THOC2
THO complex subunit 2, the group of THO complex
Basic information
Region (hg38): X:123600560-123733056
Previous symbols: [ "CXorf3", "MRX12", "MRX35" ]
Links
Phenotypes
GenCC
Source:
- X-linked intellectual disability-short stature-overweight syndrome (Strong), mode of inheritance: XLR
- X-linked intellectual disability-short stature-overweight syndrome (Strong), mode of inheritance: XL
- X-linked intellectual disability-short stature-overweight syndrome (Supportive), mode of inheritance: XL
- X-linked intellectual disability-short stature-overweight syndrome (Moderate), mode of inheritance: XL
- X-linked intellectual disability-short stature-overweight syndrome (Strong), mode of inheritance: XL
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Intellectual developmental disorder, X-linked 12 | XL | General | Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing | Craniofacial; Genitourinary; Musculoskeletal; Neurologic | 26166480 |
ClinVar
This is a list of variants' phenotypes submitted to
- not provided (90 variants)
- X-linked intellectual disability-short stature-overweight syndrome (32 variants)
- Inborn genetic diseases (20 variants)
- THOC2-related condition (8 variants)
- not specified (2 variants)
- Intellectual disability (1 variants)
- Neurodevelopmental disorder (1 variants)
- See cases (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the THOC2 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 | 12 | 19 | ||||
| missense | 90 | 101 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 3 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region ? | 5 | 3 | 1 | 9 | ||
| non coding ? | 8 | |||||
| Total | 0 | 8 | 94 | 15 | 14 |
Variants in THOC2
This is a list of pathogenic ClinVar variants found in the THOC2 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| THOC2 | protein_coding | protein_coding | ENST00000245838 | 38 | 132495 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.00 | 2.50e-9 | 116512 | 0 | 1 | 116513 | 0.00000429 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 5.53 | 178 | 539 | 0.330 | 0.0000389 | 10545 |
| Missense in Polyphen | 13 | 109.03 | 0.11923 | 2322 | ||
| Synonymous | 0.201 | 183 | 186 | 0.981 | 0.0000135 | 2793 |
| Loss of Function | 6.99 | 1 | 58.9 | 0.0170 | 0.00000433 | 1237 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000389 | 0.0000389 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.00 | 0.00 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Required for efficient export of polyadenylated RNA and spliced mRNA. Acts as component of the THO subcomplex of the TREX complex which is thought to couple mRNA transcription, processing and nuclear export, and which specifically associates with spliced mRNA and not with unspliced pre-mRNA. TREX is recruited to spliced mRNAs by a transcription-independent mechanism, binds to mRNA upstream of the exon-junction complex (EJC) and is recruited in a splicing- and cap-dependent manner to a region near the 5' end of the mRNA where it functions in mRNA export to the cytoplasm via the TAP/NFX1 pathway. The TREX complex is essential for the export of Kaposi's sarcoma-associated herpesvirus (KSHV) intronless mRNAs and infectious virus production. THOC2 (and probably the THO complex) is involved in releasing mRNA from nuclear speckle domains. Required for NXF1 localization to the nuclear rim. Plays a role for proper neuronal development. {ECO:0000269|PubMed:11979277, ECO:0000269|PubMed:15833825, ECO:0000269|PubMed:15998806, ECO:0000269|PubMed:17190602, ECO:0000269|PubMed:18974867, ECO:0000269|PubMed:22893130, ECO:0000269|PubMed:23222130, ECO:0000269|PubMed:26166480}.;
- Pathway
- RNA transport - Homo sapiens (human);Spliceosome - Homo sapiens (human);Gene expression (Transcription);RNA Polymerase II Transcription;Metabolism of RNA;Cleavage of Growing Transcript in the Termination Region ;RNA Polymerase II Transcription Termination;Transport of Mature mRNA derived from an Intron-Containing Transcript;mRNA 3,-end processing;Transport of Mature Transcript to Cytoplasm;Processing of Capped Intron-Containing Pre-mRNA
(Consensus)
Recessive Scores
- pRec
- 0.118
Intolerance Scores
- loftool
- 0.0182
- rvis_EVS
- -0.58
- rvis_percentile_EVS
- 18.59
Haploinsufficiency Scores
- pHI
- 0.495
- hipred
- Y
- hipred_score
- 0.696
- ghis
- 0.667
Essentials
- essential_gene_CRISPR
- E
- essential_gene_CRISPR2
- E
- essential_gene_gene_trap
- gene_indispensability_pred
- N
- gene_indispensability_score
- 0.215
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Thoc2
- Phenotype
Zebrafish Information Network
- Gene name
- thoc2
- Affected structure
- hepatocyte
- Phenotype tag
- abnormal
- Phenotype quality
- increased size
Gene ontology
- Biological process
- RNA export from nucleus;mRNA export from nucleus;RNA splicing;poly(A)+ mRNA export from nucleus;mRNA 3'-end processing;viral mRNA export from host cell nucleus;neuron development;generation of neurons
- Cellular component
- transcription export complex;THO complex;THO complex part of transcription export complex;nuclear chromosome, telomeric region;nucleoplasm;nuclear speck
- Molecular function
- mRNA binding;protein binding