AICDA

Chr 12AR

activation induced cytidine deaminase

Also known as: AID, ARP2, CDA2, HEL-S-284, HIGM2

NCBI Gene: 57379 ENSG00000111732 UniProt: Q9GZX7 OMIM: 605257

This gene encodes a single-stranded DNA cytidine deaminase that is essential for somatic hypermutation, gene conversion, and class-switch recombination of immunoglobulin genes in germinal center B cells. Mutations cause autosomal recessive immunodeficiency with hyper-IgM type 2, characterized by defective antibody class switching and impaired humoral immune responses. The gene shows low constraint to loss-of-function variation (pLI near 0), consistent with its autosomal recessive inheritance pattern.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a RNA-editing deaminase that is a member of the cytidine deaminase family. AICDA is specifically expressed and active in germinal center-like B cells. In the germinal center, AICDA is involved in somatic hypermutation, gene conversion, and class-switch recombination of immunoglobulin genes. An epigenetic role in neoplastic transformation and lymphoma progression has been experimentally ascribed to AICDA using mouse models. Defects in this gene are the cause of autosomal recessive hyper-IgM immunodeficiency syndrome type 2 (HIGM2). [provided by RefSeq, Jul 2020]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Immunodeficiency with hyper-IgM, type 2MIM #605258

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · hyper-IgM syndrome type 2 · AR · ClinGen 2024

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.33

LOEUF

Multiple*

Mechanism· predicted

📖

GeneReview available — AICDA

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.33LOEUF

pLI 0.000

Z-score 0.75

OE 0.76 (0.46–1.33)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

1.34Z-score

OE missense 0.67 (0.57–0.80)

89 obs / 132.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.76 (0.46–1.33)

0≤0.351.4

Missense OE?0.67 (0.57–0.80)

0≤0.61.4

Synonymous OE?1.23

0≤1.21.6

LoF obs/exp: 9 / 11.8Missense obs/exp: 89 / 132.3Syn Z: -1.23

Background carrier burden — how many people carry a rare variant somewhere in AICDA?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 350

246 rare PASS variants

Rare truncating (LoF)

1 in 4,900

48 rare PASS variants

Rare synonymous (reference)

1 in 230

113 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for AICDA. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 510	1 in 6,200
South Asian	~43k	1 in 550	1 in 1,700
Remaining (unassigned)	~30k	1 in 230	≈ 1 in 10,000
European (Finnish)	~27k	1 in 1,800	≈ 1 in 27,000
Admixed American	~22k	1 in 350	1 in 820
African / African American	~21k	1 in 730	≈ 1 in 4,600
East Asian	~20k	1 in 250	≈ 1 in 6,600
Ashkenazi Jewish	~13k	≈ 1 in 6,500	none seen
Middle Eastern	~2,884	1 in 480	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 5 of 5 coding exons well covered in gnomAD exomes. Genomes: 4 of 5 (exon 4 below).? see exons ↓