THOC1

THO complex subunit 1, the group of THO complex

Basic information

Region (hg38): 18:214520-268050

Links

ENSG00000079134 ∙ NCBI:9984 ∙ OMIM:606930 ∙ HGNC:19070 ∙ Uniprot:Q96FV9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• sensorineural hearing loss disorder (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Deafness, autosomal dominant 86	AD	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	Audiologic/Otolaryngologic	32776944

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the THOC1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the THOC1 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			29	1		30
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	29	1	0

Variants in THOC1

This is a list of pathogenic ClinVar variants found in the THOC1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
18-214640-C-T		not specified	Uncertain significance (Mar 08, 2024)
18-214789-C-T		not specified	Uncertain significance (Dec 02, 2024)
18-214793-C-T		not specified	Uncertain significance (May 27, 2022)
18-214799-G-C		not specified	Uncertain significance (Jun 10, 2024)
18-214849-T-C		not specified	Uncertain significance (Jan 22, 2024)
18-214910-G-A		not specified	Uncertain significance (Oct 16, 2023)
18-216514-A-G		not specified	Uncertain significance (Dec 15, 2022)
18-218892-T-G		not specified	Uncertain significance (Oct 09, 2024)
18-218904-A-G		not specified	Uncertain significance (Oct 25, 2024)
18-218907-T-C		not specified	Uncertain significance (Feb 20, 2025)
18-218946-T-C		not specified	Uncertain significance (Nov 18, 2022)
18-224105-G-A		Hearing loss, autosomal dominant 86	Uncertain significance (Aug 08, 2024)
18-224154-T-C		not specified	Likely benign (May 17, 2023)
18-224177-G-A		not specified	Uncertain significance (Apr 26, 2024)
18-224178-T-A		not specified	Uncertain significance (Feb 08, 2025)
18-224963-G-A		not specified	Uncertain significance (May 21, 2024)
18-224982-T-C		not specified	Uncertain significance (Aug 15, 2023)
18-224984-T-C		not specified	Uncertain significance (May 13, 2024)
18-226810-T-C		not specified	Uncertain significance (Mar 02, 2023)
18-246382-T-C		not specified	Uncertain significance (Jun 22, 2023)
18-252543-T-C		not specified	Uncertain significance (Jul 12, 2023)
18-252574-T-G		not specified	Uncertain significance (Dec 03, 2024)
18-252575-T-C		not specified	Uncertain significance (Dec 03, 2024)
18-254329-G-C		Hearing loss, autosomal dominant 86	Pathogenic (Mar 13, 2023)
18-260189-T-G		not specified	Uncertain significance (Jan 03, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
THOC1	protein_coding	protein_coding	ENST00000261600	21	53531

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.000455	124628	0	8	124636	0.0000321

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.58	185	313	0.590	0.0000151	4309
Missense in Polyphen		35	101.76	0.34394		1508
Synonymous	0.601	100	108	0.926	0.00000506	1125
Loss of Function	5.26	4	39.8	0.101	0.00000190	551

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000654	0.0000646
Ashkenazi Jewish	0.000199	0.000199
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000196	0.0000177
Middle Eastern	0.00	0.00
South Asian	0.0000656	0.0000654
Other	0.000175	0.000165

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Required for efficient export of polyadenylated RNA. 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. Regulates transcriptional elongation of a subset of genes. Involved in genome stability by preventing co-transcriptional R-loop formation.
• 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: 0.106

Intolerance Scores

• rvis_EVS: -0.45
• rvis_percentile_EVS: 24.19

Haploinsufficiency Scores

• pHI: 0.921
• hipred: Y
• hipred_score: 0.714
• ghis: 0.633

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.990

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Thoc1
• Phenotype: cellular phenotype; growth/size/body region phenotype; embryo 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)

Gene ontology

• Biological process: regulation of DNA recombination;RNA processing;RNA export from nucleus;mRNA export from nucleus;apoptotic process;signal transduction;RNA splicing;mRNA 3'-end processing;replication fork processing;regulation of DNA-templated transcription, elongation;positive regulation of DNA-templated transcription, elongation;viral mRNA export from host cell nucleus;negative regulation of isotype switching to IgA isotypes;negative regulation of DNA damage checkpoint
• Cellular component: transcription export complex;THO complex;THO complex part of transcription export complex;nuclear chromosome, telomeric region;nucleus;nucleoplasm;cytoplasm;cytosol;nuclear matrix;nuclear speck;intercellular bridge
• Molecular function: DNA binding;RNA binding;protein binding