NME2

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

Basic information

Region (hg38): 17:51165435-51171744

Links

ENSG00000243678

∙ NCBI:4831 ∙ OMIM:156491 ∙ HGNC:7850 ∙ Uniprot:P22392 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NME2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NME2 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				1 clinvar		1
missense						0
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	0	1	0

Variants in NME2

This is a list of pathogenic ClinVar variants found in the NME2 region.

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

Position	Phenotype	Significance	ClinVar
17-51166866-G-C	not specified	Uncertain significance (Sep 10, 2024)	3406322
17-51168327-G-T	not specified	Uncertain significance (May 24, 2024)	3300145
17-51171505-T-C		Likely benign (Feb 01, 2023)	2647946

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NME2	protein_coding	protein_coding	ENST00000393198	7	18189

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
8.85e-9	0.166	125704	0	44	125748	0.000175

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.876	132	164	0.807	0.00000939	1743
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000152	0.000150
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.000763	0.000761
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000107	0.000105
Middle Eastern	0.000763	0.000761
South Asian	0.000361	0.000359
Other	0.000163	0.000163

dbNSFP

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}.;
Pathway: 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;Zidovudine Pathway, Pharmacokinetics/Pharmacodynamics;Lamivudine Pathway, Pharmacokinetics/Pharmacodynamics;Abacavir Pathway, Pharmacokinetics/Pharmacodynamics;Adefovir Dipivoxil Metabolism Pathway;GLUT-1 deficiency syndrome;Congenital disorder of glycosylation CDG-IId;Tenofovir Metabolism Pathway;Lactose Synthesis;Pyrimidine metabolism;Nucleotide Metabolism;Neutrophil degranulation;pyrimidine deoxyribonucleotides de novo biosynthesis;UTP and CTP de novo biosynthesis;endocytotic role of ndk phosphins and dynamin;Metabolism of nucleotides;Folate metabolism;purine deoxyribonucleosides salvage;Interconversion of nucleotide di- and triphosphates;Purine metabolism;Innate Immune System;Immune System;Metabolism;Pyrimidine metabolism;superpathway of pyrimidine ribonucleotides de novo biosynthesis;superpathway of pyrimidine deoxyribonucleoside salvage;Purine nucleotides nucleosides metabolism;CMP phosphorylation;superpathway of purine nucleotide salvage;Pyrimidine nucleotides nucleosides metabolism;pyrimidine deoxyribonucleotide phosphorylation;superpathway of pyrimidine deoxyribonucleotides de novo biosynthesis;pyrimidine deoxyribonucleotides biosynthesis from CTP;guanosine deoxyribonucleotides de novo biosynthesis;guanosine nucleotides de novo biosynthesis;adenosine deoxyribonucleotides de novo biosynthesis;guanosine ribonucleotides de novo biosynthesis;purine nucleotides de novo biosynthesis;Validated targets of C-MYC transcriptional activation (Consensus)

Recessive Scores

pRec: 0.461

Intolerance Scores

loftool
rvis_EVS: -0.19
rvis_percentile_EVS: 39.68

Haploinsufficiency Scores

pHI
hipred: N
hipred_score: 0.296
ghis: 0.420

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap
gene_indispensability_pred: N
gene_indispensability_score: 0.0683

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Nme2
Phenotype: hematopoietic system phenotype; immune system phenotype;

Zebrafish Information Network

Gene name: nme2b.2
Affected structure: GTP biosynthetic process
Phenotype tag: abnormal
Phenotype quality: decreased rate

Gene ontology

Biological process: negative regulation of myeloid leukocyte differentiation;nucleoside diphosphate phosphorylation;GTP biosynthetic process;UTP biosynthetic process;CTP biosynthetic process;cell adhesion;adenylate cyclase-activating G protein-coupled receptor signaling pathway;integrin-mediated signaling pathway;nucleoside triphosphate biosynthetic process;positive regulation of neuron projection development;nucleobase-containing small molecule interconversion;peptidyl-histidine phosphorylation;cellular response to oxidative stress;negative regulation of apoptotic process;neutrophil degranulation;positive regulation of keratinocyte differentiation;regulation of epidermis development;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;protein autophosphorylation;positive regulation of epithelial cell proliferation;protein complex oligomerization;response to growth hormone;cellular response to glucose stimulus;cellular response to fatty acid
Cellular component: ruffle;extracellular region;nucleus;cytoplasm;cytosol;intermediate filament;focal adhesion;lamellipodium;mitochondrial membrane;secretory granule lumen;myelin sheath;perinuclear region of cytoplasm;extracellular exosome;cell periphery;ficolin-1-rich granule lumen
Molecular function: DNA binding;transcription coactivator activity;nucleoside diphosphate kinase activity;protein histidine kinase activity;protein serine/threonine kinase activity;fatty acid binding;protein binding;ATP binding;GDP binding;intermediate filament binding;enzyme binding;metal ion binding;G-quadruplex DNA binding