NT5E
protein-coding5'-nucleotidase ecto, the group of 5'-nucleotidases|CD molecules
Gene summary
The protein encoded by this gene is a plasma membrane protein that catalyzes the conversion of extracellular nucleotides to membrane-permeable nucleosides. The encoded protein is used as a determinant of lymphocyte differentiation. Defects in this gene can lead to the calcification of joints and arteries. Two transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Mar 2011]
- NT5
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~46.2 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0008895
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0008895
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0008895
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0008895
Submitter: Ambry Genetics
Clinical Genomic Database (CGD)
Manifestation: Cardiovascular; Musculoskeletal
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to NT5E variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002526.4. 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 | 1 | 13 | 4 | 18 | ||
| missense | 1 | 86 | 5 | 2 | 94 | |
| nonsense | 1 | 2 | 2 | 5 | ||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | 2 | |||
| Total | 2 | 4 | 90 | 18 | 6 | 120 |
Highest pathogenic variant AF is 0.00009913824
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002517.1 | 9 | MANE Select | |
| Ensembl | ENSP00000257770.3 | 9 | MANE Select | |
| RefSeq | NP_001191742.1 | 8 | Standard | |
| Ensembl | ENSP00000358660.3 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Pyrimidine metabolism - Homo sapiens (human)
- Nicotinate and nicotinamide metabolism - Homo sapiens (human)
- Purine metabolism - Homo sapiens (human)
- Thiopurine Pathway, Pharmacokinetics/Pharmacodynamics
- miR-targeted genes in epithelium - TarBase
Biological Process
- purine nucleotide catabolic process
- AMP catabolic process
- DNA metabolic process
- leukocyte cell-cell adhesion
- dephosphorylation
Molecular Function
- nucleotide binding
- 5'-nucleotidase activity
- metal ion binding
Cellular Component
- nucleoplasm
- cytosol
- plasma membrane
- cell surface
- membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000257770
- Coding exons
- 9
- Length
- 45692
- Individuals with no LoFs
- 125651
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 97
- Defined
- 125748
- p
- 0.000386
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.604 | 291 | 321 | 0.905 | 0.0000166 | 3733 |
| Missense (PolyPhen) | 88 | 103.71 | 0.84852 | 1154 | ||
| Synonymous | 1.01 | 112 | 126 | 0.886 | 0.00000683 | 1135 |
| Loss of Function | 0.877 | 19 | 23.6 | 0.805 | 0.00000117 | 288 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00062 | 0.00062 | rare |
| Latino/Admixed American | 0.00059 | 0.00058 | rare |
| Ashkenazi Jewish | 0.00050 | 0.00050 | rare |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00051 | 0.00048 | rare |
| South Asian | 0.00013 | 0.00013 | rare |
| Other | 0.00051 | 0.00049 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Hydrolyzes extracellular nucleotides into membrane permeable nucleosides. Exhibits AMP-, NAD-, and NMN-nucleosidase activities. {ECO:0000269|PubMed:21933152}.;
- Disease
- DISEASE: Calcification of joints and arteries (CALJA) [MIM:211800]: A condition characterized by adult-onset calcification of the lower extremity arteries, including the iliac, femoral and tibial arteries, and hand and foot capsule joints. Age of onset has been reported as early as the second decade of life, usually involving intense joint pain or calcification in the hands. {ECO:0000269|PubMed:21288095, ECO:0000269|PubMed:24887587}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.463
Intolerance Scores
- LoFtool
- 0.512
- RVIS EVS
- 0.04
- RVIS percentile EVS
- 57.41
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.262
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |