NUP88
protein-codingnucleoporin 88, the group of Nucleoporins
Gene summary
The nuclear pore complex is a massive structure that extends across the nuclear envelope, forming a gateway that regulates the flow of macromolecules between the nucleus and the cytoplasm. Nucleoporins, a family of 50 to 100 proteins, are the main components of the nuclear pore complex in eukaryotic cells. The protein encoded by this gene belongs to the nucleoporin family and is associated with the oncogenic nucleoporin CAN/Nup214 in a dynamic subcomplex. This protein is also overexpressed in a large number of malignant neoplasms and precancerous dysplasias. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2016]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~60.5 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0100101
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0100104
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0100104
Submitter: PanelApp Australia
Clinical Genomic Database (CGD)
Manifestation: Musculoskeletal; Neurologic
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 NUP88 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002532.6. 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 | 4 | 6 | 10 | |||
| missense | 1 | 120 | 10 | 1 | 132 | |
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 2 | 1 | 128 | 16 | 1 | 148 |
Highest pathogenic variant AF is 0.000042270734
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002523.2 | 17 | MANE Select | |
| Ensembl | ENSP00000458954.1 | 17 | MANE Select | |
| RefSeq | NP_001307582.1 | 17 | Standard | |
| Ensembl | ENSP00000225696.5 | 17 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| nup88 | Danio rerio | Structure: melanocyte Quality: quality abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- RNA transport - Homo sapiens (human)
- tRNA processing
- Disease
- Gene expression (Transcription)
- Regulation of HSF1-mediated heat shock response
Biological Process
- ribosomal large subunit export from nucleus
- ribosomal small subunit export from nucleus
- mitotic cell cycle
- mRNA export from nucleus
- protein import into nucleus
Molecular Function
- transporter activity
- structural constituent of nuclear pore
Cellular Component
- nuclear pore
- nucleoplasm
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000573584
- Coding exons
- 17
- Length
- 59223
- Individuals with no LoFs
- 125641
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 107
- Defined
- 125748
- p
- 0.000426
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.526 | 436 | 406 | 1.07 | 0.0000208 | 4821 |
| Missense (PolyPhen) | 134 | 132.61 | 1.0105 | 1623 | ||
| Synonymous | -0.231 | 161 | 157 | 1.02 | 0.00000832 | 1432 |
| Loss of Function | 3.18 | 20 | 42.3 | 0.473 | 0.00000223 | 510 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00025 | 0.00025 | rare |
| Latino/Admixed American | 0.00026 | 0.00026 | rare |
| Ashkenazi Jewish | 0.00020 | 0.00020 | rare |
| East Asian | 0.00049 | 0.00049 | rare |
| Finnish | 0.00023 | 0.00023 | rare |
| European (Non-Finnish) | 0.00052 | 0.00052 | rare |
| South Asian | 0.00056 | 0.00056 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Essential component of nuclear pore complex.;
Recessive Scores
- pRec
- 0.103
Intolerance Scores
- LoFtool
- 0.887
- RVIS EVS
- -1.11
- RVIS percentile EVS
- 6.86
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.588
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |