NUDT2 (nudix hydrolase 2)

Gene

• Entrez ID: 318
• Gene name: Nudix hydrolase 2
• Gene symbol: NUDT2
• Synonyms (NCBI Gene): APAH1, IDDPN
• Chromosome: 9
• Chromosome location: 9p13.3
• Summary: This gene encodes a member of the MutT family of nucleotide pyrophosphatases, a subset of the larger NUDIX hydrolase family. The gene product possesses a modification of the MutT sequence motif found in certain nucleotide pyrophosphatases. The enzyme asym

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs529087882	A>-	Likely-pathogenic	Coding sequence variant, frameshift variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT042526	hsa-miR-423-3p	CLASH	23622248
MIRT037637	hsa-miR-744-5p	CLASH	23622248
MIRT1198047	hsa-miR-4537	CLIP-seq
MIRT1198048	hsa-miR-4686	CLIP-seq
MIRT1198049	hsa-miR-4719	CLIP-seq
MIRT1198050	hsa-miR-4762-5p	CLIP-seq
MIRT1198051	hsa-miR-513b	CLIP-seq
MIRT1198052	hsa-miR-767-3p	CLIP-seq
MIRT1198053	hsa-miR-4687-3p	CLIP-seq
MIRT1198054	hsa-miR-634	CLIP-seq
MIRT2057338	hsa-miR-142-5p	CLIP-seq
MIRT2057339	hsa-miR-340	CLIP-seq
MIRT2057340	hsa-miR-548a-5p	CLIP-seq
MIRT2057341	hsa-miR-548ab	CLIP-seq
MIRT2057342	hsa-miR-548ak	CLIP-seq
MIRT2057343	hsa-miR-548b-5p	CLIP-seq
MIRT2057344	hsa-miR-548c-5p	CLIP-seq
MIRT2057345	hsa-miR-548d-5p	CLIP-seq
MIRT2057346	hsa-miR-548h	CLIP-seq
MIRT2057347	hsa-miR-548i	CLIP-seq
MIRT2057348	hsa-miR-548j	CLIP-seq
MIRT2057349	hsa-miR-548k	CLIP-seq
MIRT2057350	hsa-miR-548l	CLIP-seq
MIRT2057351	hsa-miR-548w	CLIP-seq
MIRT2057352	hsa-miR-548y	CLIP-seq
MIRT2057353	hsa-miR-559	CLIP-seq
MIRT2057354	hsa-miR-624	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000166	Function	Nucleotide binding	IEA
GO:0004081	Function	Bis(5'-nucleosyl)-tetraphosphatase (asymmetrical) activity	IBA
GO:0004081	Function	Bis(5'-nucleosyl)-tetraphosphatase (asymmetrical) activity	IEA
GO:0004081	Function	Bis(5'-nucleosyl)-tetraphosphatase (asymmetrical) activity	ISS	11738085
GO:0004081	Function	Bis(5'-nucleosyl)-tetraphosphatase (asymmetrical) activity	TAS
GO:0005515	Function	Protein binding	IPI	25416956, 32296183
GO:0005525	Function	GTP binding	IEA
GO:0005759	Component	Mitochondrial matrix	TAS
GO:0006139	Process	Nucleobase-containing compound metabolic process	TAS	7487923
GO:0006167	Process	AMP biosynthetic process	IBA
GO:0006754	Process	ATP biosynthetic process	IBA
GO:0006915	Process	Apoptotic process	ISS	11937063
GO:0008796	Function	Bis(5'-nucleosyl)-tetraphosphatase activity	IEA
GO:0008803	Function	Bis(5'-nucleosyl)-tetraphosphatase (symmetrical) activity	TAS	7487923
GO:0016787	Function	Hydrolase activity	IEA
GO:0034599	Process	Cellular response to oxidative stress	TAS

Other IDs

• MIM: 602852
• HGNC: 8049
• e!Ensembl: ENSG00000164978

Protein

• UniProt ID: P50583
• Protein name: Bis(5'-nucleosyl)-tetraphosphatase [asymmetrical] (EC 3.6.1.17) (Diadenosine 5',5'''-P1,P4-tetraphosphate asymmetrical hydrolase) (Ap4A hydrolase) (Ap4Aase) (Diadenosine tetraphosphatase) (Nucleoside diphosphate-linked moiety X motif 2) (Nudix motif 2)
• Protein function: Catalyzes the asymmetric hydrolysis of diadenosine 5',5'''-P1,P4-tetraphosphate (Ap4A) to yield AMP and ATP (By similarity). Exhibits decapping activity towards FAD-capped RNAs and dpCoA-capped RNAs in vitro (By similarity). {ECO:0000250|UniProt
• PDB: 1XSA, 1XSB, 1XSC, 3U53, 4ICK, 4IJX
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00293	NUDIX	12 → 137	NUDIX domain	Domain

• Sequence:

  MALRACGLIIFRRCLIPKVDNNAIEFLLLQASDGIHHWTPPKGHVEPGEDDLETALRETQ
  EEAGIEAGQLTIIEGFKRELNYVARNKPKTVIYWLAEVKDYDVEIRLSHEHQAYRWLGLE
  EACQLAQFKEMKAALQEGHQFLCSIEA

• Sequence length: 147

Pathways

KEGG:

Purine metabolism
Pyrimidine metabolism
Metabolic pathways

Reactome:

Detoxification of Reactive Oxygen Species

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Complex neurodevelopmental disorder	Likely pathogenic; Pathogenic	rs529087882	RCV002225120	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Intellectual developmental disorder with or without peripheral neuropathy	Likely pathogenic; Pathogenic	rs148119952, rs772730170, rs529087882	RCV002248318 RCV003156721 RCV002251755	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Intellectual disability	Likely pathogenic; Pathogenic	rs529087882	RCV001533201	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
NUDT2-associated condition	Likely pathogenic; Pathogenic	rs529087882	RCV000850407	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
BREAST NEOPLASMS	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GOUT	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
INTELLECTUAL DISABILITY-PERIPHERAL NEUROPATHY-CORPUS CALLOSUM ABNORMALITIES SYNDROME DUE TO NUDIX HYDROLASE 2 DEFICIENCY	—	Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NON-SPECIFIC SYNDROMIC INTELLECTUAL DISABILITY	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Attention Deficit Disorder with Hyperactivity	Attention deficit hyperactivity disorder	Pubtator	38243213	Associate	★☆☆☆☆ Found in Text Mining only
Basal Ganglia Diseases	Basal ganglia disease	Pubtator	38141063	Associate	★☆☆☆☆ Found in Text Mining only
Breast Carcinoma	Breast Carcinoma	BEFREE	20533549		★☆☆☆☆ Found in Text Mining only
Breast Carcinoma	Breast Carcinoma	CTD_human_DG	20533549		★☆☆☆☆ Found in Text Mining only
Cardiomyopathy, Familial Idiopathic	Cardiomyopathy	BEFREE	20533549		★☆☆☆☆ Found in Text Mining only
Global developmental delay	Developmental Delay	GENOMICS_ENGLAND_DG	30059600		★☆☆☆☆ Found in Text Mining only
Hypersensitivity Delayed	Hypersensitivity	Pubtator	38243213	Associate	★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Mental retardation	GENOMICS_ENGLAND_DG	30059600		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Intellectual Disability	Intellectual developmental disorder	Pubtator	33058507, 38243213	Associate	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Invasive Ductal Breast Carcinoma	Invasive Duct and Lobular Carcinoma	BEFREE	20533549		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	CTD_human_DG	20533549		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	27144453		★☆☆☆☆ Found in Text Mining only
Mammary Carcinoma, Human	Marfan Syndrome	CTD_human_DG	20533549		★☆☆☆☆ Found in Text Mining only
Mammary Neoplasms	Mammary Neoplasms	CTD_human_DG	20533549		★☆☆☆☆ Found in Text Mining only
Mammary Neoplasms, Human	Mammary Neoplasms	CTD_human_DG	20533549		★☆☆☆☆ Found in Text Mining only
Nervous System Diseases	Nervous system disease	Pubtator	38141063	Associate	★☆☆☆☆ Found in Text Mining only
Neurodevelopmental Disorders	Neurodevelopmental Disorders	BEFREE	30059600		★☆☆☆☆ Found in Text Mining only
Noninfiltrating Intraductal Carcinoma	Ductal carcinoma	BEFREE	20533549		★☆☆☆☆ Found in Text Mining only
Paraparesis	Paraparesis	Pubtator	33058507	Associate	★☆☆☆☆ Found in Text Mining only
Peripheral Nervous System Diseases	Peripheral nervous system disease	Pubtator	38141063	Associate	★☆☆☆☆ Found in Text Mining only
Polyneuropathies	Polyneuropathy	Pubtator	33058507	Associate	★☆☆☆☆ Found in Text Mining only