KHDRBS2
protein-codingKH RNA binding domain containing, signal transduction associated 2, the group of Signal transduction and activation of RNA metabolism family
Gene summary
Predicted to enable mRNA binding activity and poly(A) binding activity. Predicted to be involved in regulation of alternative mRNA splicing, via spliceosome. Predicted to be located in nucleoplasm. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Jul 2025]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~656.0 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 KHDRBS2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_152688.4. 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 | 0 | |||||
| missense | 63 | 63 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 64 | 0 | 0 | 64 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_689901.2 | 9 | MANE Select | |
| Ensembl | ENSP00000281156.3 | 9 | MANE Select | |
| RefSeq | NP_001337551.1 | 10 | Standard | |
| Ensembl | ENSP00000502245.1 | 8 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Signaling by PTK6
- Signal Transduction
- PTK6 Regulates Proteins Involved in RNA Processing
- Signaling by Non-Receptor Tyrosine Kinases
Biological Process
- mRNA processing
- regulation of mRNA splicing, via spliceosome
Molecular Function
- protein binding
- poly(A) binding
- poly(U) RNA binding
- SH3 domain binding
- SH2 domain binding
Cellular Component
- nucleoplasm
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000281156
- Coding exons
- 9
- Length
- 606268
- Individuals with no LoFs
- 125701
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 46
- Defined
- 125748
- p
- 0.000187
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.0168 | 196 | 197 | 0.997 | 0.0000106 | 2221 |
| Missense (PolyPhen) | 61 | 72.602 | 0.8402 | 848 | ||
| Synonymous | -2.37 | 93 | 68.1 | 1.37 | 0.00000347 | 684 |
| Loss of Function | 2.82 | 6 | 19.4 | 0.309 | 9.76e-7 | 251 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000032 | 0.000029 | rare |
| Ashkenazi Jewish | 0.0030 | 0.0029 | notable |
| East Asian | 0.000055 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00011 | 0.00011 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0.00049 | 0.00049 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: RNA-binding protein that plays a role in the regulation of alternative splicing and influences mRNA splice site selection and exon inclusion. Binds both poly(A) and poly(U) homopolymers. Phosphorylation by PTK6 inhibits its RNA-binding ability (By similarity). Induces an increased concentration-dependent incorporation of exon in CD44 pre-mRNA by direct binding to purine-rich exonic enhancer. Can regulate alternative splicing of NRXN1 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. Regulates cell-type specific alternative splicing of NRXN1 at AS4 and acts synergystically with SAM68 in exon skipping. In contrast acts antagonistically with SAM68 in NRXN3 exon skipping at AS4. Its phosphorylation by FYN inhibits its ability to regulate splice site selection. May function as an adapter protein for Src kinases during mitosis. {ECO:0000250|UniProtKB:Q920F3, ECO:0000250|UniProtKB:Q9WU01}.;
Recessive Scores
- pRec
- 0.106
Intolerance Scores
- LoFtool
- 0.500
- RVIS EVS
- -0.09
- RVIS percentile EVS
- 46.92
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.977
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |