PAX8

Summary

PAX8 (paired box 8, HGNC:8622) is a protein-coding gene on chromosome 2q14.1, encoding Paired box protein Pax-8 (Q06710). Transcription factor for the thyroid-specific expression of the genes exclusively expressed in the thyroid cell type, maintaining the functional differentiation of such cells.

This gene encodes a member of the paired box (PAX) family of transcription factors. Members of this gene family typically encode proteins that contain a paired box domain, an octapeptide, and a paired-type homeodomain. This nuclear protein is involved in thyroid follicular cell development and expression of thyroid-specific genes. Mutations in this gene have been associated with thyroid dysgenesis, thyroid follicular carcinomas and atypical follicular thyroid adenomas. Alternatively spliced transcript variants encoding different isoforms have been described.

Source: NCBI Gene 7849 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hypothyroidism, congenital, nongoitrous, 2 (Definitive, GenCC) — +2 more curated relationships
• GWAS associations: 26
• Clinical variants (ClinVar): 219 total — 7 pathogenic, 6 likely-pathogenic
• Phenotypes (HPO): 51
• Druggable target: yes — 14 molecules with ChEMBL bioactivity
• Dosage sensitivity (ClinGen): haploinsufficiency little evidence, triplosensitivity no evidence
• Transcription factor: yes — 38 downstream targets (CollecTRI)
• MANE Select transcript: NM_003466

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8622
Approved symbol	PAX8
Name	paired box 8
Location	2q14.1
Locus type	gene with protein product
Status	Approved
Aliases	PAX-8
Ensembl gene	ENSG00000125618
Ensembl biotype	protein_coding
OMIM	167415
Entrez	7849

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 11 protein_coding, 4 retained_intron

ENST00000263334, ENST00000263335, ENST00000348715, ENST00000397647, ENST00000429538, ENST00000465084, ENST00000467778, ENST00000468980, ENST00000480684, ENST00000485840, ENST00000497038, ENST00000554352, ENST00000554830, ENST00000681162, ENST00000897363

RefSeq mRNA: 4 — MANE Select: NM_003466 NM_003466, NM_013952, NM_013953, NM_013992

CCDS: CCDS42735, CCDS42736, CCDS46398, CCDS46399

Canonical transcript exons

ENST00000429538 — 12 exons

Exon	Start	End
ENSE00003488884	113242690	113242778
ENSE00003489433	113246754	113246919
ENSE00003522658	113236601	113236721
ENSE00003562615	113235394	113235582
ENSE00003568889	113215997	113218609
ENSE00003573129	113227155	113227256
ENSE00003582162	113244427	113244624
ENSE00003586913	113278370	113278469
ENSE00003632975	113242008	113242130
ENSE00003713694	113278831	113278921
ENSE00003721772	113220092	113220178
ENSE00003784534	113241551	113241726

Expression profiles

Bgee: expression breadth ubiquitous, 242 present calls, max score 99.89.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 5.6765 / max 581.4330, expressed in 1305 samples.

FANTOM5 promoters (13 alternative TSS)

Promoter ID	TPM avg	Samples expressed
30320	2.8343	137
30307	1.6033	943
30312	0.3934	167
30310	0.3343	185
30285	0.1543	61
30309	0.1342	58
30304	0.0733	27
30313	0.0520	15
30311	0.0280	11
30308	0.0274	9

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of thyroid gland	UBERON:0001119	99.89	gold quality
left lobe of thyroid gland	UBERON:0001120	99.85	gold quality
thyroid gland	UBERON:0002046	99.80	gold quality
metanephros cortex	UBERON:0010533	99.68	gold quality
right uterine tube	UBERON:0001302	99.33	gold quality
renal medulla	UBERON:0000362	98.89	gold quality
adult mammalian kidney	UBERON:0000082	98.37	gold quality
caput epididymis	UBERON:0004358	96.95	gold quality
kidney	UBERON:0002113	95.82	gold quality
corpus epididymis	UBERON:0004359	95.49	gold quality
cauda epididymis	UBERON:0004360	94.28	gold quality
diaphragm	UBERON:0001103	93.75	silver quality
cortex of kidney	UBERON:0001225	92.56	gold quality
tibialis anterior	UBERON:0001385	92.40	gold quality
ileal mucosa	UBERON:0000331	92.21	gold quality
nephron tubule	UBERON:0001231	91.68	gold quality
metanephros	UBERON:0000081	91.57	gold quality
cranial nerve II	UBERON:0000941	91.19	gold quality
kidney epithelium	UBERON:0004819	91.09	gold quality
pancreatic ductal cell	CL:0002079	91.05	gold quality
endometrium	UBERON:0001295	90.00	gold quality
type B pancreatic cell	CL:0000169	89.77	silver quality
olfactory bulb	UBERON:0002264	89.31	silver quality
fallopian tube	UBERON:0003889	89.13	gold quality
seminal vesicle	UBERON:0000998	88.90	gold quality
metanephric glomerulus	UBERON:0004736	88.66	gold quality
renal glomerulus	UBERON:0000074	88.60	gold quality
left uterine tube	UBERON:0001303	87.06	gold quality
gluteal muscle	UBERON:0002000	86.59	silver quality
epithelial cell of pancreas	CL:0000083	86.12	silver quality

Single-cell (SCXA)

Detected in 9 experiment(s), a significant marker in 9.

Experiment	Marker?	Max mean expression
E-GEOD-131882	yes	2448.45
E-MTAB-6678	yes	865.88
E-GEOD-114530	yes	779.87
E-GEOD-124472	yes	504.17
E-HCAD-10	yes	409.67
E-CURD-119	yes	34.03
E-MTAB-10287	yes	29.96
E-MTAB-6701	yes	18.33
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

38 targets.

Target	Regulation
BCL2	Activation
BPIFA4P
CDH17
DUOX1	Activation
DUOX2	Repression
E2F1	Activation
F2R
FOXE1	Unknown
GATA3	Unknown
HCRT
HHEX
HLA-A	Unknown
INS
L1CAM
NCAM1	Activation
NKX2-1	Repression
NUPR1	Activation
PAX8
PPARG	Unknown
RB1
RET
SLC25A5
SLC3A1	Activation
SLC5A5	Activation
TERC
TERT	Unknown
TG	Repression
TH
TNF
TNFRSF11A

JASPAR motifs

Motif	Name	Family
MA2094.1	PAX8	Paired domain only

JASPAR matrix evidence (PMIDs): PMID:22531031

Upstream regulators (CollecTRI, top): CTNNB1, DLX3, EZH2, FOXI1, HNF1B, LHX1, NKX2-1, OSR2, PAX2, PAX5, PAX8, TTF1

miRNA regulators (miRDB)

84 targeting PAX8, 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-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-380-3P	99.89	70.18	1978
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-6516-3P	99.65	68.57	1238
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-4762-5P	99.57	68.54	1424
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-6853-3P	99.36	70.79	1558
HSA-MIR-145-3P	99.33	67.66	764

Functional genomics

ClinGen dosage: haploinsufficiency 1 (little evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• TTF-1 and Pax 8 cooperatively activate their target genes and their synergistic activity requires the cross-talk between enhancer and gene promoter (PMID:11923479)
• Expression of PAX8-PPAR gamma 1 rearrangements in both follicular thyroid carcinomas and adenomas. (PMID:12161538)
• directly interacts with TTF-1 and synergistically activates transcription (PMID:12441357)
• Detection of the PAX8-PPAR gamma fusion oncogene in both follicular thyroid carcinomas and adenomas. (PMID:12519876)
• transcription factor Pax-8 could be involved in the upregulation of D2 expression in the thyroid of Graves’ patients (PMID:12699588)
• results suggest that conventional follicular thyroid carcinomas develop through at least two distinct molecular pathways initiated by either RAS point mutation or PAX8-peroxisome proliferator-activated receptor gamma rearrangement (PMID:12727991)
• lack of the PAX8/PPAR gamma rearrangement in the anaplastic thyroid carcinoma group suggests that the tumorigenic pathway in these tumors is likely to be independent of this fusion (PMID:12970322)
• Pax8 regulates the transcriptional activity of Hex promoter; several Pax8 binding sites in the Hex promoter are present (PMID:15062550)
• HNF1beta partially rescues Pax8/lim1-induced kidney malformations. (PMID:15355349)
• the PAX8-PPARgamma1 translocation characterizes a subset of thyroid follicular carcinomas (PMID:15362967)
• A novel and unique PAX8 mutation provides evidence for a crucial role of the p300 coactivator in mediating the functional synergism between PAX8 and TTF-1 in thyroid-specific gene expression. (PMID:15718293)
• in JAR cells, hCG activates a cAMP-dependent pathway that can up-regulate WT1 expression through PAX8 (PMID:15961562)
• Pax8 may have a role in re-differentiation of thyroid cancer cells (PMID:16029487)
• PAX8-PPARgamma disrupts normal transcriptional regulation by stimulating some genes and inhibiting others, the net effect of which may mediate follicular thyroid cell growth and loss of differentiation. (PMID:16179407)
• In follicular variant of papillary thyroid carcinoma, the PAX8-PPARgamma rearrangement was significantly associated with multifocality and vascular invasion (PMID:16219715)
• Suppression of NORE1A, a known Ras effector, in PAX8-PPARgamma fusion-carrying follicular thyroid cancer. (PMID:16352687)
• Oligomerization chain reaction (OCR) strategy allows identification of Foxe1, TTF-1, and thyroid oxidase 2 as new direct targets of Pax8. (PMID:16613988)
• Results showed no direct involvement of PAX-2 genes in Wilms tumor pathogenesis. (PMID:16814811)
• PAX8 is expressed in ovarian cancer but not in the precursor ovarian surface epithelia of healthy individuals. PAX8 is expressed in the non-ciliated, secretory cells of healthy fallopian tube mucosal linings but not in the adjacent ciliated epithelia. (PMID:17064757)
• PAX8 mutations in congenital hypothyroidism due to dysgenetic or orthotopic thyroid glands are rare. PAX8-T225M is probably a rare variant. (PMID:17437516)
• identification of a novel PAX8 mutation in a particular variant of non-congenital early-onset hypothyroidism indicates a key function of PAX8 in the postnatal growth and functional maintenance of the thyroid gland (PMID:17468187)
• PAX8PPARgamma increases thyroid cell viability and has opposite effects on thyroid-specific gene expression, suggesting that the presence of this rearrangement may contribute to the malignant transformation of thyroid follicular cells. (PMID:17614769)
• We report the occurrence of one novel (p.G336S), and two novel synonymous substitutions (p.L233L and p.A439A) in the PAX8 gene (PMID:17980011)
• Pax8 is a useful marker for the diagnosis of anaplastic carcinomas. (PMID:18084247)
• PAX8 binds directly to the hTERT and hTR promoters, up-regulating hTERT and hTR mRNA, as well as telomerase activity (PMID:18632625)
• PAX8 is an additional marker for identifying nephrogenic adenoma (PMID:18670350)
• Pax8 is a useful marker in the differential diagnosis of ovarian and breast carcinomas. (PMID:18724243)
• Results suggest that PARP1 behaves as an important negative co-factor involved in the regulation of Pax8-dependent gene expression. (PMID:18768662)
• Pax-8 activity is regulated via a redox-based mechanism centered on the glutathionylation of specific cysteines in the N-terminal region (Cys45 and Cys57). (PMID:18829450)
• Data show that Pax8 is targeted in the SUMO nuclear bodies, and that the steady-state protein level of Pax8 is controlled by sumoylation. (PMID:18974227)
• Clinical analysis revealed distinct hormonal patterns in thyroid hypoplasia when compared with other variants of thyroid dysgenesis, with genetic abnormalities identified only in few cases in the TSH-R, PAX8, and NKX2.5 genes. (PMID:18976153)
• PAX8 may be a useful additional marker for renal epithelial tumors (PMID:19525927)
• Pax8-PPARG fusion protein and Pten synergistically cause thyroid hyperplasia in transgenic mice. (PMID:19797117)
• It is hereby concluded that 3p25 aneusomy or PAX8-PPARG translocation may play an important role in the molecular pathogenesis of follicular thyroid tumors (PMID:19963130)
• genetics and phenomics of hypothyroidism and thyroid dysgenesis due to PAX8 mutations (Review) (PMID:20302910)
• PAX8 may also be a prognostic marker in pancreatic endocrine tumors, as loss of expression is associated with malignant behavior. (PMID:20414099)
• We propose the use of the combination of PAX8 and p63 in the diagnosis of poorly differentiated renal sinus epithelial neoplasms where the differential diagnosis includes collecting duct carcinoma versus upper urinary tract urothelial carcinoma. (PMID:20463571)
• a thyroid-specific regulatory element in the 5’ upstream region of the Pax8 gene (PMID:20470391)
• PAX8 expression is a useful marker that effectively discriminated metastatic ovarian carcinomas from metastatic breast carcinomas and primary adnexal tumors. (PMID:20492080)
• The combined use of MS procedures and protein-functional assays to investigate the redox state of a protein-regulating gene expression in thyroid, namely Pax-8, a member of the Pax family of transcription factors. (PMID:20513481)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	pax8	ENSDARG00000015879
mus_musculus	Pax8	ENSMUSG00000026976
rattus_norvegicus	Pax8	ENSRNOG00000026203

Paralogs (50): ARX (ENSG00000004848), PAX6 (ENSG00000007372), PAX7 (ENSG00000009709), ALX4 (ENSG00000052850), GSC2 (ENSG00000063515), PITX1 (ENSG00000069011), PAX2 (ENSG00000075891), RHOXF1 (ENSG00000101883), CRX (ENSG00000105392), EVX1 (ENSG00000106038), PAX4 (ENSG00000106331), NOBOX (ENSG00000106410), PITX3 (ENSG00000107859), PHOX2B (ENSG00000109132), OTX1 (ENSG00000115507), PRRX1 (ENSG00000116132), VSX2 (ENSG00000119614), ESX1 (ENSG00000123576), PAX1 (ENSG00000125813), RHOXF2 (ENSG00000131721), GSC (ENSG00000133937), RAX (ENSG00000134438), PAX3 (ENSG00000135903), ALX3 (ENSG00000156150), HESX1 (ENSG00000163666), PITX2 (ENSG00000164093), UNCX (ENSG00000164853), PHOX2A (ENSG00000165462), OTX2 (ENSG00000165588), DRGX (ENSG00000165606), PRRX2 (ENSG00000167157), SHOX2 (ENSG00000168779), OTP (ENSG00000171540), RAX2 (ENSG00000173976), EVX2 (ENSG00000174279), PROP1 (ENSG00000175325), ISX (ENSG00000175329), ALX1 (ENSG00000180318), MIXL1 (ENSG00000185155), SHOX (ENSG00000185960)

Protein

Protein identifiers

Paired box protein Pax-8 — Q06710 (reviewed: Q06710)

All UniProt accessions (8): A0A024R531, A0A140TA56, A0A7P0T907, Q06710, G3V3F3, H0YJD1, H0YJZ5, R9W7C9

UniProt curated annotations — full annotation on UniProt →

Function. Transcription factor for the thyroid-specific expression of the genes exclusively expressed in the thyroid cell type, maintaining the functional differentiation of such cells.

Subunit / interactions. Interacts with WWTR1.

Subcellular location. Nucleus.

Tissue specificity. Expressed in the excretory system, thyroid gland and Wilms tumors.

Disease relevance. Hypothyroidism, congenital, non-goitrous, 2 (CHNG2) [MIM:218700] A disease characterized by thyroid dysgenesis, the most frequent cause of congenital hypothyroidism, accounting for 85% of case. The thyroid gland can be completely absent (athyreosis), ectopically located and/or severely hypoplastic. Ectopic thyroid gland is the most frequent malformation, with thyroid tissue being found most often at the base of the tongue. The disease is caused by variants affecting the gene represented in this entry.

Isoforms (5)

UniProt ID	Names	Canonical?
Q06710-1	1, Pax8a	yes
Q06710-2	2, Pax8b
Q06710-3	3, Pax8c
Q06710-4	4, Pax8d
Q06710-5	5, Pax8e

RefSeq proteins (4): NP_003457, NP_039246, NP_039247, NP_054698 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001523	Paired_dom	Domain
IPR009057	Homeodomain-like_sf	Homologous_superfamily
IPR022130	Pax2_C	Domain
IPR036388	WH-like_DNA-bd_sf	Homologous_superfamily
IPR043182	PAIRED_DNA-bd_site	Conserved_site
IPR043565	PAX_fam	Family

Pfam: PF00292, PF12403

UniProt features (28 total): helix 6, sequence variant 5, splice variant 4, sequence conflict 3, region of interest 3, strand 2, chain 1, DNA-binding region 1, turn 1, compositionally biased region 1, modified residue 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2K27	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q06710-F1	58.09	0.24

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): 303

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-9761174	Formation of intermediate mesoderm
R-HSA-9830364	Formation of the nephric duct

MSigDB gene sets: 380 (showing top): GOBP_CARDIAC_CHAMBER_DEVELOPMENT, GOBP_POSITIVE_REGULATION_OF_EPITHELIAL_CELL_DIFFERENTIATION, MORF_RAGE, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_PHENOL_CONTAINING_COMPOUND_METABOLIC_PROCESS, GOBP_METANEPHRIC_NEPHRON_MORPHOGENESIS, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_SOMATIC_STEM_CELL_POPULATION_MAINTENANCE, MORF_FLT1, BENPORATH_ES_WITH_H3K27ME3, GOBP_CARDIAC_SEPTUM_DEVELOPMENT, GOBP_REGULATION_OF_MORPHOGENESIS_OF_A_BRANCHING_STRUCTURE, GOBP_METANEPHROS_DEVELOPMENT, XU_HGF_TARGETS_REPRESSED_BY_AKT1_UP, GOBP_MESENCHYMAL_TO_EPITHELIAL_TRANSITION

GO Biological Process (45): urogenital system development (GO:0001655), branching involved in ureteric bud morphogenesis (GO:0001658), kidney development (GO:0001822), mesonephros development (GO:0001823), ventricular septum development (GO:0003281), mesenchymal to epithelial transition involved in metanephros morphogenesis (GO:0003337), DNA-templated transcription (GO:0006351), regulation of transcription by RNA polymerase II (GO:0006357), nervous system development (GO:0007399), central nervous system development (GO:0007417), sensory organ development (GO:0007423), anatomical structure morphogenesis (GO:0009653), negative regulation of cardiac muscle cell apoptotic process (GO:0010667), thyroid gland development (GO:0030878), pronephric field specification (GO:0039003), inner ear morphogenesis (GO:0042472), regulation of apoptotic process (GO:0042981), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), pronephros development (GO:0048793), cellular response to gonadotropin stimulus (GO:0071371), otic vesicle development (GO:0071599), positive regulation of mesenchymal to epithelial transition involved in metanephros morphogenesis (GO:0072108), metanephric epithelium development (GO:0072207), metanephric distal convoluted tubule development (GO:0072221), metanephric comma-shaped body morphogenesis (GO:0072278), metanephric S-shaped body morphogenesis (GO:0072284), metanephric nephron tubule formation (GO:0072289), obsolete negative regulation of mesenchymal cell apoptotic process involved in metanephric nephron morphogenesis (GO:0072305), regulation of metanephric nephron tubule epithelial cell differentiation (GO:0072307), positive regulation of branching involved in ureteric bud morphogenesis (GO:0090190), negative regulation of mesenchymal cell apoptotic process involved in metanephros development (GO:1900212), obsolete negative regulation of apoptotic process involved in metanephric collecting duct development (GO:1900215), obsolete negative regulation of apoptotic process involved in metanephric nephron tubule development (GO:1900218), positive regulation of metanephric DCT cell differentiation (GO:2000594), positive regulation of thyroid hormone generation (GO:2000611), regulation of thyroid-stimulating hormone secretion (GO:2000612), metanephros development (GO:0001656), regulation of DNA-templated transcription (GO:0006355), cell differentiation (GO:0030154)

GO Molecular Function (8): transcription cis-regulatory region binding (GO:0000976), RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700), thyroid-stimulating hormone receptor activity (GO:0004996), sequence-specific double-stranded DNA binding (GO:1990837), protein binding (GO:0005515)

GO Cellular Component (3): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Gastrulation	1
Kidney development	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
system development	3
regulation of DNA-templated transcription	3
renal system development	2
animal organ development	2
kidney development	2
transcription by RNA polymerase II	2
regulation of transcription by RNA polymerase II	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
cellular anatomical structure	2
branching morphogenesis of an epithelial tube	1
ureteric bud morphogenesis	1
cardiac ventricle development	1
cardiac septum development	1
metanephros morphogenesis	1
epithelial cell differentiation involved in kidney development	1
mesenchymal to epithelial transition	1
metanephric renal vesicle morphogenesis	1
gene expression	1
RNA biosynthetic process	1
nervous system development	1
developmental process	1
anatomical structure development	1
cardiac muscle cell apoptotic process	1
negative regulation of striated muscle cell apoptotic process	1
regulation of cardiac muscle cell apoptotic process	1
endocrine system development	1
gland development	1
pronephros development	1
kidney field specification	1
ear morphogenesis	1
embryonic morphogenesis	1
inner ear development	1
apoptotic process	1
regulation of programmed cell death	1
DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
positive regulation of DNA-templated transcription	1
transcription regulatory region nucleic acid binding	1
sequence-specific double-stranded DNA binding	1
cis-regulatory region sequence-specific DNA binding	1

Protein interactions and networks

STRING

1818 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PAX8	NKX2-1	P43699	973
PAX8	PPARG	P37231	946
PAX8	FOXE1	O00358	940
PAX8	TG	P01266	932
PAX8	TSHR	P16473	918
PAX8	KRT7	P08729	872
PAX8	SLC5A5	Q92911	867
PAX8	SMAD3	P84022	837
PAX8	NRAS	P01111	803
PAX8	KRT20	P35900	797
PAX8	LIAT1	Q6ZQX7	791
PAX8	WT1	P19544	778
PAX8	LGALS3	P17931	764
PAX8	TP53	P04637	759
PAX8	KRAS	P01116	748

IntAct

59 interactions, top by confidence:

A	B	Type	Score
HOXC9	PAX8	psi-mi:“MI:0915”(physical association)	0.560
CDK3	PAX8	psi-mi:“MI:0915”(physical association)	0.560
HOXC8	PAX8	psi-mi:“MI:0915”(physical association)	0.560
PAX8	LONRF1	psi-mi:“MI:0915”(physical association)	0.560
GCM2	PAX8	psi-mi:“MI:0915”(physical association)	0.560
SS18L1	PAX8	psi-mi:“MI:0915”(physical association)	0.560
PAX8	TLE5	psi-mi:“MI:0915”(physical association)	0.560
PAX8	SAE1	psi-mi:“MI:0915”(physical association)	0.560
PAX8	DOK4	psi-mi:“MI:0915”(physical association)	0.560
PAX8	SERINC1	psi-mi:“MI:0915”(physical association)	0.520
NFIA	PAX8	psi-mi:“MI:0915”(physical association)	0.470
NFIB	PAX8	psi-mi:“MI:0915”(physical association)	0.470
NFIC	PAX8	psi-mi:“MI:0915”(physical association)	0.400
PAX8	RB1	psi-mi:“MI:0915”(physical association)	0.400
PAX2	PAX8	psi-mi:“MI:0915”(physical association)	0.400
	PAX8	psi-mi:“MI:0915”(physical association)	0.370
IL3	PAX8	psi-mi:“MI:0915”(physical association)	0.370
IL36A	PAX8	psi-mi:“MI:0915”(physical association)	0.370
TNFSF14	PAX8	psi-mi:“MI:0915”(physical association)	0.370
POU2AF1	PAX8	psi-mi:“MI:0915”(physical association)	0.370
PAX8	CHUK	psi-mi:“MI:0915”(physical association)	0.370
PAX8	CXCL9	psi-mi:“MI:0915”(physical association)	0.370
PKM	PAX8	psi-mi:“MI:0915”(physical association)	0.370
PAX8	CIT	psi-mi:“MI:0914”(association)	0.350
PAX8		psi-mi:“MI:0914”(association)	0.350
PAX5	PAX8	psi-mi:“MI:0914”(association)	0.350
PAX8	BCL9	psi-mi:“MI:2364”(proximity)	0.270
SMAD4	PAX8	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (117): PAX8 (Two-hybrid), PAX8 (Reconstituted Complex), PAX8 (Affinity Capture-Western), PAX8 (Two-hybrid), PAX8 (Two-hybrid), PAX8 (Two-hybrid), PAX8 (Two-hybrid), SAE1 (Two-hybrid), LONRF1 (Two-hybrid), HOXC9 (Two-hybrid), SS18L1 (Two-hybrid), CDK3 (Two-hybrid), LYAR (Affinity Capture-MS), ILF2 (Affinity Capture-MS), AURKA (Affinity Capture-MS)

ESM2 similar proteins: A0JMA6, O08656, O57682, O57685, P06601, P09022, P23759, P23760, P24610, P32114, P47239, P47240, P47242, P49639, P51974, P55166, P55771, P70056, Q00288, Q02548, Q02650, Q02962, Q06710, Q0IH87, Q28D67, Q28DP6, Q2L4T2, Q2VL50, Q2VL51, Q2VL52, Q2VL53, Q2VL54, Q2VL57, Q2VL58, Q2VL59, Q2VL60, Q2VL62, Q32NP8, Q5R9M8, Q645N4

Diamond homologs: A0JMA6, G5ED14, G5ED66, G5EDS1, O18381, O43316, O57682, O57685, O73917, O88436, P06601, P09082, P09083, P09084, P15863, P23757, P23758, P23759, P23760, P24610, P26367, P26630, P32114, P32115, P47236, P47238, P47239, P47240, P47242, P51974, P55166, P55771, P55864, P63015, P63016, Q00288, Q02548, Q02650, Q02962, Q06710

SIGNOR signaling

7 interactions.

A	Effect	B	Mechanism
WWTR1	up-regulates	PAX8	binding
PAX8	“up-regulates quantity by expression”	SLC5A5	“transcriptional regulation”
SMAD3	“down-regulates activity”	PAX8	binding
TGFB1	“down-regulates activity”	PAX8	binding
PAX8	“up-regulates quantity by expression”	TG	“transcriptional regulation”
PAX8	“up-regulates quantity by expression”	SLC3A1	“transcriptional regulation”
PAX8	“up-regulates quantity by expression”	TPO	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 34 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.

GO biological processes:

GO term	Partners	Fold	FDR
transcription by RNA polymerase II	6	13.2×	7e-04

Disease & clinical

Cancer significance

From CIViC — curated cancer-variant interpretation:

PAX8 is one of nine transcription factors within the PAX gene family. It has been observed to be expressed during embryonic development however expression attenuates after development in all but a few tissues. Research has indicated that over-expression of PAX proteins in general are not an initiating event in tumorgenesis however they may facilitate malignant development. PAX8 is expressed in 80-96% of all High-grade serous carcinomas (HGSC) and is commonly used as a marker for the disease. In addition PAX8 has become a useful biomarker for differentiating between mullerian mucinous and non-mullerian tumors. PAX8 has also been associated with neoplasms in the kidney and thyroid.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	7
Likely pathogenic	6
Uncertain significance	113
Likely benign	25
Benign	35

Top pathogenic / likely-pathogenic (13)

Variant ID	HGVS	Classification
13784	NM_003466.4(PAX8):c.92G>A (p.Arg31His)	Pathogenic
13785	NM_003466.4(PAX8):c.185T>G (p.Leu62Arg)	Pathogenic
3894534	NM_003466.4(PAX8):c.191+1G>A	Pathogenic
915465	NM_003466.4(PAX8):c.457_458del (p.Leu153fs)	Pathogenic
980470	GRCh37/hg19 2q13(chr2:113853399-114095549)x1	Pathogenic
988648	NM_003466.4(PAX8):c.101T>A (p.Ile34Asn)	Pathogenic
988649	NM_003466.4(PAX8):c.397C>T (p.Arg133Trp)	Pathogenic
1711505	NM_003466.4(PAX8):c.136G>A (p.Asp46Asn)	Likely pathogenic
3062111	NM_003466.4(PAX8):c.205G>A (p.Gly69Ser)	Likely pathogenic
3776267	NM_003466.4(PAX8):c.898+1G>C	Likely pathogenic
4279554	NM_003466.4(PAX8):c.936dup (p.Glu313fs)	Likely pathogenic
436165	NM_003466.4(PAX8):c.160A>T (p.Ser54Cys)	Likely pathogenic
4812873	NM_003466.4(PAX8):c.268_270del (p.Glu90del)	Likely pathogenic

SpliceAI

2114 predictions. Top by Δscore:

Variant	Effect	Δscore
2:113220090:A:AC	donor_gain	1.0000
2:113220091:C:CC	donor_gain	1.0000
2:113241547:TCAC:T	donor_loss	1.0000
2:113241548:CACC:C	donor_loss	1.0000
2:113241549:ACC:A	donor_loss	1.0000
2:113241550:C:CG	donor_loss	1.0000
2:113241550:CCTG:C	donor_gain	1.0000
2:113242004:TCACT:T	donor_loss	1.0000
2:113242005:CACTG:C	donor_loss	1.0000
2:113242006:A:AC	donor_gain	1.0000
2:113242006:ACTGT:A	donor_gain	1.0000
2:113242007:C:CA	donor_gain	1.0000
2:113242007:C:G	donor_loss	1.0000
2:113242007:CT:C	donor_gain	1.0000
2:113242007:CTGT:C	donor_gain	1.0000
2:113242007:CTGTC:C	donor_gain	1.0000
2:113242020:T:A	donor_gain	1.0000
2:113242126:GGGGA:G	acceptor_gain	1.0000
2:113242127:GGGA:G	acceptor_gain	1.0000
2:113242128:GGA:G	acceptor_gain	1.0000
2:113242129:GA:G	acceptor_gain	1.0000
2:113242131:C:CC	acceptor_gain	1.0000
2:113242131:CTG:C	acceptor_loss	1.0000
2:113242135:A:T	acceptor_gain	1.0000
2:113242687:CACTC:C	donor_loss	1.0000
2:113242688:A:AC	donor_gain	1.0000
2:113242688:ACTCA:A	donor_loss	1.0000
2:113242689:C:CG	donor_gain	1.0000
2:113242689:CT:C	donor_gain	1.0000
2:113242689:CTCAG:C	donor_gain	1.0000

AlphaMissense

2921 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:113242770:C:G	R133P	1.000
2:113242771:G:A	R133W	1.000
2:113242771:G:C	R133G	1.000
2:113242773:A:T	I132N	1.000
2:113242776:A:C	I131S	1.000
2:113242776:A:G	I131T	1.000
2:113242776:A:T	I131N	1.000
2:113242778:T:A	R130S	1.000
2:113242778:T:G	R130S	1.000
2:113244427:C:A	R130I	1.000
2:113244427:C:G	R130T	1.000
2:113244428:T:C	R130G	1.000
2:113244429:A:C	N129K	1.000
2:113244429:A:T	N129K	1.000
2:113244430:T:A	N129I	1.000
2:113244431:T:C	N129D	1.000
2:113244433:A:C	I128S	1.000
2:113244433:A:G	I128T	1.000
2:113244433:A:T	I128N	1.000
2:113244434:T:A	I128F	1.000
2:113244436:G:A	S127F	1.000
2:113244436:G:T	S127Y	1.000
2:113244437:A:G	S127P	1.000
2:113244438:G:C	S126R	1.000
2:113244438:G:T	S126R	1.000
2:113244439:C:A	S126I	1.000
2:113244439:C:T	S126N	1.000
2:113244440:T:A	S126C	1.000
2:113244440:T:G	S126R	1.000
2:113244442:A:G	V125A	1.000

dbSNP variants (sampled 300 via entrez): RS1000020553 (2:113277818 T>C), RS1000030869 (2:113238719 A>G), RS1000031382 (2:113235656 G>A,C), RS1000074843 (2:113244890 T>C), RS1000134430 (2:113256104 C>T), RS1000140769 (2:113242041 G>C,T), RS1000143629 (2:113251476 T>TG), RS1000172132 (2:113242311 A>G), RS1000299314 (2:113243271 A>G,T), RS1000323650 (2:113271700 C>T), RS1000347243 (2:113217690 G>T), RS1000376714 (2:113217895 C>T), RS1000382042 (2:113247974 G>A,T), RS1000432481 (2:113253947 T>C), RS1000505317 (2:113240860 T>A)

Disease associations

OMIM: gene MIM:167415 | disease phenotypes: MIM:218700

GenCC curated gene-disease

Disease	Classification	Inheritance
hypothyroidism, congenital, nongoitrous, 2	Definitive	Autosomal dominant
athyreosis	Supportive	Autosomal dominant
thyroid hypoplasia	Supportive	Autosomal dominant

Mondo (5): hypothyroidism, congenital, nongoitrous, 2 (MONDO:0024264), intellectual disability (MONDO:0001071), congenital hypothyroidism (MONDO:0018612), athyreosis (MONDO:0019855), thyroid hypoplasia (MONDO:0019861)

Orphanet (3): Thyroid ectopia (Orphanet:95712), Congenital hypothyroidism (Orphanet:442), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

51 total (30 of 51 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000158	Macroglossia
HP:0000239	Large fontanelles
HP:0000271	Abnormality of the face
HP:0000280	Coarse facial features
HP:0000282	Facial edema
HP:0000820	Abnormality of the thyroid gland
HP:0000821	Hypothyroidism
HP:0000851	Congenital hypothyroidism
HP:0000853	Goiter
HP:0000952	Jaundice
HP:0000958	Dry skin
HP:0001252	Hypotonia
HP:0001254	Lethargy
HP:0001262	Excessive daytime somnolence
HP:0001263	Global developmental delay
HP:0001324	Muscle weakness
HP:0001510	Growth delay
HP:0001537	Umbilical hernia
HP:0001609	Hoarse voice
HP:0001615	Hoarse cry
HP:0001618	Dysphonia
HP:0001662	Bradycardia
HP:0002015	Dysphagia
HP:0002019	Constipation
HP:0002045	Hypothermia
HP:0002750	Delayed skeletal maturation
HP:0002904	Hyperbilirubinemia
HP:0002925	Elevated circulating thyroid-stimulating hormone concentration
HP:0003270	Abdominal distention

GWAS associations

26 associations (top):

Study	Trait	p-value
GCST001610_3	Renal function-related traits (BUN)	3.000000e-10
GCST002711_1	Sleep duration	1.000000e-10
GCST002967_1	Mucinous ovarian carcinoma	3.000000e-08
GCST002967_4	Mucinous ovarian carcinoma	8.000000e-07
GCST003839_1	Sleep duration	2.000000e-23
GCST003840_1	Sleep duration (oversleepers vs undersleepers)	1.000000e-07
GCST003980_1	Sleep duration	5.000000e-14
GCST003982_5	Sleep traits (multi-trait analysis)	8.000000e-13
GCST004627_82	Lymphocyte count	4.000000e-11
GCST005984_4	Glomerular filtration rate	2.000000e-15
GCST005985_5	Creatinine levels	5.000000e-14
GCST006627_96	Diastolic blood pressure	7.000000e-15
GCST007344_107	Estimated glomerular filtration rate	8.000000e-15
GCST007559_3	Sleep duration (short sleep)	3.000000e-18
GCST007560_1	Sleep duration (long sleep)	3.000000e-13
GCST007876_76	Estimated glomerular filtration rate	4.000000e-11
GCST008062_42	Blood urea nitrogen levels	1.000000e-27
GCST008152_55	Weight	1.000000e-06
GCST008158_41	Body mass index	3.000000e-07
GCST008841_1	Depressive symptom (sleep problems) (binary trait)	1.000000e-10
GCST008971_110	Urate levels	7.000000e-07
GCST008972_249	Urate levels	4.000000e-08
GCST009462_35	Optic disc size	8.000000e-10
GCST012475_1	Cervical intraepithelial neoplasia grade 3 and invasive cervical cancer	1.000000e-09
GCST012476_1	Cervical intraepithelial neoplasia grade 3	4.000000e-08
GCST90093325_3	Language functional connectivity	9.000000e-10

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0007875	excessive daytime sleepiness measurement
EFO:0007876	insomnia measurement
EFO:0004587	lymphocyte count
EFO:0006336	diastolic blood pressure
EFO:0004338	body weight
EFO:0004340	body mass index
EFO:0007006	depressive symptom measurement
EFO:0004531	urate measurement
EFO:0007797	language measurement

MeSH disease descriptors (3)

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
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
C566852	Hypothyroidism, Congenital, Nongoitrous, 2 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2362980 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

14 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 805,531 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1200485	SORAFENIB TOSYLATE	4	30,403
CHEMBL1417019	MITOXANTRONE HYDROCHLORIDE	4	69,932
CHEMBL1516474	TEGASEROD MALEATE	4	1,823
CHEMBL1563	DAUNORUBICIN HYDROCHLORIDE	4	28,670
CHEMBL1751	DIGOXIN	4	67,342
CHEMBL359744	DOXORUBICIN HYDROCHLORIDE	4	141,917
CHEMBL496	HEXACHLOROPHENE	4	26,164
CHEMBL727	THIOGUANINE	4	294,612
CHEMBL790	CHLORHEXIDINE	4	85,053
CHEMBL98	VORINOSTAT	4	50,361
CHEMBL1327821	ENPIROLINE	2	8
CHEMBL46874	PINAFIDE	2	2,444
CHEMBL506569	LANATOSIDE C	2	2,218
CHEMBL86754	IODOQUINOL	2	4,584

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

ChEMBL bioactivities

1187 potent at pChembl≥5 of 1659 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.58	AC50	264	nM	CHEMBL2355724
6.57	AC50	267	nM	CHEMBL1573994
6.56	AC50	275	nM	CHEMBL1735419
6.54	AC50	286	nM	CHEMBL2005533
6.53	AC50	294	nM	CHEMBL171699
6.50	AC50	317	nM	CHEMBL1342336
6.49	AC50	323	nM	CHEMBL1499544
6.49	AC50	325	nM	CHEMBL1728514
6.46	AC50	345	nM	CHEMBL3391717
6.43	AC50	372	nM	CHEMBL2358582
6.43	AC50	370	nM	N-ACETYLCOLCHINOL
6.42	AC50	376	nM	CHEMBL1445297
6.42	AC50	379	nM	CHEMBL1301042
6.38	AC50	414	nM	DIGOXIN
6.37	AC50	426	nM	CHEMBL1728992
6.35	AC50	449	nM	CHEMBL1868520
6.33	AC50	469	nM	NANAOMYCIN
6.33	AC50	465	nM	CHEMBL2361658
6.32	AC50	479	nM	CHEMBL2354622
6.32	AC50	480	nM	CHEMBL2358770
6.27	AC50	533	nM	CHEMBL1444020
6.27	AC50	538	nM	CHEMBL1901000
6.26	AC50	546	nM	CHEMBL1700479
6.26	AC50	546	nM	CHEMBL531268
6.26	AC50	553	nM	CHEMBL1312935
6.24	AC50	572	nM	CHEMBL1973122
6.21	AC50	619	nM	CHEMBL1592124
6.20	AC50	635	nM	CHEMBL3199673
6.19	AC50	650	nM	CHEMBL1366838
6.17	AC50	676	nM	CHEMBL1497549
6.17	AC50	673	nM	CHEMBL1900870
6.17	AC50	677	nM	CHEMBL536166
6.16	AC50	690	nM	MITOXANTRONE HYDROCHLORIDE
6.16	AC50	693	nM	CHEMBL3191107
6.15	AC50	709	nM	CHEMBL1368103
6.14	AC50	728	nM	CHEMBL3196760
6.13	AC50	733	nM	CHEMBL1347023
6.13	AC50	734	nM	CHEMBL1445297
6.13	AC50	747	nM	CHEMBL1359120
6.13	AC50	742	nM	ANGUSTIBALIN
6.12	AC50	759	nM	CHEMBL1698341
6.11	AC50	785	nM	CHEMBL1867000
6.11	AC50	770	nM	CHEMBL1997171
6.10	AC50	801	nM	LANATOSIDE C
6.10	AC50	799	nM	CHEMBL2361755
6.09	AC50	811	nM	CHEMBL589238
6.09	AC50	809	nM	CHEMBL3391720
6.08	AC50	833	nM	CHEMBL1700268
6.07	AC50	844	nM	IRINOTECAN HYDROCHLORIDE HYDRATE
6.07	AC50	852	nM	CHEMBL1990598

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression, increases methylation	2
perfluorooctanoic acid	decreases expression, increases expression	2
Resveratrol	increases expression, affects cotreatment, decreases expression, decreases reaction	2
Acetaminophen	decreases expression, increases expression	2
Diethylhexyl Phthalate	increases abundance, increases expression, affects reaction	2
Tretinoin	affects cotreatment, increases expression, decreases expression	2
aristolochic acid I	decreases expression	1
ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate	increases expression	1
2,5,2’,5’-tetrachlorobiphenyl	increases expression	1
ethyl-p-hydroxybenzoate	increases expression	1
beta-lapachone	decreases expression	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
diallyl trisulfide	increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
perfluoro-n-nonanoic acid	decreases expression	1
perfluorohexanesulfonic acid	decreases expression	1
mono(2-ethyl-5-hydroxyhexyl) phthalate	increases abundance, increases expression	1
ammonium 4,8-dioxa-3H-perfluorononanoate	increases expression	1
Decitabine	affects cotreatment, increases expression	1
Carmustine	decreases expression	1
Cisplatin	affects response to substance	1
Cocaine	increases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Folic Acid	affects methylation	1
Colforsin	increases expression	1
Lead	decreases expression	1
Nicotine	increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Quercetin	decreases expression	1

ChEMBL screening assays

3 unique, capped per target: 3 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2354215	Functional	PubChem BioAssay. SA5-Pax8: Cytotoxicity IOSE-T80 Measured in Cell-Based System Using Plate Reader - 7054-07_Inhibitor_Dose_CherryPick_Activity. (Class of assay: confirmatory)	PubChem BioAssay data set

Cellosaurus cell lines

9 cell lines: 5 cancer cell line, 4 embryonic stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A5E4	SEES3-1V human PAX8, clone1	Embryonic stem cell	Male
CVCL_A5E5	SEES3-1V human PAX8, clone2	Embryonic stem cell	Male
CVCL_A5E6	SEES3-1V human PAX8, clone3	Embryonic stem cell	Male
CVCL_A5HA	ESIBIe003-A-6	Embryonic stem cell	Female
CVCL_B8M4	Abcam HCT 116 PAX8 KO	Cancer cell line	Male
CVCL_B9A0	Abcam MCF-7 PAX8 KO	Cancer cell line	Female
CVCL_B9PB	Abcam A-549 PAX8 KO	Cancer cell line	Male
CVCL_TC31	HAP1 PAX8 (-) 1	Cancer cell line	Male
CVCL_XR39	HAP1 PAX8 (-) 2	Cancer cell line	Male

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
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