UNC13B
protein-codingunc-13 homolog B, the group of UNC13 homologs
Gene summary
This gene is expressed in the kidney cortical epithelial cells and is upregulated by hyperglycemia. The encoded protein shares a high level of similarity to the rat homolog, and contains 3 C2 domains and a diacylglycerol-binding C1 domain. Hyperglycemia increases the levels of diacylglycerol, which has been shown to induce apoptosis in cells transfected with this gene and thus contribute to the renal cell complications of hyperglycemia. Studies in other species also indicate a role for this protein in the priming step of synaptic vesicle exocytosis. [provided by RefSeq, Jul 2008]
- UNC13
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~243.3 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0005027
Submitter: PanelApp Australia
Inheritance Pattern: AD
Disease ID:MONDO:0005027
Submitter: PanelApp Australia
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to UNC13B variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001371189.2. 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 | 2 | 2 | 7 | ||
| missense | 217 | 9 | 2 | 228 | ||
| nonsense | 3 | 3 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 6 | 6 | ||||
| Total | 0 | 0 | 230 | 11 | 4 | 245 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001358118.1 | 40 | MANE Select | |
| Ensembl | ENSP00000490228.1 | 40 | MANE Select | |
| RefSeq | NP_001317582.1 | 40 | Standard | |
| RefSeq | NP_001358115.1 | 39 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Synaptic vesicle cycle - Homo sapiens (human)
- Synaptic Vesicle Pathway
- Monoamine Transport
- Effects of Botulinum toxin
- Neuronal System
Biological Process
- chemical synaptic transmission
- neuromuscular junction development
- positive regulation of synaptic vesicle priming
- synaptic vesicle docking
- synaptic vesicle priming
Molecular Function
- calcium ion binding
- protein binding
- calmodulin binding
- phospholipid binding
- syntaxin-1 binding
Cellular Component
- Golgi apparatus
- cytosol
- plasma membrane
- membrane
- cell junction
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000378495
- Coding exons
- 39
- Length
- 243337
- Individuals with no LoFs
- 125622
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 126
- Defined
- 125748
- p
- 0.000501
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.45 | 794 | 917 | 0.866 | 0.0000534 | 10513 |
| Missense (PolyPhen) | 318 | 368.65 | 0.86262 | 4269 | ||
| Synonymous | 1.30 | 311 | 341 | 0.911 | 0.0000194 | 3015 |
| Loss of Function | 4.99 | 45 | 98.4 | 0.457 | 0.00000562 | 1048 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00062 | 0.00062 | rare |
| Latino/Admixed American | 0.00084 | 0.00084 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00092 | 0.00092 | rare |
| Finnish | 0.000092 | 0.000092 | rare |
| European (Non-Finnish) | 0.00049 | 0.00049 | rare |
| South Asian | 0.00033 | 0.00033 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Plays a role in vesicle maturation during exocytosis as a target of the diacylglycerol second messenger pathway. Is involved in neurotransmitter release by acting in synaptic vesicle priming prior to vesicle fusion and participates in the activity- depending refilling of readily releasable vesicle pool (RRP). Essential for synaptic vesicle maturation in a subset of excitatory/glutamatergic but not inhibitory/GABA-mediated synapses (By similarity). {ECO:0000250}.;
Recessive Scores
- pRec
- 0.141
Intolerance Scores
- LoFtool
- 0.183
- RVIS EVS
- -2.89
- RVIS percentile EVS
- 0.59
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.759
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |