ALKBH8

alkB homolog 8, tRNA methyltransferase, the group of 7BS DNA/RNA methyltransferases|RNA binding motif containing|Alkylation repair homologs

Basic information

Region (hg38): 11:107502727-107565742

Links

ENSG00000137760 ∙ NCBI:91801 ∙ OMIM:613306 ∙ HGNC:25189 ∙ Uniprot:Q96BT7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intellectual developmental disorder, autosomal recessive 71 (Limited), mode of inheritance: AR
• intellectual developmental disorder, autosomal recessive 71 (Strong), mode of inheritance: AR
• autosomal recessive non-syndromic intellectual disability (Supportive), mode of inheritance: AR
• intellectual developmental disorder, autosomal recessive 71 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder, autosomal recessive 71	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Genitourinary; Musculoskeletal; Neurologic	31079898

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ALKBH8 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ALKBH8 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				7	2	9
missense			45	8	6	59
nonsense		2	1			3
start loss						0
frameshift		1	1			2
inframe indel		1				1
splice donor/acceptor (+/-2bp)			1			1
splice region				1	2	3
non coding				1	3	4
Total	0	4	48	16	11

Variants in ALKBH8

This is a list of pathogenic ClinVar variants found in the ALKBH8 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
11-107504685-G-C		Intellectual developmental disorder, autosomal recessive 71	Uncertain significance (Jul 17, 2023)
11-107504687-T-G			Uncertain significance (Apr 27, 2022)
11-107504693-G-A			Uncertain significance (Jan 06, 2021)
11-107504696-C-A		ALKBH8-related disorder	Benign (Oct 30, 2019)
11-107504761-C-T		ALKBH8-related disorder • Intellectual developmental disorder, autosomal recessive 71	Uncertain significance (Mar 25, 2024)
11-107504779-C-T		Intellectual developmental disorder, autosomal recessive 71	Uncertain significance (Mar 17, 2024)
11-107504794-C-A		not specified	Uncertain significance (Feb 17, 2023)
11-107504819-C-A		ALKBH8-related disorder	Benign (Nov 13, 2019)
11-107504833-G-C		Intellectual developmental disorder, autosomal recessive 71	Benign/Likely benign (Apr 06, 2022)
11-107504867-AG-A		Intellectual developmental disorder, autosomal recessive 71	Pathogenic (Sep 22, 2024)
11-107504941-C-T		ALKBH8-related disorder	Benign (Jan 02, 2020)
11-107504944-G-A		not specified	Uncertain significance (Apr 11, 2023)
11-107504953-C-T		ALKBH8-related disorder	Likely benign (Feb 01, 2024)
11-107504960-C-T		not specified	Uncertain significance (Feb 17, 2023)
11-107504975-T-C			Uncertain significance (Apr 10, 2023)
11-107504977-C-T		ALKBH8-related disorder	Likely benign (Jun 17, 2022)
11-107504977-CG-C		Intellectual developmental disorder, autosomal recessive 71	Pathogenic (Oct 13, 2022)
11-107504978-G-A			Uncertain significance (Feb 22, 2024)
11-107505002-G-A		Intellectual developmental disorder, autosomal recessive 71	Conflicting classifications of pathogenicity (Mar 14, 2024)
11-107505007-C-T		not specified	Uncertain significance (Feb 09, 2023)
11-107505056-T-C		not specified	Uncertain significance (Oct 02, 2023)
11-107505063-C-T			Likely benign (Aug 01, 2024)
11-107505101-G-A		ALKBH8-related disorder • not specified	Uncertain significance (Aug 17, 2021)
11-107505211-C-T		Intellectual developmental disorder, autosomal recessive 71 • not specified	Uncertain significance (Jan 04, 2022)
11-107510892-T-C		ALKBH8-related disorder	Likely benign (Jun 01, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ALKBH8	protein_coding	protein_coding	ENST00000428149	11	63021

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000204	0.999	125713	0	13	125726	0.0000517

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.854	290	334	0.869	0.0000169	4363
Missense in Polyphen		109	131.53	0.8287		1740
Synonymous	0.708	107	117	0.917	0.00000593	1226
Loss of Function	2.90	11	27.3	0.402	0.00000129	397

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000305	0.000305
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000180	0.0000176
Middle Eastern	0.00	0.00
South Asian	0.0000993	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: 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 (PubMed:20123966, PubMed:20308323). Catalyzes the last step in the formation of 5-methylcarboxymethyl uridine at the wobble position of the anticodon loop in target tRNA (PubMed:20123966, PubMed:20308323). Has a preference for tRNA(Arg) and tRNA(Glu), and does not bind tRNA(Lys)(PubMed:20308323). 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) (PubMed:21285950). Required for normal survival after DNA damage (PubMed:20308323). May inhibit apoptosis and promote cell survival and angiogenesis (PubMed:19293182). {ECO:0000269|PubMed:19293182, ECO:0000269|PubMed:20123966, ECO:0000269|PubMed:20308323, ECO:0000269|PubMed:21285950}.
• Pathway: tRNA modification in the nucleus and cytosol;tRNA processing;Metabolism of RNA (Consensus)

Intolerance Scores

• loftool: 0.873
• rvis_EVS: 1.24
• rvis_percentile_EVS: 93.42

Haploinsufficiency Scores

• pHI: 0.407
• hipred: N
• hipred_score: 0.197
• ghis: 0.438

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: H
• gene_indispensability_pred: N
• gene_indispensability_score: 0.146

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Alkbh8
• Phenotype: normal phenotype

Gene ontology

• Biological process: tRNA wobble uridine modification;cellular response to DNA damage stimulus;tRNA methylation;oxidation-reduction process
• Cellular component: nucleus;nucleoplasm;cytoplasm;cytosol;nuclear body
• Molecular function: tRNA binding;iron ion binding;protein binding;zinc ion binding;tRNA (uracil) methyltransferase activity;2-oxoglutarate-dependent dioxygenase activity