GDF15

growth differentiation factor 15, the group of Transforming growth factor beta superfamily|MicroRNA protein coding host genes

Basic information

Region (hg38): 19:18374730-18389176

Links

ENSG00000130513 ∙ NCBI:9518 ∙ OMIM:605312 ∙ HGNC:30142 ∙ Uniprot:Q99988 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GDF15 gene.

• Inborn genetic diseases (17 variants)
• not provided (4 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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous					2	2
missense			15	2	2	19
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	15	2	4

Variants in GDF15

This is a list of pathogenic ClinVar variants found in the GDF15 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
19-18386195-C-T			Benign (Jul 06, 2018)
19-18386200-A-G		not specified	Uncertain significance (Apr 07, 2022)
19-18386200-A-T		not specified	Uncertain significance (Dec 27, 2023)
19-18386238-G-A		not specified	Likely benign (Mar 14, 2023)
19-18386251-T-C		not specified	Uncertain significance (Feb 22, 2023)
19-18386256-T-C		not specified	Uncertain significance (Mar 24, 2023)
19-18386370-G-A		not specified	Uncertain significance (Mar 17, 2023)
19-18386374-A-C		not specified	Uncertain significance (Feb 28, 2024)
19-18386436-G-A		not specified	Uncertain significance (Dec 08, 2023)
19-18386449-G-A		not specified	Uncertain significance (Sep 07, 2022)
19-18388288-C-T		not specified	Uncertain significance (Aug 10, 2021)
19-18388312-C-A		not specified	Uncertain significance (Oct 10, 2023)
19-18388340-C-T		not specified	Uncertain significance (Aug 02, 2021)
19-18388352-C-A		not specified	Uncertain significance (Feb 27, 2024)
19-18388357-G-A			Benign (Aug 16, 2018)
19-18388358-C-A			Benign (Aug 16, 2018)
19-18388375-G-C		not specified	Uncertain significance (Jan 26, 2022)
19-18388383-C-G		not specified	Likely benign (Sep 06, 2022)
19-18388465-C-T		not specified	Uncertain significance (Sep 21, 2023)
19-18388480-C-A			Benign (Sep 19, 2018)
19-18388537-C-T		not specified	Uncertain significance (Sep 12, 2023)
19-18388538-G-C		not specified	Uncertain significance (Jan 02, 2024)
19-18388568-A-T		not specified	Uncertain significance (Oct 17, 2023)
19-18388574-C-T		not specified	Uncertain significance (May 01, 2022)
19-18388613-A-G		not specified	Uncertain significance (Nov 29, 2021)

GnomAD

Source: gnomAD

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: dbNSFP

• 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

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