HEG1
protein-codingheart development protein with EGF like domains 1
Gene summary
Predicted to enable calcium ion binding activity. Involved in several processes, including negative regulation of Rho protein signal transduction; negative regulation of membrane permeability; and obsolete negative regulation of Rho-dependent protein serine/threonine kinase activity. Located in cell-cell junction. [provided by Alliance of Genome Resources, Jun 2026]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~90.3 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 HEG1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_020733.2. 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 | 3 | 1 | 7 | ||
| missense | 203 | 19 | 3 | 225 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 5 | 5 | ||||
| Total | 0 | 0 | 211 | 22 | 4 | 237 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_065784.1 | 17 | MANE Select | |
| Ensembl | ENSP00000311502.3 | 17 | MANE Select | |
| Ensembl | ENSP00000417494.1 | 2 | Standard | |
| Ensembl | ENSP00000515478.1 | 18 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| heg1 | Danio rerio | Structure: myocardium Quality: distended abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- vasculogenesis
- in utero embryonic development
- endothelial cell morphogenesis
- lymph vessel development
- lymph circulation
Molecular Function
- calcium ion binding
- protein binding
Cellular Component
- extracellular region
- cell-cell junction
- external side of plasma membrane
- integral component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000311127
- Coding exons
- 17
- Length
- 90249
- Individuals with no LoFs
- 124617
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 22
- Defined
- 124639
- p
- 0.0000883
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.474 | 643 | 678 | 0.949 | 0.0000368 | 8747 |
| Missense (PolyPhen) | 124 | 154.37 | 0.80326 | 1949 | ||
| Synonymous | 1.10 | 246 | 269 | 0.915 | 0.0000156 | 2956 |
| Loss of Function | 4.05 | 21 | 52.7 | 0.398 | 0.00000287 | 676 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.00023 | 0.00023 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000057 | 0.000056 | rare |
| Finnish | 0.000093 | 0.000093 | rare |
| European (Non-Finnish) | 0.000080 | 0.000080 | rare |
| South Asian | 0.000070 | 0.000065 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Receptor component of the CCM signaling pathway which is a crucial regulator of heart and vessel formation and integrity May act through the stabilization of endothelial cell junctions. {ECO:0000250}.;
Intolerance Scores
- LoFtool
- 0.166
- RVIS EVS
- 0.99
- RVIS percentile EVS
- 90.5
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.174
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | High | High | High |
| Primary Immunodeficiency | High | High | High |
| Cancer | High | High | High |