KHDRBS1
KH RNA binding domain containing, signal transduction associated 1, the group of Signal transduction and activation of RNA metabolism family
Basic information
Region (hg38): 1:32013868-32060850
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the KHDRBS1 gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 0 | |||||
| missense | 15 | 16 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 0 | |||||
| non coding | 0 | |||||
| Total | 0 | 1 | 15 | 0 | 0 |
Variants in KHDRBS1
This is a list of pathogenic ClinVar variants found in the KHDRBS1 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 1-32014033-G-C | not specified | Uncertain significance (Mar 02, 2023) | ||
| 1-32014039-C-T | not specified | Uncertain significance (May 23, 2023) | ||
| 1-32014053-T-C | not specified | Uncertain significance (Jul 13, 2022) | ||
| 1-32014108-C-T | not specified | Uncertain significance (Dec 19, 2023) | ||
| 1-32014159-C-T | not specified | Uncertain significance (Oct 21, 2021) | ||
| 1-32014218-G-C | not specified | Uncertain significance (Nov 21, 2023) | ||
| 1-32014237-C-T | not specified | Uncertain significance (Jan 02, 2024) | ||
| 1-32014295-G-T | not specified | Uncertain significance (Mar 22, 2023) | ||
| 1-32014308-C-T | not specified | Uncertain significance (May 09, 2022) | ||
| 1-32014356-G-A | not specified | Uncertain significance (May 24, 2024) | ||
| 1-32036970-C-T | not specified | Uncertain significance (Dec 19, 2022) | ||
| 1-32037875-G-A | not specified | Uncertain significance (Jul 12, 2023) | ||
| 1-32037953-G-A | not specified | Uncertain significance (Apr 13, 2023) | ||
| 1-32037956-C-T | not specified | Uncertain significance (Aug 01, 2022) | ||
| 1-32038588-G-C | not specified | Uncertain significance (Dec 19, 2022) | ||
| 1-32042535-G-A | not specified | Uncertain significance (Mar 21, 2023) | ||
| 1-32042554-C-T | Premature ovarian failure | Likely pathogenic (Mar 02, 2020) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| KHDRBS1 | protein_coding | protein_coding | ENST00000327300 | 9 | 47022 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.994 | 0.00577 | 125741 | 0 | 3 | 125744 | 0.0000119 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.42 | 130 | 234 | 0.556 | 0.0000128 | 2791 |
| Missense in 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 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000289 | 0.0000289 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000177 | 0.0000176 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
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}.;
- Pathway
- Leptin signaling pathway;JAK-STAT;Signaling by PTK6;Signal Transduction;regulation of splicing through sam68;TCR;PTK6 Regulates Proteins Involved in RNA Processing;EGFR1;Signaling by Non-Receptor Tyrosine Kinases;Leptin
(Consensus)
Recessive Scores
- pRec
- 0.0854
Intolerance Scores
- loftool
- 0.0674
- rvis_EVS
- -0.25
- rvis_percentile_EVS
- 35.42
Haploinsufficiency Scores
- pHI
- 0.803
- hipred
- Y
- hipred_score
- 0.802
- ghis
- 0.674
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.951
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Khdrbs1
- Phenotype
- immune system phenotype; skeleton phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); homeostasis/metabolism phenotype; growth/size/body region phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan);
Gene ontology
- Biological process
- G2/M transition of mitotic cell cycle;regulation of alternative mRNA splicing, via spliceosome;mRNA processing;cell cycle arrest;signal transduction;cell surface receptor signaling pathway;spermatogenesis;cell population proliferation;positive regulation of signal transduction;regulation of protein stability;negative regulation of transcription, DNA-templated;positive regulation of translational initiation;regulation of RNA export from nucleus;positive regulation of RNA export from nucleus;protein complex oligomerization
- Cellular component
- nucleus;nucleoplasm;cytoplasm;cytosol;membrane;Grb2-Sos complex
- Molecular function
- DNA binding;RNA binding;SH3/SH2 adaptor activity;protein binding;poly(A) binding;poly(U) RNA binding;SH3 domain binding;protein domain specific binding;identical protein binding;protein-containing complex binding