NME1-NME2
protein-codingNME1-NME2 readthrough
Gene summary
This locus represents naturally occurring read-through transcription between the neighboring NME1 and NME2 genes. The significance of this read-through transcription and the function of the resulting protein product have not yet been determined. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Nov 2010]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~18.2 kbGenCC 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 NME1-NME2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript . 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 | 0 | |||||
| missense | 0 | |||||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 1 | 1 | 0 | 2 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001018146.1 | 7 | Standard | |
| Ensembl | ENSP00000365572.6 | 6 | Standard | |
| Ensembl | ENSP00000376889.2 | 7 | Standard | |
| Ensembl | ENSP00000451932.1 | 8 | Standard |
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)
- Adefovir Dipivoxil Metabolism Pathway
- GLUT-1 deficiency syndrome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000393193
- Coding exons
- 7
- Length
- 18155
- 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:
- 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}.;
Intolerance Scores
- LoFtool
- 0.636
- RVIS EVS
- -0.36
- RVIS percentile EVS
- 28.63
Essentials
- Essential (CRISPR)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.409