THSD7A
protein-codingthrombospondin type 1 domain containing 7A
Gene summary
The protein encoded by this gene is found almost exclusively in endothelial cells from placenta and umbilical cord. The encoded protein appears to interact with alpha(V)beta(3) integrin and paxillin to inhibit endothelial cell migration and tube formation. This protein may be involved in cytoskeletal organization. Variations in this gene may be associated with low bone mineral density in osteoporosis. [provided by RefSeq, Aug 2010]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~461.8 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 THSD7A variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_015204.3. 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 | 7 | 6 | 14 | ||
| missense | 279 | 11 | 1 | 291 | ||
| nonsense | 0 | |||||
| start loss | 1 | 1 | ||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 5 | 5 | ||||
| Total | 0 | 0 | 287 | 18 | 7 | 312 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_056019.1 | 28 | MANE Select | |
| Ensembl | ENSP00000406482.2 | 28 | MANE Select | |
| Ensembl | ENSP00000783532.1 | 13 | Standard | |
| Ensembl | ENSP00000798788.1 | 2 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| thsd7aa | Danio rerio | Structure: endothelial tip cell Quality: morphology abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Post-translational protein modification
- Metabolism of proteins
- O-glycosylation of TSR domain-containing proteins
- O-linked glycosylation
Biological Process
- angiogenesis
- cell differentiation
- actin cytoskeleton reorganization
Cellular Component
- extracellular region
- plasma membrane
- integral component of membrane
- cell projection
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000423059
- Coding exons
- 28
- Length
- 461841
- Individuals with no LoFs
- 124619
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 27
- Defined
- 124646
- p
- 0.000108
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.598 | 947 | 897 | 1.06 | 0.0000486 | 10780 |
| Missense (PolyPhen) | 239 | 289.08 | 0.82675 | 3239 | ||
| Synonymous | -3.11 | 405 | 333 | 1.22 | 0.0000189 | 3058 |
| Loss of Function | 8.06 | 14 | 102 | 0.138 | 0.00000553 | 1115 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00013 | 0.00013 | rare |
| Latino/Admixed American | 0.000058 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000056 | 0.000056 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00016 | 0.00016 | rare |
| South Asian | 0.00016 | 0.00016 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Thrombospondin type-1 domain-containing protein 7A: Plays a role in actin cytoskeleton rearrangement. {ECO:0000269|PubMed:27214550}.;
- Disease
- DISEASE: Note=Autoantibodies against THSD7A have been detected in serum and glomeruli from patients with idiopathic membranous nephropathy (PubMed:25394321). The majority of the autoantibodies react with the two most N-terminal TSP type-1 domains (PubMed:29555830). {ECO:0000269|PubMed:25394321, ECO:0000269|PubMed:29555830}.;
Recessive Scores
- pRec
- 0.0894
Intolerance Scores
- RVIS EVS
- -1.31
- RVIS percentile EVS
- 4.87
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.237
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | High |
| Cancer | Medium | Medium | Medium |