ALKBH3

alkB homolog 3, alpha-ketoglutarate dependent dioxygenase, the group of Alkylation repair homologs

Basic information

Region (hg38): 11:43880810-43920274

Links

ENSG00000166199 ∙ NCBI:221120 ∙ OMIM:610603 ∙ HGNC:30141 ∙ Uniprot:Q96Q83 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ALKBH3 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ALKBH3 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						0
missense			18			18
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	18	0	0

Variants in ALKBH3

This is a list of pathogenic ClinVar variants found in the ALKBH3 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-43882695-G-A		not specified	Uncertain significance (Aug 28, 2023)
11-43883134-G-T		not specified	Uncertain significance (Oct 13, 2023)
11-43883150-C-T		not specified	Uncertain significance (May 17, 2023)
11-43884008-G-A		not specified	Uncertain significance (Jun 21, 2023)
11-43884014-T-C		not specified	Uncertain significance (Aug 17, 2021)
11-43886611-A-G		not specified	Uncertain significance (Oct 05, 2023)
11-43889748-T-C		not specified	Uncertain significance (Apr 09, 2024)
11-43889765-G-A		not specified	Uncertain significance (Mar 01, 2023)
11-43892070-G-T		not specified	Uncertain significance (Jan 10, 2022)
11-43892091-T-C		not specified	Uncertain significance (Apr 14, 2022)
11-43892114-G-A		not specified	Uncertain significance (May 11, 2022)
11-43901516-T-G		not specified	Uncertain significance (Aug 02, 2022)
11-43901537-C-G		not specified	Uncertain significance (Oct 05, 2023)
11-43901545-C-A		not specified	Uncertain significance (Feb 02, 2024)
11-43901549-A-G		not specified	Uncertain significance (Oct 22, 2021)
11-43901565-G-A		not specified	Uncertain significance (Sep 20, 2023)
11-43901601-G-T		not specified	Uncertain significance (Jan 26, 2022)
11-43901604-A-G		not specified	Uncertain significance (Dec 20, 2023)
11-43901696-A-C		not specified	Uncertain significance (Mar 28, 2024)
11-43919068-A-G		not specified	Uncertain significance (Aug 30, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ALKBH3	protein_coding	protein_coding	ENST00000302708	9	39456

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.74e-12	0.0756	125350	0	398	125748	0.00158

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0845	160	163	0.981	0.00000876	1857
Missense in Polyphen		66	67.352	0.97993		783
Synonymous	-0.00298	53	53.0	1.00	0.00000259	539
Loss of Function	0.414	19	21.1	0.903	0.00000132	209

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00175	0.00174
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.000381	0.000381
Finnish	0.000970	0.000971
European (Non-Finnish)	0.00274	0.00273
Middle Eastern	0.000381	0.000381
South Asian	0.000329	0.000327
Other	0.00147	0.00147

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Dioxygenase that mediates demethylation of DNA and RNA containing 1-methyladenosine (m1A) (PubMed:12486230, PubMed:12594517, PubMed:16174769, PubMed:26863196, PubMed:26863410). Repairs alkylated DNA containing 1- methyladenosine (m1A) and 3-methylcytosine (m3C) by oxidative demethylation (PubMed:12486230, PubMed:12594517, PubMed:16174769, PubMed:25944111). Has a strong preference for single-stranded DNA (PubMed:12486230, PubMed:12594517, PubMed:16174769). 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 (PubMed:22055184). Also acts on RNA (PubMed:12594517, PubMed:16174769, PubMed:26863196, PubMed:26863410, PubMed:16858410). 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 (PubMed:26863196, PubMed:26863410). Requires molecular oxygen, alpha-ketoglutarate and iron (PubMed:22055184, PubMed:16858410). {ECO:0000269|PubMed:12486230, ECO:0000269|PubMed:12594517, ECO:0000269|PubMed:16174769, ECO:0000269|PubMed:16858410, ECO:0000269|PubMed:22055184, ECO:0000269|PubMed:25944111, ECO:0000269|PubMed:26863196, ECO:0000269|PubMed:26863410}.
• Pathway: DNA Repair;ALKBH3 mediated reversal of alkylation damage;Reversal of alkylation damage by DNA dioxygenases;DNA Damage Reversal (Consensus)

Recessive Scores

• pRec: 0.139

Intolerance Scores

• loftool: 0.885
• rvis_EVS: 0.4
• rvis_percentile_EVS: 76.31

Haploinsufficiency Scores

• pHI: 0.149
• hipred: N
• hipred_score: 0.292
• ghis: 0.515

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.551

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Alkbh3
• Phenotype: cellular phenotype; homeostasis/metabolism phenotype; normal phenotype

Gene ontology

• Biological process: DNA repair;DNA dealkylation involved in DNA repair;cell population proliferation;oxidative single-stranded DNA demethylation;oxidative single-stranded RNA demethylation
• Cellular component: nucleus;nucleoplasm;mitochondrion;cytosol
• Molecular function: protein binding;ferrous iron binding;L-ascorbic acid binding;DNA-N1-methyladenine dioxygenase activity;cytosine C-5 DNA demethylase activity;RNA N1-methyladenosine dioxygenase activity