TSPAN6
protein-codingtetraspanin 6, the group of Tetraspanins
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. The protein encoded by this gene is a cell surface glycoprotein and is highly similar in sequence to the transmembrane 4 superfamily member 2 protein. It functions as a negative regulator of retinoic acid-inducible gene I-like receptor-mediated immune signaling via its interaction with the mitochondrial antiviral signaling-centered signalosome. This gene uses alternative polyadenylation sites, and multiple transcript variants result from alternative splicing. [provided by RefSeq, Jul 2013]
- TM4SF6
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~12.9 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 TSPAN6 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003270.4. 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 | 4 | 2 | 1 | 7 | ||
| missense | 47 | 2 | 49 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 10 | 10 | ||||
| Total | 0 | 0 | 62 | 4 | 1 | 67 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003261.1 | 7 | MANE Select | |
| Ensembl | ENSP00000362111.4 | 7 | MANE Select | |
| RefSeq | NP_001265669.1 | 6 | Standard | |
| RefSeq | NP_001265670.1 | 6 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- cell surface receptor signaling pathway
- negative regulation of viral-induced cytoplasmic pattern recognition receptor signaling pathway
- positive regulation of I-kappaB kinase/NF-kappaB signaling
- negative regulation of NIK/NF-kappaB signaling
Molecular Function
- protein binding
Cellular Component
- integral component of plasma membrane
- extracellular exosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000373020
- Coding exons
- 7
- Length
- 11322
- Individuals with no LoFs
- 125723
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 3
- Defined
- 125727
- p
- 0.0000159
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.592 | 66 | 81.0 | 0.815 | 0.00000591 | 1599 |
| Missense (PolyPhen) | 13 | 18.408 | 0.7062 | 384 | ||
| Synonymous | -0.475 | 34 | 30.7 | 1.11 | 0.00000248 | 457 |
| Loss of Function | 1.61 | 3 | 7.87 | 0.381 | 5.56e-7 | 166 |
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) | 0.000077 | 0.000035 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
Recessive Scores
- pRec
- 0.0692
Intolerance Scores
- LoFtool
- 0.568
- RVIS EVS
- -0.12
- RVIS percentile EVS
- 44.89
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.539
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |