CGA
protein-codingglycoprotein hormones, alpha polypeptide, the group of Receptor ligands|Glycoprotein hormone subunits
Gene summary
The four human glycoprotein hormones chorionic gonadotropin (CG), luteinizing hormone (LH), follicle stimulating hormone (FSH), and thyroid stimulating hormone (TSH) are dimers consisting of alpha and beta subunits that are associated noncovalently. The alpha subunits of these hormones are identical, however, their beta chains are unique and confer biological specificity. The protein encoded by this gene is the alpha subunit and belongs to the glycoprotein hormones alpha chain family. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2011]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~9.6 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 CGA variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_000735.4. 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 | 2 | |||
| missense | 0 | |||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 0 | 1 | 1 | 2 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_000726.1 | 3 | MANE Select | |
| Ensembl | ENSP00000486024.1 | 3 | MANE Select | |
| RefSeq | NP_001239312.1 | 4 | Standard | |
| Ensembl | ENSP00000358595.3 | 3 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| cga | Danio rerio | Structure: head Quality: orientation abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Regulation of lipolysis in adipocytes - Homo sapiens (human)
- Thyroid hormone synthesis - Homo sapiens (human)
- Autoimmune thyroid disease - Homo sapiens (human)
- GnRH signaling pathway - Homo sapiens (human)
- Prolactin signaling pathway - Homo sapiens (human)
Biological Process
- regulation of transcription by RNA polymerase II
- G protein-coupled receptor signaling pathway
- positive regulation of cell population proliferation
- regulation of signaling receptor activity
- positive regulation of steroid biosynthetic process
Molecular Function
- hormone activity
- protein binding
- follicle-stimulating hormone activity
Cellular Component
- extracellular region
- extracellular space
- Golgi lumen
- follicle-stimulating hormone complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000369582
- Coding exons
- 3
- Length
- 9609
- Individuals with no LoFs
- 117574
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 1
- Defined
- 117575
- p
- 0.00000425
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.50 | 30 | 63.7 | 0.471 | 0.00000333 | 754 |
| Missense (PolyPhen) | 9 | 31.457 | 0.28611 | 389 | ||
| Synonymous | 0.0978 | 27 | 27.7 | 0.976 | 0.00000187 | 218 |
| Loss of Function | 1.52 | 1 | 4.47 | 0.224 | 1.87e-7 | 64 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.0000094 | 0.0000094 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Shared alpha chain of the active heterodimeric glycoprotein hormones thyrotropin/thyroid stimulating hormone/TSH, lutropin/luteinizing hormone/LH, follitropin/follicle stimulating hormone/FSH and choriogonadotropin/CG. These hormones bind specific receptors on target cells that in turn activate downstream signaling pathways. {ECO:0000269|PubMed:24692546, ECO:0000269|PubMed:2494176}.;
Recessive Scores
- pRec
- 0.405
Intolerance Scores
- LoFtool
- 0.187
- RVIS EVS
- -0.05
- RVIS percentile EVS
- 49.39
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.0338