ADA2 (adenosine deaminase 2)

Gene

• Entrez ID: 51816
• Gene name: Adenosine deaminase 2
• Gene symbol: ADA2
• Synonyms (NCBI Gene): ADGF, CECR1, IDGFL, PAN, SNEDS, VAIHS
• Chromosome: 22
• Chromosome location: 22q11.1
• Summary: This gene encodes a member of a subfamily of the adenosine deaminase protein family. The encoded protein is one of two adenosine deaminases found in humans, which regulate levels of the signaling molecule, adenosine. The encoded protein is secreted from m

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs74317375	C>T	Likely-benign, pathogenic, benign-likely-benign	Coding sequence variant, missense variant
rs77563738	C>G,T	Likely-pathogenic, pathogenic	Genic upstream transcript variant, coding sequence variant, missense variant, 5 prime UTR variant
rs139750129	T>C	Pathogenic	Splice acceptor variant
rs146597836	C>T	Conflicting-interpretations-of-pathogenicity, pathogenic	Coding sequence variant, missense variant
rs148936893	G>A	Pathogenic	Missense variant, coding sequence variant, 5 prime UTR variant, genic upstream transcript variant
rs199614299	G>A	Uncertain-significance, pathogenic	Intron variant, genic upstream transcript variant, upstream transcript variant, missense variant, coding sequence variant
rs200930463	C>A,G	Pathogenic	Intron variant, genic upstream transcript variant, upstream transcript variant, missense variant, coding sequence variant
rs202134424	C>A,G,T	Conflicting-interpretations-of-pathogenicity, pathogenic-likely-pathogenic	Intron variant, genic upstream transcript variant, upstream transcript variant, missense variant, coding sequence variant
rs376785840	T>C	Pathogenic	Missense variant, coding sequence variant
rs587777240	G>T	Pathogenic	Missense variant, genic upstream transcript variant, coding sequence variant, 5 prime UTR variant
rs587777241	G>C	Pathogenic	Missense variant, genic upstream transcript variant, coding sequence variant, 5 prime UTR variant
rs587777242	C>G	Pathogenic	Missense variant, coding sequence variant, 5 prime UTR variant
rs747774101	T>C	Pathogenic	Coding sequence variant, missense variant
rs750868279	G>A	Pathogenic	Missense variant, genic upstream transcript variant, coding sequence variant, 5 prime UTR variant
rs756881285	C>-,CC	Pathogenic, likely-pathogenic	Intron variant, frameshift variant, upstream transcript variant, genic upstream transcript variant, coding sequence variant
rs766602945	GCGT>-	Pathogenic	Frameshift variant, coding sequence variant, 5 prime UTR variant, genic upstream transcript variant
rs770689762	C>T	Pathogenic	Missense variant, coding sequence variant
rs774963498	G>A,C	Likely-pathogenic	Missense variant, coding sequence variant, stop gained
rs775440641	T>C	Pathogenic	Missense variant, coding sequence variant
rs1226708979	G>A,C	Likely-pathogenic	Missense variant, synonymous variant, coding sequence variant
rs1489114116	G>T	Likely-pathogenic	Missense variant, coding sequence variant
rs1568966771	C>T	Pathogenic	Coding sequence variant, stop gained
rs1568968051	T>-	Pathogenic	Intron variant
rs1601419986	TGTAC>-	Likely-pathogenic	Coding sequence variant, frameshift variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT497202	hsa-miR-3622a-5p	PAR-CLIP	22291592
MIRT454002	hsa-miR-302c-3p	PAR-CLIP	23592263
MIRT454001	hsa-miR-520f-3p	PAR-CLIP	23592263
MIRT454000	hsa-miR-1825	PAR-CLIP	23592263
MIRT453999	hsa-miR-6089	PAR-CLIP	23592263
MIRT453998	hsa-miR-6087	PAR-CLIP	23592263
MIRT453996	hsa-miR-3656	PAR-CLIP	23592263
MIRT453997	hsa-miR-1251-3p	PAR-CLIP	23592263
MIRT453995	hsa-miR-7106-5p	PAR-CLIP	23592263
MIRT453994	hsa-miR-149-3p	PAR-CLIP	23592263
MIRT453993	hsa-miR-4728-5p	PAR-CLIP	23592263
MIRT453992	hsa-miR-6785-5p	PAR-CLIP	23592263
MIRT453991	hsa-miR-6883-5p	PAR-CLIP	23592263
MIRT453990	hsa-miR-6799-5p	PAR-CLIP	23592263
MIRT453989	hsa-miR-30c-1-3p	PAR-CLIP	23592263
MIRT453988	hsa-miR-30c-2-3p	PAR-CLIP	23592263
MIRT453986	hsa-miR-6788-5p	PAR-CLIP	23592263
MIRT453987	hsa-miR-1273h-5p	PAR-CLIP	23592263
MIRT453985	hsa-miR-30b-3p	PAR-CLIP	23592263
MIRT453984	hsa-miR-3689a-3p	PAR-CLIP	23592263
MIRT453983	hsa-miR-3689b-3p	PAR-CLIP	23592263
MIRT453982	hsa-miR-3689c	PAR-CLIP	23592263
MIRT453981	hsa-miR-6779-5p	PAR-CLIP	23592263
MIRT453980	hsa-miR-6780a-5p	PAR-CLIP	23592263
MIRT453979	hsa-miR-450a-1-3p	PAR-CLIP	23592263
MIRT453978	hsa-miR-3122	PAR-CLIP	23592263
MIRT453977	hsa-miR-3913-5p	PAR-CLIP	23592263
MIRT453976	hsa-miR-887-5p	PAR-CLIP	23592263
MIRT453975	hsa-miR-6513-5p	PAR-CLIP	23592263

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0004000	Function	Adenosine deaminase activity	IBA
GO:0004000	Function	Adenosine deaminase activity	IDA	20147294
GO:0004000	Function	Adenosine deaminase activity	IEA
GO:0005576	Component	Extracellular region	IEA
GO:0005576	Component	Extracellular region	TAS
GO:0005615	Component	Extracellular space	IBA
GO:0005615	Component	Extracellular space	IDA	20147294
GO:0005615	Component	Extracellular space	IEA
GO:0006154	Process	Adenosine catabolic process	IBA
GO:0006154	Process	Adenosine catabolic process	IDA	20147294
GO:0006154	Process	Adenosine catabolic process	IEA
GO:0007165	Process	Signal transduction	IEA
GO:0008083	Function	Growth factor activity	NAS	10756095
GO:0008201	Function	Heparin binding	IEA
GO:0008270	Function	Zinc ion binding	IDA	20147294
GO:0016787	Function	Hydrolase activity	IEA
GO:0019239	Function	Deaminase activity	IEA
GO:0031685	Function	Adenosine receptor binding	IDA	20147294
GO:0035578	Component	Azurophil granule lumen	TAS
GO:0042803	Function	Protein homodimerization activity	IPI	20147294
GO:0043394	Function	Proteoglycan binding	IDA	20147294
GO:0046103	Process	Inosine biosynthetic process	IBA
GO:0046872	Function	Metal ion binding	IEA

Other IDs

• MIM: 607575
• HGNC: 1839
• e!Ensembl: ENSG00000093072

Protein

• UniProt ID: Q9NZK5
• Protein name: Adenosine deaminase 2 (EC 3.5.4.4) (Cat eye syndrome critical region protein 1)
• Protein 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
• PDB: 3LGD, 3LGG
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF08451	A_deaminase_N	12 → 102	Adenosine/AMP deaminase N-terminal	Family
  PF00962	A_deaminase	174 → 496	Adenosine/AMP deaminase	Domain

• Tissue specificity: TISSUE SPECIFICITY: Detected in blood plasma (at protein level). Widely expressed, with most abundant expression in human adult heart, lung, lymphoblasts, and placenta as well as fetal lung, liver, and kidney. In embryo, expressed in the outflow tract and
• Sequence:

  MLVDGPSERPALCFLLLAVAMSFFGSALSIDETRAHLLLKEKMMRLGGRLVLNTKEELAN
  ERLMTLKIAEMKEAMRTLIFPPSMHFFQAKHLIERSQVFNILRMMPKGAALHLHDIGIVT
  MDWLVRNVTYRPHCHICFTPRGIMQFRFAHPTPRPSEKCSKWILLEDYRKRVQNVTEFDD
  SLLRNFTLVTQHPEVIYTNQNVVWSKFETIFFTISGLIHYAPVFRDYVFRSMQEFYEDNV
  LYMEIRARLLPVYELSGEHHDEEWSVKTYQEVAQKFVETHPEFIGIKIIYSDHRSKDVAV
  IAESIRMAMGLRIKFPTVVAGFDLVGHEDTGHSLHDYKEALMIPAKDGVKLPYFFHAGET
  DWQGTSIDRNILDALMLNTTRIGHGFALSKHPAVRTYSWKKDIPIEVCPISNQVLKLVSD
  LRNHPVATLMATGHPMVISSDDPAMFGAKGLSYDFYEVFMGIGGMKADLRTLKQLAMNSI
  KYSTLLESEKNTFMEIWKKRWDKFIADVATK

• Sequence length: 511

Pathways

KEGG:

Purine metabolism
Metabolic pathways
Nucleotide metabolism

Reactome:

Surfactant metabolism
Neutrophil degranulation

Associated diseases

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
ADA2-related disorder	Pathogenic; Likely pathogenic	rs202134424, rs200930463, rs77563738, rs1300843648, rs45511697, rs139750129	RCV003399212 RCV004751262 RCV003945041 RCV004731219 RCV003419802 RCV003411545
Autoinflammatory syndrome	Pathogenic; Likely pathogenic	rs202134424, rs376785840, rs587777241, rs77563738, rs754904956	RCV002264292 RCV002262702 RCV002262703 RCV002262704 RCV002262705 RCV002264175
Deficiency of adenosine deaminase 2	Likely pathogenic	rs772909795	RCV003459015
Hepatocellular carcinoma	Likely pathogenic; Pathogenic	rs766602945	RCV005870887
Inherited Immunodeficiency Diseases	Likely pathogenic; Pathogenic	rs77563738, rs1489114116	RCV001027542 RCV001027541
Ovarian serous cystadenocarcinoma	Pathogenic	rs139750129	RCV005900316
See cases	Pathogenic	rs775440641	RCV004584361
Sneddon syndrome	Likely pathogenic; Pathogenic	rs748893301, rs2062064773, rs202134424, rs2123699776, rs376785840, rs200930463, rs77563738, rs148936893, rs768987774, rs369924229, rs2517346966, rs775440641, rs770689762, rs2231487, rs139750129, rs756881285, rs766602945, rs1489114116, rs754904956, rs368615054, rs775997344	RCV001328777 RCV001336346 RCV001535952 RCV001523887 RCV002477260 RCV002483175 RCV001536077 RCV002498474 RCV005025173 RCV002505023 RCV005031872 RCV005023385 RCV005025743 RCV000169758 RCV000169759 RCV005036978 RCV002499121 RCV002477652 RCV002477827 RCV002487649 RCV002497346 RCV005029656 RCV002482017 RCV005029797
Splenomegaly	Likely pathogenic; Pathogenic	rs756881285	RCV000714239
Vasculitis due to ADA2 deficiency	Likely pathogenic; Pathogenic	rs748893301, rs2062095528, rs202134424, rs376785840, rs587777240, rs200930463, rs587777241, rs77563738, rs148936893, rs587777242, rs2062393838, rs745795188, rs768987774, rs1452477558, rs1300843648, rs2123651193, rs773226219, rs369924229, rs772909795, rs2517346966, rs2517294688, rs775440641, rs770689762, rs2231487, rs2517274830, rs1568988719, rs2517294181, rs778965407, rs2517360414, rs2517294264, rs2517379776, rs2517361483, rs2517360088, rs2517276433, rs2517345941, rs2062365477, rs1212466958, rs749240880, rs2517274947, rs45511697, rs139750129, rs756881285, rs747774101, rs1568966771, rs766602945, rs1601419986, rs1489114116, rs754904956, rs755007390, rs368615054, rs2062392148, rs2062118599, rs2061972270, rs775997344, rs752890414	RCV003583195 RCV001328779 RCV001390131 RCV000106380 RCV000106381 RCV000106382 RCV000106383 RCV000106384 RCV000106385 RCV000106386 RCV000106387 RCV000106388 RCV001706871 RCV001706872 RCV001942886 RCV001981686 RCV002005471 RCV001937728 RCV001980451 RCV001969417 RCV001896413 RCV001986460 RCV002468948 RCV003041402 RCV000851530 RCV001386673 RCV003111981 RCV002576984 RCV002597026 RCV002690133 RCV002761291 RCV002837548 RCV002858202 RCV003226027 RCV003746726 RCV003747433 RCV003746465 RCV003746441 RCV003747562 RCV003831484 RCV003843070 RCV003988702 RCV003990028 RCV001067680 RCV000652053 RCV000652057 RCV000810595 RCV001218334 RCV003768300 RCV000799257 RCV000793011 RCV000984922 RCV001328776 RCV001066294 RCV001069829 RCV001057009 RCV001204634 RCV001218383 RCV001235007 RCV001229165 RCV001267735

Unknown
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Acute myeloid leukemia	Benign; Likely benign	rs115986203	RCV005900317
Behcet disease	Uncertain significance; Benign; Likely benign	rs199614299, rs146597836, rs750868279, rs74317375	RCV000416313 RCV000416296 RCV000416344 RCV000495242
Cervical cancer	Benign	rs2231493	RCV005922928
Cholangiocarcinoma	Benign	rs9617966	RCV005922042
Colon adenocarcinoma	Uncertain significance	rs1292778015	RCV005908991
Deficiency of ADA2	Uncertain significance	rs1601436115, rs776351526	RCV001254865 RCV001254864
Familial cancer of breast	Benign	rs3764846	RCV005898198
Gastric cancer	Benign	rs2231493	RCV005922929
Germ cell tumor of testis	Benign	rs9617966	RCV005922043
Malignant lymphoma, large B-cell, diffuse	Benign	rs9617966	RCV005922041
Uterine corpus endometrial carcinoma	Benign	rs2231493	RCV005922930

Associations from Text Mining
Disease Name	Relationship Type	References
Adjustment Disorders	Associate	15830375
Anemia Diamond Blackfan	Associate	30503522, 30559313
Anemia Hemolytic Autoimmune	Associate	34845942
Anemia Hypoplastic Congenital	Associate	30559313
Arthritis Rheumatoid	Associate	20943049
Autoimmune Diseases	Associate	28830446
Autoimmune Lymphoproliferative Syndrome	Associate	30692987
Behcet Syndrome	Associate	30808881, 31856934
Bone Marrow Diseases	Associate	30692987
Bone Marrow Failure Disorders	Associate	28974505
Breast Neoplasms Male	Associate	36614261
Carcinogenesis	Associate	32315343
Carcinoma Adenoid Cystic	Associate	21551254
Carcinoma Hepatocellular	Associate	37171396
Carcinoma Neuroendocrine	Associate	32729306
Carcinoma Non Small Cell Lung	Associate	31591429
Carcinoma Renal Cell	Associate	35663977
Carcinosarcoma	Associate	35663977
Cerebral Hemorrhage	Associate	28522451
Cerebral Infarction	Associate	28974505
deficiency of adenosine deaminase 2	Inhibit	25278816, 30692987, 31916720, 36248833
deficiency of adenosine deaminase 2	Associate	28522451, 28830446, 28974505, 30503522, 31015188, 31856934, 31945408, 31974608, 33757531, 34361096, 34577178, 34721429, 34845942, 36248833, 36807221, 37721348
Diabetes Mellitus	Stimulate	28170537
Diabetic Retinopathy	Associate	28170537
Disease	Associate	25278816
Endometrial Neoplasms	Associate	32315343
Esophageal Neoplasms	Stimulate	35663977
Esophageal Squamous Cell Carcinoma	Associate	33789967
Fever	Associate	30692987
Fibrosarcoma	Associate	28719467
Glioblastoma	Stimulate	35663977
Glioma	Associate	28453746, 28534507
Hematologic Diseases	Associate	31945408, 34845942
Hereditary Autoinflammatory Diseases	Associate	28830446, 28974505, 30808881, 31974608
Hereditary Autoinflammatory Diseases	Inhibit	31916720
Hypertension	Associate	30192643
Hypoxia	Associate	15926889
Immunologic Deficiency Syndromes	Associate	28974505
Inflammation	Associate	15926889, 31974608
Inflammation	Inhibit	23468496
Inflammation	Stimulate	28170537, 34706243
Influenza Human	Associate	36243706
Intracranial Hemorrhages	Associate	28974505
Leukemia	Associate	3140911
Leukemia Myeloid Acute	Associate	3140911
Leukemia Myeloid Acute	Stimulate	35663977
Livedo Reticularis	Associate	28522451, 28974505
Livedoid Vasculopathy	Associate	28974505, 30692987
Liver Cirrhosis	Associate	34706243
Melanoma Cutaneous Malignant	Stimulate	35663977
Mesothelioma Malignant	Associate	15830375
Multi centric Castleman's Disease	Associate	34096620
Neoplasm Metastasis	Associate	32315343
Neoplasms	Associate	15926889, 27519690, 28534507, 32327700, 33127954, 35663977
Neutropenia	Associate	30692987, 34845942
Non alcoholic Fatty Liver Disease	Associate	34706243
Osteoporosis	Associate	36248833
Pancreatic Neoplasms	Associate	32729306, 35663977
Periodontitis	Associate	34101221
Plaque Atherosclerotic	Associate	34082770
Polyarteritis Nodosa	Associate	24552285, 25278816, 28830446, 28974505
Positive Pressure Respiration Intrinsic	Associate	30692987
Red Cell Aplasia Pure	Associate	34845942
Retinitis	Associate	28170537
Sarcoma Clear Cell	Associate	32034283
Schmid Fraccaro syndrome	Inhibit	30692987
Schmid Fraccaro syndrome	Associate	31916720, 34577178
Severe combined immunodeficiency due to adenosine deaminase deficiency	Associate	28522451
Solitary Fibrous Tumors	Associate	32034283
Squamous Cell Carcinoma of Head and Neck	Associate	35663977
Stomach Neoplasms	Stimulate	35663977
Stroke	Associate	25278816, 28522451, 32106772, 36248833
Systemic Vasculitis	Associate	25278816, 31015188, 31974608
Thymoma	Associate	35663977
Vascular Diseases	Associate	25278816
Vasculitis	Associate	24552285, 25278816, 31945408
Wilms Tumor	Associate	15543376