THSD1
protein-codingthrombospondin type 1 domain containing 1
Gene summary
The protein encoded by this gene contains a type 1 thrombospondin domain, which is found in a number of proteins involved in the complement pathway, as well as in extracellular matrix proteins. Alternatively spliced transcript variants encoding different isoforms have been observed for this gene. [provided by RefSeq, Jan 2009]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~39.2 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0009369
Submitter: King Faisal Specialist Hospital and Research Center
THSD1 was first reported in relation to autosomal recessive form of Non-immune hydrops fetalis (Shamseldin et al., 2015, PMID:26036949). At least 6 unique variants (e.g. missense, frameshift and nonsense) have been reported in humans. Variants in this gene have been reported in at least 8 probands in 5 publications (PMID:26036949; PMID:31130284;PMID:28600779; PMID:30055085; PMID: 33569873). Two publications with convincing evidence and no convincing contradictory evidence classified THSD1 as definitive. Gene is scored according to ClinGen classification.
Inheritance Pattern: AR
Disease ID:MONDO:0019042
Submitter: Ambry Genetics
Inheritance Pattern: AR
Disease ID:MONDO:0859379
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AD
Disease ID:MONDO:0016483
Submitter: Orphanet
Inheritance Pattern: AD
Disease ID:MONDO:0032891
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AD
Disease ID:MONDO:0032891
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0859379
Submitter: PanelApp Australia
Inheritance Pattern: AD
Disease ID:MONDO:0032891
Submitter: Ambry Genetics
Clinical Genomic Database (CGD)
Manifestation: Cardiovascular
Intervention: Cardiovascular
Rationale: Individuals with Aneurysm, intracranial berry, 12 have been described with intracranial aneurysms, some of which progressed to subarachnoid hemorrhage, and awareness may allow early diagnosis and management; Individuals with Lymphatic malformation 13 may have cardiovascular anomalies, and awareness may allow early diagnosis and management
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to THSD1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_018676.4. 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 | 25 | 3 | 31 | ||
| missense | 1 | 97 | 6 | 104 | ||
| nonsense | 2 | 2 | 4 | 8 | ||
| start loss | 0 | |||||
| frameshift | 1 | 2 | 1 | 4 | ||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 3 | 5 | 105 | 31 | 3 | 147 |
Highest pathogenic variant AF is 0.000009913333
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_061146.1 | 4 | MANE Select | |
| Ensembl | ENSP00000258613.4 | 4 | MANE Select | |
| RefSeq | NP_954872.1 | 3 | Standard | |
| Ensembl | ENSP00000340650.4 | 3 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| thsd1 | Danio rerio | Structure: cranial vasculature Quality: hemorrhagic 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
Cellular Component
- extracellular region
- cytosol
- integral component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000258613
- Coding exons
- 4
- Length
- 29325
- Individuals with no LoFs
- 125677
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 71
- Defined
- 125748
- p
- 0.000282
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.497 | 452 | 483 | 0.936 | 0.0000276 | 5572 |
| Missense (PolyPhen) | 105 | 122.51 | 0.85706 | 1510 | ||
| Synonymous | 0.0347 | 200 | 201 | 0.997 | 0.0000127 | 1745 |
| Loss of Function | 2.04 | 16 | 27.5 | 0.581 | 0.00000157 | 315 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00043 | 0.00043 | rare |
| Latino/Admixed American | 0.00026 | 0.00026 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00027 | 0.00027 | rare |
| Finnish | 0.00032 | 0.00032 | rare |
| European (Non-Finnish) | 0.00024 | 0.00019 | rare |
| South Asian | 0.00059 | 0.00059 | rare |
| Other | 0.00066 | 0.00049 | rare |
dbNSFP Gene Annotations
Source:
Recessive Scores
- pRec
- 0.112
Intolerance Scores
- LoFtool
- 0.878
- RVIS EVS
- 0.09
- RVIS percentile EVS
- 60.68
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.119
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |