CYTH1
protein-codingcytohesin 1, the group of Cytohesins|Pleckstrin homology domain containing
Gene summary
The protein encoded by this gene is a member of the PSCD family. Members of this family have identical structural organization that consists of an N-terminal coiled-coil motif, a central Sec7 domain, and a C-terminal pleckstrin homology (PH) domain. The coiled-coil motif is involved in homodimerization, the Sec7 domain contains guanine-nucleotide exchange protein activity, and the PH domain interacts with phospholipids and is responsible for association of PSCDs with membranes. Members of this family appear to mediate the regulation of protein sorting and membrane trafficking. This gene is highly expressed in natural killer and peripheral T cells, and regulates the adhesiveness of integrins at the plasma membrane of lymphocytes. A pseudogene of this gene has been defined on the X chromosome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]
- PSCD1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~108.2 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 CYTH1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_004762.6. 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 | 0 | |||||
| missense | 42 | 42 | ||||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 7 | 7 | ||||
| Total | 0 | 0 | 50 | 0 | 0 | 50 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_004753.1 | 14 | MANE Select | |
| Ensembl | ENSP00000389095.3 | 14 | MANE Select | |
| RefSeq | NP_001278947.1 | 11 | Standard | |
| RefSeq | NP_001278948.1 | 11 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Endocytosis - Homo sapiens (human)
- Phospholipase D signaling pathway - Homo sapiens (human)
- Vesicle-mediated transport
- thrombin signaling and protease-activated receptors
- Membrane Trafficking
Biological Process
- vesicle-mediated transport
- regulation of cell adhesion
- regulation of ARF protein signal transduction
- establishment of epithelial cell polarity
Molecular Function
- ARF guanyl-nucleotide exchange factor activity
- protein binding
- lipid binding
Cellular Component
- Golgi membrane
- cytoplasm
- cytosol
- plasma membrane
- adherens junction
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000361101
- Coding exons
- 13
- Length
- 108250
- Individuals with no LoFs
- 125587
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 2
- Defined
- 125589
- p
- 0.00000796
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.44 | 131 | 237 | 0.554 | 0.0000143 | 2657 |
| Missense (PolyPhen) | 25 | 69.095 | 0.36182 | 767 | ||
| Synonymous | -0.512 | 96 | 89.8 | 1.07 | 0.00000563 | 695 |
| Loss of Function | 4.58 | 0 | 24.5 | 0.00 | 0.00000137 | 274 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000018 | 0.000018 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Promotes guanine-nucleotide exchange on ARF1, ARF5 and ARF6. Promotes the activation of ARF factors through replacement of GDP with GTP. Plays an important role in membrane trafficking, during junctional remodeling and epithelial polarization, through regulation of ARF6 activity. {ECO:0000250|UniProtKB:Q9QX11, ECO:0000269|PubMed:10652308, ECO:0000269|PubMed:29420262, ECO:0000269|PubMed:9653114}.;
Recessive Scores
- pRec
- 0.216
Intolerance Scores
- LoFtool
- 0.380
- RVIS EVS
- -0.54
- RVIS percentile EVS
- 20.54
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- H
- Indispensability pred.
- E
- Indispensability score
- 0.856
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |