TSPAN14
protein-codingtetraspanin 14, the group of Tetraspanins
Gene summary
Enables enzyme binding activity. Involved in positive regulation of Notch signaling pathway; protein localization to plasma membrane; and protein maturation. Located in plasma membrane. [provided by Alliance of Genome Resources, Jul 2025]
- TM4SF14
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~78.9 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 TSPAN14 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_030927.4. 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 | 1 | 4 | |||
| missense | 27 | 1 | 28 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 0 | 35 | 1 | 1 | 37 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_112189.2 | 8 | MANE Select | |
| Ensembl | ENSP00000396270.2 | 8 | MANE Select | |
| RefSeq | NP_001121781.1 | 5 | Standard | |
| RefSeq | NP_001338195.1 | 8 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Neutrophil degranulation
- Innate Immune System
- Immune System
Biological Process
- cell surface receptor signaling pathway
- neutrophil degranulation
- cellular protein metabolic process
- positive regulation of Notch signaling pathway
- protein maturation
Molecular Function
- enzyme binding
Cellular Component
- endoplasmic reticulum lumen
- plasma membrane
- integral component of plasma membrane
- cell surface
- specific granule membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000429989
- Coding exons
- 8
- Length
- 78958
- Individuals with no LoFs
- 125745
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 3
- Defined
- 125748
- p
- 0.0000119
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.21 | 90 | 171 | 0.525 | 0.0000109 | 1772 |
| Missense (PolyPhen) | 23 | 69.885 | 0.32911 | 759 | ||
| Synonymous | -0.0666 | 75 | 74.3 | 1.01 | 0.00000523 | 509 |
| Loss of Function | 3.50 | 1 | 16.2 | 0.0616 | 7.78e-7 | 173 |
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) | 0.000026 | 0.000026 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Regulates maturation and trafficking of the transmembrane metalloprotease ADAM10 (PubMed:26668317, PubMed:23035126, PubMed:26686862). Negatively regulates ADAM10- mediated cleavage of GP6 (By similarity). Promotes ADAM10-mediated cleavage of CDH5 (By similarity). {ECO:0000250|UniProtKB:Q8QZY6, ECO:0000269|PubMed:23035126, ECO:0000269|PubMed:26668317, ECO:0000269|PubMed:26686862}.;
Recessive Scores
- pRec
- 0.116
Intolerance Scores
- LoFtool
- 0.162
- RVIS EVS
- -0.34
- RVIS percentile EVS
- 30.07
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.415
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |