NME1-NME2

NME1-NME2 readthrough

Basic information

Region (hg38): 17:51153590-51171744

Links

ENSG00000011052 ∙ NCBI:654364 ∙ ∙ HGNC:33531 ∙ ∙ ∙ 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 NME1-NME2 gene.

• not provided (3 variants)
• Inborn genetic diseases (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NME1-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						0
missense						0
nonsense				1		1
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			1	1	1	3
Total	0	0	2	2	1

Variants in NME1-NME2

This is a list of pathogenic ClinVar variants found in the NME1-NME2 region.

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

Position	Type	Phenotype	Significance	ClinVar
17-51154262-C-G		not specified	Benign (Jan 24, 2024)
17-51154266-G-A		not specified	Benign (Jan 24, 2024)
17-51154423-CT-C			Uncertain significance (-)
17-51155675-C-A		NME1-NME2-related disorder	Likely benign (Aug 14, 2019)
17-51161282-T-G		NME1-NME2-related disorder	Benign (May 14, 2018)
17-51161675-C-A		not specified	Benign (Jan 24, 2024)
17-51161814-C-T		not specified	Likely benign (Jul 19, 2023)
17-51161838-A-G		not specified	Uncertain significance (Jul 06, 2021)
17-51166866-G-C		not specified	Uncertain significance (Sep 10, 2024)
17-51168327-G-T		not specified	Uncertain significance (May 24, 2024)
17-51171505-T-C			Likely benign (Feb 01, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NME1-NME2	protein_coding	protein_coding	ENST00000393193	7	18155

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);Adefovir Dipivoxil Metabolism Pathway;GLUT-1 deficiency syndrome;Congenital disorder of glycosylation CDG-IId;Tenofovir Metabolism Pathway;Lactose Synthesis;Pyrimidine metabolism;Neutrophil degranulation;pyrimidine deoxyribonucleotides <i>de novo</i> biosynthesis;UTP and CTP <i>de novo</i> 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 <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;Validated targets of C-MYC transcriptional activation (Consensus)

Intolerance Scores

• loftool: 0.636
• rvis_EVS: -0.36
• rvis_percentile_EVS: 28.63

Haploinsufficiency Scores

• hipred: Y
• hipred_score: 0.508
• ghis: 0.400

Essentials

• essential_gene_CRISPR: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.409

Mouse Genome Informatics

• Gene name: Gm5566