NME7
protein-codingNME/NM23 family member 7, the group of NME/NM23 family|Cilia and flagella associated
Gene summary
This gene encodes a member of the non-metastatic expressed family of nucleoside diphosphate kinases. Members of this family are enzymes that catalyzes phosphate transfer from nucleoside triphosphates to nucleoside diphosphates. This protein contains two kinase domains, one of which is involved in autophosphorylation and the other may be inactive. This protein localizes to the centrosome and functions as a component of the gamma-tubulin ring complex which plays a role in microtubule organization. Mutations in this gene may be associated with venous thromboembolism. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2016]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~235.4 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0010029
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0010029
Submitter: LiferaOmics
Genetic Evidence – Published PMID: 27060491 – Reports two affected siblings from one consanguineous family. Case-level (biallelic non-LOF in AR model; homozygous; consanguinity) = 0.1 Segregation (≥1 affected sibling; conservative assignment) = 0.5 Case-control = 0 Family 1 total = 0.6 Published genetic evidence total = 0.6 / 12 Genetic Evidence – Our Cases Family 1 – one proband.Case-level (biallelic predicted null in AR model; homozygous canonical splice-site; consanguinity −0.5 applied) = 1.0 Segregation = 0 Case-control = 0 Family 1 total = 1.0 Our Cases Total = 1.0 / 12 Updated Total Genetic Evidence (Published + Our Cases) Published genetic evidence: 1.0 Our additional cases: 1.0 Updated genetic total = 1.6 Experimental Evidence – Published PMID: 27060491 Functional alteration in patient-derived cells (RT-PCR confirmed abnormal splicing) = 1.0 PMID: 20080492 Animal/model evidence (Nme7 knockout mice demonstrate situs inversus phenotype) = 2.0 Experimental evidence total = 3.0 / 6 Updated Overall Score Genetic evidence = 2.0 Experimental evidence = 3.0 Updated total = 4.6 / 18
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to NME7 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_013330.5. 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 | 5 | 5 | ||||
| missense | 59 | 2 | 61 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 68 | 3 | 0 | 71 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_037462.1 | 12 | MANE Select | |
| Ensembl | ENSP00000356785.3 | 12 | MANE Select | |
| RefSeq | NP_932076.1 | 11 | Standard | |
| Ensembl | ENSP00000433341.1 | 11 | 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)
- Pyrimidine metabolism
- pyrimidine deoxyribonucleotides <i>de novo</i> biosynthesis
Biological Process
- nucleoside diphosphate phosphorylation
- GTP biosynthetic process
- UTP biosynthetic process
- CTP biosynthetic process
Molecular Function
- nucleoside diphosphate kinase activity
- protein binding
- ATP binding
- metal ion binding
Cellular Component
- centrosome
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000367811
- Coding exons
- 12
- Length
- 235437
- Individuals with no LoFs
- 125698
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 48
- Defined
- 125746
- p
- 0.000191
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.505 | 184 | 204 | 0.901 | 0.0000107 | 2472 |
| Missense (PolyPhen) | 38 | 44.693 | 0.85024 | 535 | ||
| Synonymous | 0.462 | 62 | 66.8 | 0.928 | 0.00000328 | 698 |
| Loss of Function | 1.88 | 12 | 21.4 | 0.561 | 0.00000118 | 268 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00044 | 0.00043 | rare |
| Latino/Admixed American | 0.00010 | 0.000087 | rare |
| Ashkenazi Jewish | 0.00010 | 0.000099 | rare |
| East Asian | 0.00016 | 0.00016 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.00022 | 0.00022 | rare |
| South Asian | 0.00017 | 0.00016 | rare |
| Other | 0.00049 | 0.00049 | 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.;
Recessive Scores
- pRec
- 0.132
Intolerance Scores
- LoFtool
- 0.790
- RVIS EVS
- -0.47
- RVIS percentile EVS
- 23.25
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.168
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |