ALKBH8

Summary

ALKBH8 (alkB homolog 8, tRNA methyltransferase, HGNC:25189) is a protein-coding gene on chromosome 11q22.3, encoding tRNA (carboxymethyluridine(34)-5-O)-methyltransferase ALKBH8 (Q96BT7). Catalyzes the methylation of 5-carboxymethyl uridine to 5-methylcarboxymethyl uridine at the wobble position of the anticodon loop in tRNA via its methyltransferase domain.

Enables tRNA (uridine) methyltransferase activity; tRNA binding activity; and zinc ion binding activity. Involved in DNA damage response; tRNA methylation; and tRNA wobble uridine modification. Located in cytosol and nucleoplasm. Implicated in autosomal recessive intellectual developmental disorder 71.

Source: NCBI Gene 91801 — RefSeq curated summary.

At a glance

• Gene–disease (curated): intellectual developmental disorder, autosomal recessive 71 (Definitive, GenCC) — +1 more curated relationship
• GWAS associations: 3
• Clinical variants (ClinVar): 165 total — 2 pathogenic, 5 likely-pathogenic
• Phenotypes (HPO): 18
• MANE Select transcript: NM_138775

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25189
Approved symbol	ALKBH8
Name	alkB homolog 8, tRNA methyltransferase
Location	11q22.3
Locus type	gene with protein product
Status	Approved
Aliases	MGC10235, TRM9, TRMT9A
Ensembl gene	ENSG00000137760
Ensembl biotype	protein_coding
OMIM	613306
Entrez	91801

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 9 protein_coding, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000260318, ENST00000389568, ENST00000393100, ENST00000417449, ENST00000428149, ENST00000429370, ENST00000530933, ENST00000898307, ENST00000898308, ENST00000898309, ENST00000943732, ENST00000943733

RefSeq mRNA: 3 — MANE Select: NM_138775 NM_001301010, NM_001378133, NM_138775

CCDS: CCDS8337

Canonical transcript exons

ENST00000428149 — 12 exons

Exon	Start	End
ENSE00000930433	107553847	107553978
ENSE00001611673	107522299	107522555
ENSE00001634419	107510887	107511036
ENSE00001637779	107502727	107505215
ENSE00001742813	107565601	107565735
ENSE00003496144	107556766	107557003
ENSE00003499830	107532300	107532406
ENSE00003539749	107551808	107551912
ENSE00003625239	107525441	107525592
ENSE00003647741	107560765	107560899
ENSE00003685485	107553108	107553203
ENSE00003692677	107549753	107549823

Expression profiles

Bgee: expression breadth ubiquitous, 226 present calls, max score 84.87.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3.6468 / max 129.1825, expressed in 1423 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
122117	3.6468	1423

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	84.87	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.19	gold quality
cortical plate	UBERON:0005343	83.24	gold quality
oviduct epithelium	UBERON:0004804	83.16	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.02	gold quality
muscle of leg	UBERON:0001383	78.45	gold quality
ventricular zone	UBERON:0003053	78.40	gold quality
gastrocnemius	UBERON:0001388	78.14	gold quality
ganglionic eminence	UBERON:0004023	78.08	gold quality
islet of Langerhans	UBERON:0000006	76.84	gold quality
skeletal muscle organ	UBERON:0014892	76.58	gold quality
hindlimb stylopod muscle	UBERON:0004252	76.19	gold quality
stromal cell of endometrium	CL:0002255	76.18	gold quality
smooth muscle tissue	UBERON:0001135	76.18	gold quality
tendon	UBERON:0000043	76.09	gold quality
lymph node	UBERON:0000029	75.97	gold quality
leukocyte	CL:0000738	75.92	gold quality
monocyte	CL:0000576	75.77	gold quality
buccal mucosa cell	CL:0002336	75.71	silver quality
colonic epithelium	UBERON:0000397	75.29	gold quality
descending thoracic aorta	UBERON:0002345	75.07	gold quality
popliteal artery	UBERON:0002250	74.72	gold quality
tibial artery	UBERON:0007610	74.72	gold quality
fallopian tube	UBERON:0003889	74.39	gold quality
saphenous vein	UBERON:0007318	74.26	gold quality
rectum	UBERON:0001052	74.25	gold quality
epithelial cell of pancreas	CL:0000083	74.19	silver quality
aorta	UBERON:0000947	74.09	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	74.06	silver quality
right coronary artery	UBERON:0001625	74.01	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.81

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

84 targeting ALKBH8, 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-98-3P	100.00	74.08	3907
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-498-3P	99.91	71.27	1114
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-MIR-579-3P	99.86	71.66	3628
HSA-LET-7G-3P	99.85	70.43	1929

Literature-anchored findings (GeneRIF, showing 11)

• Findings indicate a role for ALKBH8 in urothelial carcinoma cell survival mediated by NOX-1-dependent ROS signals, further suggesting therapeutic strategies in human bladder cancer by inducing JNK/p38/gammaH2AX-mediated cell death by silencing of ALKBH8. (PMID:19293182)
• The methyltransferase domain of ALKBH8 is demonstrated to be a functional homologue of the Saccharomyces cerevisiae Trm9 protein, mediating the last step in the formation of the wobble uridine modification 5-methoxycarbonylmethyl-uridine in tRNA. This modification is shown to be important for efficient selenoprotein synthesis. ALKBH8 knock-out mice are generated and described. (PMID:20123966)
• Data show that human AlkB homolog 8 (ABH8) catalyzes tRNA methylation to generate 5-methylcarboxymethyl uridine (mcm(5)U) at the wobble position of certain tRNAs, a critical anticodon loop modification linked to DNA damage survival. (PMID:20308323)
• Many eukaryotic tRNAs contain the wobble modification 5-methoxycarbonylmethyl-uridine (mcm5U). It is demonstrated that (R)- and (S)-5-methoxycarbonylhydroxymethyluridine (mchm5U), hydroxylated forms of mcm(5)U, are present in mammalian tRNA-Arg(UCG), and tRNA-Gly(UCC), respectively. It is shown that the hydroxylation reaction leading to the formation of (S)-mchm5U is catalyzed by the oxygenase (AlkB) domain of ALKBH8. (PMID:21285950)
• findings suggest that the high expression of ALKBH8 is critical for the growth and progression of bladder cancer (PMID:27329810)
• Recessive Truncating Mutations in ALKBH8 Cause Intellectual Disability and Severe Impairment of Wobble Uridine Modification. (PMID:31079898)
• Loss of epitranscriptomic control of selenocysteine utilization engages senescence and mitochondrial reprogramming(). (PMID:31765888)
• Neurodevelopmental disorder in an Egyptian family with a biallelic ALKBH8 variant. (PMID:33544954)
• Insight into ALKBH8-related intellectual developmental disability based on the first pathogenic missense variant. (PMID:34757492)
• HITS-CLIP analysis of human ALKBH8 reveals interactions with fully processed substrate tRNAs and with specific noncoding RNAs. (PMID:36192131)
• The first Turkish family with a novel biallelic missense variant of the ALKBH8 gene: A study on the clinical and variant spectrum of ALKBH8-related intellectual developmental disorders. (PMID:38189198)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	alkbh8	ENSDARG00000060256
mus_musculus	Alkbh8	ENSMUSG00000025899
rattus_norvegicus	Alkbh8	ENSRNOG00000024525
drosophila_melanogaster	CG17807	FBGN0034748
caenorhabditis_elegans		WBGENE00007581

Paralogs (2): ALKBH6 (ENSG00000239382), TRMT9B (ENSG00000250305)

Protein

Protein identifiers

tRNA (carboxymethyluridine(34)-5-O)-methyltransferase ALKBH8 — Q96BT7 (reviewed: Q96BT7)

Alternative names: Alkylated DNA repair protein alkB homolog 8, Alpha-ketoglutarate-dependent dioxygenase ALKBH8, S-adenosyl-L-methionine-dependent tRNA methyltransferase ALKBH8

All UniProt accessions (2): Q96BT7, C9JQN2

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the methylation of 5-carboxymethyl uridine to 5-methylcarboxymethyl uridine at the wobble position of the anticodon loop in tRNA via its methyltransferase domain. Catalyzes the last step in the formation of 5-methylcarboxymethyl uridine at the wobble position of the anticodon loop in target tRNA. Has a preference for tRNA(Arg) and tRNA(Glu), and does not bind tRNA(Lys). Binds tRNA and catalyzes the iron and alpha-ketoglutarate dependent hydroxylation of 5-methylcarboxymethyl uridine at the wobble position of the anticodon loop in tRNA via its dioxygenase domain, giving rise to 5-(S)-methoxycarbonylhydroxymethyluridine; has a preference for tRNA(Gly). Required for normal survival after DNA damage. May inhibit apoptosis and promote cell survival and angiogenesis.

Subunit / interactions. Interacts with TRMT112.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Widely expressed, with highest expression in spleen, followed by pancreas and lung.

Disease relevance. Intellectual developmental disorder, autosomal recessive 71 (MRT71) [MIM:618504] A form of intellectual disability, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRT71 features include impaired intellectual development, global developmental delay, mildly delayed walking, poor language, seizures in the first years of life, and behavioral abnormalities. The disease is caused by variants affecting the gene represented in this entry.

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

Induction. Up-regulated after DNA damage. Induction is mediated via ATM.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. May be due to competing donor splice site.

Similarity. Belongs to the alkB family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q96BT7-1	1	yes
Q96BT7-2	2
Q96BT7-3	3
Q96BT7-4	4

RefSeq proteins (3): NP_001287939, NP_001365062, NP_620130* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000504	RRM_dom	Domain
IPR005123	Oxoglu/Fe-dep_dioxygenase_dom	Domain
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR013216	Methyltransf_11	Domain
IPR015095	AlkB_hom8_N	Domain
IPR027450	AlkB-like	Domain
IPR029063	SAM-dependent_MTases_sf	Homologous_superfamily
IPR034256	ALKBH8_RRM	Domain
IPR035979	RBD_domain_sf	Homologous_superfamily
IPR051422	AlkB_tRNA_MeTrf/Diox	Family

Pfam: PF00076, PF08241, PF09004, PF13532

Enzyme classification (BRENDA):

• EC 2.1.1.229 — tRNA (carboxymethyluridine34-5-O)-methyltransferase (BRENDA: 5 organisms, 36 substrates, 0 inhibitors, 0 Km, 0 kcat entries)

Catalyzed reactions (Rhea), 1 shown:

• 5-(carboxymethyl)uridine(34) in tRNA + S-adenosyl-L-methionine = 5-(2-methoxy-2-oxoethyl)uridine(34) in tRNA + S-adenosyl-L-homocysteine (RHEA:43208)

UniProt features (57 total): strand 23, binding site 10, helix 6, splice variant 5, turn 5, domain 2, region of interest 2, chain 1, sequence variant 1, sequence conflict 1, compositionally biased region 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
3THT	X-RAY DIFFRACTION	3.01
3THP	X-RAY DIFFRACTION	3.2
2CQ2	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96BT7-F1	80.91	0.52

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 (10): 292; 328; 334; 341; 343; 349; 227–229; 238; 240; 242

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-6782315	tRNA modification in the nucleus and cytosol
R-HSA-72306	tRNA processing
R-HSA-8953854	Metabolism of RNA

MSigDB gene sets: 149 (showing top): GGTGTGT_MIR329, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_PAIRED_DONORS_WITH_INCORPORATION_OR_REDUCTION_OF_MOLECULAR_OXYGEN, chr11q22, GOBP_TRNA_METABOLIC_PROCESS, GOBP_RNA_METHYLATION, GOBP_RNA_MODIFICATION, BRN2_01, GOBP_TRNA_METHYLATION, GOBP_DNA_DAMAGE_RESPONSE, TTGGAGA_MIR5155P_MIR519E, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, GOBP_METHYLATION, GOBP_TRNA_PROCESSING, REACTOME_METABOLISM_OF_RNA, GOBP_TRNA_MODIFICATION

GO Biological Process (5): tRNA wobble uridine modification (GO:0002098), DNA damage response (GO:0006974), tRNA methylation (GO:0030488), methylation (GO:0032259), demethylation (GO:0070988)

GO Molecular Function (15): tRNA binding (GO:0000049), iron ion binding (GO:0005506), zinc ion binding (GO:0008270), S-adenosylmethionine-dependent methyltransferase activity (GO:0008757), tRNA (uridine) methyltransferase activity (GO:0016300), 2-oxoglutarate-dependent dioxygenase activity (GO:0016706), tRNA (5-carboxymethyluridine(34)-5-O)-methyltransferase activity (GO:0106335), nucleic acid binding (GO:0003676), RNA binding (GO:0003723), catalytic activity (GO:0003824), protein binding (GO:0005515), methyltransferase activity (GO:0008168), transferase activity (GO:0016740), metal ion binding (GO:0046872), transition metal ion binding (GO:0046914)

GO Cellular Component (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
tRNA processing	1
Metabolism of RNA	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
metabolic process	2
transition metal ion binding	2
binding	2
tRNA wobble base modification	1
cellular response to stress	1
RNA methylation	1
tRNA modification	1
RNA binding	1
methyltransferase activity	1
tRNA methyltransferase activity	1
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen	1
dioxygenase activity	1
tRNA (uridine) methyltransferase activity	1
nucleic acid binding	1
molecular_function	1
transferase activity, transferring one-carbon groups	1
catalytic activity	1
cation binding	1
metal ion binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

998 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ALKBH8	TRMT112	Q9UI30	988
ALKBH8	ALKBH1	Q13686	950
ALKBH8	ALKBH2	Q6NS38	832
ALKBH8	ALKBH7	Q9BT30	812
ALKBH8	ALKBH3	Q96Q83	765
ALKBH8	ALKBH4	Q9NXW9	755
ALKBH8	FTO	Q9C0B1	742
ALKBH8	BUD23	O43709	737
ALKBH8	ELP3	Q9H9T3	736
ALKBH8	TRMT11	Q7Z4G4	736
ALKBH8	CTU1	Q7Z7A3	703
ALKBH8	HEMK2	Q9Y5N5	696
ALKBH8	ALKBH5	Q6P6C2	685
ALKBH8	NOX1	Q9Y5S8	655
ALKBH8	ELP6	Q0PNE2	643

IntAct

13 interactions, top by confidence:

A	B	Type	Score
TRMT112	BUD23	psi-mi:“MI:0914”(association)	0.910
TRMT112	ALKBH8	psi-mi:“MI:0915”(physical association)	0.790
ALKBH8	TRMT112	psi-mi:“MI:0915”(physical association)	0.790
ALKBH8	TRMT112	psi-mi:“MI:0403”(colocalization)	0.790
ALKBH8	HSP90AA1	psi-mi:“MI:0914”(association)	0.350
ALKBH8	TCP1	psi-mi:“MI:0914”(association)	0.350
CCNB1	TARS3	psi-mi:“MI:0914”(association)	0.350

BioGRID (9): ALKBH8 (Reconstituted Complex), ALKBH8 (Affinity Capture-MS), ALKBH8 (Synthetic Lethality), ALKBH8 (Two-hybrid), MFAP1 (Two-hybrid), ALKBH8 (Proximity Label-MS), ALKBH8 (Positive Genetic), ALKBH8 (Co-fractionation), ALKBH8 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A0A0R4IB93, A0JMU5, A1A4L5, A2PYH4, A2RUV5, B3M1E1, B3P4N5, B4GZ20, B4HJC0, B4KA23, B4LVS8, B4NKI9, B4PVH6, B4QVW6, B6DMK2, D3Z4R1, O75417, O93530, O94830, Q07G10, Q0P5B2, Q15326, Q28ES8, Q29B63, Q4KLT3, Q4R6F3, Q5M8E6, Q5ZIJ9, Q5ZJM3, Q6GQ76, Q6NRS1, Q6NTR1, Q6P1Q9, Q6ZPR6, Q7ZU90, Q80Y20, Q84MA1, Q8BMK1, Q8BYH3, Q8MNT9

Diamond homologs: A1A4L5, C4V9L5, P49957, Q07G10, Q08DH3, Q10224, Q55DA6, Q80WQ4, Q80Y20, Q8RWY1, Q8STN5, Q94A09, Q95K79, Q96BT7, Q9P272, Q1GC56, Q491V7, Q5UR03, Q9UT12, A0A075D654, A0A075D6M1, A0A0L1JF88, A0A8X8M501, C4LL93, E0D208, Q39227, Q8KZ94, O43709, P25627, P36571, Q10162, Q58DP0, Q7CH67, Q9CY21, Q9LVD0, C8YTM5, Q3ED65, Q72HI4, Q81ZZ8, B3PI89

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
ALKBH8	“form complex”	“ALKBH8-TRM112 methyltransferase complex”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	5
Uncertain significance	114
Likely benign	23
Benign	12

Top pathogenic / likely-pathogenic (7)

Variant ID	HGVS	Classification
1710313	NM_138775.3(ALKBH8):c.1675del (p.Arg559fs)	Pathogenic
636272	NM_138775.3(ALKBH8):c.1785del (p.Trp596fs)	Pathogenic
1012995	NM_138775.3(ALKBH8):c.960_964del (p.Leu320fs)	Likely pathogenic
1320146	NM_138775.3(ALKBH8):c.1421_1429del (p.His474_Ala477delinsPro)	Likely pathogenic
3065394	NM_138775.3(ALKBH8):c.1182G>A (p.Trp394Ter)	Likely pathogenic
3777077	NM_138775.3(ALKBH8):c.1512G>A (p.Trp504Ter)	Likely pathogenic
4537898	NM_138775.3(ALKBH8):c.878+1G>T	Likely pathogenic

SpliceAI

1926 predictions. Top by Δscore:

Variant	Effect	Δscore
11:107505211:CGCTC:C	acceptor_gain	1.0000
11:107505215:CCTAA:C	acceptor_gain	1.0000
11:107505216:C:CC	acceptor_gain	1.0000
11:107505219:A:C	acceptor_gain	1.0000
11:107510881:ACTT:A	donor_loss	1.0000
11:107510882:CT:C	donor_loss	1.0000
11:107510882:CTTA:C	donor_gain	1.0000
11:107510883:TTA:T	donor_loss	1.0000
11:107510884:TA:T	donor_loss	1.0000
11:107510885:A:AC	donor_gain	1.0000
11:107510885:A:C	donor_loss	1.0000
11:107510885:ACTG:A	donor_gain	1.0000
11:107510886:C:CT	donor_gain	1.0000
11:107510886:CT:C	donor_gain	1.0000
11:107510886:CTG:C	donor_gain	1.0000
11:107510886:CTGC:C	donor_gain	1.0000
11:107510886:CTGCT:C	donor_gain	1.0000
11:107522332:T:A	donor_gain	1.0000
11:107525439:A:AC	donor_gain	1.0000
11:107525440:C:CC	donor_gain	1.0000
11:107525440:CT:C	donor_gain	1.0000
11:107525440:CTA:C	donor_gain	1.0000
11:107525440:CTACA:C	donor_gain	1.0000
11:107525468:T:A	donor_gain	1.0000
11:107525593:C:CC	acceptor_gain	1.0000
11:107551803:CTCA:C	donor_loss	1.0000
11:107551804:TCACC:T	donor_loss	1.0000
11:107551805:CAC:C	donor_loss	1.0000
11:107551806:A:AC	donor_gain	1.0000
11:107551806:AC:A	donor_gain	1.0000

AlphaMissense

4398 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:107505143:A:G	W504R	0.998
11:107505143:A:T	W504R	0.998
11:107525470:C:A	R334M	0.998
11:107525470:C:G	R334T	0.998
11:107553154:G:C	F183L	0.998
11:107553154:G:T	F183L	0.998
11:107553156:A:G	F183L	0.998
11:107505141:C:A	W504C	0.997
11:107505141:C:G	W504C	0.997
11:107522428:G:C	F386L	0.997
11:107522428:G:T	F386L	0.997
11:107522430:A:G	F386L	0.997
11:107553181:T:A	R174S	0.997
11:107553181:T:G	R174S	0.997
11:107553182:C:G	R174T	0.997
11:107510904:G:C	H474D	0.996
11:107525469:C:A	R334S	0.996
11:107525469:C:G	R334S	0.996
11:107549765:A:C	S253R	0.996
11:107549765:A:T	S253R	0.996
11:107549767:T:G	S253R	0.996
11:107532310:A:G	W290R	0.995
11:107532310:A:T	W290R	0.995
11:107532317:T:A	R287S	0.995
11:107532317:T:G	R287S	0.995
11:107551823:A:G	Y229H	0.995
11:107553155:A:G	F183S	0.995
11:107504872:A:T	V594D	0.994
11:107510901:G:C	H475D	0.994
11:107522406:A:G	W394R	0.994

dbSNP variants (sampled 300 via entrez): RS1000090017 (11:107547123 A>G), RS1000153557 (11:107516098 G>A), RS1000168355 (11:107559140 T>C), RS1000231807 (11:107516177 A>G), RS1000277245 (11:107506772 G>A), RS1000287882 (11:107509285 C>T), RS1000408018 (11:107512845 G>T), RS1000430688 (11:107559734 A>G), RS1000509327 (11:107562652 C>G), RS1000540045 (11:107556171 A>G), RS1000566598 (11:107512456 G>C), RS1000585451 (11:107543519 G>A), RS1000605751 (11:107562338 G>A), RS1000615276 (11:107566622 C>T), RS1000765314 (11:107528827 C>T)

Disease associations

OMIM: gene MIM:613306 | disease phenotypes: MIM:618504

GenCC curated gene-disease

Disease	Classification	Inheritance
intellectual developmental disorder, autosomal recessive 71	Definitive	Autosomal recessive
autosomal recessive non-syndromic intellectual disability	Supportive	Autosomal recessive

Mondo (2): intellectual developmental disorder, autosomal recessive 71 (MONDO:0032789), autosomal recessive non-syndromic intellectual disability (MONDO:0019502)

Orphanet (0):

HPO phenotypes

18 total (18 of 18 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000054	Micropenis
HP:0000122	Unilateral renal agenesis
HP:0000256	Macrocephaly
HP:0000276	Long face
HP:0000400	Macrotia
HP:0000490	Deeply set eye
HP:0000733	Motor stereotypy
HP:0001090	Abnormally large globe
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001263	Global developmental delay
HP:0001629	Ventricular septal defect
HP:0004392	Prune belly
HP:0007018	Attention deficit hyperactivity disorder
HP:0011094	Increased overbite
HP:0034454	Arachnoid granulation

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST002288_5	Large artery stroke	6.000000e-08
GCST007676_13	3-month functional outcome in ischaemic stroke (modified Rankin score)	4.000000e-06
GCST010396_188	Gut microbiota (bacterial taxa, hurdle binary method)	3.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0009603	stroke outcome severity measurement
EFO:0007874	gut microbiome measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
(+)-JQ1 compound	decreases expression	7
Valproic Acid	affects cotreatment, increases expression	4
bisphenol S	decreases methylation, increases expression	2
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, decreases expression	2
Arsenic	affects methylation, increases abundance, increases expression	2
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
bisphenol A	increases methylation	1
methylparaben	decreases expression	1
sodium arsenite	increases abundance, increases expression	1
butyraldehyde	increases expression	1
potassium chromate(VI)	increases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
cylindrospermopsin	increases expression	1
perfluoro-n-nonanoic acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
dorsomorphin	affects cotreatment, increases expression	1
2,3,5-trichloro-6-phenyl-(1,4)benzoquinone	increases expression	1
Acetaminophen	decreases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Benzo(a)pyrene	decreases methylation	1
Estradiol	increases expression	1
Fluorouracil	decreases expression	1
Ozone	affects cotreatment, increases oxidation, increases abundance	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	decreases expression	1
Urethane	decreases expression	1
Aflatoxin B1	decreases methylation	1
Cadmium Chloride	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E1QB	HAP1 ALKBH8 (-) 2	Cancer cell line	Male
CVCL_XL30	HAP1 ALKBH8 (-) 1	Cancer cell line	Male

Clinical trials (associated diseases)

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