ALKBH2

Summary

ALKBH2 (alkB homolog 2, alpha-ketoglutarate dependent dioxygenase, HGNC:32487) is a protein-coding gene on chromosome 12q24.11, encoding DNA oxidative demethylase ALKBH2 (Q6NS38). Dioxygenase that repairs alkylated nucleic acid bases by direct reversal oxidative dealkylation.

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 and ALKBH3 (MIM 610603) are E. coli AlkB homologs that catalyze the removal of 1-methyladenine and 3-methylcytosine (Duncan et al., 2002 [PubMed 12486230]).

Source: NCBI Gene 121642 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 50 total
• Druggable target: yes
• MANE Select transcript: NM_001145374

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:32487
Approved symbol	ALKBH2
Name	alkB homolog 2, alpha-ketoglutarate dependent dioxygenase
Location	12q24.11
Locus type	gene with protein product
Status	Approved
Aliases	MGC90512, ABH2
Ensembl gene	ENSG00000189046
Ensembl biotype	protein_coding
OMIM	610602
Entrez	121642

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 22 protein_coding, 1 retained_intron

ENST00000343075, ENST00000429722, ENST00000440112, ENST00000536242, ENST00000536358, ENST00000536720, ENST00000543444, ENST00000619381, ENST00000861370, ENST00000861371, ENST00000861372, ENST00000861373, ENST00000861374, ENST00000861375, ENST00000931219, ENST00000931220, ENST00000931221, ENST00000931222, ENST00000931223, ENST00000931224, ENST00000950636, ENST00000950637, ENST00000950638

RefSeq mRNA: 5 — MANE Select: NM_001145374 NM_001001655, NM_001145374, NM_001145375, NM_001205179, NM_001205180

CCDS: CCDS31897, CCDS55883

Canonical transcript exons

ENST00000429722 — 4 exons

Exon	Start	End
ENSE00001367884	109090009	109090207
ENSE00001422228	109093247	109093472
ENSE00001732735	109092507	109092937
ENSE00002242598	109088189	109088512

Expression profiles

Bgee: expression breadth ubiquitous, 215 present calls, max score 93.13.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.9163 / max 145.9400, expressed in 1726 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
133184	8.1860	1676
133185	2.6123	697
133183	2.1180	1194

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	93.13	gold quality
calcaneal tendon	UBERON:0003701	91.79	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	90.34	gold quality
ventricular zone	UBERON:0003053	90.29	gold quality
secondary oocyte	CL:0000655	88.64	gold quality
ganglionic eminence	UBERON:0004023	88.54	gold quality
right lobe of liver	UBERON:0001114	88.42	gold quality
left uterine tube	UBERON:0001303	87.81	gold quality
skin of abdomen	UBERON:0001416	87.63	gold quality
sural nerve	UBERON:0015488	87.51	gold quality
skin of leg	UBERON:0001511	87.38	gold quality
right ovary	UBERON:0002118	86.88	gold quality
cortical plate	UBERON:0005343	86.79	gold quality
tibial nerve	UBERON:0001323	86.74	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	86.65	gold quality
gastrocnemius	UBERON:0001388	86.59	gold quality
muscle of leg	UBERON:0001383	86.33	gold quality
left ovary	UBERON:0002119	86.29	gold quality
body of uterus	UBERON:0009853	86.27	gold quality
mucosa of stomach	UBERON:0001199	85.77	gold quality
ectocervix	UBERON:0012249	85.52	gold quality
zone of skin	UBERON:0000014	85.36	gold quality
apex of heart	UBERON:0002098	85.21	gold quality
body of pancreas	UBERON:0001150	85.13	gold quality
body of stomach	UBERON:0001161	85.01	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.91	gold quality
tibial artery	UBERON:0007610	84.90	gold quality
popliteal artery	UBERON:0002250	84.88	gold quality
left coronary artery	UBERON:0001626	84.86	gold quality
muscle layer of sigmoid colon	UBERON:0035805	84.82	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.62
E-GEOD-99795	no	85.67

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TP53

Literature-anchored findings (GeneRIF, showing 22)

• first crystal structure of ABH2 (PMID:18432238)
• ABH2 is active in the direct reversal of epsilon A lesions, and that ABH2, together with the alkyl-N-adenine-DNA glycosylase, which is the most effective enzyme for the repair of epsilon A, comprise the cellular defense against epsilon A lesions (PMID:18519673)
• Mutations of ABH2 is associated with pediatric brain tumors. (PMID:19290481)
• Data show that the JMJD1A/ABH2 family of dioxygenases is highly sensitive to inhibition by carcinogenic nickel ions. (PMID:20042601)
• Divergent sequences outside of the active site determine substrate specificities of ABH2. (PMID:20525795)
• Tumour protein (TP53) is directly involved by binding to the promoter of ALKBH2 in mediating photofrin-mediaated photodynamic therapy in U87 glioma cells. (PMID:20661249)
• 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)
• ABH2 is downregulated in a subset of gastric cancers, and might be involved in the molecular mechanism of gastric cancer through inhibiting the proliferation of gastric cancer cells. (PMID:21155885)
• X-ray absorption spectroscopy structural investigation of early intermediates in the mechanism of DNA repair by human ABH2 (PMID:21510633)
• The non-enzymatic binding of AAG to 3,N(4)-ethenocytosine specifically blocks ALKBH2-catalyzed repair of 3,N(4)-ethenocytosine but not that of methylated ALKBH2 substrates. (PMID:22079122)
• combination of duplex interrogation and oxidation chemistry allows ALKBH2 to detect and process diverse lesions efficiently and correctly (PMID:22659876)
• Overexpression of ALKBH2 is associated with enhanced resistance to temozolomide in glioblastoma. (PMID:23258843)
• ALKBH2 is an upstream molecule of the oncoprotein, MUC1, and regulates cell cycle and EMT, resulting in progression of urothelial carcinomas. (PMID:23279696)
• ABH2 knockdown impairs rDNA transcription and leads to increased single-stranded and double-stranded DNA breaks in the rDNA genes. (PMID:23972994)
• It was shown for first time that DNA glycosylase ALKBH2 can repair DNA adduct 1,N2-ethenoguanine. (PMID:25797601)
• studies reveal the ALKBH2 binding interface of PCNA and indicate that both germline and somatic ALKBH2 variants could have cellular effects on ALKBH2 function in DNA repair. (PMID:26408825)
• These results revealed that N3-ethylthymidine , but not other DNA lesions, could be repaired by Alkbh2 and Alkbh3 in mammalian cells. (PMID:26930515)
• 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)
• Insights into the Direct Oxidative Repair of Etheno Lesions: MD and QM/MM Study on the Substrate Scope of ALKBH2 and AlkB. (PMID:33161373)
• ALKBH2 inhibition alleviates malignancy in colorectal cancer by regulating BMI1-mediated activation of NF-kappaB pathway. (PMID:33302959)
• Conformational Dynamics of Human ALKBH2 Dioxygenase in the Course of DNA Repair as Revealed by Stopped-Flow Fluorescence Spectroscopy. (PMID:35956910)
• Individual Contributions of Amido Acid Residues Tyr122, Ile168, and Asp173 to the Activity and Substrate Specificity of Human DNA Dioxygenase ABH2. (PMID:37508504)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	alkbh2	ENSDARG00000059856
mus_musculus	Alkbh2	ENSMUSG00000044339
rattus_norvegicus	Alkbh2	ENSRNOG00000028584

Protein

Protein identifiers

DNA oxidative demethylase ALKBH2 — Q6NS38 (reviewed: Q6NS38)

Alternative names: Alkylated DNA repair protein alkB homolog 2, Alpha-ketoglutarate-dependent dioxygenase alkB homolog 2, Oxy DC1

All UniProt accessions (4): F5GZZ0, F5H5X2, Q6NS38, S4R3T5

UniProt curated annotations — full annotation on UniProt →

Function. Dioxygenase that repairs alkylated nucleic acid bases by direct reversal oxidative dealkylation. Can process both double-stranded (ds) and single-stranded (ss) DNA substrates, with a strong preference for dsDNA. Uses molecular oxygen, 2-oxoglutarate and iron as cofactors to oxidize the alkyl groups that are subsequently released as aldehydes, regenerating the undamaged bases. Probes the base pair stability, locates a weakened base pair and flips the damaged base to accommodate the lesion in its active site for efficient catalysis. Repairs monoalkylated bases, specifically N1-methyladenine and N3-methylcytosine, as well as higher order alkyl adducts such as bases modified with exocyclic bridged adducts known as etheno adducts including 1,N6-ethenoadenine, 3,N4-ethenocytosine and 1,N2-ethenoguanine. Acts as a gatekeeper of genomic integrity under alkylation stress. Efficiently repairs alkylated lesions in ribosomal DNA (rDNA). These lesions can cause ss- and dsDNA strand breaks that severely impair rDNA transcription. In a response mechanism to DNA damage, associates with PCNA at replication forks to repair alkylated adducts prior to replication.

Subunit / interactions. Interacts with PCNA homotrimer; this interaction is enhanced during the S-phase of the cell cycle. Interacts with nucleolar proteins NCL, UBTF and NPM1. Interacts with XRCC5-XRCC6 heterodimer.

Subcellular location. Nucleus. Nucleolus. Nucleoplasm.

Tissue specificity. Detected in colon, small intestine, ovary, testis, prostate, skeletal muscle, heart, liver and urinary bladder.

Activity regulation. Activated by ascorbate and magnesium ions.

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

Domain organisation. The PCNA-binding motif (AlkB homolog 2 PCNA-interacting motif, APIM), mediates the colocalization of ALKBH2 with PCNA at the replication foci, coordinating the repair of alkylated DNA damage with DNA replication.

Similarity. Belongs to the alkB family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q6NS38-1	1	yes
Q6NS38-2	2

RefSeq proteins (5): NP_001001655, NP_001138846, NP_001138847, NP_001192108, NP_001192109 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005123	Oxoglu/Fe-dep_dioxygenase_dom	Domain
IPR027450	AlkB-like	Domain
IPR032852	ALKBH2	Family
IPR037151	AlkB-like_sf	Homologous_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)

Substrate kinetics (BRENDA)

14 substrates with measured Km, best-characterized 14. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
3-METHYLCYTOSINE IN 3’-TAILED DNA	0.0014–0.0017	2
1-METHYL-ADENINE IN 5’-DAAAA-1MEA-YYAAA	0.0004	1
1-METHYL-DAMP	0.002	1
1-METHYL-DATP	0.0055	1
2’-DEOXY-1-METHYL-ADENOSINE 3’-PHOSPHATE	0.012	1
D(TPM1A)	0.0044	1
D(TPM1APT)	0.0028	1
DNA-N1-METHYLADENINE	0.002	1
DOUBLE-STRANDED DNA-1-METHYLADENINE	0.0062	1
DOUBLE-STRANDED DNA-3-METHYLCYTOSINE	0.0093	1
N1-METHYL-ATP	0.01	1
POLY(DM1A)	0.0014	1
SINGLE-STRANDED DNA-1-METHYLADENINE	0.0054	1
SINGLE-STRANDED DNA-3-METHYLCYTOSINE	0.0034	1

Catalyzed reactions (Rhea), 10 shown:

• a methylated nucleobase within DNA + 2-oxoglutarate + O2 = a nucleobase within DNA + formaldehyde + succinate + CO2 (RHEA:30299)
• 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(3)-methyl-2’-deoxycytidine in double-stranded DNA + 2-oxoglutarate + O2 = a 2’-deoxycytidine in double-stranded DNA + formaldehyde + succinate + CO2 + H(+) (RHEA:70439)
• an N(1)-methyl-2’-deoxyadenosine in double-stranded DNA + 2-oxoglutarate + O2 = a 2’-deoxyadenosine in double-stranded DNA + formaldehyde + succinate + CO2 + H(+) (RHEA:70443)
• 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 1,N(6)-etheno-2’-deoxyadenosine in single-stranded DNA + 2-oxoglutarate + O2 + H2O = a 2’-deoxyadenosine in single-stranded DNA + glyoxal + succinate + CO2 (RHEA:70459)
• a 1,N(6)-etheno-2’-deoxyadenosine in double-stranded DNA + 2-oxoglutarate + O2 + H2O = a 2’-deoxyadenosine in double-stranded DNA + glyoxal + succinate + CO2 (RHEA:70463)
• a 3,N(4)-etheno-2’-deoxycytidine in double-stranded DNA + 2-oxoglutarate + O2 + H2O = a 2’-deoxycytidine in double-stranded DNA + glyoxal + succinate + CO2 (RHEA:70467)
• 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)
• a 1,N(2)-etheno-2’-deoxyguanosine in double-stranded DNA + 2-oxoglutarate + O2 + H2O = a 2’-deoxyguanosine in double-stranded DNA + glyoxal + succinate + CO2 (RHEA:70487)

UniProt features (61 total): mutagenesis site 17, strand 17, binding site 13, helix 5, sequence variant 3, chain 1, domain 1, splice variant 1, region of interest 1, short sequence motif 1, sequence conflict 1

Structure

Experimental structures (PDB)

18 structures.

PDB	Method	Resolution (Å)
3S57	X-RAY DIFFRACTION	1.6
3RZG	X-RAY DIFFRACTION	1.62
3S5A	X-RAY DIFFRACTION	1.7
3H8R	X-RAY DIFFRACTION	1.77
3H8X	X-RAY DIFFRACTION	1.95
3BTX	X-RAY DIFFRACTION	2
3H8O	X-RAY DIFFRACTION	2
3RZH	X-RAY DIFFRACTION	2.25
4MG2	X-RAY DIFFRACTION	2.3
3BTY	X-RAY DIFFRACTION	2.35
3BU0	X-RAY DIFFRACTION	2.5
3RZJ	X-RAY DIFFRACTION	2.5
3BUC	X-RAY DIFFRACTION	2.59
3RZL	X-RAY DIFFRACTION	2.6
4MGT	X-RAY DIFFRACTION	2.6
3RZK	X-RAY DIFFRACTION	2.78
3BTZ	X-RAY DIFFRACTION	3
3RZM	X-RAY DIFFRACTION	3.06

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6NS38-F1	84.23	0.69

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 (13): 173; 174; 236; 236; 248; 252; 254; 102–104; 122–124; 159; 161; 171 …

Mutagenesis-validated functional residues (17):

Position	Phenotype
3	impairs pcna-binding. no effect on pcna-binding; when associated with r-7.
4	complete loss of pcna-binding.
4	no effect on pcna-binding.
5–6	strong decrease in pcna-binding.
7	no effect on pcna-binding; when associated with k-3.
38–40	leads to cytoplasmic relocalization.
101–103	strong decrease of activity toward n1-methyladenine adduct in both ssdna and dsdna substrates.
101	decreases activity toward n1-methyladenine adduct in ssdna. has no effect on lesion repair in dsdna.
101	loss of activity toward n1-methyladenine adduct in either ssdna or dsdna; when associated with a-102.
102	strong decrease of activity toward n1-methyladenine adduct. loss of activity toward n1-methyladenine adduct in either ss
110	loss of activity toward n1-methyladenine adduct in either ssdna or dsdna.
122	decreases activity toward n1-methyladenine adduct in either ssdna or dsdna.
124	loss of activity toward n1-methyladenine adduct in either ssdna or dsdna.
125	strong decrease of activity toward n1-methyladenine adduct in ssdna. has no effect on lesion repair in dsdna.
173	loss of activity associated with decreased rdna transcription.
175	loss of activity.
236	decreases activity.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-112122	ALKBH2 mediated reversal of alkylation damage
R-HSA-73894	DNA Repair
R-HSA-73942	DNA Damage Reversal
R-HSA-73943	Reversal of alkylation damage by DNA dioxygenases

MSigDB gene sets: 91 (showing top): GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_PAIRED_DONORS_WITH_INCORPORATION_OR_REDUCTION_OF_MOLECULAR_OXYGEN, KAUFFMANN_DNA_REPAIR_GENES, GOBP_DNA_DAMAGE_RESPONSE, DODD_NASOPHARYNGEAL_CARCINOMA_UP, REACTOME_DNA_REPAIR, MARSON_BOUND_BY_E2F4_UNSTIMULATED, SANSOM_APC_MYC_TARGETS, SANSOM_APC_TARGETS_REQUIRE_MYC, GOCC_NUCLEOLUS, GOBP_DNA_METABOLIC_PROCESS, GOMF_DEMETHYLASE_ACTIVITY, chr12q24, GOBP_DNA_REPAIR, GOMF_DIOXYGENASE_ACTIVITY, GOMF_FERROUS_IRON_BINDING

GO Biological Process (3): DNA alkylation repair (GO:0006307), DNA repair (GO:0006281), DNA damage response (GO:0006974)

GO Molecular Function (9): rDNA binding (GO:0000182), ferrous iron binding (GO:0008198), broad specificity oxidative DNA demethylase activity (GO:0035516), cytosine C-5 DNA demethylase activity (GO:0051747), protein binding (GO:0005515), oxidoreductase activity (GO:0016491), 2-oxoglutarate-dependent dioxygenase activity (GO:0016706), metal ion binding (GO:0046872), dioxygenase activity (GO:0051213)

GO Cellular Component (3): nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Reversal of alkylation damage by DNA dioxygenases	1
DNA Repair	1
DNA Damage Reversal	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA demethylase activity	2
nuclear lumen	2
DNA repair	1
DNA metabolic process	1
DNA damage response	1
cellular response to stress	1
sequence-specific double-stranded DNA binding	1
iron ion binding	1
2-oxoglutarate-dependent dioxygenase activity	1
hydrolase activity	1
binding	1
catalytic activity	1
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen	1
dioxygenase activity	1
cation binding	1
oxidoreductase activity	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

1541 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ALKBH2	ALKBH1	Q13686	987
ALKBH2	JMJD4	Q9H9V9	852
ALKBH2	ALKBH6	Q3KRA9	837
ALKBH2	ALKBH8	Q96BT7	832
ALKBH2	ALKBH4	Q9NXW9	756
ALKBH2	ALKBH7	Q9BT30	751
ALKBH2	FTO	Q9C0B1	720
ALKBH2	ALKBH5	Q6P6C2	622
ALKBH2	MPG	P29372	595
ALKBH2	ASCC3	Q8N3C0	582
ALKBH2	ALKBH3	Q96Q83	542
ALKBH2	MGMT	P16455	507
ALKBH2	SLCO6A1	Q86UG4	463
ALKBH2	APEX1	P27695	459
ALKBH2	TDG	Q13569	459

IntAct

23 interactions, top by confidence:

A	B	Type	Score
ARL3	UNC119B	psi-mi:“MI:0914”(association)	0.730
GOLGA2	ALKBH2	psi-mi:“MI:0915”(physical association)	0.560
LCN15	POTEF	psi-mi:“MI:0914”(association)	0.530
ALKBH2	ODAD3	psi-mi:“MI:0914”(association)	0.530
ALKBH2	LCN1	psi-mi:“MI:0915”(physical association)	0.400
Nedd1		psi-mi:“MI:0914”(association)	0.350
Kif19		psi-mi:“MI:0914”(association)	0.350
Sesn2	CASTOR2	psi-mi:“MI:0914”(association)	0.350
FERMT3	BLTP3B	psi-mi:“MI:0914”(association)	0.350
AARSD1	APAF1	psi-mi:“MI:0914”(association)	0.350
SLX4	SMAP	psi-mi:“MI:0914”(association)	0.350
PIPSL	C1orf226	psi-mi:“MI:0914”(association)	0.350
FTL	SH3PXD2B	psi-mi:“MI:0914”(association)	0.350
	POLR3A	psi-mi:“MI:0914”(association)	0.350
AARSD1	MAP3K7	psi-mi:“MI:0914”(association)	0.350
FTL		psi-mi:“MI:0914”(association)	0.350
ALKBH2	ARL3	psi-mi:“MI:0915”(physical association)	0.000
ALKBH2	GOLGA2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (30): ALKBH2 (Affinity Capture-MS), ALKBH2 (Co-fractionation), DHX16 (Co-fractionation), ALKBH2 (Affinity Capture-MS), ALKBH2 (Affinity Capture-MS), ALKBH2 (Affinity Capture-MS), ALKBH2 (Affinity Capture-MS), OTUD4 (Affinity Capture-Western), SYNJ1 (Affinity Capture-MS), CCDC151 (Affinity Capture-MS), ALKBH2 (Affinity Capture-MS), ALKBH2 (Affinity Capture-MS), ARL3 (Affinity Capture-MS), ALKBH2 (Two-hybrid), ALKBH2 (Affinity Capture-MS)

ESM2 similar proteins: A0A2K3DU55, A4RPM5, A7M7B9, B2RZ55, B4FAT0, B6TN12, B8AA76, B8B016, B9DFZ0, C0PN26, C5XKZ1, E2RDZ6, F7EZ75, O35980, O43824, O54747, O70157, P28339, P28340, P38935, P52431, P54137, P78549, P97283, P97931, Q09907, Q0P595, Q1HG60, Q2KI24, Q2KID2, Q2KIF8, Q3ZBQ0, Q499X9, Q5R6G3, Q5ZAQ2, Q5ZHX9, Q6DHI5, Q6L534, Q6NS38, Q75AT3

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

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	36
Likely benign	9
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

579 predictions. Top by Δscore:

Variant	Effect	Δscore
12:109088508:TATAC:T	acceptor_gain	1.0000
12:109088510:TAC:T	acceptor_gain	1.0000
12:109088511:AC:A	acceptor_gain	1.0000
12:109088512:CC:C	acceptor_gain	1.0000
12:109088513:CTGC:C	acceptor_loss	1.0000
12:109097730:G:GT	donor_gain	1.0000
12:109088509:ATAC:A	acceptor_gain	0.9900
12:109088513:C:CC	acceptor_gain	0.9900
12:109089953:T:TA	donor_gain	0.9900
12:109092501:GCTTA:G	donor_loss	0.9900
12:109092502:CTTA:C	donor_loss	0.9900
12:109092503:TTA:T	donor_loss	0.9900
12:109092504:TA:T	donor_loss	0.9900
12:109092506:C:CT	donor_loss	0.9900
12:109092524:T:TA	donor_gain	0.9900
12:109093377:T:TA	donor_gain	0.9900
12:109097795:A:T	donor_gain	0.9900
12:109097809:GCG:G	donor_gain	0.9900
12:109088518:A:AC	acceptor_gain	0.9800
12:109093366:A:AC	donor_gain	0.9800
12:109093367:C:CC	donor_gain	0.9800
12:109093368:TGCAA:T	donor_gain	0.9800
12:109097808:GGCG:G	donor_gain	0.9800
12:109097809:GCGG:G	donor_gain	0.9800
12:109098431:GGCC:G	acceptor_gain	0.9800
12:109088517:A:T	acceptor_gain	0.9700
12:109093363:A:AC	donor_gain	0.9700
12:109097812:G:GG	donor_gain	0.9700
12:109098325:AAAT:A	acceptor_gain	0.9700
12:109098325:AAATG:A	acceptor_gain	0.9700

AlphaMissense

1699 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:109088474:T:A	D173V	0.996
12:109090116:A:C	F124L	0.996
12:109090116:A:T	F124L	0.996
12:109090118:A:G	F124L	0.996
12:109088242:A:C	N250K	0.995
12:109088242:A:T	N250K	0.995
12:109088432:A:T	V187D	0.995
12:109088473:A:C	D173E	0.995
12:109088473:A:T	D173E	0.995
12:109088286:G:C	H236D	0.994
12:109088474:T:G	D173A	0.994
12:109090159:C:G	R110T	0.994
12:109088232:G:T	R254S	0.993
12:109088413:T:A	R193S	0.993
12:109088413:T:G	R193S	0.993
12:109088479:G:C	H171Q	0.993
12:109088479:G:T	H171Q	0.993
12:109090159:C:A	R110M	0.993
12:109088438:G:T	A185D	0.992
12:109088475:C:G	D173H	0.992
12:109088481:G:C	H171D	0.992
12:109090021:A:T	V156E	0.992
12:109090158:C:A	R110S	0.992
12:109090158:C:G	R110S	0.992
12:109088233:A:C	F253L	0.991
12:109088233:A:T	F253L	0.991
12:109088235:A:G	F253L	0.991
12:109088414:C:A	R193I	0.991
12:109088477:C:G	R172P	0.991
12:109088234:A:G	F253S	0.990

dbSNP variants (sampled 300 via entrez): RS1000132569 (12:109091841 C>T), RS1000485534 (12:109093490 T>C), RS1001040899 (12:109093638 A>C,G), RS1001111881 (12:109090266 GC>G,GCC,GCCC), RS1001564522 (12:109090385 A>C), RS1002353337 (12:109093229 G>A,T), RS1002699958 (12:109090814 A>G), RS1003078446 (12:109090519 C>G,T), RS1003092724 (12:109092750 G>A), RS1003361145 (12:109091524 G>C), RS1004265100 (12:109092714 C>G,T), RS1004490805 (12:109088012 G>A,T), RS1004600113 (12:109093895 G>C), RS1004652394 (12:109094113 C>T), RS1005274217 (12:109091290 G>A)

Disease associations

OMIM: gene MIM:610602 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5169164 (SINGLE PROTEIN)

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

ChEMBL bioactivities

22 potent at pChembl≥5 of 41 total, top 21 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.51	IC50	31	nM	CHEMBL6164872
7.36	IC50	44	nM	CHEMBL6152538
7.33	IC50	47	nM	CHEMBL6164872
7.28	IC50	53	nM	CHEMBL6152503
7.14	IC50	73	nM	CHEMBL6145099
7.08	IC50	83	nM	CHEMBL6145758
7.05	IC50	89	nM	CHEMBL6161609
6.93	IC50	117	nM	CHEMBL6143281
6.65	Kd	226	nM	CHEMBL6164872
6.61	IC50	248	nM	CHEMBL220743
6.61	IC50	245	nM	CHEMBL6162317
6.56	IC50	276	nM	CHEMBL6160046
6.42	IC50	378	nM	CHEMBL6147124
6.28	IC50	527	nM	CHEMBL6147620
6.07	IC50	851	nM	CHEMBL6147098
6.02	IC50	949	nM	CHEMBL6145411
5.91	IC50	1230	nM	CHEMBL6163247
5.83	IC50	1480	nM	CHEMBL6164872
5.82	IC50	1510	nM	CHEMBL6141625
5.48	IC50	3320	nM	CHEMBL6166325
5.04	IC50	9100	nM	RHEIN

PubChem BioAssay actives

1 with measured affinity, of 22 total; 1 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
4,5-dihydroxy-9,10-dioxoanthracene-2-carboxylic acid	1926073: Inhibition of human ALKBH2 by HPLC analysis	ic50	9.1000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases methylation, increases expression	2
Benzo(a)pyrene	decreases expression, increases methylation	2
Tretinoin	decreases expression	2
Valproic Acid	affects expression, increases expression	2
1,N(6)-ethenoadenine	increases metabolic processing	1
decabromobiphenyl ether	affects expression	1
beta-lapachone	increases expression	1
sodium arsenite	decreases expression	1
alpha-hydroxyglutarate	decreases activity	1
rhein	decreases activity	1
cupric chloride	decreases activity	1
punicalagin	decreases activity	1
CPG-oligonucleotide	increases expression	1
K 7174	decreases expression	1
pentagalloylglucose	decreases activity	1
bisphenol S	affects cotreatment, increases methylation	1
ginnalin A	decreases activity	1
Temozolomide	increases expression	1
Fulvestrant	increases methylation, affects cotreatment	1
Acetaminophen	decreases expression	1
Calcitriol	decreases expression, affects cotreatment	1
Cisplatin	decreases response to substance	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Ellagic Acid	decreases activity	1
Gallic Acid	decreases activity	1
Methyl Methanesulfonate	increases response to substance	1
Ribonucleotides	affects binding	1
Testosterone	affects cotreatment, decreases expression	1
Thiram	decreases expression	1
Vanadates	increases expression	1

ChEMBL screening assays

27 unique, capped per target: 27 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5115880	Binding	Inhibition of human full lenth N-terminal His6-tagged ALKBH2 (56 to 258 residues) expressed in Escherichia coli BL21 (DE3) Rosetta cells	Discovery of a potent, selective and cell active inhibitor of m6A demethylase ALKBH5. — Eur J Med Chem

Cellosaurus cell lines

3 cell lines: 2 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2RI	Abcam HEK293T ALKBH2 KO	Transformed cell line	Female
CVCL_SC37	HAP1 ALKBH2 (-) 1	Cancer cell line	Male
CVCL_SC38	HAP1 ALKBH2 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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