NECAB3
protein-codingN-terminal EF-hand calcium binding protein 3, the group of N-terminal EF-hand calcium binding proteins|EF-hand domain containing
Gene summary
The protein encoded by this gene interacts with the amino-terminal domain of the neuron-specific X11-like protein (X11L), inhibits the association of X11L with amyloid precursor protein through a non-competitive mechanism, and abolishes the suppression of beta-amyloid production by X11L. This protein, together with X11L, may play an important role in the regulatory system of amyloid precursor protein metabolism and beta-amyloid generation. The protein is phosphorylated by NIMA-related expressed kinase 2, and localizes to the Golgi apparatus. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
- SYTIP2
- APBA2BP
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~17.4 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 NECAB3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_031232.4. 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 | 58 | 6 | 64 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 5 | 5 | ||||
| Total | 0 | 0 | 64 | 6 | 0 | 70 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_112509.3 | 12 | MANE Select | |
| Ensembl | ENSP00000246190.6 | 12 | MANE Select | |
| RefSeq | NP_112508.3 | 13 | Standard | |
| Ensembl | ENSP00000364386.4 | 13 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- protein secretion
- protein metabolic process
- regulation of amyloid precursor protein biosynthetic process
Molecular Function
- calcium ion binding
- protein binding
Cellular Component
- Golgi cis cisterna
- nucleus
- cytoplasm
- endoplasmic reticulum
- endoplasmic reticulum membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000246190
- Coding exons
- 12
- Length
- 17377
- Individuals with no LoFs
- 124778
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 18
- Defined
- 124796
- p
- 0.0000721
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.964 | 179 | 219 | 0.817 | 0.0000139 | 2510 |
| Missense (PolyPhen) | 59 | 79.019 | 0.74665 | 949 | ||
| Synonymous | 0.357 | 86 | 90.3 | 0.952 | 0.00000567 | 791 |
| Loss of Function | 2.18 | 11 | 22.0 | 0.500 | 0.00000103 | 257 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000081 | 0.000065 | rare |
| Latino/Admixed American | 0.00015 | 0.00014 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00022 | 0.00022 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000065 | 0.000062 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Inhibits the interaction of APBA2 with amyloid-beta precursor protein (APP), and hence allows formation of amyloid- beta. May enhance the activity of HIF1A and thus promote glycolysis under normoxic conditions; the function requires its ABM domain and may implicate the stabilization of the interaction between HIF1AN and APBA3. {ECO:0000269|PubMed:10833507, ECO:0000269|PubMed:26948053}.;
Recessive Scores
- pRec
- 0.0899
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.503
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |