TTF2

Summary

TTF2 (transcription termination factor 2, HGNC:12398) is a protein-coding gene on chromosome 1p13.1, encoding Transcription termination factor 2 (Q9UNY4). DsDNA-dependent ATPase which acts as a transcription termination factor by coupling ATP hydrolysis with removal of RNA polymerase II from the DNA template. It is a selective cancer dependency (DepMap: 67.8% of cell lines).

This gene encodes a member of the SWI2/SNF2 family of proteins, which play a critical role in altering protein-DNA interactions. The encoded protein has been shown to have dsDNA-dependent ATPase activity and RNA polymerase II termination activity. This protein interacts with cell division cycle 5-like, associates with human splicing complexes, and plays a role in pre-mRNA splicing.

Source: NCBI Gene 8458 — RefSeq curated summary.

At a glance

• Gene–disease (curated): congenital hypothyroidism (Limited, GenCC)
• Clinical variants (ClinVar): 200 total
• Cancer dependency (DepMap): dependent in 67.8% of screened cell lines
• MANE Select transcript: NM_003594

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12398
Approved symbol	TTF2
Name	transcription termination factor 2
Location	1p13.1
Locus type	gene with protein product
Status	Approved
Aliases	HuF2, ZGRF6
Ensembl gene	ENSG00000116830
Ensembl biotype	protein_coding
OMIM	604718
Entrez	8458

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 9 protein_coding, 5 protein_coding_CDS_not_defined

ENST00000369466, ENST00000427271, ENST00000463696, ENST00000469638, ENST00000470935, ENST00000480701, ENST00000492682, ENST00000931120, ENST00000931121, ENST00000931122, ENST00000931123, ENST00000931124, ENST00000931125, ENST00000931126

RefSeq mRNA: 1 — MANE Select: NM_003594 NM_003594

CCDS: CCDS892

Canonical transcript exons

ENST00000369466 — 23 exons

Exon	Start	End
ENSE00000913412	117092731	117092901
ENSE00000913413	117091817	117091950
ENSE00000913414	117091328	117091410
ENSE00000913415	117090532	117090623
ENSE00000913416	117090055	117090208
ENSE00000913417	117088801	117088982
ENSE00000913418	117086417	117086522
ENSE00000913419	117084018	117084168
ENSE00000913420	117081828	117081947
ENSE00001450097	117101380	117107453
ENSE00001865291	117060326	117060374
ENSE00003458367	117096149	117096299
ENSE00003485925	117062387	117062473
ENSE00003496471	117097351	117097433
ENSE00003529012	117060455	117060557
ENSE00003554896	117098833	117098907
ENSE00003557496	117076641	117076823
ENSE00003594168	117079568	117079649
ENSE00003619486	117073661	117073727
ENSE00003624797	117077916	117078043
ENSE00003656238	117074870	117075859
ENSE00003672195	117076180	117076294
ENSE00003681816	117095309	117095367

Expression profiles

Bgee: expression breadth ubiquitous, 229 present calls, max score 87.41.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 4.1200 / max 68.3181, expressed in 1322 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
4862	4.0113	1314
4863	0.1088	40

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	87.41	gold quality
adrenal tissue	UBERON:0018303	86.59	gold quality
colonic epithelium	UBERON:0000397	85.76	gold quality
calcaneal tendon	UBERON:0003701	84.21	gold quality
bone marrow cell	CL:0002092	84.02	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.96	gold quality
rectum	UBERON:0001052	83.72	gold quality
epithelium of nasopharynx	UBERON:0001951	83.72	silver quality
vermiform appendix	UBERON:0001154	83.50	gold quality
esophagus mucosa	UBERON:0002469	83.28	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.15	gold quality
tonsil	UBERON:0002372	82.86	gold quality
mucosa of transverse colon	UBERON:0004991	82.59	gold quality
monocyte	CL:0000576	82.24	gold quality
skin of abdomen	UBERON:0001416	82.01	gold quality
mononuclear cell	CL:0000842	81.80	gold quality
right adrenal gland	UBERON:0001233	81.69	gold quality
leukocyte	CL:0000738	81.55	gold quality
right adrenal gland cortex	UBERON:0035827	81.38	gold quality
lower esophagus mucosa	UBERON:0035834	81.30	gold quality
left adrenal gland	UBERON:0001234	81.12	gold quality
adrenal gland	UBERON:0002369	81.06	gold quality
left adrenal gland cortex	UBERON:0035825	81.03	gold quality
right coronary artery	UBERON:0001625	80.86	gold quality
skin of leg	UBERON:0001511	80.55	gold quality
ventricular zone	UBERON:0003053	80.14	gold quality
body of pancreas	UBERON:0001150	79.97	gold quality
transverse colon	UBERON:0001157	79.97	gold quality
esophagus	UBERON:0001043	79.88	gold quality
gingival epithelium	UBERON:0001949	79.85	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-6678	yes	7.87
E-ANND-3	yes	5.84

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

2 targets.

Target	Regulation
TPO	Activation
TSG101	Unknown

miRNA regulators (miRDB)

71 targeting TTF2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-98-3P	100.00	74.08	3907
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-187-5P	99.74	70.26	1404
HSA-MIR-8084	99.73	69.57	1760
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-1283	99.69	72.42	3009
HSA-MIR-425-5P	99.59	67.67	900
HSA-MIR-5004-3P	99.54	68.27	1371
HSA-MIR-143-3P	99.49	69.05	1457
HSA-MIR-4770	99.49	69.09	1451
HSA-MIR-548G-3P	99.48	68.67	2159
HSA-MIR-3915	99.45	68.49	1905
HSA-MIR-190B-3P	99.33	68.29	1382

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 67.8% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 3)

• hLodestar/HuF2 interacts with CDC5L and is involved in pre-mRNA splicing (PMID:12927788)
• TTF2 is the only ATP-dependent termination activity associated with Pol II transcription elongation complexes, is largely unaffected by template position, and is impervious to the phosphorylation state of the polymerase. (PMID:15125840)
• Importantly, the mitotic phenotype seen with TTF2-siRNA is rescued by expression of the siRNA-resistant GFP-tagged TTF2 proving that reduced TTF2 is responsible for the retention of RNA polymerase II on mitotic chromosomes. (PMID:15467445)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ttf2	ENSMUSG00000033222
drosophila_melanogaster	lds	FBGN0002542

Paralogs (30): HLTF (ENSG00000071794), SMARCA2 (ENSG00000080503), SRCAP (ENSG00000080603), ATRX (ENSG00000085224), RAD54L (ENSG00000085999), BTAF1 (ENSG00000095564), CHD8 (ENSG00000100888), SMARCA1 (ENSG00000102038), CHD4 (ENSG00000111642), CHD5 (ENSG00000116254), HELLS (ENSG00000119969), ZRANB3 (ENSG00000121988), CHD6 (ENSG00000124177), SMARCA4 (ENSG00000127616), INO80 (ENSG00000128908), CHD1L (ENSG00000131778), SMARCAL1 (ENSG00000138375), SHPRH (ENSG00000146414), SMARCA5 (ENSG00000153147), CHD1 (ENSG00000153922), SMARCAD1 (ENSG00000163104), RAD54L2 (ENSG00000164080), CHD3 (ENSG00000170004), CHD7 (ENSG00000171316), CHD2 (ENSG00000173575), CHD9 (ENSG00000177200), EP400 (ENSG00000183495), ERCC6L (ENSG00000186871), RAD54B (ENSG00000197275), ERCC6 (ENSG00000225830)

Protein

Protein identifiers

Transcription termination factor 2 — Q9UNY4 (reviewed: Q9UNY4)

Alternative names: Lodestar homolog, RNA polymerase II termination factor, Transcription release factor 2

All UniProt accessions (2): Q9UNY4, X6RI15

UniProt curated annotations — full annotation on UniProt →

Function. DsDNA-dependent ATPase which acts as a transcription termination factor by coupling ATP hydrolysis with removal of RNA polymerase II from the DNA template. May contribute to mitotic transcription repression. May also be involved in pre-mRNA splicing.

Subunit / interactions. Interacts with CDC5L. Part of the spliceosome.

Subcellular location. Cytoplasm. Nucleus.

Similarity. Belongs to the SNF2/RAD54 helicase family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9UNY4-1	1	yes
Q9UNY4-2	2

RefSeq proteins (1): NP_003585* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000330	SNF2_N	Domain
IPR001650	Helicase_C-like	Domain
IPR002464	DNA/RNA_helicase_DEAH_CS	Conserved_site
IPR010666	Znf_GRF	Domain
IPR014001	Helicase_ATP-bd	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR038718	SNF2-like_sf	Homologous_superfamily
IPR049730	SNF2/RAD54-like_C	Domain
IPR050628

Pfam: PF00176, PF00271, PF06839

Catalyzed reactions (Rhea), 1 shown:

• ATP + H2O = ADP + phosphate + H(+) (RHEA:13065)

UniProt features (38 total): compositionally biased region 9, binding site 5, sequence variant 5, region of interest 5, modified residue 3, sequence conflict 3, domain 2, splice variant 2, chain 1, cross-link 1, zinc finger region 1, short sequence motif 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UNY4-F1	62.70	0.14

Functional residue map

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

Ligand- & substrate-binding residues (5): 6; 9; 32; 37; 596–603

Post-translational modifications (4): 460, 883, 908, 143

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 188 (showing top): RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_DNA_TEMPLATED_TRANSCRIPTION_TERMINATION, MODULE_255, MODULE_317, CHX10_01, PUJANA_CHEK2_PCC_NETWORK, FISCHER_G2_M_CELL_CYCLE, BROWNE_HCMV_INFECTION_14HR_DN, VANHARANTA_UTERINE_FIBROID_WITH_7Q_DELETION_DN, GOBP_RNA_SPLICING, GOBP_DNA_DAMAGE_RESPONSE, TGACATY_UNKNOWN, GOBP_TERMINATION_OF_RNA_POLYMERASE_II_TRANSCRIPTION, FUJII_YBX1_TARGETS_DN, DODD_NASOPHARYNGEAL_CARCINOMA_UP

GO Biological Process (5): DNA repair (GO:0006281), DNA-templated transcription termination (GO:0006353), termination of RNA polymerase II transcription (GO:0006369), mRNA processing (GO:0006397), RNA splicing (GO:0008380)

GO Molecular Function (9): DNA binding (GO:0003677), helicase activity (GO:0004386), ATP binding (GO:0005524), ATP-dependent activity, acting on DNA (GO:0008094), zinc ion binding (GO:0008270), hydrolase activity (GO:0016787), nucleotide binding (GO:0000166), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (5): nucleus (GO:0005634), spliceosomal complex (GO:0005681), cytosol (GO:0005829), transcription elongation factor complex (GO:0008023), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA processing	2
ATP-dependent activity	2
nuclear protein-containing complex	2
cellular anatomical structure	2
DNA metabolic process	1
DNA damage response	1
DNA-templated transcription	1
RNA biosynthetic process	1
DNA-templated transcription termination	1
transcription by RNA polymerase II	1
mRNA metabolic process	1
nucleic acid binding	1
nucleic acid conformation isomerase activity	1
catalytic activity, acting on a nucleic acid	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
ATP hydrolysis activity	1
catalytic activity, acting on DNA	1
transition metal ion binding	1
catalytic activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
cation binding	1
intracellular membrane-bounded organelle	1
ribonucleoprotein complex	1
cytoplasm	1
nucleoplasm	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

2387 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TTF2	POLR2M	P0CAP2	593
TTF2	GTF2F2	P13984	476
TTF2	DENND6A	Q8IWF6	427
TTF2	WDR87	Q6ZQQ6	404
TTF2	B4GALNT4	Q76KP1	389
TTF2	YPEL4	Q96NS1	374
TTF2	TPI1	P00938	353
TTF2	HAL	P42357	353
TTF2	PPAT	Q06203	353
TTF2	NAGS	Q8N159	353
TTF2	RRM1	P23921	353
TTF2	UROS	P10746	353
TTF2	ASS1	P00966	353
TTF2	APRT	P07741	353
TTF2	PCNA	P12004	353
TTF2	GART	P22102	353
TTF2	MTHFR	P42898	353
TTF2	ALDH18A1	P54886	353
TTF2	PSPH	P78330	353

IntAct

120 interactions, top by confidence:

A	B	Type	Score
RFXANK	RFXAP	psi-mi:“MI:0914”(association)	0.780
COMMD1	VPS26C	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
ASB13	HIF1AN	psi-mi:“MI:0914”(association)	0.660
CETN1	SFI1	psi-mi:“MI:0914”(association)	0.640
TSC22D4	TSC22D2	psi-mi:“MI:0914”(association)	0.640
TTF2	CDC5L	psi-mi:“MI:0915”(physical association)	0.620
CDC5L	TTF2	psi-mi:“MI:0915”(physical association)	0.620
CLPB	TTF2	psi-mi:“MI:0915”(physical association)	0.550
HAVCR2	TCAF2	psi-mi:“MI:0914”(association)	0.530
PSMC4	PSMD3	psi-mi:“MI:0914”(association)	0.530
NRBP1	TBC1D4	psi-mi:“MI:0914”(association)	0.530
EMILIN1	METTL15	psi-mi:“MI:0914”(association)	0.530
ZNRD2	MYO9A	psi-mi:“MI:0914”(association)	0.530
PTGES3	AIP	psi-mi:“MI:0914”(association)	0.530
LPAR1	TMEM223	psi-mi:“MI:0914”(association)	0.530
TRIM10	WIZ	psi-mi:“MI:0914”(association)	0.530
SIRT3		psi-mi:“MI:0915”(physical association)	0.400
TTF2	ZSCAN1	psi-mi:“MI:0915”(physical association)	0.370
TTF2	CDKL3	psi-mi:“MI:0915”(physical association)	0.370
TTF2	SKIL	psi-mi:“MI:0915”(physical association)	0.370
TTF2	SMAD7	psi-mi:“MI:0915”(physical association)	0.370
SMAD1	TTF2	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (182): TTF2 (Affinity Capture-MS), TTF2 (Affinity Capture-MS), TTF2 (Affinity Capture-MS), TTF2 (Affinity Capture-MS), TTF2 (Affinity Capture-MS), TTF2 (Affinity Capture-MS), TOP3A (Co-fractionation), MYBL2 (Two-hybrid), TTF2 (Proximity Label-MS), TTF2 (Proximity Label-MS), TTF2 (Proximity Label-MS), TTF2 (Proximity Label-MS), TTF2 (Proximity Label-MS), TTF2 (Proximity Label-MS), TTF2 (Proximity Label-MS)

ESM2 similar proteins: A0A1D5PRR9, A4IHD2, A4PBL4, B4F769, D4ACP5, F4HQE2, I3XHK1, O09053, O12944, O75417, O94762, P0DOY1, P56960, P70270, Q08D35, Q0PCS3, Q1LWH4, Q2VPA6, Q3B7N1, Q3UWM4, Q5NC05, Q5QJC2, Q5RDL2, Q5RHD1, Q5SXJ3, Q5ZJF6, Q6NU40, Q6NZP1, Q6NZQ2, Q6PFE3, Q6ZMT4, Q80Y44, Q8BGE5, Q8CGS6, Q8GT06, Q8IYD8, Q8TDG4, Q8VID5, Q92698, Q99NG0

Diamond homologs: A0A0P0WGX7, A1C9W6, A1CZE5, A2BGR3, A2R9H9, A4H7G5, A4HVU6, A4IHD2, A4PBL4, A4R227, A5E0W5, A6QQR4, A6ZL17, A6ZU34, A7EQA8, A7TJI3, A7Z019, B3LN76, B4F769, B5VE38, B6EU02, C0H4W3, C7GQI8, E7F1C4, F4HW51, O13682, O14148, P0CO16, P0CO17, P0CO18, P0CO19, P32863, P34739, P36607, P38086, P41410, P43610, P46100, P51532, P53115

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
TTF2	“up-regulates quantity by stabilization”	CDC5L	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 166 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
Loss of Nlp from mitotic centrosomes	9	12.9×	6e-06
Loss of proteins required for interphase microtubule organization from the centrosome	9	12.9×	6e-06
AURKA Activation by TPX2	9	12.3×	6e-06
HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand	7	12.2×	1e-04
Aggrephagy	5	11.2×	5e-03
Recruitment of mitotic centrosome proteins and complexes	9	11.0×	1e-05
Recruitment of NuMA to mitotic centrosomes	10	10.5×	6e-06
Regulation of PLK1 Activity at G2/M Transition	9	10.3×	2e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	140
Likely benign	21
Benign	12

Top pathogenic / likely-pathogenic (0)

SpliceAI

3968 predictions. Top by Δscore:

Variant	Effect	Δscore
1:117060504:A:T	donor_gain	1.0000
1:117060556:GA:G	donor_gain	1.0000
1:117060558:G:GG	donor_gain	1.0000
1:117062385:A:AG	acceptor_gain	1.0000
1:117062386:G:GG	acceptor_gain	1.0000
1:117062386:GC:G	acceptor_gain	1.0000
1:117062470:ACAG:A	donor_loss	1.0000
1:117062475:T:G	donor_loss	1.0000
1:117075856:GAAG:G	donor_gain	1.0000
1:117076258:G:GT	donor_gain	1.0000
1:117078054:G:T	donor_gain	1.0000
1:117081827:GCA:G	acceptor_gain	1.0000
1:117081902:G:GT	donor_gain	1.0000
1:117082020:C:G	donor_gain	1.0000
1:117082029:G:GT	donor_gain	1.0000
1:117086415:A:AG	acceptor_gain	1.0000
1:117086416:G:GG	acceptor_gain	1.0000
1:117088983:G:GG	donor_gain	1.0000
1:117090526:TTCCA:T	acceptor_loss	1.0000
1:117090527:TCCA:T	acceptor_loss	1.0000
1:117090528:CCAG:C	acceptor_loss	1.0000
1:117090529:CAGG:C	acceptor_loss	1.0000
1:117092897:CCAAG:C	donor_loss	1.0000
1:117092898:CAAG:C	donor_loss	1.0000
1:117092899:AAG:A	donor_loss	1.0000
1:117092900:AGGT:A	donor_loss	1.0000
1:117092901:GGTAC:G	donor_loss	1.0000
1:117092902:G:GA	donor_loss	1.0000
1:117092903:T:A	donor_loss	1.0000
1:117096147:A:AG	acceptor_gain	1.0000

AlphaMissense

7581 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:117084080:T:A	W656R	0.998
1:117084080:T:C	W656R	0.998
1:117088924:T:A	W762R	0.998
1:117088924:T:C	W762R	0.998
1:117081849:A:T	K602I	0.997
1:117084048:T:C	L645P	0.996
1:117097432:T:A	W1090R	0.996
1:117097432:T:C	W1090R	0.996
1:117098865:G:C	R1101P	0.996
1:117079617:G:C	R584P	0.995
1:117088853:A:T	E738V	0.995
1:117090092:T:A	W794R	0.995
1:117090092:T:C	W794R	0.995
1:117081839:G:C	G599R	0.994
1:117084058:T:G	C648W	0.994
1:117088831:T:A	W731R	0.994
1:117088831:T:C	W731R	0.994
1:117088838:G:C	R733P	0.994
1:117088844:T:A	I735K	0.993
1:117090056:T:C	F782L	0.993
1:117090058:T:A	F782L	0.993
1:117090058:T:G	F782L	0.993
1:117091913:T:C	L923P	0.993
1:117079588:G:C	Q574H	0.992
1:117079588:G:T	Q574H	0.992
1:117081830:G:C	D596H	0.992
1:117084082:G:C	W656C	0.992
1:117084082:G:T	W656C	0.992
1:117088922:G:C	R761P	0.991
1:117088926:G:C	W762C	0.991

dbSNP variants (sampled 300 via entrez): RS1000032946 (1:117106272 T>A,C), RS1000039347 (1:117067351 G>A), RS1000284773 (1:117087376 C>G), RS1000405612 (1:117106530 T>C), RS1000467403 (1:117081370 T>C), RS1000499116 (1:117067835 G>A), RS1000578070 (1:117062726 A>G,T), RS1000686483 (1:117101250 A>G), RS1000697780 (1:117101668 T>C), RS1000818312 (1:117081744 T>C), RS1000831002 (1:117082964 C>T), RS1000941464 (1:117107786 C>T), RS1000993238 (1:117063164 T>A), RS1001053729 (1:117062612 T>C), RS1001101918 (1:117069297 G>A)

Disease associations

OMIM: gene MIM:604718 | disease phenotypes: MIM:148050

GenCC curated gene-disease

Disease	Classification	Inheritance
congenital hypothyroidism	Limited	Autosomal dominant

Mondo (2): KBG syndrome (MONDO:0007846), congenital hypothyroidism (MONDO:0018612)

Orphanet (1): KBG syndrome (Orphanet:2332)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D003409	Congenital Hypothyroidism	C05.116.099.343.347; C05.116.132.256; C16.320.240.625; C19.297.155; C19.874.482.281
C537015	KBG syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, affects expression, decreases expression	3
Valproic Acid	affects expression, decreases methylation, increases expression	3
Aflatoxin B1	affects expression, increases expression, increases methylation	3
cobaltous chloride	decreases expression	2
Doxorubicin	decreases expression, affects response to substance	2
Tetrachlorodibenzodioxin	affects expression	2
GSK-J4	decreases expression	1
FR900359	decreases phosphorylation	1
triphenyl phosphate	affects expression	1
pirinixic acid	increases activity, increases expression, affects binding, decreases expression	1
trichostatin A	increases expression	1
butyraldehyde	decreases expression	1
manganese chloride	decreases expression, increases abundance	1
CGP 52608	affects binding, increases reaction	1
erucylphospho-N,N,N-trimethylpropylammonium	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	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	increases expression	1
Sunitinib	decreases expression	1
Troglitazone	decreases expression	1
Acetaminophen	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Atrazine	decreases expression	1
Caffeine	decreases phosphorylation	1
Coumestrol	affects cotreatment, increases expression	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Estradiol	increases expression	1
Ketoconazole	affects expression	1
Manganese	decreases expression, increases abundance	1
Methotrexate	affects response to substance	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05228184	PHASE4	TERMINATED	Use of Tirosint®-SOL or Tablet Formulations of Levothyroxine in Pediatric Patients With Congenital Hypothyroidism (CH)
NCT05371262	PHASE4	COMPLETED	Influence of Initial Levothyroxine Dose on Neurodevelopmental and Growth Outcomes in Congenital Hypothyroidism
NCT06465641	PHASE4	RECRUITING	Methylphenidate in KBG Syndrome: N-of-1 Series
NCT00403390	Not specified	COMPLETED	Generic vs. Name-Brand Levothyroxine
NCT00493103	Not specified	COMPLETED	TG Gene Mutations and Congenital Hypothyroidism
NCT00497575	Not specified	COMPLETED	Diagnosis and Follow-up of Patients With Subclinical Hypothyroidism
NCT00505479	Not specified	UNKNOWN	Iodine Status in Pregnant Women and Their Newborns: is Congenital Hypothyroidism Related to Iodine Deficiency in Pregnancy?
NCT01223638	Not specified	WITHDRAWN	The Prevalence of Hearing Loss Among Children With Congenital Hypothyroidism
NCT01349634	Not specified	COMPLETED	The Effects of Iodized Salt on Cognitive Development in Ethiopia
NCT01488721	Not specified	COMPLETED	Clinical Evaluation of NeoPlex4 Assay and NeoPlex System
NCT01916018	Not specified	COMPLETED	Clinical and Genetic Analysis in Congenital Hypothyroidism Due to Thyroid Dysgenesis.
NCT02307175	Not specified	COMPLETED	A Study of 99m Tc Pertechnetate Produced in High Energy Cyclotron in Patients With Thyroid Scan Indication
NCT02374593	Not specified	COMPLETED	Targeted Levothyroxine Dosing in Infants With Congenital Hypothyroidism
NCT03655223	Not specified	ENROLLING_BY_INVITATION	Early Check: Expanded Screening in Newborns
NCT04712760	Not specified	UNKNOWN	Congenital Hypothyroidism in Children With Eutopic Gland or Thyroid Hemiagenesis: Predictive Factors for Transient vs Permanent Hypothyroidism.
NCT04734457	Not specified	UNKNOWN	Final Height in Patients With CH Diagnosed by the Screening
NCT05687474	Not specified	COMPLETED	Baby Detect : Genomic Newborn Screening
NCT06724224	Not specified	RECRUITING	Comparison of Levothyroxine Formulations in the Treatment of Congenital Hypothyroidism
NCT06728735	Not specified	RECRUITING	Role of Next Generation Sequencing in the Etiological Diagnosis of Permanent Congenital Hypothyroidism With in Situ Thyroid
NCT06864039	Not specified	ENROLLING_BY_INVITATION	Quality of Life and Long-term Outcome of Adequately Treated Congenital Hypothyroidism
NCT06864351	Not specified	RECRUITING	Prospective Evaluation of OptiThyDose
NCT07126353	Not specified	NOT_YET_RECRUITING	Metabolic Risk Assessment in Prepubertal Children With Congenital Hypothyroidism
NCT07280104	Not specified	RECRUITING	Infants With Primary Congenital Hypothyroidism and Development
NCT07425028	Not specified	NOT_YET_RECRUITING	Evaluation of an Intensified Systematic Screening for Congenital Hypothyroidism in Premature Newborns
NCT07579988	Not specified	NOT_YET_RECRUITING	Ultrasound Measurement of Thyroid Volume in Term Newborns
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT06938542	Not specified	ENROLLING_BY_INVITATION	Palliative Care Needs of Children With Rare Diseases and Their Families