AICDA

activation induced cytidine deaminase, the group of Apolipoprotein B mRNA editing enzyme catalytic subunits

Basic information

Region (hg38): 12:8602154-8613242

Links

ENSG00000111732 ∙ NCBI:57379 ∙ OMIM:605257 ∙ HGNC:13203 ∙ Uniprot:Q9GZX7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hyper-IgM syndrome type 2 (Definitive), mode of inheritance: AR
• hyper-IgM syndrome type 2 (Strong), mode of inheritance: AR
• hyper-IgM syndrome type 2 (Definitive), mode of inheritance: AR
• hyper-IgM syndrome type 2 (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Immunodeficiency with hyper-IgM, type 2	AR	Allergy/Immunology/Infectious	Individuals have elevated serum IgM levels and absent IgG, IgA, and IgE, and are thus highly susceptible to severe bacterial infections (eg, bacterial respiratory and GI infections), such that antiinfectious prophylaxis (including with IVIG, which has been reported to be effective) and early and aggressive treatment of infections may be beneficial; Individuals may also have autoimmune and inflammatory manifestions, some of which may benefit from early knowledge and interventions, including hemolytic anemia and immune thrombocytopenia	Allergy/Immunology/Infectious	11007475; 14962793; 15358621; 19575287; 21192628

ClinVar

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

• Hyper-IgM syndrome type 2 (190 variants)
• not provided (36 variants)
• not specified (8 variants)
• Hyperimmunoglobulin M syndrome (5 variants)
• Inborn genetic diseases (4 variants)
• AICDA-related condition (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the AICDA 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				22	4	26
missense	5	7	61	2		75
nonsense	4	4	2			10
start loss						0
frameshift						0
inframe indel			1			1
splice donor/acceptor (+/-2bp)		3				3
splice region			3	4	1	8
non coding			32	26	18	76
Total	9	14	96	50	22

Highest pathogenic variant AF is 0.000177

Variants in AICDA

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

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

Position	Type	Phenotype	Significance	ClinVar
12-8602350-G-A		Hyper-IgM syndrome type 2	Likely benign (Jan 12, 2018)
12-8602482-A-G		Hyper-IgM syndrome type 2	Uncertain significance (Jan 13, 2018)
12-8602580-G-A		Hyper-IgM syndrome type 2	Likely benign (Jan 12, 2018)
12-8602590-T-C		Hyper-IgM syndrome type 2	Benign (Jan 13, 2018)
12-8602600-A-G		Hyper-IgM syndrome type 2	Uncertain significance (Jan 13, 2018)
12-8602618-C-A		Hyper-IgM syndrome type 2	Benign (Jan 13, 2018)
12-8602622-G-T		Hyper-IgM syndrome type 2	Likely benign (Jan 13, 2018)
12-8602829-C-T		Hyper-IgM syndrome type 2	Uncertain significance (Jan 13, 2018)
12-8602830-T-TC		Hyperimmunoglobulin M syndrome	Uncertain significance (Jun 14, 2016)
12-8602831-T-C		Hyper-IgM syndrome type 2	Uncertain significance (Jan 12, 2018)
12-8602904-T-C		Hyper-IgM syndrome type 2	Uncertain significance (Jan 12, 2018)
12-8602971-C-G		Hyper-IgM syndrome type 2	Uncertain significance (Jan 12, 2018)
12-8602987-C-T		Hyper-IgM syndrome type 2	Benign (Jan 13, 2018)
12-8602988-G-A		Hyper-IgM syndrome type 2	Uncertain significance (Jan 13, 2018)
12-8603022-G-A		Hyper-IgM syndrome type 2	Uncertain significance (Jan 13, 2018)
12-8603058-T-G		Hyper-IgM syndrome type 2	Uncertain significance (Jan 12, 2018)
12-8603071-T-C		Hyper-IgM syndrome type 2	Uncertain significance (Jan 13, 2018)
12-8603078-G-A		Hyper-IgM syndrome type 2	Benign (Jan 13, 2018)
12-8603111-G-A		Hyper-IgM syndrome type 2	Uncertain significance (Jan 12, 2018)
12-8603145-T-C		Hyper-IgM syndrome type 2	Likely benign (Jan 12, 2018)
12-8603146-T-C		Hyper-IgM syndrome type 2	Uncertain significance (Jan 13, 2018)
12-8603147-T-C		Hyper-IgM syndrome type 2	Uncertain significance (Jan 13, 2018)
12-8603148-T-C		Hyper-IgM syndrome type 2	Uncertain significance (Jan 13, 2018)
12-8603178-T-C		Hyper-IgM syndrome type 2	Uncertain significance (Jan 12, 2018)
12-8603195-G-A		Hyper-IgM syndrome type 2	Benign (Jan 12, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
AICDA	protein_coding	protein_coding	ENST00000229335	5	10706

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000921	0.557	124773	0	22	124795	0.0000881

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.34	89	132	0.673	0.0000103	1285
Missense in Polyphen		30	54.543	0.55003		548
Synonymous	-1.23	58	47.3	1.23	0.00000325	384
Loss of Function	0.755	9	11.8	0.763	6.78e-7	117

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000125	0.000123
Ashkenazi Jewish	0.00	0.00
East Asian	0.000278	0.000278
Finnish	0.00	0.00
European (Non-Finnish)	0.0000774	0.0000706
Middle Eastern	0.000278	0.000278
South Asian	0.000172	0.000163
Other	0.000165	0.000165

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Single-stranded DNA-specific cytidine deaminase. Involved in somatic hypermutation (SHM), gene conversion, and class-switch recombination (CSR) in B-lymphocytes by deaminating C to U during transcription of Ig-variable (V) and Ig-switch (S) region DNA. Required for several crucial steps of B-cell terminal differentiation necessary for efficient antibody responses (PubMed:18722174, PubMed:21385873, PubMed:21518874, PubMed:27716525). May also play a role in the epigenetic regulation of gene expression by participating in DNA demethylation (PubMed:21496894). {ECO:0000269|PubMed:18722174, ECO:0000269|PubMed:21385873, ECO:0000269|PubMed:21496894, ECO:0000269|PubMed:21518874, ECO:0000269|PubMed:27716525}.
• Disease: DISEASE: Immunodeficiency with hyper-IgM 2 (HIGM2) [MIM:605258]: A rare immunodeficiency syndrome characterized by normal or elevated serum IgM levels with absence of IgG, IgA, and IgE. It results in a profound susceptibility to bacterial infections. {ECO:0000269|PubMed:11007475, ECO:0000269|PubMed:14962793, ECO:0000269|PubMed:23803409, ECO:0000269|PubMed:26545377, ECO:0000269|PubMed:27716525}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Primary immunodeficiency - Homo sapiens (human);Intestinal immune network for IgA production - Homo sapiens (human);Pyrimidine nucleotides nucleosides metabolism;IL4-mediated signaling events (Consensus)

Recessive Scores

• pRec: 0.442

Intolerance Scores

• loftool: 0.491
• rvis_EVS: 0.04
• rvis_percentile_EVS: 56.92

Haploinsufficiency Scores

• pHI: 0.137
• hipred: Y
• hipred_score: 0.518

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.964

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Aicda
• Phenotype: hematopoietic system 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); normal phenotype; neoplasm; digestive/alimentary phenotype; immune system phenotype; cellular phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan)

Gene ontology

• Biological process: mRNA processing;cytidine deamination;negative regulation of transposition;somatic diversification of immunoglobulins;somatic hypermutation of immunoglobulin genes;cytidine to uridine editing;B cell differentiation;regulation of nuclear cell cycle DNA replication;defense response to bacterium;isotype switching;negative regulation of single stranded viral RNA replication via double stranded DNA intermediate;defense response to virus;DNA cytosine deamination;cellular response to lipopolysaccharide;DNA demethylation;negative regulation of methylation-dependent chromatin silencing
• Cellular component: exosome (RNase complex);P-body;nucleus;cytoplasm
• Molecular function: RNA binding;cytidine deaminase activity;protein binding;zinc ion binding;ubiquitin protein ligase binding;identical protein binding