ISM1
protein-codingisthmin 1, the group of Isthmin family
Gene summary
Predicted to be involved in negative regulation of angiogenesis. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Jul 2025]
- C20orf82
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~79.4 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 ISM1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_080826.2. 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 | 5 | 5 | ||||
| missense | 67 | 5 | 3 | 75 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 69 | 10 | 3 | 82 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_543016.1 | 6 | MANE Select | |
| Ensembl | ENSP00000262487.3 | 6 | MANE Select | |
| Ensembl | ENSP00000690887.1 | 4 | Standard | |
| Ensembl | ENSP00000803333.1 | 6 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| ism1 | Danio rerio | Structure: neutrophil Quality: decreased amount abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- negative regulation of angiogenesis
Cellular Component
- extracellular region
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000262487
- Coding exons
- 6
- Length
- 78881
- Individuals with no LoFs
- 124605
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 35
- Defined
- 124640
- p
- 0.000140
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.07 | 216 | 265 | 0.815 | 0.0000164 | 3040 |
| Missense (PolyPhen) | 63 | 112.83 | 0.55836 | 1285 | ||
| Synonymous | 0.297 | 110 | 114 | 0.965 | 0.00000836 | 894 |
| Loss of Function | 2.53 | 7 | 18.9 | 0.371 | 9.82e-7 | 204 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00032 | 0.00032 | rare |
| Latino/Admixed American | 0.00012 | 0.00012 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000056 | 0.000056 | rare |
| Finnish | 0.00070 | 0.00070 | rare |
| European (Non-Finnish) | 0.000081 | 0.000080 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Acts as an angiogenesis inhibitor. {ECO:0000250|UniProtKB:A2ATD1}.;
Recessive Scores
- pRec
- 0.124
Intolerance Scores
- LoFtool
- 0.619
- RVIS EVS
- 0.15
- RVIS percentile EVS
- 64.61
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 |