GDNF
glial cell derived neurotrophic factor, the group of GDNF family ligands
Basic information
Region (hg38): 5:37812677-37840041
Links
Phenotypes
GenCC
Source:
No genCC data.
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Central hypoventilation syndrome; Hirschsprung disease, susceptibility to, 3 | AD | Gastrointestinal; Neurologic | In Central hypoventilation syndrome, early recognition and interventions to support ventilation (as well as avoidance of exacerbating factors) can reduce morbidity and mortality; In conditions that may involve Hirschsprung disease, recognition of potential GI anomalies (eg, aganglionosis) may allow prompt recognition and treatment | Gastrointestinal; Neurologic | 8896568; 8968758; 8896569; 9497256; 11973622; 11823451; 22729463 |
ClinVar
This is a list of variants' phenotypes submitted to
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the GDNF 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 | 5 | |||||
| missense | 16 | 20 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 0 | |||||
| non coding | 46 | 14 | 24 | 84 | ||
| Total | 0 | 0 | 62 | 22 | 25 |
Variants in GDNF
This is a list of pathogenic ClinVar variants found in the GDNF region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 5-37812768-C-T | Hirschsprung disease, susceptibility to, 3 | Benign (Jan 13, 2018) | ||
| 5-37812820-GGT-G | Hirschsprung Disease, Dominant | Uncertain significance (Jun 14, 2016) | ||
| 5-37812823-A-T | Hirschsprung disease, susceptibility to, 3 | Uncertain significance (Jan 13, 2018) | ||
| 5-37812938-C-T | Hirschsprung disease, susceptibility to, 3 | Benign (Jan 12, 2018) | ||
| 5-37813000-G-C | Hirschsprung disease, susceptibility to, 3 | Uncertain significance (Jan 13, 2018) | ||
| 5-37813005-G-C | Hirschsprung disease, susceptibility to, 3 | Uncertain significance (Jan 12, 2018) | ||
| 5-37813008-G-A | Hirschsprung disease, susceptibility to, 3 | Benign (Jan 13, 2018) | ||
| 5-37813095-A-T | Hirschsprung disease, susceptibility to, 3 | Uncertain significance (Jan 13, 2018) | ||
| 5-37813205-C-T | Hirschsprung disease, susceptibility to, 3 | Uncertain significance (Jan 12, 2018) | ||
| 5-37813211-C-T | Hirschsprung disease, susceptibility to, 3 | Likely benign (Apr 27, 2017) | ||
| 5-37813333-C-T | Hirschsprung disease, susceptibility to, 3 | Uncertain significance (Jan 13, 2018) | ||
| 5-37813384-C-T | Hirschsprung disease, susceptibility to, 3 | Uncertain significance (Jan 13, 2018) | ||
| 5-37813386-A-G | Hirschsprung disease, susceptibility to, 3 | Uncertain significance (Jan 13, 2018) | ||
| 5-37813438-C-T | Hirschsprung disease, susceptibility to, 3 | Uncertain significance (Jan 12, 2018) | ||
| 5-37813447-C-A | Hirschsprung disease, susceptibility to, 3 | Benign (Jan 13, 2018) | ||
| 5-37813489-C-A | Hirschsprung disease, susceptibility to, 3 | Benign (Jan 13, 2018) | ||
| 5-37813501-A-C | Hirschsprung disease, susceptibility to, 3 | Likely benign (Jan 13, 2018) | ||
| 5-37813532-G-C | Hirschsprung disease, susceptibility to, 3 | Uncertain significance (Apr 27, 2017) | ||
| 5-37813583-TG-T | Hirschsprung Disease, Dominant | Uncertain significance (Jun 14, 2016) | ||
| 5-37813592-G-A | Hirschsprung disease, susceptibility to, 3 | Uncertain significance (Jan 12, 2018) | ||
| 5-37813637-C-T | Hirschsprung disease, susceptibility to, 3 | Likely benign (Jan 12, 2018) | ||
| 5-37813724-G-A | Hirschsprung disease, susceptibility to, 3 | Uncertain significance (Jan 12, 2018) | ||
| 5-37813753-G-T | Hirschsprung disease, susceptibility to, 3 | Benign (Jan 12, 2018) | ||
| 5-37813863-C-T | Hirschsprung disease, susceptibility to, 3 | Uncertain significance (Jan 13, 2018) | ||
| 5-37813866-C-A | Hirschsprung disease, susceptibility to, 3 | Benign (Jan 13, 2018) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| GDNF | protein_coding | protein_coding | ENST00000427982 | 3 | 27010 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.203 | 0.757 | 123085 | 0 | 1 | 123086 | 0.00000406 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.10 | 100 | 136 | 0.735 | 0.00000741 | 1483 |
| Missense in Polyphen | 22 | 45.424 | 0.48432 | 544 | ||
| Synonymous | -0.973 | 67 | 57.6 | 1.16 | 0.00000343 | 459 |
| Loss of Function | 1.72 | 2 | 6.86 | 0.292 | 2.89e-7 | 97 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.00 | 0.00 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.0000328 | 0.0000328 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Neurotrophic factor that enhances survival and morphological differentiation of dopaminergic neurons and increases their high-affinity dopamine uptake. {ECO:0000269|PubMed:8493557}.;
- Disease
- DISEASE: Hirschsprung disease 3 (HSCR3) [MIM:613711]: A disorder of neural crest development characterized by absence of enteric ganglia along a variable length of the intestine. It is the most common cause of congenital intestinal obstruction. Early symptoms range from complete acute neonatal obstruction, characterized by vomiting, abdominal distention and failure to pass stool, to chronic constipation in the older child. {ECO:0000269|PubMed:10917288, ECO:0000269|PubMed:8896568, ECO:0000269|PubMed:8896569, ECO:0000269|PubMed:8968758}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.; DISEASE: Congenital central hypoventilation syndrome (CCHS) [MIM:209880]: Rare disorder characterized by abnormal control of respiration in the absence of neuromuscular or lung disease, or an identifiable brain stem lesion. A deficiency in autonomic control of respiration results in inadequate or negligible ventilatory and arousal responses to hypercapnia and hypoxemia. {ECO:0000269|PubMed:9497256}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Pheochromocytoma (PCC) [MIM:171300]: A catecholamine- producing tumor of chromaffin tissue of the adrenal medulla or sympathetic paraganglia. The cardinal symptom, reflecting the increased secretion of epinephrine and norepinephrine, is hypertension, which may be persistent or intermittent. {ECO:0000269|PubMed:9215674}. Note=The gene represented in this entry may act as a disease modifier.;
- Pathway
- Allograft Rejection;Spinal Cord Injury;Developmental Biology;Signal Transduction;GPCR signaling-G alpha q;GPCR signaling-cholera toxin;GPCR signaling-pertussis toxin;GPCR signaling-G alpha s Epac and ERK;GPCR signaling-G alpha s PKA and ERK;RAF/MAP kinase cascade;MAPK1/MAPK3 signaling;MAPK family signaling cascades;NCAM signaling for neurite out-growth;Posttranslational regulation of adherens junction stability and dissassembly;Signaling events regulated by Ret tyrosine kinase;NCAM1 interactions;RET signaling;Axon guidance;GPCR signaling-G alpha i
(Consensus)
Recessive Scores
- pRec
- 0.714
Intolerance Scores
- loftool
- 0.0280
- rvis_EVS
- 0.19
- rvis_percentile_EVS
- 66.82
Haploinsufficiency Scores
- pHI
- 0.710
- hipred
- Y
- hipred_score
- 0.751
- ghis
- 0.432
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.673
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Gdnf
- Phenotype
- digestive/alimentary 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); immune system phenotype; renal/urinary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); 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); reproductive system phenotype; 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); endocrine/exocrine gland phenotype; muscle phenotype; cellular phenotype;
Zebrafish Information Network
- Gene name
- gdnfa
- Affected structure
- afferent neuron
- Phenotype tag
- abnormal
- Phenotype quality
- truncated
Gene ontology
- Biological process
- MAPK cascade;metanephros development;branching involved in ureteric bud morphogenesis;neural crest cell migration;organ induction;postsynaptic membrane organization;mesenchymal to epithelial transition involved in metanephros morphogenesis;signal transduction;nervous system development;axon guidance;positive regulation of cell population proliferation;adult locomotory behavior;regulation of gene expression;regulation of signaling receptor activity;dorsal spinal cord development;postganglionic parasympathetic fiber development;peristalsis;neuron projection development;positive regulation of monooxygenase activity;positive regulation of dopamine secretion;negative regulation of apoptotic process;negative regulation of neuron apoptotic process;positive regulation of cell differentiation;positive regulation of transcription by RNA polymerase II;mRNA stabilization;enteric nervous system development;sympathetic nervous system development;embryonic organ development;regulation of dopamine uptake involved in synaptic transmission;ureteric bud formation;regulation of morphogenesis of a branching structure;chemoattraction of axon;commissural neuron axon guidance;positive regulation of ureteric bud formation;positive regulation of mesenchymal to epithelial transition involved in metanephros morphogenesis;positive regulation of branching involved in ureteric bud morphogenesis;regulation of stem cell differentiation;negative regulation of extrinsic apoptotic signaling pathway in absence of ligand;regulation of semaphorin-plexin signaling pathway
- Cellular component
- extracellular region
- Molecular function
- Ras guanyl-nucleotide exchange factor activity;signaling receptor binding;protein binding;growth factor activity;protein homodimerization activity;chemoattractant activity involved in axon guidance