NCKIPSD
protein-codingNCK interacting protein with SH3 domain
Gene summary
The protein encoded by this gene contains a nuclear localization signal. It plays a role in signal transduction, and may function in the maintenance of sarcomeres and in the assembly of myofibrils into sarcomeres. It also plays an important role in stress fiber formation This protein is involved in the formation and maintenance of dendritic spines, and modulates synaptic activity in neurons. The gene is involved in therapy-related leukemia by a chromosomal translocation t(3;11)(p21;q23) that involves this gene and the myeloid/lymphoid leukemia gene. Alternative splicing results in multiple transcript variants of this gene. [provided by RefSeq, Aug 2019]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~12.5 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 NCKIPSD variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_016453.4. 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 | 2 | |||
| missense | 113 | 4 | 117 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 6 | 6 | ||||
| Total | 0 | 0 | 121 | 4 | 1 | 126 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_057537.1 | 13 | MANE Select | |
| Ensembl | ENSP00000294129.2 | 13 | MANE Select | |
| RefSeq | NP_909119.1 | 13 | Standard | |
| Ensembl | ENSP00000396683.1 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Signal Transduction
- Fcgamma receptor (FCGR) dependent phagocytosis
- Innate Immune System
- Immune System
- RHO GTPases Activate WASPs and WAVEs
Biological Process
- NLS-bearing protein import into nucleus
- cytoskeleton organization
- signal transduction
- positive regulation of neuron projection development
- Fc-gamma receptor signaling pathway involved in phagocytosis
Molecular Function
- protein binding
- cytoskeletal protein binding
- SH3 domain binding
Cellular Component
- cytosol
- intermediate filament
- COP9 signalosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000294129
- Coding exons
- 13
- Length
- 22434
- Individuals with no LoFs
- 125643
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 105
- Defined
- 125748
- p
- 0.000418
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.607 | 400 | 436 | 0.918 | 0.0000266 | 4590 |
| Missense (PolyPhen) | 133 | 143.32 | 0.92802 | 1532 | ||
| Synonymous | 0.833 | 169 | 183 | 0.922 | 0.0000111 | 1564 |
| Loss of Function | 3.27 | 12 | 32.0 | 0.375 | 0.00000178 | 342 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00025 | 0.00025 | rare |
| Latino/Admixed American | 0.00023 | 0.00023 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.0039 | 0.0038 | notable |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00014 | 0.00014 | rare |
| South Asian | 0.00023 | 0.00023 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Has an important role in stress fiber formation induced by active diaphanous protein homolog 1 (DRF1). Induces microspike formation, in vivo (By similarity). In vitro, stimulates N-WASP- induced ARP2/3 complex activation in the absence of CDC42 (By similarity). May play an important role in the maintenance of sarcomeres and/or in the assembly of myofibrils into sarcomeres. Implicated in regulation of actin polymerization and cell adhesion. Plays a role in angiogenesis. {ECO:0000250, ECO:0000269|PubMed:22419821}.;
Recessive Scores
- pRec
- 0.109
Intolerance Scores
- LoFtool
- 0.845
- RVIS EVS
- -1
- RVIS percentile EVS
- 8.54
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.879
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |