ADA2

adenosine deaminase 2, the group of Adenosine deaminase family

Basic information

Region (hg38): 22:17178790-17258235

Previous symbols: [ "IDGFL", "CECR1" ]

Links

ENSG00000093072 ∙ NCBI:51816 ∙ OMIM:607575 ∙ HGNC:1839 ∙ Uniprot:Q9NZK5 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• vasculitis due to ADA2 deficiency (Strong), mode of inheritance: AR
• Sneddon syndrome (Moderate), mode of inheritance: AR
• polyarteritis nodosa (Moderate), mode of inheritance: AR
• Diamond-Blackfan anemia (Supportive), mode of inheritance: AD
• Sneddon syndrome (Supportive), mode of inheritance: AD
• vasculitis due to ADA2 deficiency (Supportive), mode of inheritance: AR
• vasculitis due to ADA2 deficiency (Strong), mode of inheritance: AR
• deficiency of adenosine deaminase 2 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Vasculitis, autoinflammation, immunodeficiency, and hematologic defects syndrome; Sneddon syndrome	AR	Allergy/Immunology/Infectious	Among other manifestations, individuals have been described as presenting with hypogammaglobulinemia, as well as recurrent bacterial and viral infections, and immunosuppressive treatment has been described as beneficial, though other manifestations have been described as recalcitrant to these types of therapies; Medical management (eg, with TNF inhibitor) has been described as beneficial.	Allergy/Immunology/Infectious; Cardiovascular; Dermatologic	12804991; 24552284; 24552285; 25075844; 25075847

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ADA2 gene.

• Vasculitis due to ADA2 deficiency (34 variants)
• not provided (8 variants)
• Vasculitis due to ADA2 deficiency;Sneddon syndrome (3 variants)
• ADA2-related disorder (3 variants)
• Sneddon syndrome (3 variants)
• Sneddon syndrome;Vasculitis due to ADA2 deficiency (2 variants)
• Autoinflammatory syndrome (1 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ADA2 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			3	77	3	83
missense	9	13	203	4	1	230
nonsense	7	2				9
start loss	2		1			3
frameshift	12	4				16
inframe indel	1					1
splice donor/acceptor (+/-2bp)	4	6				10
splice region	1		10	19	1	31
non coding	1		1	49	34	85
Total	36	25	208	130	38

Highest pathogenic variant AF is 0.000171

Variants in ADA2

This is a list of pathogenic ClinVar variants found in the ADA2 region.

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

Position	Type	Phenotype	Significance	ClinVar
22-17181488-T-G		Vasculitis due to ADA2 deficiency • Sneddon syndrome;Vasculitis due to ADA2 deficiency	Uncertain significance (May 27, 2022)
22-17181497-C-T		Vasculitis due to ADA2 deficiency	Uncertain significance (Aug 17, 2022)
22-17181506-T-C		Vasculitis due to ADA2 deficiency	Uncertain significance (Jul 30, 2022)
22-17181518-A-G			Uncertain significance (Jun 16, 2016)
22-17181522-C-T		Vasculitis due to ADA2 deficiency	Likely benign (Jan 01, 2023)
22-17181545-T-C		Vasculitis due to ADA2 deficiency • ADA2-related disorder	Uncertain significance (May 09, 2023)
22-17181546-A-ATT		Vasculitis due to ADA2 deficiency	Likely pathogenic (Jan 18, 2024)
22-17181552-C-G		Vasculitis due to ADA2 deficiency • not specified • Autoinflammatory syndrome	Conflicting classifications of pathogenicity (Dec 28, 2023)
22-17181554-C-G		Vasculitis due to ADA2 deficiency • Autoinflammatory syndrome • Vasculitis due to ADA2 deficiency;Sneddon syndrome	Uncertain significance (Sep 01, 2022)
22-17181554-C-T		Autoinflammatory syndrome	Uncertain significance (Jul 23, 2021)
22-17181564-C-T		Vasculitis due to ADA2 deficiency	Likely benign (Apr 26, 2022)
22-17181567-G-C		Vasculitis due to ADA2 deficiency	Likely benign (Sep 29, 2022)
22-17181567-GGTACT-G		Vasculitis due to ADA2 deficiency	Pathogenic (May 08, 2023)
22-17181572-T-G		Vasculitis due to ADA2 deficiency	Likely pathogenic (Mar 25, 2024)
22-17181574-T-C		Vasculitis due to ADA2 deficiency	Uncertain significance (Oct 24, 2022)
22-17181576-C-A		Vasculitis due to ADA2 deficiency	Uncertain significance (Jan 15, 2024)
22-17181582-G-C		Vasculitis due to ADA2 deficiency	Likely benign (Dec 11, 2023)
22-17181583-GA-G		Vasculitis due to ADA2 deficiency	Likely benign (Aug 07, 2023)
22-17181586-G-T		Vasculitis due to ADA2 deficiency	Likely benign (Oct 13, 2021)
22-17181589-G-A		Vasculitis due to ADA2 deficiency	Likely benign (Oct 28, 2021)
22-17181592-G-A		Vasculitis due to ADA2 deficiency	Likely benign (Mar 10, 2022)
22-17181594-G-A		Vasculitis due to ADA2 deficiency	Likely benign (Sep 02, 2022)
22-17181701-C-G		not specified	Benign (Nov 12, 2023)
22-17181789-C-T		not specified	Benign (Nov 12, 2023)
22-17181800-G-C		Vasculitis due to ADA2 deficiency	Likely benign (Dec 04, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ADA2	protein_coding	protein_coding	ENST00000399839	9	42686

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
8.14e-8	0.736	125667	0	80	125747	0.000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.357	280	297	0.942	0.0000159	3403
Missense in Polyphen		87	90.478	0.96156		1101
Synonymous	0.367	108	113	0.956	0.00000657	959
Loss of Function	1.32	14	20.5	0.684	0.00000104	239

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000793	0.000793
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.0000464	0.0000462
European (Non-Finnish)	0.000388	0.000387
Middle Eastern	0.000109	0.000109
South Asian	0.000229	0.000229
Other	0.000326	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Adenosine deaminase that may contribute to the degradation of extracellular adenosine, a signaling molecule that controls a variety of cellular responses. Requires elevated adenosine levels for optimal enzyme activity. Binds to cell surfaces via proteoglycans and may play a role in the regulation of cell proliferation and differentiation, independently of its enzyme activity. {ECO:0000269|PubMed:20147294, ECO:0000269|PubMed:20453107}.
• Disease: DISEASE: Polyarteritis nodosa (PAN) [MIM:615688]: A systemic necrotizing vasculitis that affects medium and small arteries. The ensuing tissue ischemia can affect any organ, including the skin, musculoskeletal system, kidneys, gastrointestinal tract, and the cardiovascular and nervous systems. Organ involvement and disease severity are highly variable. Clinical features include recurrent ischemic stroke affecting the small vessels of the brain and resulting in neurologic dysfunction, recurrent fever, myalgias, livedoid rash, gastrointestinal pain and hepatosplenomegaly. {ECO:0000269|PubMed:24552284, ECO:0000269|PubMed:24552285}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Sneddon syndrome (SNDDS) [MIM:182410]: A systemic non- inflammatory thrombotic vasculopathy characterized by the association of livedo racemosa, and in some cases livedo reticularis, with cerebrovascular disease. Livedo racemosa is a persistent net-like violaceous-cyanotic, mottled discoloration of the skin affecting the legs, the arms, the buttocks and the trunk; livedo reticularis is limited to the extremities and is visible only in the cold. Cerebrovascular features include recurrent transient ischemic attacks, infarcts, and rarely spinal strokes or intracranial or subarachnoid hemorrhages. Headache and vertigo may precede the onset of livedo racemosa and cerebrovascular manifestations by several years. Rare neurologic symptoms include seizures, chorea, or myelopathies. {ECO:0000269|PubMed:25075847}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Purine metabolism - Homo sapiens (human);Neutrophil degranulation;Surfactant metabolism;Metabolism of proteins;Innate Immune System;Immune System (Consensus)

Recessive Scores

• pRec: 0.0931

Intolerance Scores

• rvis_EVS: -0.35
• rvis_percentile_EVS: 29.43

Haploinsufficiency Scores

• pHI: 0.308
• hipred: N
• hipred_score: 0.187
• ghis: 0.505

Essentials

• essential_gene_gene_trap: N

Zebrafish Information Network

• Gene name: ada2b
• Affected structure: neutrophil
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: adenosine catabolic process;multicellular organism development;regulation of signaling receptor activity;neutrophil degranulation;cellular protein metabolic process;inosine biosynthetic process
• Cellular component: extracellular region;extracellular space;azurophil granule lumen
• Molecular function: adenosine deaminase activity;growth factor activity;heparin binding;zinc ion binding;adenosine receptor binding;protein homodimerization activity;proteoglycan binding