NCALD
protein-codingneurocalcin delta, the group of EF-hand domain containing
Gene summary
This gene encodes a member of the neuronal calcium sensor (NCS) family of calcium-binding proteins. The protein contains an N-terminal myristoylation signal and four EF-hand calcium binding loops. The protein is cytosolic at resting calcium levels; however, elevated intracellular calcium levels induce a conformational change that exposes the myristoyl group, resulting in protein association with membranes and partial co-localization with the perinuclear trans-golgi network. The protein is thought to be a regulator of G protein-coupled receptor signal transduction. Several alternatively spliced variants of this gene have been determined, all of which encode the same protein; additional variants may exist but their biological validity has not been determined. [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 ~438.4 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to NCALD variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_032041.3. 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 | 1 | 1 | ||||
| missense | 13 | 13 | ||||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 16 | 0 | 0 | 16 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_114430.2 | 3 | MANE Select | |
| Ensembl | ENSP00000220931.6 | 3 | MANE Select | |
| RefSeq | NP_001035714.1 | 3 | Standard | |
| RefSeq | NP_001035715.1 | 3 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| ncaldb | Danio rerio | Structure: CaP motoneuron Quality: increased occurrence abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Olfactory transduction - Homo sapiens (human)
- Activation of Ca-permeable Kainate Receptor
- Ionotropic activity of kainate receptors
- Activation of kainate receptors upon glutamate binding
- Neuronal System
Biological Process
- regulation of systemic arterial blood pressure
- vesicle-mediated transport
- calcium-mediated signaling
Molecular Function
- actin binding
- calcium ion binding
- protein binding
- tubulin binding
- clathrin binding
Cellular Component
- cytosol
- clathrin coat of trans-Golgi network vesicle
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000395923
- Coding exons
- 3
- Length
- 438365
- Individuals with no LoFs
- 125744
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 2
- Defined
- 125746
- p
- 0.00000795
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.56 | 70 | 118 | 0.595 | 0.00000675 | 1295 |
| Missense (PolyPhen) | 12 | 36.568 | 0.32815 | 451 | ||
| Synonymous | -0.147 | 46 | 44.8 | 1.03 | 0.00000290 | 333 |
| Loss of Function | 2.50 | 0 | 7.25 | 0.00 | 3.03e-7 | 99 |
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) | 0.000018 | 0.000018 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: May be involved in the calcium-dependent regulation of rhodopsin phosphorylation. Binds three calcium ions.;
Recessive Scores
- pRec
- 0.146
Intolerance Scores
- RVIS EVS
- 0.08
- RVIS percentile EVS
- 59.76
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.961
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |