TM4SF4
protein-codingtransmembrane 4 L six family member 4
Gene summary
The protein encoded by this gene is a member of the transmembrane 4 superfamily, also known as the tetraspanin family. Most of these members are cell-surface proteins that are characterized by the presence of four hydrophobic domains. The proteins mediate signal transduction events that play a role in the regulation of cell development, activation, growth and motility. This encoded protein is a cell surface glycoprotein that can regulate cell proliferation.[provided by RefSeq, Mar 2011]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~28.7 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 TM4SF4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_004617.4. 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 | 3 | 3 | ||||
| missense | 37 | 3 | 40 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 42 | 3 | 0 | 45 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_004608.1 | 5 | MANE Select | |
| Ensembl | ENSP00000305852.4 | 5 | MANE Select | |
| Ensembl | ENSP00000419367.1 | 2 | Standard | |
| Ensembl | ENSP00000535287.1 | 6 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| tm4sf4 | Danio rerio | Structure: pancreatic A cell Quality: increased amount abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- tissue regeneration
Molecular Function
- protein binding
Cellular Component
- integral component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000305354
- Coding exons
- 5
- Length
- 29308
- Individuals with no LoFs
- 124569
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 82
- Defined
- 124651
- p
- 0.000329
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.181 | 123 | 117 | 1.05 | 0.00000619 | 1307 |
| Missense (PolyPhen) | 37 | 39.931 | 0.9266 | 459 | ||
| Synonymous | -1.11 | 58 | 48.2 | 1.20 | 0.00000298 | 397 |
| Loss of Function | 0.0229 | 11 | 11.1 | 0.993 | 6.40e-7 | 113 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00026 | 0.00026 | rare |
| Latino/Admixed American | 0.00093 | 0.00087 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00017 | 0.00017 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00031 | 0.00030 | rare |
| South Asian | 0.00020 | 0.00020 | rare |
| Other | 0.00089 | 0.00083 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Regulates the adhesive and proliferative status of intestinal epithelial cells. Can mediate density-dependent cell proliferation.;
Recessive Scores
- pRec
- 0.0833
Intolerance Scores
- LoFtool
- 0.754
- RVIS EVS
- -0.27
- RVIS percentile EVS
- 34.32
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.0220
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |