NUDT2

protein-coding

nudix hydrolase 2, the group of Nudix hydrolase family

Gene 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 asymmetrically hydrolyzes Ap4A to yield AMP and ATP and is responsible for maintaining the intracellular level of the dinucleotide Ap4A, the function of which has yet to be established. This gene may be a candidate tumor suppressor gene. Alternative splicing has been observed at this locus and four transcript variants, all encoding the same protein, have been identified. [provided by RefSeq, Sep 2011]

Previous symbols:

APAH1

MANE transcript

NM_001161.5

Inheritance

ClinVar variants

P:3U:17B:5

Top phenotype

Intellectual developmental disorder with or without peripheral neuropathy

gnomAD constraint

pLI —, LoF o/e 0.65

Max pathogenic AF

—

Genomic locus

chr9:34,329,506-34,343,713

External References & Databases

Ensembl (ENSG00000164978)

Transcript & Mutation Effects

hg38 • Region Span ~14.2 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

intellectual developmental disorder with or without peripheral neuropathySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0859240

Submitter: Labcorp Genetics (formerly Invitae)

intellectual developmental disorder with or without peripheral neuropathyLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0859240

Submitter: Ambry Genetics

intellectual developmental disorder with or without peripheral neuropathyDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0859240

Submitter: G2P

intellectual developmental disorder with or without peripheral neuropathySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0859240

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Intellectual developmental disorder with or without peripheral neuropathyAR

Manifestation: Craniofacial; Musculoskeletal; Neurologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 27431290; 30059600; 33058507

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to NUDT2 variants in ClinVar

7 Conditions Cataloged

not specifiedTotal: 15

not providedTotal: 8

Intellectual developmental disorder with or without peripheral neuropathyTotal: 4

NUDT2-associated conditionTotal: 1

NUDT2-related conditionTotal: 1

Intellectual disabilityTotal: 1

Complex neurodevelopmental disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001161.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				3 clinvar		3
missense		1 clinvar	16 clinvar	2 clinvar		19
nonsense		1 clinvar	1 clinvar			2
start loss						0
frameshift		1 clinvar				1
splice donor/acceptor (+/-2bp)						0
Total	0	3	17	5	0	25

Highest pathogenic variant AF is 0.00027756885

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 43 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001161.5	RefSeq	NP_001152.1	2	MANE Select
ENST00000379158.7	Ensembl	ENSP00000368455.1	2	MANE Select
NM_001244390.2	RefSeq	NP_001231319.1	2	Standard
NM_147172.3	RefSeq	NP_671701.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Pyrimidine metabolism - Homo sapiens (human)
Purine metabolism - Homo sapiens (human)
Purine Nucleoside Phosphorylase Deficiency
Mercaptopurine Action Pathway
Azathioprine Action Pathway

Biological Process

nucleobase-containing compound metabolic process
apoptotic process
cellular response to oxidative stress

Molecular Function

bis(5'-nucleosyl)-tetraphosphatase (asymmetrical) activity
protein binding
GTP binding
bis(5'-nucleosyl)-tetraphosphatase (symmetrical) activity

Cellular Component

mitochondrial matrix

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000379158
Coding exons: 2
Length: 14206
Individuals with no LoFs: 125710
Homozygous LoFs: 0
Heterozygous LoFs: 37
Defined: 125747
p: 0.000147

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.485	68	80.2	0.848	0.00000407	953
Missense (PolyPhen)		28	31.863	0.87877		401
Synonymous	-0.177	33	31.7	1.04	0.00000164	281
Loss of Function	0.818	4	6.20	0.645	3.47e-7	69

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.00028	0.00028	rare
South Asian	0	0.0	absent
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Asymmetrically hydrolyzes Ap4A to yield AMP and ATP. Plays a major role in maintaining homeostasis.;

Recessive Scores

pRec: 0.109

Intolerance Scores

LoFtool: 0.671
RVIS EVS: 0.15
RVIS percentile EVS: 64.11

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.754

Gene Damage Prediction

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