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ALKBH3

gene
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Also known as DEPC-1

Summary

ALKBH3 (alkB homolog 3, alpha-ketoglutarate dependent dioxygenase, HGNC:30141) is a protein-coding gene on chromosome 11p11.2, encoding Alpha-ketoglutarate-dependent dioxygenase alkB homolog 3 (Q96Q83). Dioxygenase that mediates demethylation of DNA and RNA containing 1-methyladenosine (m1A).

The Escherichia coli AlkB protein protects against the cytotoxicity of methylating agents by repair of the specific DNA lesions generated in single-stranded DNA. ALKBH2 (MIM 610602) and ALKBH3 are E. coli AlkB homologs that catalyze the removal of 1-methyladenine and 3-methylcytosine (Duncan et al., 2002 [PubMed 12486230]).

Source: NCBI Gene 221120 — RefSeq curated summary.

At a glance

  • GWAS associations: 3
  • Clinical variants (ClinVar): 66 total
  • Druggable target: yes
  • MANE Select transcript: NM_139178

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:30141
Approved symbolALKBH3
NamealkB homolog 3, alpha-ketoglutarate dependent dioxygenase
Location11p11.2
Locus typegene with protein product
StatusApproved
AliasesDEPC-1
Ensembl geneENSG00000166199
Ensembl biotypeprotein_coding
OMIM610603
Entrez221120

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 9 protein_coding, 3 retained_intron, 3 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000302708, ENST00000524742, ENST00000527029, ENST00000529366, ENST00000529434, ENST00000530754, ENST00000530803, ENST00000532129, ENST00000532410, ENST00000532962, ENST00000533200, ENST00000534171, ENST00000856729, ENST00000856730, ENST00000856731, ENST00000916780, ENST00000943080

RefSeq mRNA: 1 — MANE Select: NM_139178 NM_139178

CCDS: CCDS7906

Canonical transcript exons

ENST00000302708 — 10 exons

ExonStartEnd
ENSE000012484174388258343882731
ENSE000021818404388083143881179
ENSE000021910744391991843920274
ENSE000034771344391903843919136
ENSE000035151014390151643901725
ENSE000035219454388398343884017
ENSE000036011224388308543883188
ENSE000036026774388660643886653
ENSE000036581144389204143892129
ENSE000036677144388972543889828

Expression profiles

Bgee: expression breadth ubiquitous, 227 present calls, max score 92.73.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 14.6934 / max 79.6555, expressed in 1800 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter IDTPM avgSamples expressed
11396212.94571795
1139631.4376912
2062590.3100124

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
right uterine tubeUBERON:000130292.73gold quality
calcaneal tendonUBERON:000370192.56gold quality
hindlimb stylopod muscleUBERON:000425292.50gold quality
primordial germ cell in gonadCL:0000670 ∩ UBERON:000099191.96gold quality
muscle of legUBERON:000138391.42gold quality
gastrocnemiusUBERON:000138891.42gold quality
stromal cell of endometriumCL:000225591.06gold quality
islet of LangerhansUBERON:000000690.86gold quality
body of pancreasUBERON:000115090.84gold quality
skin of legUBERON:000151190.74gold quality
left ovaryUBERON:000211990.73gold quality
body of uterusUBERON:000985390.67gold quality
right ovaryUBERON:000211890.65gold quality
tendonUBERON:000004390.40gold quality
tibial nerveUBERON:000132390.29gold quality
skin of abdomenUBERON:000141690.24gold quality
ectocervixUBERON:001224990.16gold quality
tibial arteryUBERON:000761090.10gold quality
popliteal arteryUBERON:000225090.09gold quality
olfactory segment of nasal mucosaUBERON:000538690.04gold quality
left uterine tubeUBERON:000130390.00gold quality
granulocyteCL:000009489.95gold quality
minor salivary glandUBERON:000183089.88gold quality
pancreasUBERON:000126489.85gold quality
endocervixUBERON:000045889.78gold quality
male germ line stem cell (sensu Vertebrata) in testisCL:0000089 ∩ UBERON:000047389.66gold quality
body of stomachUBERON:000116189.64gold quality
left coronary arteryUBERON:000162689.64gold quality
aortaUBERON:000094789.63gold quality
skeletal muscle organUBERON:001489289.53gold quality

Single-cell (SCXA)

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

ExperimentMarker?Max mean expression
E-ANND-3yes5.24

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

15 targeting ALKBH3, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-7110-3P100.0073.182486
HSA-MIR-188-3P100.0068.761240
HSA-MIR-6873-3P100.0071.422626
HSA-MIR-569699.9872.364487
HSA-MIR-477599.9875.006394
HSA-MIR-447099.6669.351767
HSA-MIR-5580-5P99.3866.961139
HSA-MIR-449B-3P99.2067.241047
HSA-MIR-4774-3P98.9067.82737
HSA-MIR-4691-3P98.1166.831204
HSA-MIR-805597.6266.091023
HSA-MIR-9851-5P97.5767.491067
HSA-MIR-6890-3P97.5065.71997
HSA-MIR-6781-3P97.4466.85970
HSA-MIR-2682-3P97.1066.16840

Literature-anchored findings (GeneRIF, showing 28)

  • Crystallographic study reveals beta-strand jelly-roll fold of hABH3 that coordinates a catalytically active iron center by a conserved His1-X-Asp/Glu-X(n)-His2 motif [ABH3] (PMID:16858410)
  • PCA-1 might be a novel diagnostic marker for prostate cancer, and increased PCA-1 expression might denote more aggressive variants of prostate cancer [PCA-1]. (PMID:17968469)
  • Divergent sequences outside of the active site determine substrate specificities of ABH3. (PMID:20525795)
  • This work has provided a detailed understanding of the structural features of the single-stranded DNA and double-stranded DNA preferences of ABH2 and ABH3. (PMID:20714506)
  • ALKBH3 contributes significantly to cancer cell survival and may be a therapeutic target for human adenocarcinoma of the lung. (PMID:21285982)
  • DNA unwinding by ASCC3 helicase is coupled to ALKBH3-dependent DNA alkylation repair and cancer cell proliferation. (PMID:22055184)
  • ALKBH3 gene silencing markedly induces apoptosis in hormone-independent prostate cancer cell line DU145. (PMID:22515525)
  • Our results establish PCA-1/ALKBH3 as important gene in pancreatic cancer (PMID:22826605)
  • ALKBH3 contributes to development of urothelial carcinomas by accelerating their survival, angiogenesis, and invasion (PMID:22850567)
  • It was shown for first time that DNA glycosylase ALKBH3 can repair DNA adduct 3,N4-ethenocytosine from single-stranded DNA. (PMID:25797601)
  • Results show that PCA1 expression was positively correlated with advanced stages in renal cell carcinoma and strongly suggest that PCA-1 may be functionally important and a novel molecular target for human renal cell carcinoma. (PMID:26035443)
  • These results revealed that N3-ethylthymidine , but not other DNA lesions, could be repaired by Alkbh2 and Alkbh3 in mammalian cells. (PMID:26930515)
  • These data highlight a novel role for ALKBH3 in tumor progression via RNA demethylation and subsequent protein synthesis promotion. (PMID:28205560)
  • The TP53 knockout shifted the phenotypes of A549 cells induced by ALKBH3 knockdown from cell cycle arrest to apoptosis induction, suggesting that the TP53 gene status is a critical determinant of the phenotypes induced by ALKBH3 knockdown in NSCLC cells. (PMID:28479246)
  • ALKBH3 is a novel addition to the catalogue of DNA repair genes found inactivated in breast cancer. Our results underscore a link between defective alkylation repair and breast cancer which, additionally, is found in association with poor disease outcome. (PMID:28679371)
  • The alteration of ALKBH3 expression, an m1A demethylase, regulates the CSF-1 mRNA stability in breast and ovarian cancer cells (PMID:30342176)
  • In vivo study confirms the regulation effects of ALKBH3 on growth of tumor xenograft. The m1A demethylated tRNA is more sensitive to angiogenin (ANG) cleavage, followed by generating tRNA-derived small RNAs (tDRs) around the anticodon regions. (PMID:30541109)
  • 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)
  • ALKBH overexpression in head and neck cancer: potential target for novel anticancer therapy. (PMID:31519943)
  • Evidence that RAD51C-ALKBH3 interaction stimulates ALKBH3-mediated repair of methyl-adduct located within 3’-tailed DNA, which serves as a substrate for the RAD51 recombinase. The lack of RAD51C-ALKBH3 interaction affects ALKBH3 function in vitro and in vivo. (PMID:31642493)
  • Epigenetic loss of m1A RNA demethylase ALKBH3 in Hodgkin lymphoma targets collagen, conferring poor clinical outcome. (PMID:32915956)
  • Programmable RNA N(1) -Methyladenosine Demethylation by a Cas13d-Directed Demethylase. (PMID:34081827)
  • ALKBH3 partner ASCC3 mediates P-body formation and selective clearance of MMS-induced 1-methyladenosine and 3-methylcytosine from mRNA. (PMID:34217309)
  • LncRNA ALKBH3-AS1 enhances ALKBH3 mRNA stability to promote hepatocellular carcinoma cell proliferation and invasion. (PMID:36098205)
  • Histone lactylation-boosted ALKBH3 potentiates tumor progression and diminished promyelocytic leukemia protein nuclear condensates by m1A demethylation of SP100A. (PMID:38118002)
  • The Molecular Basis of Human ALKBH3 Mediated RNA N[1] -methyladenosine (m[1] A) Demethylation. (PMID:38158383)
  • The Role of Key Amino Acids of the Human Fe(II)/2OG-Dependent Dioxygenase ALKBH3 in Structural Dynamics and Repair Activity toward Methylated DNA. (PMID:38256217)
  • PUS7-dependent pseudouridylation of ALKBH3 mRNA inhibits gastric cancer progression. (PMID:39175405)

Cross-species orthologs

3 orthologs

OrganismSymbolGene ID
danio_rerioalkbh3ENSDARG00000045606
mus_musculusAlkbh3ENSMUSG00000040174
rattus_norvegicusAlkbh3ENSRNOG00000021678

Protein

Protein identifiers

Alpha-ketoglutarate-dependent dioxygenase alkB homolog 3 — Q96Q83 (reviewed: Q96Q83)

Alternative names: Alkylated DNA repair protein alkB homolog 3, DEPC-1, Prostate cancer antigen 1

All UniProt accessions (6): E9PN35, E9PRD0, E9PRJ2, Q96Q83, E9PSA5, H0YDH4

UniProt curated annotations — full annotation on UniProt →

Function. Dioxygenase that mediates demethylation of DNA and RNA containing 1-methyladenosine (m1A). Repairs alkylated DNA containing 1-methyladenosine (m1A) and 3-methylcytosine (m3C) by oxidative demethylation. Has a strong preference for single-stranded DNA. Able to process alkylated m3C within double-stranded regions via its interaction with ASCC3, which promotes DNA unwinding to generate single-stranded substrate needed for ALKBH3. Can repair exocyclic 3,N4-ethenocytosine adducs in single-stranded DNA. Also acts on RNA. Demethylates N(1)-methyladenosine (m1A) RNA, an epigenetic internal modification of messenger RNAs (mRNAs) highly enriched within 5’-untranslated regions (UTRs) and in the vicinity of start codons. Requires molecular oxygen, alpha-ketoglutarate and iron.

Subunit / interactions. Interacts with the ASCC complex composed of ASCC1, ASCC2 and ASCC3. Interacts directly with ASCC3, and is thereby recruited to the ASCC complex. Interacts with OTUD4; the interaction is direct. Interacts with USP7 and USP9X.

Subcellular location. Nucleus. Cytoplasm.

Tissue specificity. Ubiquitous. Detected in heart, pancreas, skeletal muscle, thymus, testis, ovary, spleen, prostate, small intestine, peripheral blood leukocytes, urinary bladder and colon.

Post-translational modifications. Ubiquitinated; undergoes ‘Lys-48’-linked polyubiquitination. OTUD4 promotes USP7 and USP9X-dependent deubiquitination of ‘Lys-48’-polyubiquitinated ALKBH3 promoting the repair of alkylated DNA lesions.

Activity regulation. Activated by ascorbate.

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

Similarity. Belongs to the alkB family.

Isoforms (2)

UniProt IDNamesCanonical?
Q96Q83-11yes
Q96Q83-22

RefSeq proteins (1): NP_631917* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR005123Oxoglu/Fe-dep_dioxygenase_domDomain
IPR027450AlkB-likeDomain
IPR032854ALKBH3Family
IPR037151AlkB-like_sfHomologous_superfamily

Pfam: PF13532

Enzyme classification (BRENDA):

  • EC 1.14.11.33 — DNA oxidative demethylase (BRENDA: 11 organisms, 153 substrates, 5 inhibitors, 16 Km, 15 kcat entries)
  • EC 1.14.11.54 — mRNA N1-methyladenine demethylase (BRENDA: 4 organisms, 12 substrates, 0 inhibitors, 5 Km, 5 kcat entries)

Substrate kinetics (BRENDA)

16 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

SubstrateKm (mM)Measurements
RNA-N6-METHYLADENINE0.0028–0.01494
3-METHYLCYTOSINE IN 3’-TAILED DNA0.0014–0.00172
1-METHYL-ADENINE IN 5’-DAAAA-1MEA-YYAAA0.00041
1-METHYL-DAMP0.0021
1-METHYL-DATP0.00551
2’-DEOXY-1-METHYL-ADENOSINE 3’-PHOSPHATE0.0121
D(TPM1A)0.00441
D(TPM1APT)0.00281
DNA-N1-METHYLADENINE0.0021
DOUBLE-STRANDED DNA-1-METHYLADENINE0.00621
DOUBLE-STRANDED DNA-3-METHYLCYTOSINE0.00931
N1-METHYL-ATP0.011
POLY(DM1A)0.00141
SINGLE-STRANDED DNA-1-METHYLADENINE0.00541
SINGLE-STRANDED DNA-3-METHYLCYTOSINE0.00341

Catalyzed reactions (Rhea), 5 shown:

  • a methylated nucleobase within DNA + 2-oxoglutarate + O2 = a nucleobase within DNA + formaldehyde + succinate + CO2 (RHEA:30299)
  • an N(1)-methyladenosine in mRNA + 2-oxoglutarate + O2 = an adenosine in mRNA + formaldehyde + succinate + CO2 (RHEA:49516)
  • an N(3)-methyl-2’-deoxycytidine in single-stranded DNA + 2-oxoglutarate + O2 = a 2’-deoxycytidine in single-stranded DNA + formaldehyde + succinate + CO2 + H(+) (RHEA:70435)
  • an N(1)-methyl-2’-deoxyadenosine in single-stranded DNA + 2-oxoglutarate + O2 = a 2’-deoxyadenosine in single-stranded DNA + formaldehyde + succinate + CO2 + H(+) (RHEA:70447)
  • a 3,N(4)-etheno-2’-deoxycytidine in single-stranded DNA + 2-oxoglutarate + O2 + H2O = a 2’-deoxycytidine in single-stranded DNA + glyoxal + succinate + CO2 (RHEA:70471)

UniProt features (59 total): mutagenesis site 17, strand 17, binding site 9, helix 5, splice variant 3, modified residue 2, sequence variant 2, chain 1, domain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

4 structures.

PDBMethodResolution (Å)
2IUWX-RAY DIFFRACTION1.5
9NCZX-RAY DIFFRACTION1.97
8JNKX-RAY DIFFRACTION2.69
8JNRX-RAY DIFFRACTION3.66

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-Q96Q83-F182.200.62

Antibody-complex structures (SAbDab): 2 — 8JNK, 8JNR

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 (9): 257; 269–275; 275; 115; 141–143; 179–181; 191; 193; 194

Post-translational modifications (2): 177, 177

Mutagenesis-validated functional residues (17):

PositionPhenotype
122–124acquires the capacity to efficiently repair n1-methyladenine adduct in dsdna.
122decreases activity towards ssdna by 25%. loss of activity towards dsdna.
123strongly increases activity towards dsdna, possibly by facilitating access to the active site.
131loss of activity.
177loss of activity against n1-methyladenine.
177loss of activity.
177decreases activity against n1-methyladenine.
177no effect.
179decreases activity by about 60%.
181strong decrease of activity.
189strongly increases activity towards dsdna, possibly by facilitating access to the active site.
191loss of activity.
193loss of activity.
257decreases activity by about 65%.
269strong decrease of activity.
271no effect.
275loss of activity.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

IDPathway
R-HSA-112126ALKBH3 mediated reversal of alkylation damage
R-HSA-73894DNA Repair
R-HSA-73942DNA Damage Reversal
R-HSA-73943Reversal of alkylation damage by DNA dioxygenases

MSigDB gene sets: 123 (showing top): GOBP_CYTOPLASMIC_TRANSLATION, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_PAIRED_DONORS_WITH_INCORPORATION_OR_REDUCTION_OF_MOLECULAR_OXYGEN, KAUFFMANN_DNA_REPAIR_GENES, CHANDRAN_METASTASIS_DN, GOBP_NEGATIVE_REGULATION_OF_TRANSLATION, GOBP_TRANSLATION, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, GOBP_DNA_DAMAGE_RESPONSE, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_METABOLIC_PROCESS, REACTOME_DNA_REPAIR, GOBP_REGULATION_OF_CYTOPLASMIC_TRANSLATION, MODULE_48, MODULE_95, GOBP_REGULATION_OF_TRANSLATION, GOBP_DNA_METABOLIC_PROCESS

GO Biological Process (5): DNA repair (GO:0006281), DNA alkylation repair (GO:0006307), cell population proliferation (GO:0008283), negative regulation of cytoplasmic translation (GO:2000766), DNA damage response (GO:0006974)

GO Molecular Function (9): ferrous iron binding (GO:0008198), L-ascorbic acid binding (GO:0031418), oxidative RNA demethylase activity (GO:0035515), broad specificity oxidative DNA demethylase activity (GO:0035516), mRNA N1-methyladenosine dioxygenase activity (GO:1990930), protein binding (GO:0005515), oxidoreductase activity (GO:0016491), metal ion binding (GO:0046872), dioxygenase activity (GO:0051213)

GO Cellular Component (5): nucleoplasm (GO:0005654), mitochondrion (GO:0005739), cytosol (GO:0005829), nucleus (GO:0005634), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-3 pathways:

CategoryPathways
Reversal of alkylation damage by DNA dioxygenases1
DNA Repair1
DNA Damage Reversal1

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
cellular anatomical structure3
2-oxoglutarate-dependent dioxygenase activity2
cytoplasm2
intracellular membrane-bounded organelle2
DNA metabolic process1
DNA damage response1
DNA repair1
cellular process1
cytoplasmic translation1
negative regulation of translation1
regulation of cytoplasmic translation1
cellular response to stress1
iron ion binding1
vitamin binding1
carboxylic acid binding1
monosaccharide binding1
heterocyclic compound binding1
demethylase activity1
catalytic activity, acting on RNA1
DNA demethylase activity1
oxidative RNA demethylase activity1
binding1
catalytic activity1
cation binding1
oxidoreductase activity1
nuclear lumen1
intracellular anatomical structure1

Protein interactions and networks

STRING

2561 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
ALKBH3ALKBH1Q13686990
ALKBH3FTOQ9C0B1814
ALKBH3ALKBH8Q96BT7765
ALKBH3ASCC3Q8N3C0748
ALKBH3ALKBH5Q6P6C2716
ALKBH3TRMT6Q9UJA5709
ALKBH3TRMT61AQ96FX7670
ALKBH3ALKBH4Q9NXW9669
ALKBH3ALKBH6Q3KRA9669
ALKBH3TRMT61BQ9BVS5667
ALKBH3ALKBH7Q9BT30644
ALKBH3TRMT10CQ7L0Y3643
ALKBH3YTHDF1Q9BYJ9642
ALKBH3YTHDC1Q96MU7641
ALKBH3JMJD4Q9H9V9625

IntAct

29 interactions, top by confidence:

ABTypeScore
GOLGA2ALKBH3psi-mi:“MI:0915”(physical association)0.740
ALKBH3IKZF1psi-mi:“MI:0915”(physical association)0.740
ALKBH3GOLGA2psi-mi:“MI:0915”(physical association)0.740
IKZF1ALKBH3psi-mi:“MI:0915”(physical association)0.740
ALKBH3GLRX3psi-mi:“MI:0915”(physical association)0.560
ALKBH3LNX1psi-mi:“MI:0915”(physical association)0.560
AK8ALKBH3psi-mi:“MI:0915”(physical association)0.560
LNX1ALKBH3psi-mi:“MI:0915”(physical association)0.560
ALKBH3AK8psi-mi:“MI:0915”(physical association)0.560
ALKBH3INPPL1psi-mi:“MI:0914”(association)0.530
ALKBH3TRIP4psi-mi:“MI:0914”(association)0.530
SRPK2ALKBH3psi-mi:“MI:0217”(phosphorylation reaction)0.440
ALKBH3SRPK1psi-mi:“MI:0217”(phosphorylation reaction)0.440
GSK3AALKBH3psi-mi:“MI:0915”(physical association)0.370
NEU2PEX14psi-mi:“MI:0914”(association)0.350
hspa1a_hspa1b_human-1SHTN1psi-mi:“MI:0914”(association)0.350

BioGRID (77): ALKBH3 (Two-hybrid), ALKBH3 (Two-hybrid), ALKBH3 (Two-hybrid), ALKBH3 (Two-hybrid), ALKBH3 (Two-hybrid), ALKBH3 (Two-hybrid), ASCC3 (Affinity Capture-MS), SMEK1 (Affinity Capture-MS), ASCC2 (Affinity Capture-MS), TRIP4 (Affinity Capture-MS), INPPL1 (Affinity Capture-MS), ASCC1 (Affinity Capture-MS), ALKBH3 (Affinity Capture-MS), ALKBH3 (Synthetic Lethality), HSPA5 (Affinity Capture-MS)

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: Q32L00, Q58DM4, Q5XIC8, Q6NS38, Q6P6J4, Q8K1E6, Q96Q83, Q9SIE0, Q5UQK2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance54
Likely benign0
Benign0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1820 predictions. Top by Δscore:

VariantEffectΔscore
11:43882686:G:GTdonor_gain1.0000
11:43883184:AGCAG:Adonor_loss1.0000
11:43883185:GCAGG:Gdonor_loss1.0000
11:43883186:CAGG:Cdonor_loss1.0000
11:43883187:AGG:Adonor_loss1.0000
11:43883188:GGT:Gdonor_loss1.0000
11:43883189:G:Adonor_loss1.0000
11:43883190:T:Adonor_loss1.0000
11:43886605:GCAGA:Gacceptor_gain1.0000
11:43889697:T:TAacceptor_gain1.0000
11:43889702:A:AGacceptor_gain1.0000
11:43889705:AAT:Aacceptor_gain1.0000
11:43889719:A:AGacceptor_gain1.0000
11:43889720:C:Gacceptor_gain1.0000
11:43889720:CCCA:Cacceptor_loss1.0000
11:43889722:CAGG:Cacceptor_loss1.0000
11:43889723:A:AGacceptor_gain1.0000
11:43889723:A:Tacceptor_loss1.0000
11:43889723:AG:Aacceptor_gain1.0000
11:43889723:AGG:Aacceptor_gain1.0000
11:43889724:G:GGacceptor_gain1.0000
11:43889724:GG:Gacceptor_gain1.0000
11:43889724:GGG:Gacceptor_gain1.0000
11:43889724:GGGT:Gacceptor_gain1.0000
11:43889824:AGAGG:Adonor_gain1.0000
11:43889825:GAGG:Gdonor_gain1.0000
11:43889825:GAGGG:Gdonor_gain1.0000
11:43889826:AGG:Adonor_gain1.0000
11:43889826:AGGG:Adonor_loss1.0000
11:43889827:GG:Gdonor_gain1.0000

AlphaMissense

1862 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
11:43901678:A:CS208R0.999
11:43901680:T:AS208R0.999
11:43901680:T:GS208R0.999
11:43901624:T:AW190R0.995
11:43901624:T:CW190R0.995
11:43901627:C:GH191D0.995
11:43901634:A:TD193V0.995
11:43919131:T:AW255R0.995
11:43919131:T:CW255R0.995
11:43889801:T:AW115R0.994
11:43889801:T:CW115R0.994
11:43892062:G:CR131T0.994
11:43901635:T:AD193E0.994
11:43901635:T:GD193E0.994
11:43901670:C:AA205D0.994
11:43901693:C:AR213S0.994
11:43919918:C:GH257D0.994
11:43919962:C:AN271K0.994
11:43919962:C:GN271K0.994
11:43892073:T:AW135R0.993
11:43892073:T:CW135R0.993
11:43901629:C:AH191Q0.993
11:43901629:C:GH191Q0.993
11:43901694:G:CR213P0.993
11:43919964:T:CL272P0.993
11:43919922:G:CR258P0.992
11:43901579:T:CS175P0.991
11:43901588:T:CC178R0.991
11:43901593:T:AN179K0.991
11:43901593:T:GN179K0.991

dbSNP variants (sampled 300 via entrez): RS1000116828 (11:43891231 A>G), RS1000186486 (11:43919366 C>G,T), RS1000266609 (11:43916552 G>A,T), RS1000326399 (11:43909425 C>A,T), RS1000432239 (11:43902823 C>G), RS1000460045 (11:43884395 T>A,C), RS1000516298 (11:43880182 C>T), RS1000576453 (11:43896289 ACACACACACACG>A), RS1000611439 (11:43909633 G>C), RS1000716669 (11:43916334 A>G), RS1000732270 (11:43913113 A>C,G), RS1000846960 (11:43907902 C>A,T), RS1000973090 (11:43898771 G>A), RS1001080883 (11:43885734 T>C), RS1001082751 (11:43892261 A>G)

Disease associations

OMIM: gene MIM:610603 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

StudyTraitp-value
GCST007565_130Morning person4.000000e-14
GCST007576_24Chronotype4.000000e-14
GCST012490_483Femur bone mineral density x serum urate levels interaction1.000000e-09

EFO canonical traits (2, from GWAS)

EFO IDTrait name
EFO:0008328chronotype measurement
EFO:0004531urate measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3112376 (SINGLE PROTEIN)

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

ChEMBL bioactivities

45 potent at pChembl≥5 of 61 total, top 42 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChemblTypeValueUnitMolecule
6.32IC50480nMCHEMBL3114983
6.31IC50490nMCHEMBL3145446
6.27IC50540nMCHEMBL3145436
6.26IC50550nMCHEMBL3145440
6.24IC50570nMCHEMBL3145451
6.22IC50600nMCHEMBL3145441
6.21IC50610nMCHEMBL3145447
6.20IC50630nMCHEMBL3145442
6.19IC50640nMCHEMBL3145448
6.17IC50680nMCHEMBL3145452
6.17IC50670nMCHEMBL3145419
6.17IC50670nMCHEMBL3115002
6.14IC50720nMCHEMBL3145410
6.14IC50720nMCHEMBL3145443
6.12IC50750nMCHEMBL3145412
6.12IC50750nMCHEMBL3145430
6.11IC50780nMCHEMBL3145413
6.09IC50810nMCHEMBL3145449
6.04IC50910nMCHEMBL3145411
5.82IC501500nMCHEMBL3145408
5.77IC501700nMCHEMBL3145246
5.70IC502000nMCHEMBL3114990
5.68IC502100nMCHEMBL3145409
5.58IC502600nMCHEMBL3145427
5.54IC502900nMCHEMBL5288450
5.51IC503100nMCHEMBL3145439
5.48IC503300nMCHEMBL3145435
5.44IC503600nMCHEMBL3114982
5.43IC503700nMCHEMBL3145414
5.43IC503700nMCHEMBL5282569
5.40IC504000nMCHEMBL3145421
5.39IC504100nMCHEMBL3145444
5.37IC504300nMCHEMBL3145431
5.35IC504500nMCHEMBL3145445
5.28IC505300nMCHEMBL3145415
5.28IC505300nMRHEIN
5.24IC505800nMCHEMBL3114991
5.23IC505900nMCHEMBL3145450
5.21IC506200nMCHEMBL5169684
5.14IC507200nMCHEMBL3145067
5.11Kd7810nMCHEMBL4239759
5.01IC509800nMCHEMBL4239759

PubChem BioAssay actives

42 with measured affinity, of 122 total; 40 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

CompoundAssayTypeValueUnit
2-(1H-benzimidazol-2-yl)-4-benzyl-5-methyl-1H-pyrazol-3-one1070065: Inhibition of demethylase activity of PCA-1 (unknown origin) using 3-methyl cytosine oligo DNA as substrate after 1 hr by RT-PCR analysisic500.4800uM
4-benzyl-2-(6-bromo-1H-benzimidazol-2-yl)-5-methyl-1H-pyrazol-3-one1070065: Inhibition of demethylase activity of PCA-1 (unknown origin) using 3-methyl cytosine oligo DNA as substrate after 1 hr by RT-PCR analysisic500.4900uM
2-(1H-benzimidazol-2-yl)-4-[(3-chlorophenyl)methyl]-5-methyl-1H-pyrazol-3-one1070065: Inhibition of demethylase activity of PCA-1 (unknown origin) using 3-methyl cytosine oligo DNA as substrate after 1 hr by RT-PCR analysisic500.5400uM
2-(1H-benzimidazol-2-yl)-5-methyl-4-[[4-(trifluoromethyl)phenyl]methyl]-1H-pyrazol-3-one1070065: Inhibition of demethylase activity of PCA-1 (unknown origin) using 3-methyl cytosine oligo DNA as substrate after 1 hr by RT-PCR analysisic500.5500uM
5-methyl-2-(6-methyl-1H-benzimidazol-2-yl)-4-[[4-(trifluoromethyl)phenyl]methyl]-1H-pyrazol-3-one1070065: Inhibition of demethylase activity of PCA-1 (unknown origin) using 3-methyl cytosine oligo DNA as substrate after 1 hr by RT-PCR analysisic500.5700uM
2-(1H-benzimidazol-2-yl)-4-[(4-fluorophenyl)methyl]-5-methyl-1H-pyrazol-3-one1070065: Inhibition of demethylase activity of PCA-1 (unknown origin) using 3-methyl cytosine oligo DNA as substrate after 1 hr by RT-PCR analysisic500.6000uM
4-benzyl-5-methyl-2-[6-(trifluoromethyl)-1H-benzimidazol-2-yl]-1H-pyrazol-3-one1070065: Inhibition of demethylase activity of PCA-1 (unknown origin) using 3-methyl cytosine oligo DNA as substrate after 1 hr by RT-PCR analysisic500.6100uM
2-(1H-benzimidazol-2-yl)-4-[(4-methoxyphenyl)methyl]-5-methyl-1H-pyrazol-3-one1070065: Inhibition of demethylase activity of PCA-1 (unknown origin) using 3-methyl cytosine oligo DNA as substrate after 1 hr by RT-PCR analysisic500.6300uM
4-benzyl-2-(6-tert-butyl-1H-benzimidazol-2-yl)-5-methyl-1H-pyrazol-3-one1070065: Inhibition of demethylase activity of PCA-1 (unknown origin) using 3-methyl cytosine oligo DNA as substrate after 1 hr by RT-PCR analysisic500.6400uM
4-benzyl-5-methyl-2-(6-methyl-1H-benzimidazol-2-yl)-1H-pyrazol-3-one1070065: Inhibition of demethylase activity of PCA-1 (unknown origin) using 3-methyl cytosine oligo DNA as substrate after 1 hr by RT-PCR analysisic500.6700uM
4-[(4-methoxyphenyl)methyl]-5-methyl-2-(6-methyl-1H-benzimidazol-2-yl)-1H-pyrazol-3-one1070065: Inhibition of demethylase activity of PCA-1 (unknown origin) using 3-methyl cytosine oligo DNA as substrate after 1 hr by RT-PCR analysisic500.6800uM
4-[(3,4-dichlorophenyl)methyl]-5-methyl-2-(6-methyl-1H-benzimidazol-2-yl)-1H-pyrazol-3-one1070065: Inhibition of demethylase activity of PCA-1 (unknown origin) using 3-methyl cytosine oligo DNA as substrate after 1 hr by RT-PCR analysisic500.7200uM
2-(1H-benzimidazol-2-yl)-5-methyl-4-[(4-phenylphenyl)methyl]-1H-pyrazol-3-one1070065: Inhibition of demethylase activity of PCA-1 (unknown origin) using 3-methyl cytosine oligo DNA as substrate after 1 hr by RT-PCR analysisic500.7200uM
4-[(4-chlorophenyl)methyl]-5-methyl-2-(6-methyl-1H-benzimidazol-2-yl)-1H-pyrazol-3-one1070065: Inhibition of demethylase activity of PCA-1 (unknown origin) using 3-methyl cytosine oligo DNA as substrate after 1 hr by RT-PCR analysisic500.7500uM
2-(1H-benzimidazol-2-yl)-5-methyl-4-(naphthalen-2-ylmethyl)-1H-pyrazol-3-one1070065: Inhibition of demethylase activity of PCA-1 (unknown origin) using 3-methyl cytosine oligo DNA as substrate after 1 hr by RT-PCR analysisic500.7500uM
4-[(4-fluorophenyl)methyl]-5-methyl-2-(6-methyl-1H-benzimidazol-2-yl)-1H-pyrazol-3-one1070065: Inhibition of demethylase activity of PCA-1 (unknown origin) using 3-methyl cytosine oligo DNA as substrate after 1 hr by RT-PCR analysisic500.7800uM
4-benzyl-5-methyl-2-(6-phenyl-1H-benzimidazol-2-yl)-1H-pyrazol-3-one1070065: Inhibition of demethylase activity of PCA-1 (unknown origin) using 3-methyl cytosine oligo DNA as substrate after 1 hr by RT-PCR analysisic500.8100uM
4-[(2-chlorophenyl)methyl]-5-methyl-2-(6-methyl-1H-benzimidazol-2-yl)-1H-pyrazol-3-one1070065: Inhibition of demethylase activity of PCA-1 (unknown origin) using 3-methyl cytosine oligo DNA as substrate after 1 hr by RT-PCR analysisic500.9100uM
4-benzyl-2-[6-(4-chlorophenyl)-1H-benzimidazol-2-yl]-5-methyl-1H-pyrazol-3-one1070065: Inhibition of demethylase activity of PCA-1 (unknown origin) using 3-methyl cytosine oligo DNA as substrate after 1 hr by RT-PCR analysisic501.5000uM
5-methyl-3-oxo-N-phenyl-2-pyridin-2-yl-1H-pyrazole-4-carboxamide1070065: Inhibition of demethylase activity of PCA-1 (unknown origin) using 3-methyl cytosine oligo DNA as substrate after 1 hr by RT-PCR analysisic501.7000uM
2-(6-chloro-1H-benzimidazol-2-yl)-4,5-diphenyl-1H-pyrazol-3-one1070065: Inhibition of demethylase activity of PCA-1 (unknown origin) using 3-methyl cytosine oligo DNA as substrate after 1 hr by RT-PCR analysisic502.0000uM
4-benzyl-5-methyl-2-[6-(4-methylphenyl)-1H-benzimidazol-2-yl]-1H-pyrazol-3-one1070065: Inhibition of demethylase activity of PCA-1 (unknown origin) using 3-methyl cytosine oligo DNA as substrate after 1 hr by RT-PCR analysisic502.1000uM
4,5-dimethyl-2-(6-methyl-1H-benzimidazol-2-yl)-1H-pyrazol-3-one1070065: Inhibition of demethylase activity of PCA-1 (unknown origin) using 3-methyl cytosine oligo DNA as substrate after 1 hr by RT-PCR analysisic502.6000uM
2-(6-fluoro-1H-benzimidazol-2-yl)-5-methyl-4-phenyl-1H-pyrazol-3-one1926084: Inhibition of ALKBH3 (unknown origin) using 3-methyl cytosine oligo DNA as substrate incubated for 1 hr by SYBR green dye based RT-PCR analysisic502.9000uM
2-(1H-benzimidazol-2-yl)-4-[(3,4-dichlorophenyl)methyl]-5-methyl-1H-pyrazol-3-one1070065: Inhibition of demethylase activity of PCA-1 (unknown origin) using 3-methyl cytosine oligo DNA as substrate after 1 hr by RT-PCR analysisic503.1000uM
4-methyl-2-(6-methyl-1H-benzimidazol-2-yl)-5-phenyl-1H-pyrazol-3-one1070065: Inhibition of demethylase activity of PCA-1 (unknown origin) using 3-methyl cytosine oligo DNA as substrate after 1 hr by RT-PCR analysisic503.3000uM
2-(1H-benzimidazol-2-yl)-5-methyl-1H-pyrazol-3-one1070065: Inhibition of demethylase activity of PCA-1 (unknown origin) using 3-methyl cytosine oligo DNA as substrate after 1 hr by RT-PCR analysisic503.6000uM
2-[(2-methylphenyl)sulfonylcarbamoyl]pyridine-4-carboxylic acid1926067: Inhibition of human ALKBH3 expressed in Escherichia coli BL21 (DE3) Rosetta cellsic503.7000uM
4-[(4-tert-butylphenyl)methyl]-5-methyl-2-(6-methyl-1H-benzimidazol-2-yl)-1H-pyrazol-3-one1070065: Inhibition of demethylase activity of PCA-1 (unknown origin) using 3-methyl cytosine oligo DNA as substrate after 1 hr by RT-PCR analysisic503.7000uM
2-(1H-benzimidazol-2-yl)-4,5-dimethyl-1H-pyrazol-3-one1070065: Inhibition of demethylase activity of PCA-1 (unknown origin) using 3-methyl cytosine oligo DNA as substrate after 1 hr by RT-PCR analysisic504.0000uM
2-(1H-benzimidazol-2-yl)-4-[(4-tert-butylphenyl)methyl]-5-methyl-1H-pyrazol-3-one1070065: Inhibition of demethylase activity of PCA-1 (unknown origin) using 3-methyl cytosine oligo DNA as substrate after 1 hr by RT-PCR analysisic504.1000uM
methyl 2-[2-(1H-benzimidazol-2-yl)-5-methyl-3-oxo-1H-pyrazol-4-yl]acetate1070065: Inhibition of demethylase activity of PCA-1 (unknown origin) using 3-methyl cytosine oligo DNA as substrate after 1 hr by RT-PCR analysisic504.3000uM
4-benzyl-2-(6-chloro-1H-benzimidazol-2-yl)-5-methyl-1H-pyrazol-3-one1070065: Inhibition of demethylase activity of PCA-1 (unknown origin) using 3-methyl cytosine oligo DNA as substrate after 1 hr by RT-PCR analysisic504.5000uM
4,5-dihydroxy-9,10-dioxoanthracene-2-carboxylic acid1926074: Inhibition of human ALKBH3 by HPLC analysisic505.3000uM
5-methyl-2-(6-methyl-1H-benzimidazol-2-yl)-4-[(4-phenylphenyl)methyl]-1H-pyrazol-3-one1070065: Inhibition of demethylase activity of PCA-1 (unknown origin) using 3-methyl cytosine oligo DNA as substrate after 1 hr by RT-PCR analysisic505.3000uM
2-(6-methyl-1H-benzimidazol-2-yl)-4,5-diphenyl-1H-pyrazol-3-one1070065: Inhibition of demethylase activity of PCA-1 (unknown origin) using 3-methyl cytosine oligo DNA as substrate after 1 hr by RT-PCR analysisic505.8000uM
4-benzyl-5-methyl-2-(4-methyl-1H-benzimidazol-2-yl)-1H-pyrazol-3-one1070065: Inhibition of demethylase activity of PCA-1 (unknown origin) using 3-methyl cytosine oligo DNA as substrate after 1 hr by RT-PCR analysisic505.9000uM
2-[(2-nitrophenyl)sulfonylcarbamoyl]pyridine-4-carboxylic acid1860811: Inhibition of human full lenth N-terminal His6-tagged ALKBH3 (1 to 286 residues) expressed in Escherichia coli BL21 (DE3) Rosetta cellsic506.2000uM
2-(1H-benzimidazol-2-yl)-5-phenyl-1H-pyrazol-3-one1070065: Inhibition of demethylase activity of PCA-1 (unknown origin) using 3-methyl cytosine oligo DNA as substrate after 1 hr by RT-PCR analysisic507.2000uM
2-chloro-3-(4-methoxyphenyl)-5-(4-methylphenyl)inden-1-one1398344: Binding affinity to recombinant human AlkBH3 incubated for 2 mins by isothermal titration calorimetric methodkd7.8100uM

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

ChemicalActions (top 5)PubMed papers
Benzo(a)pyreneaffects methylation2
Cyclosporineincreases expression2
triphenyl phosphateaffects expression1
bisphenol Aaffects cotreatment, increases methylation1
terbufosincreases methylation1
tris(1,3-dichloro-2-propyl)phosphateincreases expression1
alpha-hydroxyglutaratedecreases activity1
aflatoxin B2increases methylation1
cupric chloridedecreases activity1
di-n-butylphosphoric acidaffects expression1
CGP 52608affects binding, increases reaction1
CPG-oligonucleotideincreases expression1
ICG 001increases expression1
(+)-JQ1 compounddecreases expression1
Resveratrolaffects cotreatment, increases expression1
Sunitinibincreases expression1
Fulvestrantaffects cotreatment, increases methylation1
Air Pollutantsincreases expression, increases abundance1
Atrazinedecreases expression1
Fonofosincreases methylation1
Methyl Methanesulfonateincreases expression1
Parathionincreases methylation1
Plant Extractsaffects cotreatment, increases expression1
Smokeincreases abundance, increases expression1
Tunicamycinincreases expression1
Valproic Acidincreases expression, increases methylation1
Aflatoxin B1increases methylation1
Lactic Aciddecreases expression1
Acrylamideincreases expression1

ChEMBL screening assays

30 unique, capped per target: 29 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay IDTypeDescriptionSource paper
CHEMBL3119202BindingInhibition of PCA-1 (unknown origin) at 10 uMDesign and synthesis of prostate cancer antigen-1 (PCA-1/ALKBH3) inhibitors as anti-prostate cancer drugs. — Bioorg Med Chem Lett
CHEMBL5723248FunctionalAffinity Biochemical interaction: (inhibition of substrate demethylation measured by PCR) EUB0002596a ALKBH3Affinity Biochemical Literature for EUbOPEN Chemogenomic Library

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

CellosaurusNameCategorySex
CVCL_SC39HAP1 ALKBH3 (-) 1Cancer cell lineMale
CVCL_XL28HAP1 ALKBH3 (-) 2Cancer cell lineMale

Clinical trials (associated diseases)

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

No linked Atlas pages yet — the cross-entity mesh grows as the corpus expands.

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.4
BioBTree
v2.0.2

Sources 78

This page pulls from 78 datasets indexed by BioBTree:

alphafoldalphamissenseantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticsccdscellosauruschembl_activitychembl_assaychembl_documentchembl_moleculechembl_targetciviccivic_evidenceclingen_dosageclingen_gene_validityclinical_trialsclinvarcollectrictd_gene_interactiondbsnpdepmapdiamond_similarityefoensemblentrezesm2_similarityexonfantom5_genefantom5_promotergenccgenerifgogoparentgtopdbgwasgwas_studyhgnchpointactinterprointogenjasparmeshmimmirdbmondomsigdborphanetorthologparalogpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assaypubmedreactomereactomeparentrefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorspliceaistring_interactiontranscriptufeatureuniprot