SESTD1
protein-codingSEC14 and spectrin domain containing 1
Gene summary
Enables phosphatidylinositol-3,4-bisphosphate binding activity and phospholipid binding activity. Involved in negative regulation of calcium ion transmembrane transport via high voltage-gated calcium channel. Located in calcium channel complex and intermediate filament cytoskeleton. [provided by Alliance of Genome Resources, Jul 2025]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~163.2 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 SESTD1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_178123.5. 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 | 2 | 2 | ||||
| missense | 60 | 60 | ||||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 7 | 7 | ||||
| Total | 0 | 0 | 69 | 0 | 2 | 71 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_835224.3 | 17 | MANE Select | |
| Ensembl | ENSP00000415332.2 | 17 | MANE Select | |
| Ensembl | ENSP00000334183.5 | 5 | Standard | |
| Ensembl | ENSP00000410286.1 | 5 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| sestd1 | Danio rerio | Structure: dorsal aorta Quality: fused with abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- negative regulation of calcium ion transmembrane transport via high voltage-gated calcium channel
Molecular Function
- phosphatidylserine binding
- protein binding
- 1-phosphatidylinositol binding
- phosphatidylinositol-4,5-bisphosphate binding
- phosphatidylinositol-5-phosphate binding
Cellular Component
- calcium channel complex
- intermediate filament cytoskeleton
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000428443
- Coding exons
- 17
- Length
- 163099
- Individuals with no LoFs
- 125729
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 12
- Defined
- 125741
- p
- 0.0000477
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.31 | 235 | 358 | 0.657 | 0.0000181 | 4549 |
| Missense (PolyPhen) | 45 | 92.041 | 0.48891 | 1266 | ||
| Synonymous | 0.918 | 117 | 130 | 0.898 | 0.00000672 | 1252 |
| Loss of Function | 5.36 | 6 | 44.6 | 0.134 | 0.00000227 | 518 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0.00014 | 0.000099 | rare |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000092 | 0.000092 | rare |
| European (Non-Finnish) | 0.000053 | 0.000053 | rare |
| South Asian | 0.000066 | 0.000065 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: May act as the primary docking protein directing membrane turnover and assembly of the transient receptor potential channels TRPC4 and TRPC5. Binds phospholipids such as phosphatidylinositol monophosphates, phosphatidylinositol diphosphates (PIP2s) and phosphatidic acid, but not less polar lipids including phosphatidylcholine, phosphatidylserine, and phosphatidylinositol. The binding to PIP2s is calcium dependent. Might be involved in the plasma membrane localization of CTNNB1. {ECO:0000269|PubMed:20164195}.;
Recessive Scores
- pRec
- 0.112
Intolerance Scores
- LoFtool
- 0.478
- RVIS EVS
- -0.47
- RVIS percentile EVS
- 23.43
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.316
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |