THOC6

Summary

THOC6 (THO complex subunit 6, HGNC:28369) is a protein-coding gene on chromosome 16p13.3, encoding THO complex subunit 6 (Q86W42). 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. It is a selective cancer dependency (DepMap: 35.8% of cell lines).

This gene encodes a subunit of the multi-protein THO complex, which is involved in coordination between transcription and mRNA processing. The THO complex is a component of the TREX (transcription/export) complex, which is involved in transcription and export of mRNAs. A missense mutation in this gene is associated with a neurodevelopmental disorder called Beaulieu-Boycott-Innes syndrome.

Source: NCBI Gene 79228 — RefSeq curated summary.

At a glance

• Gene–disease (curated): THOC6-related developmental delay-microcephaly-facial dysmorphism syndrome (Definitive, ClinGen)
• Clinical variants (ClinVar): 138 total — 9 pathogenic, 9 likely-pathogenic
• Phenotypes (HPO): 54
• Cancer dependency (DepMap): dependent in 35.8% of screened cell lines
• MANE Select transcript: NM_024339

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28369
Approved symbol	THOC6
Name	THO complex subunit 6
Location	16p13.3
Locus type	gene with protein product
Status	Approved
Aliases	MGC2655, fSAP35
Ensembl gene	ENSG00000131652
Ensembl biotype	protein_coding
OMIM	615403
Entrez	79228

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 13 protein_coding, 6 retained_intron

ENST00000253952, ENST00000326266, ENST00000571046, ENST00000571057, ENST00000573704, ENST00000574498, ENST00000574549, ENST00000574957, ENST00000575576, ENST00000576143, ENST00000873903, ENST00000873904, ENST00000873905, ENST00000873906, ENST00000873907, ENST00000915279, ENST00000915280, ENST00000915281, ENST00000915282

RefSeq mRNA: 4 — MANE Select: NM_024339 NM_001142350, NM_001347703, NM_001347704, NM_024339

CCDS: CCDS10491, CCDS45392, CCDS86500

Canonical transcript exons

ENST00000326266 — 13 exons

Exon	Start	End
ENSE00000901615	3026867	3026916
ENSE00000901616	3027011	3027073
ENSE00000901617	3027170	3027280
ENSE00000901618	3027366	3027500
ENSE00002650436	3027577	3027750
ENSE00003482161	3024035	3024365
ENSE00003486593	3025924	3025988
ENSE00003493848	3026063	3026166
ENSE00003531628	3026516	3026587
ENSE00003588368	3026251	3026288
ENSE00003645594	3026679	3026781
ENSE00003660311	3026365	3026413
ENSE00003688635	3025708	3025823

Expression profiles

Bgee: expression breadth ubiquitous, 184 present calls, max score 91.65.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.7615 / max 90.4846, expressed in 1780 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
152367	12.7615	1780

Top tissues by expression

277 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	91.65	gold quality
lower esophagus mucosa	UBERON:0035834	91.38	gold quality
apex of heart	UBERON:0002098	91.14	gold quality
mucosa of transverse colon	UBERON:0004991	90.93	gold quality
monocyte	CL:0000576	90.47	gold quality
esophagus mucosa	UBERON:0002469	90.20	gold quality
mononuclear cell	CL:0000842	90.10	gold quality
leukocyte	CL:0000738	89.91	gold quality
skin of abdomen	UBERON:0001416	89.78	gold quality
left uterine tube	UBERON:0001303	89.43	gold quality
skin of leg	UBERON:0001511	89.38	gold quality
adenohypophysis	UBERON:0002196	89.23	gold quality
small intestine Peyer’s patch	UBERON:0003454	89.09	gold quality
metanephros cortex	UBERON:0010533	88.99	gold quality
transverse colon	UBERON:0001157	88.88	gold quality
right coronary artery	UBERON:0001625	88.87	gold quality
upper lobe of left lung	UBERON:0008952	88.86	gold quality
body of uterus	UBERON:0009853	88.83	gold quality
secondary oocyte	CL:0000655	88.76	gold quality
ascending aorta	UBERON:0001496	88.75	gold quality
thoracic aorta	UBERON:0001515	88.69	gold quality
gastrocnemius	UBERON:0001388	88.61	gold quality
body of stomach	UBERON:0001161	88.49	gold quality
esophagus	UBERON:0001043	88.40	gold quality
minor salivary gland	UBERON:0001830	87.77	gold quality
left coronary artery	UBERON:0001626	87.69	gold quality
omental fat pad	UBERON:0010414	87.68	gold quality
peritoneum	UBERON:0002358	87.55	gold quality
right adrenal gland cortex	UBERON:0035827	87.53	gold quality
body of pancreas	UBERON:0001150	87.51	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-112	yes	7.12
E-ANND-3	yes	7.02

Regulation

Is transcription factor: no

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 35.8% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 3)

• In addition to confirming the morbid nature of THOC6 by providing an independent homozygous apparently loss of function allele in a patient with a compatible phenotype, our data also expand THOC6-related phenotype to include previously unreported imperforate anus and undescended testicles. (PMID:26739162)
• Results indicate three unrelated patients with bi-allelic mutations in THOC6 associated with intellectual disability and additional clinical features. (PMID:27102954)
• Biallelic THOC6 pathogenic variants: Prenatal phenotype and review of the literature. (PMID:35426486)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	thoc6	ENSDARG00000037966
mus_musculus	Thoc6	ENSMUSG00000041319
rattus_norvegicus	Thoc6	ENSRNOG00000003497

Protein

Protein identifiers

THO complex subunit 6 — Q86W42 (reviewed: Q86W42)

Alternative names: Functional spliceosome-associated protein 35, WD repeat-containing protein 58

All UniProt accessions (1): Q86W42

UniProt curated annotations — full annotation on UniProt →

Function. 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. Plays a key structural role in the oligomerization of the THO-DDX39B complex. 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/NXF1 pathway. Plays a role in apoptosis negative control involved in brain development. (Microbial infection) The TREX complex is essential for the export of Kaposi’s sarcoma-associated herpesvirus (KSHV) intronless mRNAs and infectious virus production.

Subunit / interactions. Component of the THO subcomplex, which is composed of THOC1, THOC2, THOC3, THOC5, THOC6 and THOC7. The THO subcomplex interacts with DDX39B to form the THO-DDX39B complex which multimerizes into a 28-subunit tetrameric assembly. Component of the transcription/export (TREX) complex at least composed of ALYREF/THOC4, DDX39B, SARNP/CIP29, CHTOP and the THO subcomplex; in the complex interacts with THOC5; together with THOC5 and THOC7, plays a key structural role in the oligomerization of the THO-DDX39B complex. TREX seems to have a dynamic structure involving ATP-dependent remodeling.

Subcellular location. Nucleus. Nucleus speckle.

Disease relevance. 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. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the WD repeat THOC6 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q86W42-1	1	yes
Q86W42-2	2, hTREX40
Q86W42-3	3

RefSeq proteins (4): NP_001135822, NP_001334632, NP_001334633, NP_077315* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001680	WD40_rpt	Repeat
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR019775	WD40_repeat_CS	Conserved_site
IPR036322	WD40_repeat_dom_sf	Homologous_superfamily
IPR042626	THOC6	Family

Pfam: PF00400

UniProt features (52 total): strand 28, repeat 7, turn 6, helix 4, splice variant 2, sequence conflict 2, chain 1, sequence variant 1, modified residue 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
7APK	ELECTRON MICROSCOPY	3.3
7ZNL	ELECTRON MICROSCOPY	3.45
7ZNK	ELECTRON MICROSCOPY	3.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86W42-F1	93.63	0.89

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 180

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-159236	Transport of Mature mRNA derived from an Intron-Containing Transcript
R-HSA-72187	mRNA 3’-end processing
R-HSA-73856	RNA Polymerase II Transcription Termination
R-HSA-72202	Transport of Mature Transcript to Cytoplasm
R-HSA-72203	Processing of Capped Intron-Containing Pre-mRNA
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-8953854	Metabolism of RNA

MSigDB gene sets: 249 (showing top): RNGTGGGC_UNKNOWN, GGGTGGRR_PAX4_03, SP1_Q2_01, AACWWCAANK_UNKNOWN, GOBP_NUCLEAR_TRANSPORT, RGTTAMWNATT_HNF1_01, REACTOME_MRNA_3_END_PROCESSING, REACTOME_PROCESSING_OF_CAPPED_INTRON_CONTAINING_PRE_MRNA, GOBP_NUCLEOBASE_CONTAINING_COMPOUND_TRANSPORT, GOBP_RNA_SPLICING, TGANTCA_AP1_C, AACTTT_UNKNOWN, EGR1_01, GOBP_NUCLEAR_EXPORT, GOBP_RNA_LOCALIZATION

GO Biological Process (6): mRNA processing (GO:0006397), mRNA export from nucleus (GO:0006406), apoptotic process (GO:0006915), central nervous system development (GO:0007417), RNA splicing (GO:0008380), mRNA transport (GO:0051028)

GO Molecular Function (2): RNA binding (GO:0003723), protein binding (GO:0005515)

GO Cellular Component (8): transcription export complex (GO:0000346), THO complex (GO:0000347), THO complex part of transcription export complex (GO:0000445), nucleus (GO:0005634), nucleoplasm (GO:0005654), nuclear body (GO:0016604), nuclear speck (GO:0016607), chromosome, telomeric region (GO:0000781)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Processing of Capped Intron-Containing Pre-mRNA	2
Transport of Mature Transcript to Cytoplasm	1
RNA Polymerase II Transcription	1
Metabolism of RNA	1
Gene expression (Transcription)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA processing	2
nuclear protein-containing complex	2
mRNA metabolic process	1
RNA export from nucleus	1
gene expression	1
mRNA transport	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
nervous system development	1
system development	1
RNA transport	1
nucleic acid binding	1
binding	1
transcription export complex	1
THO complex	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1
nucleoplasm	1
intracellular membraneless organelle	1
nuclear ribonucleoprotein granule	1
chromosomal region	1

Protein interactions and networks

STRING

968 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
THOC6	THOC7	Q6I9Y2	998
THOC6	THOC5	Q13769	998
THOC6	THOC2	Q8NI27	997
THOC6	THOC1	Q96FV9	997
THOC6	THOC3	Q96J01	997
THOC6	DDX39B	Q13838	873
THOC6	ALYREF	Q86V81	794
THOC6	SARNP	P82979	764
THOC6	NXF1	Q9UBU9	737
THOC6	FYTTD1	Q96QD9	660
THOC6	DDX39A	O00148	581
THOC6	ZC3H11A	O75152	579
THOC6	NCBP3	Q53F19	569
THOC6	DDB1	Q16531	546
THOC6	RAE1	P78406	542

IntAct

68 interactions, top by confidence:

A	B	Type	Score
THOC1	THOC5	psi-mi:“MI:0914”(association)	0.930
DDX39B	THOC5	psi-mi:“MI:0915”(physical association)	0.800
THOC2	THOC5	psi-mi:“MI:0914”(association)	0.730
THOC1	EIF4A3	psi-mi:“MI:0914”(association)	0.660
THOC1	DDX39A	psi-mi:“MI:0914”(association)	0.640
NCBP3	SAP18	psi-mi:“MI:0914”(association)	0.530
THOC3	CLUH	psi-mi:“MI:0914”(association)	0.530
	EIF4A3	psi-mi:“MI:0915”(physical association)	0.490
CPSF6	DDX39A	psi-mi:“MI:0914”(association)	0.480
DDX21	MED19	psi-mi:“MI:2364”(proximity)	0.480
CHTOP	SAP18	psi-mi:“MI:0915”(physical association)	0.400
NUDC	THOC6	psi-mi:“MI:0915”(physical association)	0.400
THOC2		psi-mi:“MI:0914”(association)	0.350
THOC1	TARS3	psi-mi:“MI:0914”(association)	0.350
THOC5	MYO1G	psi-mi:“MI:0914”(association)	0.350
THOC7	ALYREF	psi-mi:“MI:0914”(association)	0.350
NCBP3	ALYREF	psi-mi:“MI:0914”(association)	0.350
BCLAF1	PABPN1	psi-mi:“MI:0914”(association)	0.350
ID1	TCF3	psi-mi:“MI:0914”(association)	0.350
Srsf1	SRRM1	psi-mi:“MI:0914”(association)	0.350
ABI1	NHSL1	psi-mi:“MI:0914”(association)	0.350
JUN		psi-mi:“MI:0914”(association)	0.350
DDX41	DDX39A	psi-mi:“MI:0914”(association)	0.350
NCBP3	RSL1D1	psi-mi:“MI:0914”(association)	0.350
L1TD1	MYO1C	psi-mi:“MI:0914”(association)	0.350
ARHGAP26	NUDT21	psi-mi:“MI:0914”(association)	0.350

BioGRID (129): THOC6 (Affinity Capture-MS), THOC6 (Affinity Capture-MS), PPP2R1A (Co-fractionation), THOC1 (Co-fractionation), THOC6 (Co-fractionation), THOC6 (Co-fractionation), THOC6 (Co-fractionation), THOC6 (Co-fractionation), THOC7 (Co-fractionation), THOC6 (Affinity Capture-MS), THOC6 (Affinity Capture-MS), THOC6 (Affinity Capture-MS), THOC6 (Affinity Capture-MS), THOC6 (Affinity Capture-MS), THOC6 (Affinity Capture-MS)

ESM2 similar proteins: A2AKB9, A2RRH5, A2RUS2, O43379, O60336, P58742, Q08BB3, Q0VBY8, Q148I1, Q15334, Q3MHH0, Q3SZD4, Q3U3T8, Q499N3, Q4R3J7, Q4VBE8, Q5FW06, Q5QP82, Q5RCX2, Q5T6F0, Q5U4D9, Q5U4F6, Q5VW00, Q5ZJL7, Q63ZP7, Q6AX81, Q6AY87, Q6NS57, Q6NWH1, Q6P1M3, Q6P809, Q7Z5U6, Q80Y17, Q86W42, Q8AVS9, Q8BGW4, Q8BGZ3, Q8C5V5, Q8HXL3, Q8K4K5

Diamond homologs: A0A1W2PR48, A6ZQL5, A8XZJ9, O02482, O13166, O13168, O42469, O42470, O42478, P16371, P40066, P47025, P63002, P63003, P79083, Q04724, Q04725, Q04726, Q04727, Q06078, Q07141, Q08117, Q08122, Q08924, Q0VA16, Q15291, Q54H44, Q54MZ3, Q5ZJH5, Q62440, Q62441, Q6AY87, Q6GPP0, Q7RXH4, Q86W42, Q8BX09, Q9H808, Q9JIT3, Q9WVB2, Q9WVB3

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
THOC6	“form complex”	“TREX complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 79 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
mRNA 3’-end processing	14	51.0×	1e-18
Transport of Mature Transcript to Cytoplasm	6	42.3×	2e-07
RNA Polymerase II Transcription Termination	10	40.7×	4e-12
Transport of Mature mRNA derived from an Intron-Containing Transcript	11	31.0×	4e-12
Processing of Capped Intron-Containing Pre-mRNA	13	19.8×	4e-12
mRNA Polyadenylation	9	14.6×	3e-07
mRNA Splicing	7	14.2×	2e-05
mRNA Splicing - Major Pathway	14	14.2×	4e-11

GO biological processes:

GO term	Partners	Fold	FDR
mRNA export from nucleus	11	45.8×	3e-13
RNA splicing	13	16.1×	2e-10
mRNA processing	14	15.5×	6e-11
mRNA splicing, via spliceosome	12	15.5×	2e-09

Disease & clinical

Clinical variants and AI predictions

ClinVar

138 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	9
Likely pathogenic	9
Uncertain significance	69
Likely benign	21
Benign	4

Top pathogenic / likely-pathogenic (18)

Variant ID	HGVS	Classification
3894536	NM_024339.5(THOC6):c.587-2A>G	Pathogenic
520614	NM_024339.5(THOC6):c.259C>T (p.Arg87Ter)	Pathogenic
561206	NM_024339.5(THOC6):c.611A>C (p.Gln204Pro)	Pathogenic
633695	NM_024339.5(THOC6):c.139C>T (p.Gln47Ter)	Pathogenic
976677	NM_024339.5(THOC6):c.445C>T (p.Gln149Ter)	Pathogenic
982264	NM_024339.5(THOC6):c.577C>T (p.Arg193Ter)	Pathogenic
982265	NM_024339.5(THOC6):c.793_794del (p.Thr265fs)	Pathogenic
985892	NM_024339.5(THOC6):c.838del (p.Val280fs)	Pathogenic
988438	NM_024339.5(THOC6):c.893del (p.Pro298fs)	Pathogenic
1068138	NM_024339.5(THOC6):c.156-2del	Likely pathogenic
1325193	NM_024339.5(THOC6):c.44_45del (p.Glu15fs)	Likely pathogenic
2629835	NM_024339.5(THOC6):c.510C>A (p.Tyr170Ter)	Likely pathogenic
3765708	NM_024339.5(THOC6):c.363-2A>C	Likely pathogenic
633694	NM_024339.5(THOC6):c.299G>A (p.Trp100Ter)	Likely pathogenic
64681	NM_024339.5(THOC6):c.136G>A (p.Gly46Arg)	Likely pathogenic
828106	NM_024339.5(THOC6):c.837C>A (p.Cys279Ter)	Likely pathogenic
870677	NM_024339.5(THOC6):c.553T>C (p.Ser185Pro)	Likely pathogenic
870678	NM_024339.5(THOC6):c.739C>T (p.Arg247Ter)	Likely pathogenic

SpliceAI

1696 predictions. Top by Δscore:

Variant	Effect	Δscore
16:3024083:G:GT	donor_gain	1.0000
16:3025703:T:TA	acceptor_gain	1.0000
16:3025703:TGCAG:T	acceptor_loss	1.0000
16:3025704:GCA:G	acceptor_loss	1.0000
16:3025705:CAGAC:C	acceptor_loss	1.0000
16:3025706:A:AG	acceptor_gain	1.0000
16:3025706:A:C	acceptor_loss	1.0000
16:3025707:G:GA	acceptor_gain	1.0000
16:3025707:GAC:G	acceptor_gain	1.0000
16:3025707:GACA:G	acceptor_gain	1.0000
16:3025776:G:T	donor_gain	1.0000
16:3025820:TCAGG:T	donor_loss	1.0000
16:3025821:CAGGT:C	donor_loss	1.0000
16:3025822:AGGT:A	donor_loss	1.0000
16:3025823:GGTAC:G	donor_loss	1.0000
16:3025824:G:T	donor_loss	1.0000
16:3025825:T:G	donor_loss	1.0000
16:3025920:GCAGC:G	acceptor_loss	1.0000
16:3025921:CA:C	acceptor_loss	1.0000
16:3025922:A:AC	acceptor_loss	1.0000
16:3025922:A:AG	acceptor_gain	1.0000
16:3025923:G:A	acceptor_loss	1.0000
16:3025923:G:GA	acceptor_gain	1.0000
16:3025923:GC:G	acceptor_gain	1.0000
16:3025923:GCT:G	acceptor_gain	1.0000
16:3025923:GCTT:G	acceptor_gain	1.0000
16:3026059:TTAG:T	acceptor_loss	1.0000
16:3026061:A:AG	acceptor_gain	1.0000
16:3026061:A:G	acceptor_loss	1.0000
16:3026062:G:GC	acceptor_gain	1.0000

AlphaMissense

2200 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:3026113:A:C	S91R	0.999
16:3026115:T:A	S91R	0.999
16:3026115:T:G	S91R	0.999
16:3026770:T:A	V192D	0.999
16:3027200:T:A	W244R	0.999
16:3027200:T:C	W244R	0.999
16:3026146:T:A	W102R	0.998
16:3026146:T:C	W102R	0.998
16:3026778:T:A	W195R	0.998
16:3026778:T:C	W195R	0.998
16:3027068:T:A	W232R	0.998
16:3027068:T:C	W232R	0.998
16:3027070:G:C	W232C	0.998
16:3027070:G:T	W232C	0.998
16:3027614:T:A	V328D	0.998
16:3025784:T:C	L39P	0.997
16:3025805:G:T	G46V	0.997
16:3025820:T:C	F51S	0.997
16:3026078:T:A	V79D	0.997
16:3026752:G:A	G186D	0.997
16:3026780:G:C	W195C	0.997
16:3026780:G:T	W195C	0.997
16:3027171:T:A	V234D	0.997
16:3027177:G:A	G236E	0.997
16:3027198:T:C	L243P	0.997
16:3027204:A:G	H245R	0.997
16:3027205:C:A	H245Q	0.997
16:3027205:C:G	H245Q	0.997
16:3025787:C:A	A40E	0.996
16:3025793:G:A	G42D	0.996

dbSNP variants (sampled 300 via entrez): RS1000616190 (16:3023970 T>C), RS1000918889 (16:3023716 G>A,C), RS1000950947 (16:3022677 C>T), RS1001001726 (16:3023017 G>A,C), RS1001728763 (16:3027815 G>C,T), RS1001777650 (16:3028063 G>A), RS1001940172 (16:3023534 G>A,C), RS1002006199 (16:3022250 G>A,C,T), RS1002542776 (16:3023368 A>G), RS1003657271 (16:3027755 G>A,C), RS1003810930 (16:3022219 G>C), RS1003846663 (16:3026212 G>C), RS1003914622 (16:3022459 C>G,T), RS1004892878 (16:3022571 C>T), RS1005175924 (16:3022284 C>T)

Disease associations

OMIM: gene MIM:615403 | disease phenotypes: MIM:613680, MIM:619681

GenCC curated gene-disease

Disease	Classification	Inheritance
THOC6-related developmental delay-microcephaly-facial dysmorphism syndrome	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
THOC6-related developmental delay-microcephaly-facial dysmorphism syndrome	Definitive	AR

Mondo (3): THOC6-related developmental delay-microcephaly-facial dysmorphism syndrome (MONDO:0013362), intellectual disability (MONDO:0001071), dystonia, early-onset, and/or spastic paraplegia (MONDO:0859215)

Orphanet (2): THOC6-related developmental delay-microcephaly-facial dysmorphism syndrome (Orphanet:363444), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

54 total (30 of 54 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000010	Recurrent urinary tract infections
HP:0000047	Hypospadias
HP:0000054	Micropenis
HP:0000077	Abnormality of the kidney
HP:0000085	Horseshoe kidney
HP:0000119	Abnormality of the genitourinary system
HP:0000122	Unilateral renal agenesis
HP:0000164	Abnormality of the dentition
HP:0000215	Thick upper lip vermilion
HP:0000220	Velopharyngeal insufficiency
HP:0000252	Microcephaly
HP:0000278	Retrognathia
HP:0000286	Epicanthus
HP:0000307	Pointed chin
HP:0000319	Smooth philtrum
HP:0000337	Broad forehead
HP:0000347	Micrognathia
HP:0000348	High forehead
HP:0000365	Hearing impairment
HP:0000490	Deeply set eye
HP:0000545	Myopia
HP:0000582	Upslanted palpebral fissure
HP:0000670	Carious teeth
HP:0000689	Dental malocclusion
HP:0000750	Delayed speech and language development
HP:0001249	Intellectual disability
HP:0001263	Global developmental delay
HP:0001328	Specific learning disability
HP:0001627	Abnormal heart morphology

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

39 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Estradiol	affects cotreatment, decreases expression	3
sodium arsenite	decreases expression, affects cotreatment, increases abundance	2
Benzo(a)pyrene	decreases expression	2
GSK-J4	decreases expression	1
FR900359	increases phosphorylation	1
propionaldehyde	decreases expression	1
bisphenol A	decreases expression	1
decabromobiphenyl ether	increases expression	1
perfluorooctanoic acid	increases expression	1
methacrylaldehyde	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
K 7174	decreases expression	1
bromovanin	increases expression	1
pentabrominated diphenyl ether 100	increases expression	1
jinfukang	affects cotreatment, decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	increases expression	1
Sunitinib	increases expression	1
Acetaminophen	increases expression	1
Acrolein	affects cotreatment, decreases expression	1
Arsenic	increases abundance, affects cotreatment, decreases expression	1
Vehicle Emissions	affects expression, increases abundance	1
Caffeine	decreases phosphorylation	1
Cisplatin	decreases expression, affects cotreatment	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Ivermectin	decreases expression	1
Lead	affects expression	1
Methyl Methanesulfonate	decreases expression	1

Clinical trials (associated diseases)

197 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT03479476	PHASE2/PHASE3	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome
NCT02616796	PHASE1/PHASE2	COMPLETED	Effects of Social Gaze Training on Brain and Behavior in Fragile X Syndrome
NCT06860672	EARLY_PHASE1	RECRUITING	Clinical Trial of the Dual Vector Base Editor for the Treatment of the CHD3-R1025W Mutation
NCT00597948	Not specified	COMPLETED	Healthy Lifestyles for People With Intellectual Disabilities
NCT01087320	Not specified	RECRUITING	Genome Medical Sequencing for Gene Discovery
NCT01652963	Not specified	UNKNOWN	Picture-based Computerised Assessment and Training of Cognitive Behaviour Therapy Skills
NCT01695395	Not specified	COMPLETED	Mental Health Care Provision for Adults With Intellectual Disability and a Mental Disorder
NCT01867554	Not specified	COMPLETED	Research and Characterization of New Genes Involved in Intellectual Disability
NCT01915381	Not specified	COMPLETED	Improving Adherence Healthy Lifestyle With a Smartphone Application Based on Adults With Intellectual Disabilities
NCT01988623	Not specified	COMPLETED	Pivotal Response Treatment for Individuals With Intellectual Disabilities
NCT02099773	Not specified	COMPLETED	Support Staff-client Interactions With Augmentative and Alternative Communication
NCT02136849	Not specified	COMPLETED	Inter-regional Project of the Great Western Exploration Approach for Exome Molecular Causes Severe Intellectual Disability Isolated or Syndromic
NCT02225041	Not specified	COMPLETED	Sedation Strategy and Cognitive Outcome After Critical Illness in Early Childhood
NCT02414438	Not specified	COMPLETED	Establishing the Clinical Utility of First StepDx PLUS and NextStepDx PLUS Study
NCT02451761	Not specified	COMPLETED	Apparently Balanced Chromosomal Translocation/ Next-generation Sequencing/ Intellectual Disability
NCT02461420	Not specified	ACTIVE_NOT_RECRUITING	Mapping the Genotype, Phenotype, and Natural History of Phelan-McDermid Syndrome
NCT02461459	Not specified	ACTIVE_NOT_RECRUITING	Autism Spectrum Disorder (ASD) and Intellectual Disability (ID) Determinants in Tuberous Sclerosis Complex (TSC)
NCT02486081	Not specified	COMPLETED	Development and Application-Smart Football for Movement Evaluation and Training in the Special Education Population
NCT02504502	Not specified	COMPLETED	Enhancing Genomic Laboratory Reports to Enhance Communication and Empower Patients
NCT02513277	Not specified	COMPLETED	Diabetes Screening & Prevention for People With Learning (Intellectual) Disabilities:STOP Diabetes Study
NCT02561754	Not specified	COMPLETED	Weight Management for Adolescents With IDD
NCT02591446	Not specified	COMPLETED	Transcranial Magnetic Stimulation Studies in Autism Spectrum Disorders
NCT02714868	Not specified	COMPLETED	Evaluation of Project TEAM (Teens Making Environmental and Activity Modifications)
NCT02721394	Not specified	UNKNOWN	FCT With Young Children With ID in the UK: A Feasibility Project V.1
NCT02746614	Not specified	COMPLETED	Psychomotor Therapy Effects in Adaptive Behavior and Motor Proficiency in Intellectual Disability
NCT02836405	Not specified	COMPLETED	TMS for the Investigation of Brain Plasticity in Autism Spectrum Disorders