	CHEMBL5593769
7.00	IC50	99	nM	CHEMBL5592202
6.96	IC50	110	nM	CHEMBL5595585
6.96	IC50	110	nM	CHEMBL5595088
6.95	IC50	113	nM	CHEMBL5590866
6.93	IC50	117	nM	CHEMBL5592901
6.93	IC50	118	nM	CHEMBL5595720
6.92	IC50	120	nM	CHEMBL5592192
6.91	IC50	123	nM	CHEMBL5593650
6.91	IC50	124	nM	CHEMBL5592499
6.87	IC50	134	nM	CHEMBL5591761
6.87	IC50	135	nM	CHEMBL5592216
6.86	IC50	138	nM	CHEMBL5593405
6.84	IC50	146	nM	CHEMBL5595815
6.83	IC50	148	nM	CHEMBL5594637
6.83	IC50	148	nM	CHEMBL5593013
6.81	Kd	156	nM	CHEMBL5594860
6.74	IC50	183	nM	CHEMBL5590799
6.72	IC50	189	nM	CHEMBL5595760
6.70	IC50	198	nM	CHEMBL5592198
6.51	IC50	308	nM	CHEMBL5593535
6.38	IC50	416	nM	CHEMBL5595355
6.26	IC50	543	nM	CHEMBL5594625
6.25	IC50	558	nM	CHEMBL5593235
6.16	IC50	694	nM	CHEMBL5595924
6.00	IC50	997	nM	CHEMBL5583749
5.98	IC50	1048	nM	CHEMBL5595126
5.62	IC50	2417	nM	CHEMBL5583910
5.62	IC50	2425	nM	CHEMBL5592491
5.60	IC50	2503	nM	CHEMBL5592709
5.58	IC50	2620	nM	CHEMBL5594860
5.00	IC50	9877	nM	CHEMBL5583746

PubChem BioAssay actives

47 with measured affinity, of 79 total; 45 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
1-[5-[(3-methoxyphenyl)methoxy]pyrimidin-2-yl]pyrazole-4-carboxylic acid	2118278: Inhibition of N-terminal 6xHis-tagged human ALKBH1 extracted from Escherichia coli BL21(DE3) using 5’-AACTTCGTGCAGGCATGGG(6mA)TCTTGTCTACT-3’/5’-FAM-AGTAGACACATGCCTGCACGAAGTT-3’ as substrate preincubated for 30 mins followed by substrate addition by fluorescence polarization assay	ic50	0.0310	uM
1-[5-[(2,5-dichlorophenyl)methoxy]pyrimidin-2-yl]pyrazole-4-carboxylic acid	2118278: Inhibition of N-terminal 6xHis-tagged human ALKBH1 extracted from Escherichia coli BL21(DE3) using 5’-AACTTCGTGCAGGCATGGG(6mA)TCTTGTCTACT-3’/5’-FAM-AGTAGACACATGCCTGCACGAAGTT-3’ as substrate preincubated for 30 mins followed by substrate addition by fluorescence polarization assay	ic50	0.0450	uM
1-[5-[(3-phenoxyphenyl)methoxy]pyrimidin-2-yl]pyrazole-4-carboxylic acid	2118278: Inhibition of N-terminal 6xHis-tagged human ALKBH1 extracted from Escherichia coli BL21(DE3) using 5’-AACTTCGTGCAGGCATGGG(6mA)TCTTGTCTACT-3’/5’-FAM-AGTAGACACATGCCTGCACGAAGTT-3’ as substrate preincubated for 30 mins followed by substrate addition by fluorescence polarization assay	ic50	0.0460	uM
1-[5-[[2-fluoro-5-(trifluoromethoxy)phenyl]methoxy]pyrimidin-2-yl]pyrazole-4-carboxylic acid	2118278: Inhibition of N-terminal 6xHis-tagged human ALKBH1 extracted from Escherichia coli BL21(DE3) using 5’-AACTTCGTGCAGGCATGGG(6mA)TCTTGTCTACT-3’/5’-FAM-AGTAGACACATGCCTGCACGAAGTT-3’ as substrate preincubated for 30 mins followed by substrate addition by fluorescence polarization assay	ic50	0.0490	uM
1-[5-[[3-(difluoromethoxy)phenyl]methoxy]pyrimidin-2-yl]pyrazole-4-carboxylic acid	2118278: Inhibition of N-terminal 6xHis-tagged human ALKBH1 extracted from Escherichia coli BL21(DE3) using 5’-AACTTCGTGCAGGCATGGG(6mA)TCTTGTCTACT-3’/5’-FAM-AGTAGACACATGCCTGCACGAAGTT-3’ as substrate preincubated for 30 mins followed by substrate addition by fluorescence polarization assay	ic50	0.0570	uM
1-[5-[(2,3-difluorophenyl)methoxy]pyrimidin-2-yl]pyrazole-4-carboxylic acid	2118278: Inhibition of N-terminal 6xHis-tagged human ALKBH1 extracted from Escherichia coli BL21(DE3) using 5’-AACTTCGTGCAGGCATGGG(6mA)TCTTGTCTACT-3’/5’-FAM-AGTAGACACATGCCTGCACGAAGTT-3’ as substrate preincubated for 30 mins followed by substrate addition by fluorescence polarization assay	ic50	0.0630	uM
1-[5-[(4-fluoro-3-methoxyphenyl)methoxy]pyrimidin-2-yl]pyrazole-4-carboxylic acid	2118278: Inhibition of N-terminal 6xHis-tagged human ALKBH1 extracted from Escherichia coli BL21(DE3) using 5’-AACTTCGTGCAGGCATGGG(6mA)TCTTGTCTACT-3’/5’-FAM-AGTAGACACATGCCTGCACGAAGTT-3’ as substrate preincubated for 30 mins followed by substrate addition by fluorescence polarization assay	ic50	0.0660	uM
1-[5-[(3-morpholin-4-ylphenyl)methoxy]pyrimidin-2-yl]pyrazole-4-carboxylic acid	2118278: Inhibition of N-terminal 6xHis-tagged human ALKBH1 extracted from Escherichia coli BL21(DE3) using 5’-AACTTCGTGCAGGCATGGG(6mA)TCTTGTCTACT-3’/5’-FAM-AGTAGACACATGCCTGCACGAAGTT-3’ as substrate preincubated for 30 mins followed by substrate addition by fluorescence polarization assay	ic50	0.0690	uM
1-[5-[(3-benzoylphenyl)methoxy]pyrimidin-2-yl]pyrazole-4-carboxylic acid	2118278: Inhibition of N-terminal 6xHis-tagged human ALKBH1 extracted from Escherichia coli BL21(DE3) using 5’-AACTTCGTGCAGGCATGGG(6mA)TCTTGTCTACT-3’/5’-FAM-AGTAGACACATGCCTGCACGAAGTT-3’ as substrate preincubated for 30 mins followed by substrate addition by fluorescence polarization assay	ic50	0.0750	uM
1-[5-[(2,5-difluorophenyl)methoxy]pyrimidin-2-yl]pyrazole-4-carboxylic acid	2118278: Inhibition of N-terminal 6xHis-tagged human ALKBH1 extracted from Escherichia coli BL21(DE3) using 5’-AACTTCGTGCAGGCATGGG(6mA)TCTTGTCTACT-3’/5’-FAM-AGTAGACACATGCCTGCACGAAGTT-3’ as substrate preincubated for 30 mins followed by substrate addition by fluorescence polarization assay	ic50	0.0760	uM
1-[5-[(3,5-dimethoxyphenyl)methoxy]pyrimidin-2-yl]pyrazole-4-carboxylic acid	2118278: Inhibition of N-terminal 6xHis-tagged human ALKBH1 extracted from Escherichia coli BL21(DE3) using 5’-AACTTCGTGCAGGCATGGG(6mA)TCTTGTCTACT-3’/5’-FAM-AGTAGACACATGCCTGCACGAAGTT-3’ as substrate preincubated for 30 mins followed by substrate addition by fluorescence polarization assay	ic50	0.0800	uM
1-[5-[(2-chlorophenyl)methoxy]pyrimidin-2-yl]pyrazole-4-carboxylic acid	2118278: Inhibition of N-terminal 6xHis-tagged human ALKBH1 extracted from Escherichia coli BL21(DE3) using 5’-AACTTCGTGCAGGCATGGG(6mA)TCTTGTCTACT-3’/5’-FAM-AGTAGACACATGCCTGCACGAAGTT-3’ as substrate preincubated for 30 mins followed by substrate addition by fluorescence polarization assay	ic50	0.0820	uM
1-[5-[(4-methoxyphenyl)methoxy]pyrimidin-2-yl]pyrazole-4-carboxylic acid	2118278: Inhibition of N-terminal 6xHis-tagged human ALKBH1 extracted from Escherichia coli BL21(DE3) using 5’-AACTTCGTGCAGGCATGGG(6mA)TCTTGTCTACT-3’/5’-FAM-AGTAGACACATGCCTGCACGAAGTT-3’ as substrate preincubated for 30 mins followed by substrate addition by fluorescence polarization assay	ic50	0.0820	uM
1-(5-phenylmethoxypyrimidin-2-yl)pyrazole-4-carboxylic acid	2118277: Inhibition of ALKBH1 (unknown origin) by FP assay	ic50	0.0910	uM
1-[5-[(4-fluorophenyl)methoxy]pyrimidin-2-yl]pyrazole-4-carboxylic acid	2118278: Inhibition of N-terminal 6xHis-tagged human ALKBH1 extracted from Escherichia coli BL21(DE3) using 5’-AACTTCGTGCAGGCATGGG(6mA)TCTTGTCTACT-3’/5’-FAM-AGTAGACACATGCCTGCACGAAGTT-3’ as substrate preincubated for 30 mins followed by substrate addition by fluorescence polarization assay	ic50	0.0980	uM
1-[5-[(4-chlorophenyl)methoxy]pyrimidin-2-yl]pyrazole-4-carboxylic acid	2118278: Inhibition of N-terminal 6xHis-tagged human ALKBH1 extracted from Escherichia coli BL21(DE3) using 5’-AACTTCGTGCAGGCATGGG(6mA)TCTTGTCTACT-3’/5’-FAM-AGTAGACACATGCCTGCACGAAGTT-3’ as substrate preincubated for 30 mins followed by substrate addition by fluorescence polarization assay	ic50	0.0980	uM
1-[5-[(2-fluorophenyl)methoxy]pyrimidin-2-yl]pyrazole-4-carboxylic acid	2118278: Inhibition of N-terminal 6xHis-tagged human ALKBH1 extracted from Escherichia coli BL21(DE3) using 5’-AACTTCGTGCAGGCATGGG(6mA)TCTTGTCTACT-3’/5’-FAM-AGTAGACACATGCCTGCACGAAGTT-3’ as substrate preincubated for 30 mins followed by substrate addition by fluorescence polarization assay	ic50	0.0990	uM
1-[5-[(2-cyanophenyl)methoxy]pyrimidin-2-yl]pyrazole-4-carboxylic acid	2118278: Inhibition of N-terminal 6xHis-tagged human ALKBH1 extracted from Escherichia coli BL21(DE3) using 5’-AACTTCGTGCAGGCATGGG(6mA)TCTTGTCTACT-3’/5’-FAM-AGTAGACACATGCCTGCACGAAGTT-3’ as substrate preincubated for 30 mins followed by substrate addition by fluorescence polarization assay	ic50	0.1100	uM
1-[5-[(3-fluoro-4-methoxyphenyl)methoxy]pyrimidin-2-yl]pyrazole-4-carboxylic acid	2118278: Inhibition of N-terminal 6xHis-tagged human ALKBH1 extracted from Escherichia coli BL21(DE3) using 5’-AACTTCGTGCAGGCATGGG(6mA)TCTTGTCTACT-3’/5’-FAM-AGTAGACACATGCCTGCACGAAGTT-3’ as substrate preincubated for 30 mins followed by substrate addition by fluorescence polarization assay	ic50	0.1100	uM
1-[5-[(2,3,4-trifluorophenyl)methoxy]pyrimidin-2-yl]pyrazole-4-carboxylic acid	2118278: Inhibition of N-terminal 6xHis-tagged human ALKBH1 extracted from Escherichia coli BL21(DE3) using 5’-AACTTCGTGCAGGCATGGG(6mA)TCTTGTCTACT-3’/5’-FAM-AGTAGACACATGCCTGCACGAAGTT-3’ as substrate preincubated for 30 mins followed by substrate addition by fluorescence polarization assay	ic50	0.1130	uM
1-[5-[(2-methoxyphenyl)methoxy]pyrimidin-2-yl]pyrazole-4-carboxylic acid	2118278: Inhibition of N-terminal 6xHis-tagged human ALKBH1 extracted from Escherichia coli BL21(DE3) using 5’-AACTTCGTGCAGGCATGGG(6mA)TCTTGTCTACT-3’/5’-FAM-AGTAGACACATGCCTGCACGAAGTT-3’ as substrate preincubated for 30 mins followed by substrate addition by fluorescence polarization assay	ic50	0.1170	uM
1-[5-[(2-fluoro-3-methoxyphenyl)methoxy]pyrimidin-2-yl]pyrazole-4-carboxylic acid	2118278: Inhibition of N-terminal 6xHis-tagged human ALKBH1 extracted from Escherichia coli BL21(DE3) using 5’-AACTTCGTGCAGGCATGGG(6mA)TCTTGTCTACT-3’/5’-FAM-AGTAGACACATGCCTGCACGAAGTT-3’ as substrate preincubated for 30 mins followed by substrate addition by fluorescence polarization assay	ic50	0.1180	uM
1-[5-[(4-cyanophenyl)methoxy]pyrimidin-2-yl]pyrazole-4-carboxylic acid	2118278: Inhibition of N-terminal 6xHis-tagged human ALKBH1 extracted from Escherichia coli BL21(DE3) using 5’-AACTTCGTGCAGGCATGGG(6mA)TCTTGTCTACT-3’/5’-FAM-AGTAGACACATGCCTGCACGAAGTT-3’ as substrate preincubated for 30 mins followed by substrate addition by fluorescence polarization assay	ic50	0.1200	uM
1-[5-[(3-fluorophenyl)methoxy]pyrimidin-2-yl]pyrazole-4-carboxylic acid	2118278: Inhibition of N-terminal 6xHis-tagged human ALKBH1 extracted from Escherichia coli BL21(DE3) using 5’-AACTTCGTGCAGGCATGGG(6mA)TCTTGTCTACT-3’/5’-FAM-AGTAGACACATGCCTGCACGAAGTT-3’ as substrate preincubated for 30 mins followed by substrate addition by fluorescence polarization assay	ic50	0.1230	uM
1-[5-[(2,4-difluorophenyl)methoxy]pyrimidin-2-yl]pyrazole-4-carboxylic acid	2118278: Inhibition of N-terminal 6xHis-tagged human ALKBH1 extracted from Escherichia coli BL21(DE3) using 5’-AACTTCGTGCAGGCATGGG(6mA)TCTTGTCTACT-3’/5’-FAM-AGTAGACACATGCCTGCACGAAGTT-3’ as substrate preincubated for 30 mins followed by substrate addition by fluorescence polarization assay	ic50	0.1240	uM
1-[5-[(3,4-dichlorophenyl)methoxy]pyrimidin-2-yl]pyrazole-4-carboxylic acid	2118278: Inhibition of N-terminal 6xHis-tagged human ALKBH1 extracted from Escherichia coli BL21(DE3) using 5’-AACTTCGTGCAGGCATGGG(6mA)TCTTGTCTACT-3’/5’-FAM-AGTAGACACATGCCTGCACGAAGTT-3’ as substrate preincubated for 30 mins followed by substrate addition by fluorescence polarization assay	ic50	0.1340	uM
1-[5-[(3-fluoro-5-methoxyphenyl)methoxy]pyrimidin-2-yl]pyrazole-4-carboxylic acid	2118278: Inhibition of N-terminal 6xHis-tagged human ALKBH1 extracted from Escherichia coli BL21(DE3) using 5’-AACTTCGTGCAGGCATGGG(6mA)TCTTGTCTACT-3’/5’-FAM-AGTAGACACATGCCTGCACGAAGTT-3’ as substrate preincubated for 30 mins followed by substrate addition by fluorescence polarization assay	ic50	0.1350	uM
1-[5-[(3-chlorophenyl)methoxy]pyrimidin-2-yl]pyrazole-4-carboxylic acid	2118278: Inhibition of N-terminal 6xHis-tagged human ALKBH1 extracted from Escherichia coli BL21(DE3) using 5’-AACTTCGTGCAGGCATGGG(6mA)TCTTGTCTACT-3’/5’-FAM-AGTAGACACATGCCTGCACGAAGTT-3’ as substrate preincubated for 30 mins followed by substrate addition by fluorescence polarization assay	ic50	0.1380	uM
1-[5-[(3-phenylmethoxyphenyl)methoxy]pyrimidin-2-yl]pyrazole-4-carboxylic acid	2118278: Inhibition of N-terminal 6xHis-tagged human ALKBH1 extracted from Escherichia coli BL21(DE3) using 5’-AACTTCGTGCAGGCATGGG(6mA)TCTTGTCTACT-3’/5’-FAM-AGTAGACACATGCCTGCACGAAGTT-3’ as substrate preincubated for 30 mins followed by substrate addition by fluorescence polarization assay	ic50	0.1460	uM
1-[5-[[4-(difluoromethoxy)phenyl]methoxy]pyrimidin-2-yl]pyrazole-4-carboxylic acid	2118278: Inhibition of N-terminal 6xHis-tagged human ALKBH1 extracted from Escherichia coli BL21(DE3) using 5’-AACTTCGTGCAGGCATGGG(6mA)TCTTGTCTACT-3’/5’-FAM-AGTAGACACATGCCTGCACGAAGTT-3’ as substrate preincubated for 30 mins followed by substrate addition by fluorescence polarization assay	ic50	0.1480	uM
1-[5-[(3,5-dimethylphenyl)methoxy]pyrimidin-2-yl]pyrazole-4-carboxylic acid	2118278: Inhibition of N-terminal 6xHis-tagged human ALKBH1 extracted from Escherichia coli BL21(DE3) using 5’-AACTTCGTGCAGGCATGGG(6mA)TCTTGTCTACT-3’/5’-FAM-AGTAGACACATGCCTGCACGAAGTT-3’ as substrate preincubated for 30 mins followed by substrate addition by fluorescence polarization assay	ic50	0.1480	uM
1-[5-[(3-cyanophenyl)methoxy]pyrimidin-2-yl]pyrazole-4-carboxylic acid	2118278: Inhibition of N-terminal 6xHis-tagged human ALKBH1 extracted from Escherichia coli BL21(DE3) using 5’-AACTTCGTGCAGGCATGGG(6mA)TCTTGTCTACT-3’/5’-FAM-AGTAGACACATGCCTGCACGAAGTT-3’ as substrate preincubated for 30 mins followed by substrate addition by fluorescence polarization assay	ic50	0.1830	uM
1-[5-[(2-chloro-6-fluorophenyl)methoxy]pyrimidin-2-yl]pyrazole-4-carboxylic acid	2118278: Inhibition of N-terminal 6xHis-tagged human ALKBH1 extracted from Escherichia coli BL21(DE3) using 5’-AACTTCGTGCAGGCATGGG(6mA)TCTTGTCTACT-3’/5’-FAM-AGTAGACACATGCCTGCACGAAGTT-3’ as substrate preincubated for 30 mins followed by substrate addition by fluorescence polarization assay	ic50	0.1890	uM
1-[5-(1,3-benzodioxol-4-ylmethoxy)pyrimidin-2-yl]pyrazole-4-carboxylic acid	2118278: Inhibition of N-terminal 6xHis-tagged human ALKBH1 extracted from Escherichia coli BL21(DE3) using 5’-AACTTCGTGCAGGCATGGG(6mA)TCTTGTCTACT-3’/5’-FAM-AGTAGACACATGCCTGCACGAAGTT-3’ as substrate preincubated for 30 mins followed by substrate addition by fluorescence polarization assay	ic50	0.1980	uM
1-[5-[[2-(difluoromethoxy)phenyl]methoxy]pyrimidin-2-yl]pyrazole-4-carboxylic acid	2118278: Inhibition of N-terminal 6xHis-tagged human ALKBH1 extracted from Escherichia coli BL21(DE3) using 5’-AACTTCGTGCAGGCATGGG(6mA)TCTTGTCTACT-3’/5’-FAM-AGTAGACACATGCCTGCACGAAGTT-3’ as substrate preincubated for 30 mins followed by substrate addition by fluorescence polarization assay	ic50	0.3080	uM
1-[5-[(2,6-difluorophenyl)methoxy]pyrimidin-2-yl]pyrazole-4-carboxylic acid	2118278: Inhibition of N-terminal 6xHis-tagged human ALKBH1 extracted from Escherichia coli BL21(DE3) using 5’-AACTTCGTGCAGGCATGGG(6mA)TCTTGTCTACT-3’/5’-FAM-AGTAGACACATGCCTGCACGAAGTT-3’ as substrate preincubated for 30 mins followed by substrate addition by fluorescence polarization assay	ic50	0.4160	uM
1-[5-(1-phenylethoxy)pyrimidin-2-yl]pyrazole-4-carboxylic acid	2118278: Inhibition of N-terminal 6xHis-tagged human ALKBH1 extracted from Escherichia coli BL21(DE3) using 5’-AACTTCGTGCAGGCATGGG(6mA)TCTTGTCTACT-3’/5’-FAM-AGTAGACACATGCCTGCACGAAGTT-3’ as substrate preincubated for 30 mins followed by substrate addition by fluorescence polarization assay	ic50	0.5430	uM
1-[5-(phenoxymethyl)pyrimidin-2-yl]pyrazole-4-carboxylic acid	2118278: Inhibition of N-terminal 6xHis-tagged human ALKBH1 extracted from Escherichia coli BL21(DE3) using 5’-AACTTCGTGCAGGCATGGG(6mA)TCTTGTCTACT-3’/5’-FAM-AGTAGACACATGCCTGCACGAAGTT-3’ as substrate preincubated for 30 mins followed by substrate addition by fluorescence polarization assay	ic50	0.5580	uM
1-(5-phenoxypyrimidin-2-yl)pyrazole-4-carboxylic acid	2118278: Inhibition of N-terminal 6xHis-tagged human ALKBH1 extracted from Escherichia coli BL21(DE3) using 5’-AACTTCGTGCAGGCATGGG(6mA)TCTTGTCTACT-3’/5’-FAM-AGTAGACACATGCCTGCACGAAGTT-3’ as substrate preincubated for 30 mins followed by substrate addition by fluorescence polarization assay	ic50	0.6940	uM
1-[5-(1-phenylpropoxy)pyrimidin-2-yl]pyrazole-4-carboxylic acid	2118278: Inhibition of N-terminal 6xHis-tagged human ALKBH1 extracted from Escherichia coli BL21(DE3) using 5’-AACTTCGTGCAGGCATGGG(6mA)TCTTGTCTACT-3’/5’-FAM-AGTAGACACATGCCTGCACGAAGTT-3’ as substrate preincubated for 30 mins followed by substrate addition by fluorescence polarization assay	ic50	0.9970	uM
1-(5-benzamidopyrimidin-2-yl)pyrazole-4-carboxylic acid	2118278: Inhibition of N-terminal 6xHis-tagged human ALKBH1 extracted from Escherichia coli BL21(DE3) using 5’-AACTTCGTGCAGGCATGGG(6mA)TCTTGTCTACT-3’/5’-FAM-AGTAGACACATGCCTGCACGAAGTT-3’ as substrate preincubated for 30 mins followed by substrate addition by fluorescence polarization assay	ic50	1.0480	uM
3-chloro-1-(5-phenylmethoxypyrimidin-2-yl)pyrazole-4-carboxylic acid	2118278: Inhibition of N-terminal 6xHis-tagged human ALKBH1 extracted from Escherichia coli BL21(DE3) using 5’-AACTTCGTGCAGGCATGGG(6mA)TCTTGTCTACT-3’/5’-FAM-AGTAGACACATGCCTGCACGAAGTT-3’ as substrate preincubated for 30 mins followed by substrate addition by fluorescence polarization assay	ic50	2.4170	uM
1-[5-(2-phenylethoxy)pyrimidin-2-yl]pyrazole-4-carboxylic acid	2118278: Inhibition of N-terminal 6xHis-tagged human ALKBH1 extracted from Escherichia coli BL21(DE3) using 5’-AACTTCGTGCAGGCATGGG(6mA)TCTTGTCTACT-3’/5’-FAM-AGTAGACACATGCCTGCACGAAGTT-3’ as substrate preincubated for 30 mins followed by substrate addition by fluorescence polarization assay	ic50	2.4250	uM
3-methyl-1-(5-phenylmethoxypyrimidin-2-yl)pyrazole-4-carboxylic acid	2118278: Inhibition of N-terminal 6xHis-tagged human ALKBH1 extracted from Escherichia coli BL21(DE3) using 5’-AACTTCGTGCAGGCATGGG(6mA)TCTTGTCTACT-3’/5’-FAM-AGTAGACACATGCCTGCACGAAGTT-3’ as substrate preincubated for 30 mins followed by substrate addition by fluorescence polarization assay	ic50	2.5030	uM
5-chloro-1-(5-phenylmethoxypyrimidin-2-yl)pyrazole-4-carboxylic acid	2118278: Inhibition of N-terminal 6xHis-tagged human ALKBH1 extracted from Escherichia coli BL21(DE3) using 5’-AACTTCGTGCAGGCATGGG(6mA)TCTTGTCTACT-3’/5’-FAM-AGTAGACACATGCCTGCACGAAGTT-3’ as substrate preincubated for 30 mins followed by substrate addition by fluorescence polarization assay	ic50	9.8770	uM

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
dicrotophos	increases expression	1
deoxynivalenol	increases expression	1
salinomycin	decreases expression	1
beta-lapachone	increases expression	1
sodium arsenite	increases expression	1
di-n-butylphosphoric acid	affects expression	1
cylindrospermopsin	increases expression	1
CGP 52608	affects binding, increases reaction	1
abrine	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Doxorubicin	decreases expression	1
Methotrexate	affects expression	1
Methyl Methanesulfonate	increases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	decreases expression	1
Vitamin E	decreases expression	1
Aflatoxin B1	decreases methylation	1
Copper Sulfate	decreases expression	1
Acrylamide	increases expression	1
Particulate Matter	decreases expression, increases abundance	1

ChEMBL screening assays

28 unique, capped per target: 28 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5115888	Binding	Binding affinity to ALKHB1 (unknown origin) demethylation activity assessed as thermal stability by measuring change in melting temperature at 100 uM by differential scanning fluorimetry assay	Discovery of a potent, selective and cell active inhibitor of m6A demethylase ALKBH5. — Eur J Med Chem

Cellosaurus cell lines

5 cell lines: 5 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B7VY	Abcam Raji ALKBH1 KO	Cancer cell line	Male
CVCL_B9WG	Abcam THP-1 ALKBH1 KO	Cancer cell line	Male
CVCL_C6YH	Abcam PC-3 ALKBH1 KO	Cancer cell line	Male
CVCL_SC36	HAP1 ALKBH1 (-) 1	Cancer cell line	Male
CVCL_XL27	HAP1 ALKBH1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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