NCDN
protein-codingneurochondrin, the group of Armadillo like helical domain containing
Gene summary
This gene encodes a leucine-rich cytoplasmic protein, which is highly similar to a mouse protein that negatively regulates Ca/calmodulin-dependent protein kinase II phosphorylation and may be essential for spatial learning processes. Several alternatively spliced transcript variants of this gene have been described. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~9.8 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0859162
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AD
Disease ID:MONDO:0859162
Submitter: G2P
Inheritance Pattern: AR
Disease ID:MONDO:0859162
Submitter: PanelApp Australia
Inheritance Pattern: AD
Disease ID:MONDO:0859162
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0700092
Submitter: G2P
Inheritance Pattern: AR
Disease ID:MONDO:0019502
Submitter: Orphanet
Clinical Genomic Database (CGD)
Manifestation: Craniofacial; Musculoskeletal; Neurologic
Intervention: General
Rationale: 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
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to NCDN variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_014284.3. 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 | 23 | 1 | 24 | |||
| missense | 3 | 2 | 93 | 7 | 105 | |
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 2 | 2 | 4 | |||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 3 | 4 | 100 | 30 | 1 | 138 |
Highest pathogenic variant AF is 6.84369e-7
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_055099.1 | 7 | MANE Select | |
| Ensembl | ENSP00000362340.2 | 7 | MANE Select | |
| RefSeq | NP_001014839.1 | 7 | Standard | |
| RefSeq | NP_001014841.1 | 6 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Splicing factor NOVA regulated synaptic proteins
Biological Process
- neuron projection development
- bone resorption
- regulation of neuronal synaptic plasticity
Molecular Function
- protein binding
Cellular Component
- nucleus
- cytosol
- membrane
- axon
- dendrite
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000373243
- Coding exons
- 7
- Length
- 9802
- Individuals with no LoFs
- 125715
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 5
- Defined
- 125720
- p
- 0.0000199
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 3.76 | 235 | 463 | 0.508 | 0.0000303 | 4608 |
| Missense (PolyPhen) | 35 | 121.62 | 0.28779 | 1273 | ||
| Synonymous | 0.732 | 203 | 217 | 0.937 | 0.0000148 | 1647 |
| Loss of Function | 4.65 | 1 | 27.1 | 0.0369 | 0.00000134 | 281 |
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) | 0.000079 | 0.000044 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Probably involved in signal transduction, in the nervous system, via increasing cell surface localization of GRM5 and positively regulating its signaling (By similarity). Required for the spatial learning process. Acts as a negative regulator of Ca(2+)-calmodulin-dependent protein kinase 2 (CaMK2) phosphorylation. May play a role in modulating melanin- concentrating hormone-mediated functions via its interaction with MCHR1 that interferes with G protein-coupled signal transduction. May be involved in bone metabolism. May also be involved in neurite outgrowth. {ECO:0000250, ECO:0000269|PubMed:16945926}.;
Recessive Scores
- pRec
- 0.128
Intolerance Scores
- LoFtool
- 0.0479
- RVIS EVS
- -0.98
- RVIS percentile EVS
- 8.75
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.989
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |