THOC6

THO complex subunit 6, the group of WD repeat domain containing|THO complex

Basic information

Region (hg38): 16:3024027-3027755

Previous symbols: [ "WDR58" ]

Links

ENSG00000131652 ∙ NCBI:79228 ∙ OMIM:615403 ∙ HGNC:28369 ∙ Uniprot:Q86W42 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• THOC6-related developmental delay-microcephaly-facial dysmorphism syndrome (Definitive), mode of inheritance: AR
• THOC6-related developmental delay-microcephaly-facial dysmorphism syndrome (Supportive), mode of inheritance: AR
• THOC6-related developmental delay-microcephaly-facial dysmorphism syndrome (Moderate), mode of inheritance: AR
• THOC6-related developmental delay-microcephaly-facial dysmorphism syndrome (Strong), mode of inheritance: AR
• THOC6-related developmental delay-microcephaly-facial dysmorphism syndrome (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Beaulieu-Boycott-Innes syndrome	AR	Cardiovascular	The condition can involve congenital cardiac anomalies, and awareness may allow early management	Cardiovascular; Craniofacial; Dental; Genitourinary; Neurologic; Renal	23621916; 26739162; 27102954; 30476144

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the THOC6 gene.

• Inborn_genetic_diseases (62 variants)
• not_provided (30 variants)
• THOC6-related_developmental_delay-microcephaly-facial_dysmorphism_syndrome (29 variants)
• THOC6-related_disorder (8 variants)
• Intellectual_disability (4 variants)
• Dystonia,_early-onset,_and/or_spastic_paraplegia (3 variants)
• not_specified (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the THOC6 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000024339.5. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				15	2	17
missense	3	3	62	2		70
nonsense	4	5				9
start loss						0
frameshift	3	2	1			6
splice donor/acceptor (+/-2bp)	1	4	1			6
Total	11	14	64	17	2

Highest pathogenic variant AF is 0.000364347

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
THOC6	protein_coding	protein_coding	ENST00000326266	13	3729

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000478	0.998	125714	0	34	125748	0.000135

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.402	223	207	1.08	0.0000128	2189
Missense in Polyphen		54	55.926	0.96557		646
Synonymous	-1.47	101	83.9	1.20	0.00000527	697
Loss of Function	2.81	10	25.2	0.397	0.00000131	256

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000187	0.000185
Ashkenazi Jewish	0.00	0.00
East Asian	0.000489	0.000489
Finnish	0.00	0.00
European (Non-Finnish)	0.000150	0.000149
Middle Eastern	0.000489	0.000489
South Asian	0.000132	0.000131
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: 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. Plays a role in apoptosis negative control involved in brain development. {ECO:0000269|PubMed:15833825, ECO:0000269|PubMed:15998806, ECO:0000269|PubMed:17190602, ECO:0000269|PubMed:18974867, ECO:0000269|PubMed:23621916}.
• Disease: DISEASE: Beaulieu-Boycott-Innes syndrome (BBIS) [MIM:613680]: An autosomal recessive neurodevelopmental disorder characterized by delayed development, moderate intellectual disability, and dysmorphic facial features. Other developmental anomalies, such as cardiac and renal defects, may also occur. {ECO:0000269|PubMed:23621916}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: RNA transport - 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: 0.110

Intolerance Scores

• loftool: 0.904
• rvis_EVS: -1.11
• rvis_percentile_EVS: 6.72

Haploinsufficiency Scores

• pHI: 0.250
• hipred: Y
• hipred_score: 0.528
• ghis: 0.595

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: H
• gene_indispensability_pred: E
• gene_indispensability_score: 0.758

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Thoc6

Gene ontology

• Biological process: RNA export from nucleus;mRNA export from nucleus;apoptotic process;central nervous system development;RNA splicing;mRNA 3'-end processing;negative regulation of apoptotic process;viral mRNA export from host cell nucleus
• Cellular component: transcription export complex;THO complex;THO complex part of transcription export complex;nuclear chromosome, telomeric region;nucleus;nucleoplasm;nuclear body;nuclear speck
• Molecular function: RNA binding