DHX9
DExH-box helicase 9, the group of DEAH-box helicases
Basic information
Region (hg38): 1:182839347-182887982
Previous symbols: [ "LKP", "DDX9" ]
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 DHX9 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 | 2 | |||||
| missense | 25 | 26 | ||||
| nonsense | 1 | |||||
| start loss | 0 | |||||
| frameshift | 2 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | |||||
| splice region | 2 | 2 | ||||
| non coding | 0 | |||||
| Total | 0 | 2 | 29 | 0 | 2 |
Variants in DHX9
This is a list of pathogenic ClinVar variants found in the DHX9 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 1-182843412-G-A | Inborn genetic diseases | Uncertain significance (May 26, 2023) | ||
| 1-182843432-G-A | Inborn genetic diseases | Uncertain significance (Dec 19, 2023) | ||
| 1-182852350-G-T | Benign (Dec 31, 2019) | |||
| 1-182853354-C-T | Inborn genetic diseases | Uncertain significance (Dec 01, 2022) | ||
| 1-182853363-G-A | INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL DOMINANT 75 | Pathogenic (Oct 28, 2024) | ||
| 1-182854048-G-A | Uncertain significance (Jul 19, 2024) | |||
| 1-182854132-A-T | Inborn genetic diseases | Uncertain significance (Aug 08, 2023) | ||
| 1-182854146-T-A | Uncertain significance (Sep 21, 2022) | |||
| 1-182854163-G-A | Uncertain significance (Apr 25, 2024) | |||
| 1-182854175-A-G | Inborn genetic diseases | Uncertain significance (May 29, 2024) | ||
| 1-182858115-C-T | INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL DOMINANT 75 | Pathogenic (Oct 28, 2024) | ||
| 1-182858138-A-AT | Charcot-Marie-Tooth disease | Likely pathogenic (Nov 30, 2023) | ||
| 1-182858162-G-A | Benign (Dec 31, 2019) | |||
| 1-182858196-G-T | Uncertain significance (Dec 01, 2023) | |||
| 1-182858557-C-G | Inborn genetic diseases | Uncertain significance (May 09, 2023) | ||
| 1-182858564-A-G | Inborn genetic diseases | Uncertain significance (Oct 08, 2024) | ||
| 1-182859067-C-T | Inborn genetic diseases | Uncertain significance (May 31, 2023) | ||
| 1-182859103-C-G | Inborn genetic diseases | Uncertain significance (Feb 27, 2024) | ||
| 1-182859992-G-A | Uncertain significance (Dec 16, 2023) | |||
| 1-182860044-C-A | Uncertain significance (Dec 25, 2023) | |||
| 1-182860064-T-A | Uncertain significance (Sep 28, 2022) | |||
| 1-182860092-G-A | DHX9-related disorder • INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL DOMINANT 75 | Pathogenic/Likely pathogenic (Oct 28, 2024) | ||
| 1-182866465-T-G | Inborn genetic diseases | Uncertain significance (Nov 09, 2024) | ||
| 1-182866508-G-A | Uncertain significance (Jul 16, 2024) | |||
| 1-182866531-C-T | Likely pathogenic (Feb 21, 2024) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| DHX9 | protein_coding | protein_coding | ENST00000367549 | 27 | 48383 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.00 | 2.82e-10 | 124784 | 0 | 9 | 124793 | 0.0000361 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 5.84 | 264 | 699 | 0.378 | 0.0000367 | 8320 |
| Missense in Polyphen | 47 | 259.53 | 0.1811 | 3176 | ||
| Synonymous | -1.21 | 255 | 232 | 1.10 | 0.0000116 | 2460 |
| Loss of Function | 7.62 | 3 | 73.6 | 0.0408 | 0.00000464 | 802 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000290 | 0.0000290 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.0000556 | 0.0000556 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000265 | 0.0000265 |
| Middle Eastern | 0.0000556 | 0.0000556 |
| South Asian | 0.000134 | 0.000131 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Multifunctional ATP-dependent nucleic acid helicase that unwinds DNA and RNA in a 3' to 5' direction and that plays important roles in many processes, such as DNA replication, transcriptional activation, post-transcriptional RNA regulation, mRNA translation and RNA-mediated gene silencing (PubMed:9111062, PubMed:11416126, PubMed:12711669, PubMed:15355351, PubMed:16680162, PubMed:17531811, PubMed:20669935, PubMed:21561811, PubMed:24049074, PubMed:25062910, PubMed:24990949, PubMed:28221134). Requires a 3'-single-stranded tail as entry site for acid nuclei unwinding activities as well as the binding and hydrolyzing of any of the four ribo- or deoxyribo- nucleotide triphosphates (NTPs) (PubMed:1537828). Unwinds numerous nucleic acid substrates such as double-stranded (ds) DNA and RNA, DNA:RNA hybrids, DNA and RNA forks composed of either partially complementary DNA duplexes or DNA:RNA hybrids, respectively, and also DNA and RNA displacement loops (D- and R-loops), triplex- helical DNA (H-DNA) structure and DNA and RNA-based G-quadruplexes (PubMed:20669935, PubMed:21561811, PubMed:24049074). Binds dsDNA, single-stranded DNA (ssDNA), dsRNA, ssRNA and poly(A)-containing RNA (PubMed:9111062, PubMed:10198287). Binds also to circular dsDNA or dsRNA of either linear and/or circular forms and stimulates the relaxation of supercoiled DNAs catalyzed by topoisomerase TOP2A (PubMed:12711669). Plays a role in DNA replication at origins of replication and cell cycle progression (PubMed:24990949). Plays a role as a transcriptional coactivator acting as a bridging factor between polymerase II holoenzyme and transcription factors or cofactors, such as BRCA1, CREBBP, RELA and SMN1 (PubMed:11149922, PubMed:9323138, PubMed:9662397, PubMed:11038348, PubMed:11416126, PubMed:15355351, PubMed:28221134). Binds to the CDKN2A promoter (PubMed:11038348). Plays several roles in post-transcriptional regulation of gene expression (PubMed:28221134, PubMed:28355180). In cooperation with NUP98, promotes pre-mRNA alternative splicing activities of a subset of genes (PubMed:11402034, PubMed:16680162, PubMed:28221134, PubMed:28355180). As component of a large PER complex, is involved in the negative regulation of 3' transcriptional termination of circadian target genes such as PER1 and NR1D1 and the control of the circadian rhythms (By similarity). Acts also as a nuclear resolvase that is able to bind and neutralize harmful massive secondary double-stranded RNA structures formed by inverted-repeat Alu retrotransposon elements that are inserted and transcribed as parts of genes during the process of gene transposition (PubMed:28355180). Involved in the positive regulation of nuclear export of constitutive transport element (CTE)-containing unspliced mRNA (PubMed:9162007, PubMed:10924507, PubMed:11402034). Component of the coding region determinant (CRD)-mediated complex that promotes cytoplasmic MYC mRNA stability (PubMed:19029303). Plays a role in mRNA translation (PubMed:28355180). Positively regulates translation of selected mRNAs through its binding to post-transcriptional control element (PCE) in the 5'-untranslated region (UTR) (PubMed:16680162). Involved with LARP6 in the translation stimulation of type I collagen mRNAs for CO1A1 and CO1A2 through binding of a specific stem-loop structure in their 5'-UTRs (PubMed:22190748). Stimulates LIN28A-dependent mRNA translation probably by facilitating ribonucleoprotein remodeling during the process of translation (PubMed:21247876). Plays also a role as a small interfering (siRNA)-loading factor involved in the RNA-induced silencing complex (RISC) loading complex (RLC) assembly, and hence functions in the RISC-mediated gene silencing process (PubMed:17531811). Binds preferentially to short double-stranded RNA, such as those produced during rotavirus intestinal infection (PubMed:28636595). This interaction may mediate NLRP9 inflammasome activation and trigger inflammatory response, including IL18 release and pyroptosis (PubMed:28636595). Finally, mediates the attachment of heterogeneous nuclear ribonucleoproteins (hnRNPs) to actin filaments in the nucleus (PubMed:11687588). {ECO:0000250|UniProtKB:O70133, ECO:0000269|PubMed:10198287, ECO:0000269|PubMed:10924507, ECO:0000269|PubMed:11038348, ECO:0000269|PubMed:11149922, ECO:0000269|PubMed:11402034, ECO:0000269|PubMed:11416126, ECO:0000269|PubMed:11687588, ECO:0000269|PubMed:12711669, ECO:0000269|PubMed:15355351, ECO:0000269|PubMed:1537828, ECO:0000269|PubMed:16680162, ECO:0000269|PubMed:17531811, ECO:0000269|PubMed:19029303, ECO:0000269|PubMed:20669935, ECO:0000269|PubMed:21247876, ECO:0000269|PubMed:21561811, ECO:0000269|PubMed:22190748, ECO:0000269|PubMed:24049074, ECO:0000269|PubMed:24990949, ECO:0000269|PubMed:25062910, ECO:0000269|PubMed:28221134, ECO:0000269|PubMed:28355180, ECO:0000269|PubMed:28636595, ECO:0000269|PubMed:9111062, ECO:0000269|PubMed:9162007, ECO:0000269|PubMed:9323138, ECO:0000269|PubMed:9662397}.;
- Pathway
- mRNA Processing;Toll Like Receptor 7/8 (TLR7/8) Cascade;Signaling by Interleukins;Cytokine Signaling in Immune system;Toll Like Receptor 9 (TLR9) Cascade;MyD88 cascade initiated on plasma membrane;Toll Like Receptor 10 (TLR10) Cascade;Toll Like Receptor 3 (TLR3) Cascade;Toll Like Receptor 5 (TLR5) Cascade;ZBP1(DAI) mediated induction of type I IFNs;Toll-Like Receptors Cascades;TRAF6 mediated NF-kB activation;DDX58/IFIH1-mediated induction of interferon-alpha/beta;DEx/H-box helicases activate type I IFN and inflammatory cytokines production ;Interleukin-1 signaling;Metabolism of RNA;Innate Immune System;Immune System;mRNA Splicing - Major Pathway;RIP-mediated NFkB activation via ZBP1;TAK1 activates NFkB by phosphorylation and activation of IKKs complex;TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation;MyD88 dependent cascade initiated on endosome;Cytosolic sensors of pathogen-associated DNA ;TRIF(TICAM1)-mediated TLR4 signaling ;MyD88-independent TLR4 cascade ;Toll Like Receptor 4 (TLR4) Cascade;MyD88:Mal cascade initiated on plasma membrane;Toll Like Receptor TLR1:TLR2 Cascade;Toll Like Receptor TLR6:TLR2 Cascade;Toll Like Receptor 2 (TLR2) Cascade;mRNA Splicing;Processing of Capped Intron-Containing Pre-mRNA;Interleukin-1 family signaling
(Consensus)
Recessive Scores
- pRec
- 0.133
Intolerance Scores
- loftool
- 0.103
- rvis_EVS
- -1.16
- rvis_percentile_EVS
- 6.17
Haploinsufficiency Scores
- pHI
- 0.909
- hipred
- Y
- hipred_score
- 0.831
- ghis
- 0.718
Essentials
- essential_gene_CRISPR
- E
- essential_gene_CRISPR2
- E
- essential_gene_gene_trap
- E
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.930
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Dhx9
- Phenotype
- cellular phenotype; 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); hematopoietic system phenotype; embryo phenotype; immune system phenotype;
Gene ontology
- Biological process
- alternative mRNA splicing, via spliceosome;mRNA splicing, via spliceosome;osteoblast differentiation;DNA replication;DNA-templated transcription, termination;regulation of transcription by RNA polymerase II;inflammatory response;RNA secondary structure unwinding;targeting of mRNA for destruction involved in RNA interference;positive regulation of type I interferon production;DNA duplex unwinding;positive regulation of interleukin-18 production;positive regulation of interferon-beta secretion;DNA-templated viral transcription;G-quadruplex DNA unwinding;innate immune response;positive regulation of innate immune response;positive regulation of DNA repair;positive regulation of DNA replication;positive regulation of transcription by RNA polymerase II;positive regulation of RNA export from nucleus;positive regulation of fibroblast proliferation;rhythmic process;positive regulation of viral transcription;regulation of mRNA processing;regulation of defense response to virus by host;positive regulation of inflammatory response;mRNA transport;positive regulation of NF-kappaB transcription factor activity;positive regulation of response to cytokine stimulus;pyroptosis;small RNA loading onto RISC;CRD-mediated mRNA stabilization;cellular response to tumor necrosis factor;cellular response to exogenous dsRNA;positive regulation of interferon-alpha secretion;protein localization to cytoplasmic stress granule;positive regulation of tumor necrosis factor secretion;positive regulation of viral translation;positive regulation of polysome binding;positive regulation of DNA topoisomerase (ATP-hydrolyzing) activity;positive regulation of gene silencing by miRNA;regulation of cytoplasmic translation;positive regulation of cytoplasmic translation;positive regulation of interleukin-6 secretion
- Cellular component
- nucleus;nucleoplasm;perichromatin fibrils;nucleolus;cytoplasm;centrosome;cytosol;polysome;actin cytoskeleton;membrane;nuclear body;protein-containing complex;micro-ribonucleoprotein complex;cytoplasmic ribonucleoprotein granule;polysomal ribosome;RISC-loading complex;CRD-mediated mRNA stability complex;nuclear stress granule;ribonucleoprotein complex
- Molecular function
- RNA polymerase II proximal promoter sequence-specific DNA binding;RNA polymerase II complex binding;regulatory region RNA binding;RNA polymerase II transcription factor binding;DNA binding;DNA replication origin binding;double-stranded DNA binding;single-stranded DNA binding;transcription coregulator activity;transcription coactivator activity;RNA binding;RNA helicase activity;double-stranded RNA binding;single-stranded RNA binding;mRNA binding;ATP-dependent DNA helicase activity;ATP-dependent RNA helicase activity;protein binding;ATP binding;ATPase activity;nucleoside-triphosphatase activity;chromatin DNA binding;ATP-dependent 3'-5' DNA/RNA helicase activity;ATP-dependent 3'-5' RNA helicase activity;siRNA binding;RNA stem-loop binding;ATP-dependent 3'-5' DNA helicase activity;triplex DNA binding;metal ion binding;nucleoside-triphosphate diphosphatase activity;importin-alpha family protein binding;RNA polymerase binding;RISC complex binding;polysome binding;single-stranded DNA-dependent ATP-dependent 3'-5' DNA helicase activity;sequence-specific mRNA binding;promoter-specific chromatin binding