NME2

protein-coding

NME/NM23 nucleoside diphosphate kinase 2, the group of NME/NM23 family

Gene summary

Nucleoside diphosphate kinase (NDK) exists as a hexamer composed of 'A' (encoded by NME1) and 'B' (encoded by this gene) isoforms. Multiple alternatively spliced transcript variants have been found for this gene. Read-through transcription from the neighboring upstream gene (NME1) generates naturally-occurring transcripts (NME1-NME2) that encode a fusion protein comprised of sequence sharing identity with each individual gene product. [provided by RefSeq, Nov 2010]

MANE transcript

NM_002512.4

Inheritance

—

ClinVar variants

U:3B:1

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.92

Max pathogenic AF

—

Genomic locus

chr17:51,165,435-51,171,744

External References & Databases

Ensembl (ENSG00000243678)

Transcript & Mutation Effects

hg38 • Region Span ~6.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to NME2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 3

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002512.4. 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				1 clinvar		1
missense			2 clinvar			2
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)						0
Total	0	0	3	1	0	4

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 74 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002512.4	RefSeq	NP_002503.1	4	MANE Select
ENST00000512737.6	Ensembl	ENSP00000421064.1	4	MANE Select
NM_001018137.3	RefSeq	NP_001018147.1	4	Standard
NM_001018138.1	RefSeq	NP_001018148.1	4	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
nme2b.2	Danio rerio	Structure: GTP biosynthetic process Quality: decreased rate abnormal

Gene / Model

Organism

Observed Phenotype

nme2b.2

Danio rerio

Structure: GTP biosynthetic process

Quality: decreased rate

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Pyrimidine metabolism - Homo sapiens (human)
Drug metabolism - other enzymes - Homo sapiens (human)
Purine metabolism - Homo sapiens (human)
Tenofovir/Adefovir Pathway, Pharmacodynamics
Tenofovir/Adefovir Pathway, Pharmacokinetics

Biological Process

negative regulation of myeloid leukocyte differentiation
nucleoside diphosphate phosphorylation
GTP biosynthetic process
UTP biosynthetic process
CTP biosynthetic process

Molecular Function

DNA binding
transcription coactivator activity
nucleoside diphosphate kinase activity
protein histidine kinase activity
protein serine/threonine kinase activity

Cellular Component

ruffle
extracellular region
nucleus
cytoplasm
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000393198
Coding exons: 7
Length: 18189
Individuals with no LoFs: 125704
Homozygous LoFs: 0
Heterozygous LoFs: 44
Defined: 125748
p: 0.000175

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.876	132	164	0.807	0.00000939	1743
Missense (PolyPhen)		51	58.612	0.87013		592
Synonymous	0.666	53	59.5	0.890	0.00000340	517
Loss of Function	0.271	13	14.1	0.922	8.57e-7	145

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000063	0.000062	rare
Latino/Admixed American	0.000089	0.000087	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00076	0.00076	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00011	0.00011	rare
South Asian	0.00036	0.00036	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Major role in the synthesis of nucleoside triphosphates other than ATP. The ATP gamma phosphate is transferred to the NDP beta phosphate via a ping-pong mechanism, using a phosphorylated active-site intermediate (By similarity). Negatively regulates Rho activity by interacting with AKAP13/LBC (PubMed:15249197). Acts as a transcriptional activator of the MYC gene; binds DNA non- specifically (PubMed:8392752, PubMed:19435876). Binds to both single-stranded guanine- and cytosine-rich strands within the nuclease hypersensitive element (NHE) III(1) region of the MYC gene promoter. Does not bind to duplex NHE III(1) (PubMed:19435876). Has G-quadruplex (G4) DNA-binding activity, which is independent of its nucleotide-binding and kinase activity. Binds both folded and unfolded G4 with similar low nanomolar affinities. Stabilizes folded G4s regardless of whether they are prefolded or not (PubMed:25679041). Exhibits histidine protein kinase activity (PubMed:20946858). {ECO:0000250|UniProtKB:P36010, ECO:0000269|PubMed:15249197, ECO:0000269|PubMed:19435876, ECO:0000269|PubMed:20946858, ECO:0000269|PubMed:25679041, ECO:0000269|PubMed:8392752}.;

Recessive Scores

pRec: 0.461

Intolerance Scores

RVIS EVS: -0.19
RVIS percentile EVS: 39.68

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: N
Indispensability score: 0.0683

Gene Damage Prediction

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