IST1
protein-codingIST1 factor associated with ESCRT-III, the group of ESCRT-III associated factors
Gene summary
This gene encodes a protein with MIT-interacting motifs that interacts with components of endosomal sorting complexes required for transport (ESCRT). ESCRT functions in vesicle budding, such as that which occurs during membrane abscission in cytokinesis. There is a pseudogene for this gene on chromosome 19. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Aug 2012]
- KIAA0174
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~85.2 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 IST1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001270975.2. 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 | 1 | 1 | 6 | ||
| missense | 46 | 1 | 47 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 53 | 2 | 1 | 56 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001257904.1 | 9 | MANE Select | |
| Ensembl | ENSP00000368076.6 | 9 | MANE Select | |
| RefSeq | NP_001257905.1 | 10 | Standard | |
| RefSeq | NP_001257906.1 | 8 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| ist1 | Danio rerio | Structure: whole organism Quality: decreased mobility abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Endocytosis - Homo sapiens (human)
- Neutrophil degranulation
- Innate Immune System
- Immune System
Biological Process
- protein localization
- abscission
- protein transport
- viral release from host cell
- multivesicular body assembly
Molecular Function
- protein binding
- protein domain specific binding
- protein-containing complex binding
- cadherin binding
- MIT domain binding
Cellular Component
- chromatin
- extracellular region
- nuclear envelope
- endoplasmic reticulum-Golgi intermediate compartment
- centrosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000535424
- Coding exons
- 10
- Length
- 83015
- Individuals with no LoFs
- 125711
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 36
- Defined
- 125747
- p
- 0.000143
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.661 | 237 | 210 | 1.13 | 0.0000107 | 2449 |
| Missense (PolyPhen) | 26 | 50.91 | 0.51071 | 626 | ||
| Synonymous | -2.62 | 104 | 75.1 | 1.39 | 0.00000360 | 769 |
| Loss of Function | 2.41 | 7 | 18.1 | 0.387 | 9.23e-7 | 234 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00025 | 0.00025 | rare |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.00071 | 0.00038 | rare |
| Finnish | 0.00028 | 0.00028 | rare |
| European (Non-Finnish) | 0.00012 | 0.00011 | rare |
| South Asian | 0.000098 | 0.000065 | rare |
| Other | 0.00049 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: ESCRT-III-like protein involved in specific functions of the ESCRT machinery. Is required for efficient abscission during cytokinesis, but not for HIV-1 budding. The involvement in the MVB pathway is not established. Involved in recruiting VPS4A and/or VPS4B to the midbody of dividing cells (PubMed:19129479, PubMed:19129480). During late anaphase, involved in nuclear envelope reassembly and mitotic spindle disassembly together with the ESCRT-III complex: IST1 acts by mediating the recruitment of SPAST to the nuclear membrane, leading to microtubule severing (PubMed:26040712). Regulates early endosomal tubulation together with the ESCRT-III complex by mediating the recruitment of SPAST (PubMed:23897888). {ECO:0000269|PubMed:19129479, ECO:0000269|PubMed:19129480, ECO:0000269|PubMed:23897888, ECO:0000269|PubMed:26040712}.;
Recessive Scores
- pRec
- 0.127
Intolerance Scores
- RVIS EVS
- -0.49
- RVIS percentile EVS
- 22.36
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.114
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |