ESYT1
protein-codingextended synaptotagmin 1, the group of Extended synaptotagmins
Gene summary
Enables identical protein binding activity and phospholipid transfer activity. Involved in intermembrane lipid transfer. Located in endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Jul 2025]
- FAM62A
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~26.4 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 ESYT1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_015292.3. 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 | 4 | 4 | 8 | |||
| missense | 185 | 4 | 189 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 8 | 8 | ||||
| Total | 0 | 0 | 197 | 4 | 4 | 205 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_056107.1 | 31 | MANE Select | |
| Ensembl | ENSP00000377612.5 | 31 | MANE Select | |
| RefSeq | NP_001171725.1 | 31 | Standard | |
| Ensembl | ENSP00000267113.4 | 31 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Metabolism of lipids
- Metabolism
- EGFR1
- Glycosphingolipid metabolism
- Sphingolipid metabolism
Biological Process
- lipid transport
- endoplasmic reticulum-plasma membrane tethering
Molecular Function
- calcium ion binding
- protein binding
- calcium-dependent phospholipid binding
- phosphatidylethanolamine binding
- phosphatidylcholine binding
Cellular Component
- endoplasmic reticulum
- endoplasmic reticulum membrane
- membrane
- integral component of endoplasmic reticulum membrane
- intrinsic component of endoplasmic reticulum membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000541590
- Coding exons
- 31
- Length
- 26422
- Individuals with no LoFs
- 125601
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 146
- Defined
- 125748
- p
- 0.000585
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.846 | 568 | 628 | 0.905 | 0.0000358 | 7145 |
| Missense (PolyPhen) | 179 | 224.1 | 0.79876 | 2577 | ||
| Synonymous | 1.88 | 210 | 248 | 0.848 | 0.0000129 | 2315 |
| Loss of Function | 4.21 | 34 | 72.8 | 0.467 | 0.00000425 | 748 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00037 | 0.00037 | rare |
| Latino/Admixed American | 0.00014 | 0.00014 | rare |
| Ashkenazi Jewish | 0.0040 | 0.0039 | notable |
| East Asian | 0.00033 | 0.00033 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.00056 | 0.00055 | rare |
| South Asian | 0.00062 | 0.00062 | rare |
| Other | 0.0013 | 0.0013 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Binds glycerophospholipids in a barrel-like domain and may play a role in cellular lipid transport (By similarity). Binds calcium (via the C2 domains) and translocates to sites of contact between the endoplasmic reticulum and the cell membrane in response to increased cytosolic calcium levels. Helps tether the endoplasmic reticulum to the cell membrane and promotes the formation of appositions between the endoplasmic reticulum and the cell membrane. {ECO:0000250, ECO:0000269|PubMed:23791178, ECO:0000269|PubMed:24183667}.;
Recessive Scores
- pRec
- 0.100
Intolerance Scores
- LoFtool
- 0.930
- RVIS EVS
- -1.86
- RVIS percentile EVS
- 2.02
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.354
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |