GNG5
protein-codingG protein subunit gamma 5, the group of G protein subunits gamma
Gene summary
G proteins are trimeric (alpha-beta-gamma) membrane-associated proteins that regulate flow of information from cell surface receptors to a variety of internal metabolic effectors. Interaction of a G protein with its activated receptor promotes exchange of GTP for GDP that is bound to the alpha subunit. The alpha-GTP complex dissociates from the beta-gamma heterodimer so that the subunits, in turn, may interact with and regulate effector molecules (Gilman, 1987 [PubMed 3113327]; summary by Ahmad et al., 1995) [PubMed 7606925].[supplied by OMIM, Nov 2010]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~8.3 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 GNG5 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_005274.3. 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 | 0 | |||||
| missense | 5 | 5 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 6 | 0 | 0 | 6 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_005265.1 | 2 | MANE Select | |
| Ensembl | ENSP00000359679.4 | 2 | MANE Select | |
| Ensembl | ENSP00000359675.3 | 2 | Standard | |
| Ensembl | ENSP00000359675.3 | 2 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- PI3K-Akt signaling pathway - Homo sapiens (human)
- Relaxin signaling pathway - Homo sapiens (human)
- Kaposi,s sarcoma-associated herpesvirus infection - Homo sapiens (human)
- Retrograde endocannabinoid signaling - Homo sapiens (human)
- GABAergic synapse - Homo sapiens (human)
Biological Process
- signal transduction
- G protein-coupled receptor signaling pathway
- positive regulation of secondary heart field cardioblast proliferation
- positive regulation of neural precursor cell proliferation
Molecular Function
- GTPase activity
- protein binding
- PDZ domain binding
Cellular Component
- heterotrimeric G-protein complex
- plasma membrane
- membrane
- G-protein beta/gamma-subunit complex
- extracellular exosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000370641
- Coding exons
- 2
- Length
- 8241
- Individuals with no LoFs
- 125601
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 1
- Defined
- 125602
- p
- 0.00000398
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.376 | 27 | 33.1 | 0.816 | 0.00000142 | 425 |
| Missense (PolyPhen) | 7 | 7.6831 | 0.91109 | 113 | ||
| Synonymous | 0.410 | 12 | 13.9 | 0.860 | 6.07e-7 | 142 |
| Loss of Function | 0.924 | 1 | 2.61 | 0.383 | 1.10e-7 | 34 |
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) | 0.0000088 | 0.0000088 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein- effector interaction.;
Recessive Scores
- pRec
- 0.136
Intolerance Scores
- RVIS EVS
- 0.15
- RVIS percentile EVS
- 63.81
Essentials
- Essential (CRISPR)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.539
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |