THOC1

protein-coding

THO complex subunit 1, the group of THO complex

Gene summary

Enables identical protein binding activity. Involved in mRNA export from nucleus. Located in chromosome, telomeric region; cytoplasm; and nuclear speck. Part of THO complex part of transcription export complex. Implicated in autosomal dominant nonsyndromic deafness 86. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_005131.3

Inheritance

ClinVar variants

P:1U:62B:2

Top phenotype

Deafness, autosomal dominant 86

gnomAD constraint

pLI —, LoF o/e 0.1

Max pathogenic AF

—

Genomic locus

chr18:214,520-268,050

External References & Databases

Ensembl (ENSG00000079134)

Transcript & Mutation Effects

hg38 • Region Span ~53.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

hearing loss disorderMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0005365

Submitter: PanelApp Australia

sensorineural hearing loss disorderLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0020678

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Deafness, autosomal dominant 86AD

Manifestation: Audiologic/Otolaryngologic

Intervention: General

Rationale: 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

Refs: 32776944

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to THOC1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 53

Hearing loss, autosomal dominant 86Total: 2

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005131.3. 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			2 clinvar	1 clinvar		3
missense	1 clinvar		51 clinvar	1 clinvar		53
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			8 clinvar			8
Total	1	0	62	2	0	65

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 31 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005131.3	RefSeq	NP_005122.2	21	MANE Select
ENST00000261600.11	Ensembl	ENSP00000261600.6	21	MANE Select
ENST00000579891.5	Ensembl	ENSP00000473276.1	9	Standard
ENST00000580038.5	Ensembl	ENSP00000462757.1	11	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

RNA transport - Homo sapiens (human)
Spliceosome - Homo sapiens (human)
Gene expression (Transcription)
RNA Polymerase II Transcription
Metabolism of RNA

Biological Process

regulation of DNA recombination
RNA processing
RNA export from nucleus
mRNA export from nucleus
apoptotic process

Molecular Function

DNA binding
RNA binding
protein binding

Cellular Component

transcription export complex
THO complex
THO complex part of transcription export complex
nuclear chromosome, telomeric region
nucleus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000261600
Coding exons: 21
Length: 53531
Individuals with no LoFs: 124628
Homozygous LoFs: 0
Heterozygous LoFs: 8
Defined: 124636
p: 0.0000321

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.58	185	313	0.590	0.0000151	4309
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000065	0.000065	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000020	0.000018	rare
South Asian	0.000066	0.000065	rare
Other	0.00017	0.00017	rare

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec: 0.106

Intolerance Scores

RVIS EVS: -0.45
RVIS percentile EVS: 24.19

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.990

Gene Damage Prediction

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