CHGA
protein-codingchromogranin A, the group of Granins|Neuropeptides
Gene summary
The protein encoded by this gene is a member of the chromogranin/secretogranin family of neuroendocrine secretory proteins. It is found in secretory vesicles of neurons and endocrine cells. This gene product is a precursor to three biologically active peptides; vasostatin, pancreastatin, and parastatin. These peptides act as autocrine or paracrine negative modulators of the neuroendocrine system. Two other peptides, catestatin and chromofungin, have antimicrobial activity and antifungal activity, respectively. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2014]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~12.1 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 CHGA variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001275.4. 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 | 1 | 1 | ||||
| missense | 53 | 6 | 59 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 56 | 6 | 0 | 62 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001266.1 | 8 | MANE Select | |
| Ensembl | ENSP00000216492.5 | 8 | MANE Select | |
| RefSeq | NP_001288619.1 | 7 | Standard | |
| Ensembl | ENSP00000334023.4 | 7 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Antimicrobial peptides
- Innate Immune System
- Immune System
Biological Process
- regulation of the force of heart contraction
- mast cell chemotaxis
- organelle organization
- regulation of blood pressure
- antimicrobial humoral response
Cellular Component
- extracellular region
- extracellular space
- secretory granule
- transport vesicle membrane
- chromaffin granule
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000216492
- Coding exons
- 8
- Length
- 12214
- Individuals with no LoFs
- 125726
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 20
- Defined
- 125747
- p
- 0.0000835
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.821 | 215 | 252 | 0.854 | 0.0000146 | 2918 |
| Missense (PolyPhen) | 65 | 75.834 | 0.85714 | 976 | ||
| Synonymous | 0.134 | 102 | 104 | 0.983 | 0.00000634 | 868 |
| Loss of Function | 3.11 | 7 | 23.2 | 0.302 | 0.00000132 | 264 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.00012 | 0.00012 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0.000049 | 0.000046 | rare |
| European (Non-Finnish) | 0.000054 | 0.000053 | rare |
| South Asian | 0.00024 | 0.00020 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Pancreastatin: Strongly inhibits glucose induced insulin release from the pancreas.; FUNCTION: Serpinin: Regulates granule biogenesis in endocrine cells by up-regulating the transcription of protease nexin 1 (SERPINE2) via a cAMP-PKA-SP1 pathway. This leads to inhibition of granule protein degradation in the Golgi complex which in turn promotes granule formation. {ECO:0000250|UniProtKB:P26339}.;
Recessive Scores
- pRec
- 0.487
Intolerance Scores
- LoFtool
- 0.669
- RVIS EVS
- 2.11
- RVIS percentile EVS
- 97.88
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.828
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |