DCC
DCC netrin 1 receptor, the group of MicroRNA protein coding host genes|Fibronectin type III domain containing|I-set domain containing
Basic information
Region (hg38): 18:52340197-53535899
Links
Phenotypes
GenCC
Source:
- mirror movements 1 (Definitive), mode of inheritance: AD
- mirror movements 1 (Strong), mode of inheritance: AD
- colorectal cancer (No Known Disease Relationship), mode of inheritance: Unknown
- esophageal cancer (No Known Disease Relationship), mode of inheritance: Unknown
- connective tissue disorder (Moderate), mode of inheritance: AR
- gaze palsy, familial horizontal, with progressive scoliosis, 2 (Limited), mode of inheritance: AR
- mirror movements 1 (Strong), mode of inheritance: AD
- Kallmann syndrome (Supportive), mode of inheritance: AD
- familial congenital mirror movements (Supportive), mode of inheritance: AD
- mirror movements 1 and/or agenesis of the corpus callosum (Definitive), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Mirror movements 1; Gaze palsy, familial horizontal, with progressive scoliosis 2 | AD/AR | General | Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing | Musculoskeletal; Neurologic | 19127048; 19720981; 20431009; 21242494; 28250456 |
ClinVar
This is a list of variants' phenotypes submitted to
- not provided (8 variants)
- Mirror movements 1 (5 variants)
- Inborn genetic diseases (4 variants)
- Mirror movements 1 and/or agenesis of the corpus callosum (1 variants)
- Corpus callosum, agenesis of (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the DCC 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 | 22 | 28 | ||||
| missense | 92 | 19 | 119 | |||
| nonsense | 13 | |||||
| start loss | 1 | |||||
| frameshift | 11 | |||||
| inframe indel | 1 | |||||
| splice donor/acceptor (+/-2bp) | 7 | |||||
| splice region | 3 | 5 | 3 | 11 | ||
| non coding | 6 | |||||
| Total | 16 | 14 | 98 | 42 | 16 |
Highest pathogenic variant AF is 0.00000657
Variants in DCC
This is a list of pathogenic ClinVar variants found in the DCC region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| DCC | protein_coding | protein_coding | ENST00000442544 | 29 | 1191243 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.994 | 0.00552 | 125720 | 0 | 28 | 125748 | 0.000111 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.372 | 752 | 781 | 0.963 | 0.0000435 | 9358 |
| Missense in Polyphen | 179 | 246.72 | 0.72552 | 2906 | ||
| Synonymous | -2.18 | 335 | 288 | 1.16 | 0.0000167 | 2959 |
| Loss of Function | 6.83 | 15 | 81.6 | 0.184 | 0.00000530 | 856 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000148 | 0.000148 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.000272 | 0.000217 |
| Finnish | 0.0000924 | 0.0000924 |
| European (Non-Finnish) | 0.000132 | 0.000132 |
| Middle Eastern | 0.000272 | 0.000217 |
| South Asian | 0.0000981 | 0.0000980 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Receptor for netrin required for axon guidance. Mediates axon attraction of neuronal growth cones in the developing nervous system upon ligand binding. Its association with UNC5 proteins may trigger signaling for axon repulsion. It also acts as a dependence receptor required for apoptosis induction when not associated with netrin ligand. Implicated as a tumor suppressor gene. {ECO:0000269|PubMed:8187090, ECO:0000269|PubMed:8861902}.;
- Disease
- DISEASE: Mirror movements 1 (MRMV1) [MIM:157600]: A disorder characterized by contralateral involuntary movements that mirror voluntary ones. While mirror movements are occasionally found in young children, persistence beyond the age of 10 is abnormal. Mirror movements occur more commonly in the upper extremities. Some MRMV1 patients have agenesis of the corpus callosum. {ECO:0000269|PubMed:20431009, ECO:0000269|PubMed:28250454}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Gaze palsy, familial horizontal, with progressive scoliosis, 2 (HGPPS2) [MIM:617542]: An autosomal recessive neurologic disorder characterized by global developmental delay, delayed walking, intellectual disability, horizontal gaze palsy, and childhood-onset progressive scoliosis. {ECO:0000269|PubMed:28250456}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Axon guidance - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Colorectal cancer - Homo sapiens (human);Chromosomal and microsatellite instability in colorectal cancer;Developmental Biology;DSCAM interactions;Caspase activation via extrinsic apoptotic signalling pathway;Apoptosis;Programmed Cell Death;Regulation of commissural axon pathfinding by SLIT and ROBO;DCC mediated attractive signaling;Netrin mediated repulsion signals;Role of second messengers in netrin-1 signaling;Ligand-independent caspase activation via DCC;Netrin-1 signaling;Signaling by ROBO receptors;Axon guidance;Netrin-mediated signaling events
(Consensus)
Recessive Scores
- pRec
- 0.230
Intolerance Scores
- loftool
- 0.313
- rvis_EVS
- -1.36
- rvis_percentile_EVS
- 4.52
Haploinsufficiency Scores
- pHI
- 0.977
- hipred
- Y
- hipred_score
- 0.736
- ghis
- 0.532
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.762
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | High | High | High |
| Primary Immunodeficiency | High | High | High |
| Cancer | High | High | High |
Mouse Genome Informatics
- Gene name
- Dcc
- Phenotype
- behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; hematopoietic 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); pigmentation phenotype; neoplasm; 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); vision/eye phenotype; immune system phenotype; cellular phenotype;
Zebrafish Information Network
- Gene name
- dcc
- Affected structure
- efferent neuron
- Phenotype tag
- abnormal
- Phenotype quality
- decreased amount
Gene ontology
- Biological process
- neuron migration;apoptotic process;axonogenesis;axon guidance;negative regulation of neuron projection development;spinal cord ventral commissure morphogenesis;dorsal/ventral axon guidance;anterior/posterior axon guidance;netrin-activated signaling pathway;negative regulation of collateral sprouting;extrinsic apoptotic signaling pathway in absence of ligand;postsynaptic modulation of chemical synaptic transmission;regulation of neuron death;negative regulation of netrin-activated signaling pathway;negative regulation of dendrite development
- Cellular component
- cytosol;plasma membrane;axon;Schaffer collateral - CA1 synapse;integral component of postsynaptic density membrane
- Molecular function
- transmembrane signaling receptor activity;netrin receptor activity;protein binding