GDF15
growth differentiation factor 15, the group of Transforming growth factor beta superfamily|MicroRNA protein coding host genes
Basic information
Region (hg38): 19:18374731-18389176
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
- not_specified (46 variants)
- not_provided (4 variants)
- Hyperemesis_gravidarum,_susceptibility_to (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the GDF15 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000004864.4. Only rare variants are included in the table.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | |||||
| missense | 44 | 48 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 44 | 3 | 3 |
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| GDF15 | protein_coding | protein_coding | ENST00000252809 | 2 | 14446 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 3.01e-7 | 0.0992 | 125690 | 1 | 26 | 125717 | 0.000107 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.292 | 189 | 201 | 0.942 | 0.0000118 | 1893 |
| Missense in Polyphen | 37 | 44.297 | 0.83527 | 473 | ||
| Synonymous | -0.240 | 102 | 99.0 | 1.03 | 0.00000592 | 706 |
| Loss of Function | -0.597 | 9 | 7.26 | 1.24 | 3.99e-7 | 65 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000336 | 0.000308 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.0000580 | 0.0000544 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.000138 | 0.000123 |
| Middle Eastern | 0.0000580 | 0.0000544 |
| South Asian | 0.000233 | 0.000196 |
| Other | 0.000184 | 0.000163 |
dbNSFP
Source:
- Function
- FUNCTION: Regulates food intake, energy expenditure and body weight in response to metabolic and toxin-induced stresses (PubMed:28953886, PubMed:28846097, PubMed:28846098, PubMed:28846099, PubMed:23468844, PubMed:29046435). Binds to its receptor, GFRAL, and activates GFRAL-expressing neurons localized in the area postrema and nucleus tractus solitarius of the brainstem (PubMed:28953886, PubMed:28846097, PubMed:28846098, PubMed:28846099). It then triggers the activation of neurons localized within the parabrachial nucleus and central amygdala, which contitutes part of the 'emergency circuit' that shapes feeding responses to stressful conditions (PubMed:28953886). On hepatocytes, inhibits growth hormone signaling (By similarity). {ECO:0000250|UniProtKB:Q9Z0J7, ECO:0000269|PubMed:23468844, ECO:0000269|PubMed:28846097, ECO:0000269|PubMed:28846098, ECO:0000269|PubMed:28846099, ECO:0000269|PubMed:28953886, ECO:0000269|PubMed:29046435}.;
- Disease
- DISEASE: Note=Plasma levels are increased in children with concomitant heart disease and failure to thrive but not in children with heart disease and normal body weight. {ECO:0000269|PubMed:28572090}.;
- Pathway
- EMT transition in Colorectal Cancer;p73 transcription factor network;Validated transcriptional targets of TAp63 isoforms;Direct p53 effectors
(Consensus)
Recessive Scores
- pRec
- 0.360
Intolerance Scores
- loftool
- 0.353
- rvis_EVS
- 0.73
- rvis_percentile_EVS
- 86.08
Haploinsufficiency Scores
- pHI
- 0.329
- hipred
- N
- hipred_score
- 0.247
- ghis
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- S
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.570
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | High |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Gdf15
- Phenotype
- growth/size/body region phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); homeostasis/metabolism phenotype; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system phenotype; renal/urinary system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan);
Gene ontology
- Biological process
- activation of MAPK activity;reduction of food intake in response to dietary excess;signal transduction;transforming growth factor beta receptor signaling pathway;cell-cell signaling;regulation of signaling receptor activity;positive regulation of pathway-restricted SMAD protein phosphorylation;BMP signaling pathway;glial cell-derived neurotrophic factor receptor signaling pathway;negative regulation of multicellular organism growth;regulation of apoptotic process;regulation of MAPK cascade;positive regulation of MAPK cascade;cell development;positive regulation of protein kinase B signaling;SMAD protein signal transduction;negative regulation of growth hormone receptor signaling pathway;positive regulation of myoblast fusion
- Cellular component
- extracellular region;extracellular space;nucleus;cytoplasm;Golgi apparatus;collagen-containing extracellular matrix;extracellular exosome
- Molecular function
- cytokine activity;transforming growth factor beta receptor binding;protein binding;growth factor activity;protein homodimerization activity