NCKAP1
NCK associated protein 1, the group of SCAR/WAVE complex
Basic information
Region (hg38): 2:182909115-183038858
Links
Phenotypes
GenCC
Source:
- complex neurodevelopmental disorder (Definitive), mode of inheritance: AD
- neurodevelopmental disorder (Limited), mode of inheritance: AD
ClinVar
This is a list of variants' phenotypes submitted to
- not_provided (91 variants)
- Inborn_genetic_diseases (56 variants)
- NCKAP1-related_disorder (15 variants)
- Neurodevelopmental_disorder (6 variants)
- Global_developmental_delay (2 variants)
- not_specified (2 variants)
- NCKAP1-associated_Neurodevelopmental_disorder (2 variants)
- Autistic_behavior (2 variants)
- Focal_sensory_seizure_with_somatosensory_features (1 variants)
- Autism_spectrum_disorder (1 variants)
- Immunodeficiency_72_with_autoinflammation (1 variants)
- Intellectual_disability (1 variants)
- Complex_neurodevelopmental_disorder (1 variants)
- Neurodevelopmental_abnormality (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the NCKAP1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000013436.5. Only rare variants are included in the table.
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.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 10 | 11 | ||||
| missense | 125 | 130 | ||||
| nonsense | 8 | |||||
| start loss | 0 | |||||
| frameshift | 8 | |||||
| splice donor/acceptor (+/-2bp) | 3 | |||||
| Total | 9 | 10 | 129 | 12 | 0 |
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| NCKAP1 | protein_coding | protein_coding | ENST00000360982 | 32 | 129744 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.00 | 2.15e-11 | 0 | 0 | 0 | 0 | 0.00 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 4.27 | 291 | 581 | 0.501 | 0.0000287 | 7483 |
| Missense in Polyphen | 56 | 154.07 | 0.36346 | 2017 | ||
| Synonymous | 0.221 | 194 | 198 | 0.980 | 0.00000984 | 2051 |
| Loss of Function | 7.60 | 0 | 67.2 | 0.00 | 0.00000352 | 850 |
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 | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Part of the WAVE complex that regulates lamellipodia formation. The WAVE complex regulates actin filament reorganization via its interaction with the Arp2/3 complex. Actin remodeling activity is regulated by RAC1. As component of the WAVE1 complex, required for BDNF-NTRK2 endocytic trafficking and signaling from early endosomes. {ECO:0000250|UniProtKB:P28660}.;
- Pathway
- Regulation of actin cytoskeleton - Homo sapiens (human);Exercise-induced Circadian Regulation;Regulation of Actin Cytoskeleton;Signal Transduction;VEGFA-VEGFR2 Pathway;y branching of actin filaments;Fcgamma receptor (FCGR) dependent phagocytosis;Innate Immune System;Immune System;RHO GTPases Activate WASPs and WAVEs;RHO GTPase Effectors;Signaling by Rho GTPases;ErbB1 downstream signaling;Regulation of actin dynamics for phagocytic cup formation;Signaling by VEGF;Signaling by Receptor Tyrosine Kinases;Stabilization and expansion of the E-cadherin adherens junction;RAC1 signaling pathway;PDGFR-beta signaling pathway;E-cadherin signaling in the nascent adherens junction
(Consensus)
Recessive Scores
- pRec
- 0.186
Intolerance Scores
- loftool
- 0.0326
- rvis_EVS
- -1.2
- rvis_percentile_EVS
- 5.76
Haploinsufficiency Scores
- pHI
- 0.531
- hipred
- Y
- hipred_score
- 0.809
- ghis
- 0.595
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- E
- essential_gene_gene_trap
- H
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.801
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Nckap1
- 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); digestive/alimentary 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); 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); embryo phenotype; cellular phenotype;
Zebrafish Information Network
- Gene name
- nckap1
- Affected structure
- CaP motoneuron
- Phenotype tag
- abnormal
- Phenotype quality
- has fewer parts of type
Gene ontology
- Biological process
- cell morphogenesis;apoptotic process;central nervous system development;positive regulation of lamellipodium assembly;viral process;cell migration;Rac protein signal transduction;cell projection assembly;positive regulation of actin filament polymerization;cortical actin cytoskeleton organization;Fc-gamma receptor signaling pathway involved in phagocytosis;vascular endothelial growth factor receptor signaling pathway;neuron projection morphogenesis;positive regulation of Arp2/3 complex-mediated actin nucleation
- Cellular component
- ruffle;cytosol;focal adhesion;integral component of membrane;lamellipodium;SCAR complex;lamellipodium membrane;filamentous actin;extracellular exosome
- Molecular function
- protein binding;Rac GTPase binding