ADARB1

adenosine deaminase RNA specific B1, the group of Adenosine deaminases acting on RNA

Basic information

Region (hg38): 21:45073852-45226560

Links

ENSG00000197381 ∙ NCBI:104 ∙ OMIM:601218 ∙ HGNC:226 ∙ Uniprot:P78563 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• neurodevelopmental disorder with hypotonia, microcephaly, and seizures (Moderate), mode of inheritance: AR
• neurodevelopmental disorder with hypotonia, microcephaly, and seizures (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neurodevelopmental disorder with hypotonia, microcephaly, and seizures	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; Neurologic	32220291

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ADARB1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ADARB1 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				8	3	11
missense			26	1	1	28
nonsense						0
start loss						0
frameshift			1			1
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region			1	1		2
non coding				1		1
Total	0	0	28	10	4

Variants in ADARB1

This is a list of pathogenic ClinVar variants found in the ADARB1 region.

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

Position	Type	Phenotype	Significance	ClinVar
21-45134743-C-G			Likely benign (Nov 01, 2022)
21-45175760-G-A		Inborn genetic diseases	Uncertain significance (Jan 17, 2023)
21-45175835-G-A		Inborn genetic diseases	Uncertain significance (May 02, 2024)
21-45175840-G-C			Uncertain significance (Jun 08, 2022)
21-45175897-C-T		Neurodevelopmental disorder with hypotonia, microcephaly, and seizures	Uncertain significance (Sep 15, 2022)
21-45175934-T-G		Inborn genetic diseases	Uncertain significance (May 25, 2022)
21-45176010-C-T			Benign (Mar 29, 2018)
21-45176080-A-G		Neurodevelopmental disorder with hypotonia, microcephaly, and seizures	Pathogenic (Apr 30, 2020)
21-45176107-GAGA-G		Neurodevelopmental disorder with hypotonia, microcephaly, and seizures	Uncertain significance (Dec 14, 2022)
21-45176157-C-T			Likely benign (Feb 01, 2022)
21-45176187-C-T			Likely benign (May 01, 2023)
21-45176189-C-G		Inborn genetic diseases	Uncertain significance (Apr 07, 2021)
21-45176225-C-T		Inborn genetic diseases	Uncertain significance (Sep 12, 2023)
21-45176311-G-T		Inborn genetic diseases	Uncertain significance (Feb 12, 2024)
21-45176414-T-C		Neurodevelopmental disorder with hypotonia, microcephaly, and seizures	Uncertain significance (Dec 06, 2021)
21-45176424-C-T			Likely benign (Jul 01, 2022)
21-45176425-G-A		Inborn genetic diseases	Uncertain significance (Mar 20, 2024)
21-45176431-C-G			Uncertain significance (Feb 02, 2023)
21-45176432-G-A		Inborn genetic diseases	Uncertain significance (Apr 23, 2024)
21-45176460-C-T			Likely benign (Mar 01, 2023)
21-45176467-G-A		Inborn genetic diseases	Uncertain significance (Mar 14, 2023)
21-45176531-C-T		Inborn genetic diseases	Uncertain significance (May 23, 2023)
21-45176544-G-A			Likely benign (Apr 01, 2024)
21-45180351-C-T		Inborn genetic diseases	Uncertain significance (Mar 16, 2022)
21-45180440-A-G			Likely benign (Aug 01, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ADARB1	protein_coding	protein_coding	ENST00000539173	10	152711

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.803	0.197	125745	0	2	125747	0.00000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.52	242	453	0.535	0.0000281	4827
Missense in Polyphen		127	229.87	0.5525		2366
Synonymous	0.603	181	192	0.945	0.0000130	1535
Loss of Function	3.67	4	23.0	0.174	0.00000105	310

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000622	0.0000615
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00000879	0.00000879
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the hydrolytic deamination of adenosine to inosine in double-stranded RNA (dsRNA) referred to as A-to-I RNA editing. This may affect gene expression and function in a number of ways that include mRNA translation by changing codons and hence the amino acid sequence of proteins; pre-mRNA splicing by altering splice site recognition sequences; RNA stability by changing sequences involved in nuclease recognition; genetic stability in the case of RNA virus genomes by changing sequences during viral RNA replication; and RNA structure-dependent activities such as microRNA production or targeting or protein-RNA interactions. Can edit both viral and cellular RNAs and can edit RNAs at multiple sites (hyper-editing) or at specific sites (site-specific editing). Its cellular RNA substrates include: bladder cancer- associated protein (BLCAP), neurotransmitter receptors for glutamate (GRIA2 and GRIK2) and serotonin (HTR2C), GABA receptor (GABRA3) and potassium voltage-gated channel (KCNA1). Site- specific RNA editing of transcripts encoding these proteins results in amino acid substitutions which consequently alter their functional activities. Edits GRIA2 at both the Q/R and R/G sites efficiently but converts the adenosine in hotspot1 much less efficiently. Can exert a proviral effect towards human immunodeficiency virus type 1 (HIV-1) and enhances its replication via both an editing-dependent and editing-independent mechanism. The former involves editing of adenosines in the 5'UTR while the latter occurs via suppression of EIF2AK2/PKR activation and function. Can inhibit cell proliferation and migration and can stimulate exocytosis. {ECO:0000269|PubMed:18178553, ECO:0000269|PubMed:19908260, ECO:0000269|PubMed:21289159}.
• Pathway: Metabolism of RNA;Formation of editosomes by ADAR proteins;C6 deamination of adenosine;mRNA Editing: A to I Conversion;mRNA Editing (Consensus)

Recessive Scores

• pRec: 0.134

Intolerance Scores

• loftool: 0.0192
• rvis_EVS: -0.8
• rvis_percentile_EVS: 12.33

Haploinsufficiency Scores

• pHI: 0.282
• hipred: Y
• hipred_score: 0.728
• ghis: 0.705

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.798

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Adarb1
• Phenotype: normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); muscle phenotype; growth/size/body region phenotype

Zebrafish Information Network

• Gene name: adarb1a
• Affected structure: anterior lateral line neuromast
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: adenosine to inosine editing;RNA processing;mRNA processing;neuromuscular synaptic transmission;negative regulation of cell population proliferation;facial nerve morphogenesis;hypoglossal nerve morphogenesis;spinal cord ventral commissure morphogenesis;negative regulation of cell migration;multicellular organism growth;negative regulation of protein kinase activity by regulation of protein phosphorylation;positive regulation of viral genome replication;innate immune response;neuromuscular process controlling posture;defense response to virus;regulation of cell cycle;innervation;muscle tissue morphogenesis;motor behavior;motor neuron apoptotic process
• Cellular component: nucleus;nucleoplasm;nucleolus;cytoplasm;cytosol
• Molecular function: RNA binding;double-stranded RNA binding;double-stranded RNA adenosine deaminase activity;mRNA binding;protein binding;tRNA-specific adenosine deaminase activity;metal ion binding