QKI
protein-codingQKI, KH domain containing RNA binding
Gene summary
The protein encoded by this gene is an RNA-binding protein that regulates pre-mRNA splicing, export of mRNAs from the nucleus, protein translation, and mRNA stability. The encoded protein is involved in myelinization and oligodendrocyte differentiation and may play a role in schizophrenia. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2014]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~164.6 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0001071
Submitter: G2P
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to QKI variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_006775.3. 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 | 3 | 3 | ||||
| missense | 23 | 23 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 5 | 5 | ||||
| Total | 0 | 0 | 28 | 3 | 0 | 31 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_006766.1 | 8 | MANE Select | |
| Ensembl | ENSP00000355094.3 | 8 | MANE Select | |
| RefSeq | NP_001288014.1 | 8 | Standard | |
| RefSeq | NP_996735.1 | 7 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| qkia | Danio rerio | Structure: fast muscle cell Quality: immature abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Exercise-induced Circadian Regulation
- Disease
- Signaling by BRAF and RAF fusions
- Oncogenic MAPK signaling
- Diseases of signal transduction
Biological Process
- mRNA processing
- regulation of translation
- multicellular organism development
- RNA splicing
- cell differentiation
Molecular Function
- RNA binding
- protein binding
- SH3 domain binding
Cellular Component
- nucleus
- cytoplasm
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000361752
- Coding exons
- 8
- Length
- 164597
- Individuals with no LoFs
- 125617
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 115
- Defined
- 125732
- p
- 0.000457
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 3.02 | 77 | 196 | 0.393 | 0.0000102 | 2210 |
| Missense (PolyPhen) | 20 | 69.23 | 0.28889 | 815 | ||
| Synonymous | -0.922 | 83 | 73.0 | 1.14 | 0.00000419 | 673 |
| Loss of Function | 3.24 | 3 | 17.7 | 0.169 | 9.90e-7 | 209 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00046 | 0.00031 | rare |
| Latino/Admixed American | 0.0011 | 0.00055 | notable |
| Ashkenazi Jewish | 0.0022 | 0.0012 | notable |
| East Asian | 0.00012 | 0.00011 | rare |
| Finnish | 0.00058 | 0.00032 | rare |
| European (Non-Finnish) | 0.00090 | 0.00048 | rare |
| South Asian | 0.00057 | 0.00029 | rare |
| Other | 0.0018 | 0.00098 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: RNA-binding protein that plays a central role in myelinization (PubMed:16641098). Binds to the 5'-NACUAAY-N(1,20)- UAAY-3' RNA core sequence. Regulates target mRNA stability (PubMed:23630077). In addition, acts by regulating pre-mRNA splicing, mRNA export and protein translation. Required to protect and promote stability of mRNAs such as MBP and CDKN1B. Regulator of oligodendrocyte differentiation and maturation in the brain that may play a role in myelin and oligodendrocyte dysfunction in schizophrenia (PubMed:16641098). Participates in mRNA transport by regulating the nuclear export of MBP mRNA. Also involved in regulation of mRNA splicing of MAG pre-mRNA. Acts as a translational repressor (By similarity). {ECO:0000250|UniProtKB:Q9QYS9, ECO:0000269|PubMed:16641098, ECO:0000269|PubMed:23630077}.;
Recessive Scores
- pRec
- 0.198
Intolerance Scores
- LoFtool
- 0.0249
- RVIS EVS
- -0.23
- RVIS percentile EVS
- 36.86
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.914
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |