KHDRBS1
protein-codingKH RNA binding domain containing, signal transduction associated 1, the group of Signal transduction and activation of RNA metabolism family
Gene summary
This gene encodes a member of the K homology domain-containing, RNA-binding, signal transduction-associated protein family. The encoded protein appears to have many functions and may be involved in a variety of cellular processes, including alternative splicing, cell cycle regulation, RNA 3'-end formation, tumorigenesis, and regulation of human immunodeficiency virus gene expression. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2012]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~47.0 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0005387
Submitter: PanelApp Australia
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to KHDRBS1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_006559.3. 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 | 0 | |||||
| missense | 1 | 36 | 37 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 7 | 7 | ||||
| Total | 0 | 1 | 44 | 0 | 0 | 45 |
Highest pathogenic variant AF is 0.000013014894
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_006550.1 | 9 | MANE Select | |
| Ensembl | ENSP00000313829.7 | 9 | MANE Select | |
| RefSeq | NP_001258807.1 | 8 | Standard | |
| Ensembl | ENSP00000417731.1 | 8 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Leptin signaling pathway
- JAK-STAT
- Signaling by PTK6
- Signal Transduction
- regulation of splicing through sam68
Biological Process
- G2/M transition of mitotic cell cycle
- regulation of alternative mRNA splicing, via spliceosome
- mRNA processing
- cell cycle arrest
- signal transduction
Molecular Function
- DNA binding
- RNA binding
- SH3/SH2 adaptor activity
- protein binding
- poly(A) binding
Cellular Component
- nucleus
- nucleoplasm
- cytoplasm
- cytosol
- membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000327300
- Coding exons
- 9
- Length
- 47022
- Individuals with no LoFs
- 125741
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 3
- Defined
- 125744
- p
- 0.0000119
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.42 | 130 | 234 | 0.556 | 0.0000128 | 2791 |
| Missense (PolyPhen) | 50 | 102.59 | 0.48736 | 1160 | ||
| Synonymous | 0.515 | 81 | 87.1 | 0.930 | 0.00000469 | 937 |
| Loss of Function | 3.91 | 1 | 19.7 | 0.0507 | 9.81e-7 | 253 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000018 | 0.000018 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Recruited and tyrosine phosphorylated by several receptor systems, for example the T-cell, leptin and insulin receptors. Once phosphorylated, functions as an adapter protein in signal transduction cascades by binding to SH2 and SH3 domain- containing proteins. Role in G2-M progression in the cell cycle. Represses CBP-dependent transcriptional activation apparently by competing with other nuclear factors for binding to CBP. Also acts as a putative regulator of mRNA stability and/or translation rates and mediates mRNA nuclear export. Positively regulates the association of constitutive transport element (CTE)-containing mRNA with large polyribosomes and translation initiation. According to some authors, is not involved in the nucleocytoplasmic export of unspliced (CTE)-containing RNA species according to (PubMed:22253824). RNA-binding protein that plays a role in the regulation of alternative splicing and influences mRNA splice site selection and exon inclusion. Binds to RNA containing 5'-[AU]UAA-3' as a bipartite motif spaced by more than 15 nucleotides. Binds poly(A). Can regulate CD44 alternative splicing in a Ras pathway-dependent manner (By similarity). In cooperation with HNRNPA1 modulates alternative splicing of BCL2L1 by promoting splicing toward isoform Bcl-X(S), and of SMN1 (PubMed:17371836, PubMed:20186123). Can regulate alternative splicing of NRXN1 and NRXN3 in the laminin G-like domain 6 containing the evolutionary conserved neurexin alternative spliced segment 4 (AS4) involved in neurexin selective targeting to postsynaptic partners. In a neuronal activity-dependent manner cooperates synergistically with KHDRBS2/SLIM-1 in regulation of NRXN1 exon skipping at AS4. The cooperation with KHDRBS2/SLIM-1 is antagonistic for regulation of NXRN3 alternative splicing at AS4 (By similarity). {ECO:0000250|UniProtKB:Q60749, ECO:0000269|PubMed:15021911, ECO:0000269|PubMed:17371836, ECO:0000269|PubMed:20186123, ECO:0000269|PubMed:20610388, ECO:0000269|PubMed:22253824, ECO:0000269|PubMed:26758068}.;
Recessive Scores
- pRec
- 0.0854
Intolerance Scores
- LoFtool
- 0.0674
- RVIS EVS
- -0.25
- RVIS percentile EVS
- 35.42
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.951
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |