SEPTIN4
protein-codingseptin 4, the group of Septins
Gene summary
This gene is a member of the septin family of nucleotide binding proteins, originally described in yeast as cell division cycle regulatory proteins. Septins are highly conserved in yeast, Drosophila, and mouse, and appear to regulate cytoskeletal organization. Disruption of septin function disturbs cytokinesis and results in large multinucleate or polyploid cells. This gene is highly expressed in brain and heart. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. One of the isoforms (known as ARTS) is distinct; it is localized to the mitochondria, and has a role in apoptosis and cancer. [provided by RefSeq, Nov 2010]
- PNUTL2
- C17orf47
- SEPT4
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~24.1 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0005372
Submitter: PanelApp Australia
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to SEPTIN4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001368771.2. 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 | 81 | 4 | 1 | 86 | ||
| nonsense | 1 | 1 | 2 | |||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 1 | 83 | 5 | 1 | 90 |
Highest pathogenic variant AF is 0.00009417211
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001355700.1 | 14 | MANE Select | |
| Ensembl | ENSP00000500383.1 | 14 | MANE Select | |
| RefSeq | NP_001033793.3 | 2 | Standard | |
| RefSeq | NP_001185642.1 | 12 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Apoptosis - multiple species - Homo sapiens (human)
- Apoptosis - Homo sapiens (human)
- Apoptosis Modulation and Signaling
Biological Process
- apoptotic process
- brain development
- regulation of exocytosis
- sperm mitochondrion organization
- positive regulation of protein ubiquitination
Molecular Function
- magnesium ion binding
- GTPase activity
- structural molecule activity
- protein binding
- GTP binding
Cellular Component
- nucleus
- nucleoplasm
- mitochondrion
- septin ring
- synaptic vesicle
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000457347
- Coding exons
- 13
- Length
- 20569
- Individuals with no LoFs
- 125717
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 31
- Defined
- 125748
- p
- 0.000123
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.36 | 222 | 287 | 0.774 | 0.0000173 | 3249 |
| Missense (PolyPhen) | 70 | 108.43 | 0.64559 | 1240 | ||
| Synonymous | 1.35 | 87 | 105 | 0.832 | 0.00000552 | 954 |
| Loss of Function | 2.83 | 11 | 26.8 | 0.411 | 0.00000164 | 290 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0.00012 | 0.00012 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.00014 | 0.00014 | rare |
| South Asian | 0.00020 | 0.00020 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Filament-forming cytoskeletal GTPase (By similarity). May play a role in cytokinesis (Potential). Forms a filamentous structure with SEPT12, SEPT6, SEPT2 and probably SEPT4 at the sperm annulus which is required for the structural integrity and motility of the sperm tail during postmeiotic differentiation (PubMed:25588830). May play a role in platelet secretion. Isoform ARTS, but not the other isoforms, is required for the induction of cell death mediated by TGF-beta and by other apoptotic stimuli. {ECO:0000250, ECO:0000269|PubMed:11146656, ECO:0000269|PubMed:15029247, ECO:0000269|PubMed:15116257, ECO:0000269|PubMed:15837787, ECO:0000269|PubMed:9889007, ECO:0000305, ECO:0000305|PubMed:25588830}.;
Recessive Scores
- pRec
- 0.205
Intolerance Scores
- LoFtool
- 0.905
- RVIS EVS
- -0.8
- RVIS percentile EVS
- 12.33
Essentials
- Essential (CRISPR)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.249
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |