ALKBH7

Summary

ALKBH7 (alkB homolog 7, RNA demethylase, HGNC:21306) is a protein-coding gene on chromosome 19p13.3, encoding RNA demethylase ALKBH7, mitochondrial (Q9BT30). RNA demethylase that demethylates N(2)-dimethylguanosine and N(1)-methyladenosine within mitochondrial pre-tRNA regions.

Predicted to enable dioxygenase activity and metal ion binding activity. Involved in DNA damage response and regulation of mitochondrial membrane permeability involved in programmed necrotic cell death. Located in mitochondrial matrix.

Source: NCBI Gene 84266 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 57 total
• MANE Select transcript: NM_032306

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21306
Approved symbol	ALKBH7
Name	alkB homolog 7, RNA demethylase
Location	19p13.3
Locus type	gene with protein product
Status	Approved
Aliases	MGC10974
Ensembl gene	ENSG00000125652
Ensembl biotype	protein_coding
OMIM	613305
Entrez	84266

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000245812, ENST00000596657, ENST00000599849, ENST00000879748

RefSeq mRNA: 1 — MANE Select: NM_032306 NM_032306

CCDS: CCDS12163

Canonical transcript exons

ENST00000245812 — 4 exons

Exon	Start	End
ENSE00000894747	6372794	6373024
ENSE00002983775	6374811	6375250
ENSE00003566631	6374465	6374589
ENSE00003659561	6374203	6374376

Expression profiles

Bgee: expression breadth ubiquitous, 258 present calls, max score 99.65.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 62.9817 / max 594.5300, expressed in 1821 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
173474	61.4578	1821
173473	0.7637	434
173471	0.6367	235
173472	0.1235	13

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	99.65	gold quality
right testis	UBERON:0004534	99.57	gold quality
adult organism	UBERON:0007023	98.95	gold quality
apex of heart	UBERON:0002098	98.49	gold quality
testis	UBERON:0000473	98.22	gold quality
hindlimb stylopod muscle	UBERON:0004252	97.62	gold quality
mucosa of transverse colon	UBERON:0004991	97.57	gold quality
right lobe of liver	UBERON:0001114	97.33	gold quality
heart left ventricle	UBERON:0002084	97.32	gold quality
cardiac ventricle	UBERON:0002082	97.20	gold quality
right atrium auricular region	UBERON:0006631	96.54	gold quality
kidney epithelium	UBERON:0004819	96.44	gold quality
body of pancreas	UBERON:0001150	96.42	gold quality
cardiac atrium	UBERON:0002081	96.32	gold quality
gastrocnemius	UBERON:0001388	96.30	gold quality
heart	UBERON:0000948	96.04	gold quality
upper arm skin	UBERON:0004263	95.94	gold quality
transverse colon	UBERON:0001157	95.87	gold quality
muscle of leg	UBERON:0001383	95.86	gold quality
right lobe of thyroid gland	UBERON:0001119	95.81	gold quality
adenohypophysis	UBERON:0002196	95.74	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	95.71	gold quality
pigmented layer of retina	UBERON:0001782	95.65	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	95.65	gold quality
retina	UBERON:0000966	95.63	gold quality
lower esophagus mucosa	UBERON:0035834	95.59	gold quality
left lobe of thyroid gland	UBERON:0001120	95.55	gold quality
duodenum	UBERON:0002114	95.52	gold quality
right hemisphere of cerebellum	UBERON:0014890	95.50	gold quality
cerebellar hemisphere	UBERON:0002245	95.46	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	2032.19
E-ANND-3	yes	13.22
E-MTAB-10042	yes	4.09
E-GEOD-106540	no	142.19
E-GEOD-100618	no	115.57

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

9 targeting ALKBH7, 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-7978	99.86	66.90	856
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-3164	99.02	68.39	1071
HSA-MIR-6820-3P	99.02	68.50	1035
HSA-MIR-6801-3P	98.04	64.64	805
HSA-MIR-6810-3P	97.96	64.57	1023
HSA-MIR-3661	97.83	67.30	705
HSA-MIR-6793-3P	97.66	65.78	1084
HSA-MIR-631	97.05	66.93	602

Literature-anchored findings (GeneRIF, showing 6)

• novel role for a AlkB homolog, human ALKBH7, in programmed necrosis, presenting a new target for therapeutic intervention in cancer cells that are resistant to apoptotic cell death (PMID:23666923)
• ALKBH7 possesses the conserved double-stranded beta-helix fold that coordinates a catalytically active iron by a conserved HX(D/E) em leader Xn em leader H motif. (PMID:25122757)
• Our results uncovered a SNP of ALKBH7, rs7540, which is associated with prostate cancer disease in a statistically significantly manner in two separate cohorts, and maintained in African American men. (PMID:28231280)
• ALKBH7-mediated demethylation regulates mitochondrial polycistronic RNA processing. (PMID:34253897)
• Transformed astrocytes confer temozolomide resistance on glioblastoma via delivering ALKBH7 to enhance APNG expression after educating by glioblastoma stem cells-derived exosomes. (PMID:38332576)
• Integrative pan-cancer analysis reveals the prognostic and immunotherapeutic value of ALKBH7 in HNSC. (PMID:39400540)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	alkbh7	ENSDARG00000037906
mus_musculus	Alkbh7	ENSMUSG00000002661
rattus_norvegicus	Alkbh7	ENSRNOG00000047089
drosophila_melanogaster	CG14130	FBGN0036210
caenorhabditis_elegans		WBGENE00012920

Protein

Protein identifiers

RNA demethylase ALKBH7, mitochondrial — Q9BT30 (reviewed: Q9BT30)

Alternative names: Alkylated DNA repair protein alkB homolog 7, Alpha-ketoglutarate-dependent dioxygenase alkB homolog 7, mitochondrial, Spermatogenesis cell proliferation-related protein, Spermatogenesis-associated protein 11, pre-tRNA N1-methyl adenine demethylase ALKBH7, pre-tRNA N2-dimethyl guanosine demethylase ALKBH7

All UniProt accessions (3): Q9BT30, M0QZH2, M0QZI0

UniProt curated annotations — full annotation on UniProt →

Function. RNA demethylase that demethylates N(2)-dimethylguanosine and N(1)-methyladenosine within mitochondrial pre-tRNA regions. This demethylation activity plays a crucial role in regulating the processing of nascent polycistronic mitochondrial RNA, thereby influencing mitochondrial gene expression and overall mitochondrial activity. In response to extensive DNA damage is required for programmed necrosis induced by alkylation and oxidation. Acts by triggering the collapse of mitochondrial membrane potential and loss of mitochondrial function that leads to energy depletion and cell death. Involved in fatty acid metabolism.

Subunit / interactions. Monomer.

Subcellular location. Mitochondrion matrix.

Tissue specificity. Widely expressed, with highest expression in pancreas, followed by spleen, prostate, ovary and placenta.

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

Similarity. Belongs to the alkB family.

RefSeq proteins (1): NP_115682* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR027450	AlkB-like	Domain
IPR032870	ALKBH7-like	Family
IPR037151	AlkB-like_sf	Homologous_superfamily

Pfam: PF13532

Catalyzed reactions (Rhea), 2 shown:

• an N(1)-methyladenosine in tRNA + 2-oxoglutarate + O2 = an adenosine in tRNA + formaldehyde + succinate + CO2 (RHEA:54576)
• N(2)-dimethylguanosine in tRNA + 2 2-oxoglutarate + 2 O2 = guanosine in tRNA + 2 formaldehyde + 2 succinate + 2 CO2 (RHEA:85431)

UniProt features (31 total): strand 10, binding site 9, helix 5, turn 2, transit peptide 1, chain 1, sequence variant 1, mutagenesis site 1, sequence conflict 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
4QKD	X-RAY DIFFRACTION	1.35
4QKF	X-RAY DIFFRACTION	1.99
4QKB	X-RAY DIFFRACTION	2.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BT30-F1	90.10	0.82

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): 203; 62; 75; 121; 123; 165; 177; 197; 199

Mutagenesis-validated functional residues (1):

Position	Phenotype
110	does not affect ability to trigger programmed necrosis.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 132 (showing top): GOBP_REGULATION_OF_LIPID_STORAGE, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_PAIRED_DONORS_WITH_INCORPORATION_OR_REDUCTION_OF_MOLECULAR_OXYGEN, GOBP_OXIDATIVE_DEMETHYLATION, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_MITOCHONDRIAL_TRANSPORT, GOBP_DEMETHYLATION, GOBP_RNA_MODIFICATION, GOBP_DNA_DAMAGE_RESPONSE, GOBP_LIPID_METABOLIC_PROCESS, GOBP_ORGANIC_ACID_METABOLIC_PROCESS, GOBP_MEMBRANE_ORGANIZATION, EGR1_01, GOBP_REGULATION_OF_MEMBRANE_PERMEABILITY, GOCC_MITOCHONDRIAL_MATRIX, GARY_CD5_TARGETS_UP

GO Biological Process (6): fatty acid metabolic process (GO:0006631), DNA damage response (GO:0006974), regulation of lipid storage (GO:0010883), oxidative RNA demethylation (GO:0035513), regulation of mitochondrial membrane permeability involved in programmed necrotic cell death (GO:1902445), programmed cell death (GO:0012501)

GO Molecular Function (6): oxidative RNA demethylase activity (GO:0035515), metal ion binding (GO:0046872), tRNA demethylase activity (GO:1990984), protein binding (GO:0005515), oxidoreductase activity (GO:0016491), dioxygenase activity (GO:0051213)

GO Cellular Component (2): mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
lipid metabolic process	1
monocarboxylic acid metabolic process	1
cellular response to stress	1
lipid storage	1
regulation of cellular process	1
RNA modification	1
oxidative demethylation	1
regulation of mitochondrial membrane permeability	1
programmed necrotic cell death	1
signal transduction	1
cell death	1
2-oxoglutarate-dependent dioxygenase activity	1
demethylase activity	1
catalytic activity, acting on RNA	1
cation binding	1
oxidative RNA demethylase activity	1
catalytic activity, acting on a tRNA	1
binding	1
catalytic activity	1
oxidoreductase activity	1
cytoplasm	1
intracellular membrane-bounded organelle	1
mitochondrion	1
intracellular organelle lumen	1

Protein interactions and networks

STRING

988 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ALKBH7	ALKBH1	Q13686	946
ALKBH7	ALKBH6	Q3KRA9	865
ALKBH7	JMJD4	Q9H9V9	864
ALKBH7	ALKBH4	Q9NXW9	852
ALKBH7	ALKBH8	Q96BT7	812
ALKBH7	ALKBH2	Q6NS38	751
ALKBH7	ALKBH3	Q96Q83	644
ALKBH7	ALKBH5	Q6P6C2	602
ALKBH7	FTO	Q9C0B1	550
ALKBH7	SAMD10	Q9BYL1	530
ALKBH7	AVPI1	Q5T686	474
ALKBH7	NCKIPSD	Q9NZQ3	432
ALKBH7	TRMT2B	Q96GJ1	410
ALKBH7	PIGP	P57054	391
ALKBH7	CLEC12B	Q2HXU8	370
ALKBH7	PEX39	Q5I0X4	370

IntAct

23 interactions, top by confidence:

A	B	Type	Score
NDUFS7	NDUFS8	psi-mi:“MI:0914”(association)	0.640
CENPN	ALKBH7	psi-mi:“MI:0915”(physical association)	0.560
ALKBH7	CIMIP1	psi-mi:“MI:0915”(physical association)	0.560
B9D2	ALKBH7	psi-mi:“MI:0915”(physical association)	0.560
KIAA1217	ALKBH7	psi-mi:“MI:0915”(physical association)	0.560
CFTR	ALKBH7	psi-mi:“MI:0915”(physical association)	0.370
NDUFS7		psi-mi:“MI:0914”(association)	0.350
ESR1		psi-mi:“MI:0914”(association)	0.350
ALKBH7	HIDE1	psi-mi:“MI:0914”(association)	0.350
PLAAT1	HIDE1	psi-mi:“MI:0914”(association)	0.350
ALKBH7	KIAA1217	psi-mi:“MI:0915”(physical association)	0.000
ALKBH7	CENPN	psi-mi:“MI:0915”(physical association)	0.000
ALKBH7	CIMIP1	psi-mi:“MI:0915”(physical association)	0.000
ALKBH7	B9D2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (15): ALKBH7 (Synthetic Lethality), ALKBH7 (Affinity Capture-MS), ALKBH7 (Two-hybrid), ALKBH7 (Two-hybrid), ALKBH7 (Two-hybrid), CENPN (Two-hybrid), LOXL2 (Affinity Capture-MS), C19orf38 (Affinity Capture-MS), ALKBH7 (Affinity Capture-MS), MTA2 (Affinity Capture-MS), ALKBH7 (Affinity Capture-MS), ALKBH7 (PCA), ALKBH7 (Reconstituted Complex), APP (Reconstituted Complex), ALKBH7 (Affinity Capture-MS)

ESM2 similar proteins: A0JMH0, A0JMH2, A5PK74, A5YM72, A6XGL0, B5DFG1, D3KCC4, D3ZU57, D3ZUM2, I3L5V6, O19179, O43304, O95382, P0CB42, P0DPD7, P52785, Q02846, Q13686, Q14166, Q1HG60, Q2M2S8, Q3UDE2, Q4KLM6, Q4R4T6, Q58DM4, Q5ZMM1, Q6JHU7, Q6N063, Q6NS38, Q6PDS3, Q6V0L0, Q6ZPS2, Q8N159, Q8N8M0, Q8R104, Q8R4H7, Q96SZ5, Q99611, Q99MQ3, Q9BT30

Diamond homologs: Q2M2S8, Q5UR03, Q9BT30, Q9D6Z0, Q9UT12, Q07G10, Q80Y20, Q8RWY1

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	49
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

606 predictions. Top by Δscore:

Variant	Effect	Δscore
19:6373022:GCG:G	donor_gain	1.0000
19:6374198:TGCAG:T	acceptor_loss	1.0000
19:6374200:CAGG:C	acceptor_loss	1.0000
19:6374201:A:AG	acceptor_gain	1.0000
19:6374201:AG:A	acceptor_gain	1.0000
19:6374202:G:GT	acceptor_gain	1.0000
19:6374202:GG:G	acceptor_gain	1.0000
19:6374202:GGC:G	acceptor_gain	1.0000
19:6374202:GGCC:G	acceptor_gain	1.0000
19:6374202:GGCCA:G	acceptor_gain	1.0000
19:6374373:CAAGG:C	donor_loss	1.0000
19:6374374:AAG:A	donor_loss	1.0000
19:6374377:G:GG	donor_gain	1.0000
19:6374377:GTG:G	donor_loss	1.0000
19:6374387:G:GT	donor_gain	1.0000
19:6374461:GCA:G	acceptor_loss	1.0000
19:6374463:A:AG	acceptor_gain	1.0000
19:6374463:AG:A	acceptor_loss	1.0000
19:6374464:G:GT	acceptor_gain	1.0000
19:6374464:GT:G	acceptor_gain	1.0000
19:6374464:GTT:G	acceptor_gain	1.0000
19:6374464:GTTC:G	acceptor_gain	1.0000
19:6374464:GTTCT:G	acceptor_gain	1.0000
19:6374542:G:GT	donor_gain	1.0000
19:6374542:G:T	donor_gain	1.0000
19:6374585:CTTAG:C	donor_loss	1.0000
19:6374586:T:TG	donor_gain	1.0000
19:6374586:TTAG:T	donor_loss	1.0000
19:6374587:TAG:T	donor_loss	1.0000
19:6374591:T:A	donor_loss	1.0000

AlphaMissense

1388 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:6374215:T:C	F73L	0.998
19:6374217:C:A	F73L	0.998
19:6374217:C:G	F73L	0.998
19:6374465:T:C	F127L	0.997
19:6374467:C:A	F127L	0.997
19:6374467:C:G	F127L	0.997
19:6374219:G:C	R74P	0.995
19:6374207:T:A	I70N	0.994
19:6374207:T:C	I70T	0.994
19:6374351:T:A	I118N	0.994
19:6374359:C:G	H121D	0.994
19:6373015:C:A	H65Q	0.993
19:6373015:C:G	H65Q	0.993
19:6374366:A:T	D123V	0.993
19:6373018:G:C	W66C	0.992
19:6373018:G:T	W66C	0.992
19:6374367:C:A	D123E	0.992
19:6374367:C:G	D123E	0.992
19:6374836:C:G	H177D	0.992
19:6374320:C:G	H108D	0.991
19:6374484:C:A	A133D	0.991
19:6374216:T:C	F73S	0.990
19:6374223:G:C	E75D	0.990
19:6374223:G:T	E75D	0.990
19:6374365:G:C	D123H	0.990
19:6373019:G:C	D67H	0.989
19:6373020:A:T	D67V	0.989
19:6374204:C:A	A69D	0.989
19:6374207:T:G	I70S	0.989
19:6374361:C:A	H121Q	0.989

dbSNP variants (sampled 300 via entrez): RS1000359758 (19:6374657 CT>C), RS1001502798 (19:6372623 G>A), RS1001834728 (19:6371510 AAAAC>A), RS1002106291 (19:6373048 G>T), RS1002298396 (19:6375623 G>A), RS1003109276 (19:6372132 A>G), RS1003118043 (19:6373304 G>T), RS1003460167 (19:6372382 G>A,T), RS1003516547 (19:6370830 C>A,G,T), RS1004126191 (19:6374389 C>T), RS1004517666 (19:6371036 C>T), RS1005584395 (19:6373703 G>A,C), RS1005854684 (19:6370843 G>A,C,T), RS1006380710 (19:6371062 C>A), RS1006466438 (19:6375352 C>G,T)

Disease associations

OMIM: gene MIM:613305 | 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: no

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

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, increases methylation	4
Air Pollutants	affects expression, increases abundance, decreases expression	2
Benzo(a)pyrene	affects methylation, decreases expression	2
Estradiol	decreases expression	2
Nickel	decreases expression	2
bisphenol F	decreases methylation	1
fluorene-9-bisphenol	decreases expression	1
triphenyl phosphate	affects expression	1
quercitrin	increases expression	1
arsenite	affects binding, increases reaction	1
jinfukang	affects cotreatment, increases expression	1
MT19c compound	decreases expression	1
Temozolomide	decreases expression	1
Arsenic	affects methylation	1
Cisplatin	affects cotreatment, increases expression	1
Coumestrol	decreases expression	1
Ivermectin	decreases expression	1
Lead	increases expression	1
Niclosamide	increases expression	1
Ozone	affects expression, increases abundance	1
Rotenone	decreases expression	1
Smoke	decreases expression	1
Tetrachlorodibenzodioxin	affects expression	1
Aflatoxin B1	decreases expression	1
Lactic Acid	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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