NME4

NME/NM23 nucleoside diphosphate kinase 4, the group of NME/NM23 family

Basic information

Region (hg38): 16:396725-410367

Links

ENSG00000103202 ∙ NCBI:4833 ∙ OMIM:601818 ∙ HGNC:7852 ∙ Uniprot:O00746 ∙ 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 NME4 gene.

• not_specified (39 variants)
• not_provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NME4 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000005009.3. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1		1	2
missense			39	1		40
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2			2
Total	0	0	42	1	1

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NME4	protein_coding	protein_coding	ENST00000219479	5	13643

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00104	0.615	125406	0	15	125421	0.0000598

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.740	138	116	1.19	0.00000811	1204
Missense in Polyphen		54	47.17	1.1448		464
Synonymous	-1.79	61	45.6	1.34	0.00000317	394
Loss of Function	0.551	5	6.52	0.767	2.79e-7	82

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.000598	0.000299
East Asian	0.0000544	0.0000544
Finnish	0.0000660	0.0000462
European (Non-Finnish)	0.000116	0.0000795
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000327	0.0000327
Other	0.00	0.00

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. Through the catalyzed exchange of gamma- phosphate between di- and triphosphonucleosides participates in regulation of intracellular nucleotide homeostasis (PubMed:10799505). Binds to anionic phospholipids, predominantly to cardiolipin; the binding inhibits its phosphotransfer activity (PubMed:18635542, PubMed:23150663). Acts as mitochondria-specific NDK; its association with cardiolipin-containing mitochondrial inner membrane is coupled to respiration suggesting that ADP locally regenerated in the mitochondrion innermembrane space by its activity is directly taken up via ANT ADP/ATP translocase into the matrix space to stimulate respiratory ATP regeneration (PubMed:18635542). Proposed to increase GTP-loading on dynamin- related GTPase OPA1 in mitochondria (PubMed:24970086). In vitro can induce liposome cross-linking suggesting that it can cross- link inner and outer membranes to form contact sites, and promotes intermembrane migration of anionic phosphoplipids. Promotes the redistribution of cardiolipin between the mitochondrial inner membrane and outer membrane which is implicated in pro-apoptotic signaling (PubMed:18635542, PubMed:17028143, PubMed:23150663). {ECO:0000269|PubMed:10799505, ECO:0000269|PubMed:17028143, ECO:0000269|PubMed:18635542, ECO:0000269|PubMed:23150663, ECO:0000305, ECO:0000305|PubMed:24970086}.
• Pathway: Pyrimidine metabolism - Homo sapiens (human);Drug metabolism - other enzymes - Homo sapiens (human);Purine metabolism - Homo sapiens (human);Pyrimidine metabolism;pyrimidine deoxyribonucleotides <i>de novo</i> biosynthesis;UTP and CTP <i>de novo</i> biosynthesis;Metabolism of nucleotides;Folate metabolism;purine deoxyribonucleosides salvage;Interconversion of nucleotide di- and triphosphates;Purine metabolism;Metabolism;Pyrimidine metabolism;superpathway of pyrimidine ribonucleotides <i>de novo</i> 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 <i>de novo</i> biosynthesis;pyrimidine deoxyribonucleotides biosynthesis from CTP;guanosine deoxyribonucleotides <i>de novo</i> biosynthesis;guanosine nucleotides <i>de novo</i> biosynthesis;adenosine deoxyribonucleotides <i>de novo</i> biosynthesis;guanosine ribonucleotides <i>de novo</i> biosynthesis;purine nucleotides <i>de novo</i> biosynthesis (Consensus)

Recessive Scores

• pRec: 0.149

Intolerance Scores

• loftool: 0.695
• rvis_EVS: -0.54
• rvis_percentile_EVS: 20.26

Haploinsufficiency Scores

• pHI: 0.150
• hipred: Y
• hipred_score: 0.600
• ghis: 0.598

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0133

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Nme4
• Phenotype: immune system phenotype; hematopoietic system phenotype

Gene ontology

• Biological process: nucleoside diphosphate phosphorylation;GTP biosynthetic process;UTP biosynthetic process;CTP biosynthetic process;lipid transport;nucleoside metabolic process;nucleobase-containing small molecule interconversion
• Cellular component: mitochondrion;mitochondrial inner membrane;mitochondrial intermembrane space;mitochondrial matrix
• Molecular function: nucleoside diphosphate kinase activity;protein binding;ATP binding;metal ion binding;cardiolipin binding