KIFAP3
protein-codingkinesin associated protein 3, the group of Armadillo like helical domain containing
Gene summary
The small G protein GDP dissociation stimulator (smg GDS) is a regulator protein having two activities on a group of small G proteins including the Rho and Rap1 family members and Ki-Ras; one is to stimulate their GDP/GTP exchange reactions, and the other is to inhibit their interactions with membranes. The protein encoded by this gene contains 9 'Armadillo' repeats and interacts with the smg GDS protein through these repeats. This protein, which is highly concentrated around the endoplasmic reticulum, is phosphorylated by v-src, and this phosphorylation reduces the affinity of the protein for smg GDS. It is thought that this protein serves as a linker between human chromosome-associated polypeptide (HCAP) and KIF3A/B, a kinesin superfamily protein in the nucleus, and that it plays a role in the interaction of chromosomes with an ATPase motor protein. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2011]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~163.9 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 KIFAP3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_014970.4. 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 | 2 | 1 | 2 | 5 | ||
| missense | 70 | 1 | 2 | 73 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 74 | 2 | 4 | 80 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_055785.2 | 20 | MANE Select | |
| Ensembl | ENSP00000354560.2 | 20 | MANE Select | |
| RefSeq | NP_001191443.1 | 18 | Standard | |
| RefSeq | NP_001191445.1 | 19 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Vesicle-mediated transport
- Membrane Trafficking
- Kinesins
- Factors involved in megakaryocyte development and platelet production
- Hemostasis
Biological Process
- retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum
- microtubule-based process
- microtubule-based movement
- signal transduction
- negative regulation of cell population proliferation
Molecular Function
- protein binding
- kinesin binding
- protein phosphatase binding
- intraciliary transport particle B binding
Cellular Component
- condensed nuclear chromosome
- endoplasmic reticulum
- Golgi apparatus
- centrosome
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000361580
- Coding exons
- 20
- Length
- 163883
- Individuals with no LoFs
- 125704
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 44
- Defined
- 125748
- p
- 0.000175
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.91 | 295 | 403 | 0.732 | 0.0000197 | 5248 |
| Missense (PolyPhen) | 79 | 145.19 | 0.54413 | 1995 | ||
| Synonymous | -0.862 | 149 | 136 | 1.09 | 0.00000633 | 1393 |
| Loss of Function | 4.05 | 17 | 47.0 | 0.362 | 0.00000283 | 557 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00019 | 0.00018 | rare |
| Latino/Admixed American | 0.00012 | 0.00012 | rare |
| Ashkenazi Jewish | 0.00021 | 0.00020 | rare |
| East Asian | 0.000055 | 0.000054 | rare |
| Finnish | 0.00048 | 0.00046 | rare |
| European (Non-Finnish) | 0.00021 | 0.00019 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Involved in tethering the chromosomes to the spindle pole and in chromosome movement. Binds to the tail domain of the KIF3A/KIF3B heterodimer to form a heterotrimeric KIF3 complex and may regulate the membrane binding of this complex (By similarity). {ECO:0000250}.;
Recessive Scores
- pRec
- 0.0897
Intolerance Scores
- LoFtool
- 0.736
- RVIS EVS
- -0.29
- RVIS percentile EVS
- 33.2
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.860
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |