LIN9
protein-codinglin-9 DREAM MuvB core complex component
Gene summary
This gene encodes a tumor suppressor protein that inhibits DNA synthesis and oncogenic transformation through association with the retinoblastoma 1 protein. The encoded protein also interacts with a complex of other cell cycle regulators to repress cell cycle-dependent gene expression in non-dividing cells. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jul 2012]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~78.7 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 LIN9 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001366245.2. 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 | 1 | 1 | ||||
| missense | 47 | 47 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 49 | 0 | 1 | 50 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001353174.1 | 15 | MANE Select | |
| Ensembl | ENSP00000505590.1 | 15 | MANE Select | |
| RefSeq | NP_001257338.1 | 14 | Standard | |
| RefSeq | NP_001257339.1 | 13 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| lin9 | Danio rerio | Structure: olfactory system Quality: apoptotic abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Cellular senescence - Homo sapiens (human)
- Gastric Cancer Network 1
- Polo-like kinase mediated events
- Transcription of E2F targets under negative control by DREAM complex
- G0 and Early G1
Biological Process
- reproduction
- transcription, DNA-templated
- cell cycle
- regulation of cell cycle
- DNA biosynthetic process
Molecular Function
- DNA binding
- protein binding
Cellular Component
- nucleoplasm
- transcriptional repressor complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000328205
- Coding exons
- 15
- Length
- 78721
- Individuals with no LoFs
- 125735
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 3
- Defined
- 125738
- p
- 0.0000119
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.39 | 176 | 291 | 0.605 | 0.0000151 | 3659 |
| Missense (PolyPhen) | 29 | 87.448 | 0.33163 | 1068 | ||
| Synonymous | 0.462 | 93 | 98.8 | 0.941 | 0.00000490 | 1030 |
| Loss of Function | 4.89 | 4 | 35.4 | 0.113 | 0.00000198 | 420 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.0000090 | 0.0000088 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Acts as a tumor suppressor. Inhibits DNA synthesis. Its ability to inhibit oncogenic transformation is mediated through its association with RB1. Plays a role in the expression of genes required for the G1/S transition. {ECO:0000269|PubMed:15538385, ECO:0000269|PubMed:16730350}.;
Recessive Scores
- pRec
- 0.421
Intolerance Scores
- LoFtool
- 0.102
- RVIS EVS
- -0.49
- RVIS percentile EVS
- 22.36
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- S
- Essential (gene trap)
- E
- Indispensability pred.
- N
- Indispensability score
- 0.239
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |