P4HTM

Summary

P4HTM (prolyl 4-hydroxylase, transmembrane, HGNC:28858) is a protein-coding gene on chromosome 3p21.31, encoding Transmembrane prolyl 4-hydroxylase (Q9NXG6). Catalyzes the post-translational formation of 4-hydroxyproline in hypoxia-inducible factor (HIF) alpha proteins.

The product of this gene belongs to the family of prolyl 4-hydroxylases. This protein is a prolyl hydroxylase that may be involved in the degradation of hypoxia-inducible transcription factors under normoxia. It plays a role in adaptation to hypoxia and may be related to cellular oxygen sensing. Alternatively spliced variants encoding different isoforms have been identified.

Source: NCBI Gene 54681 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hypotonia, hypoventilation, impaired intellectual development, dysautonomia, epilepsy, and eye abnormalities (Definitive, GenCC)
• GWAS associations: 14
• Clinical variants (ClinVar): 106 total — 5 pathogenic, 7 likely-pathogenic
• Phenotypes (HPO): 11
• Druggable target: yes
• MANE Select transcript: NM_177939

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28858
Approved symbol	P4HTM
Name	prolyl 4-hydroxylase, transmembrane
Location	3p21.31
Locus type	gene with protein product
Status	Approved
Aliases	P4H-TM, PHD4, PH4, HIFPH4, FLJ20262, EGLN4, PH-4
Ensembl gene	ENSG00000178467
Ensembl biotype	protein_coding
OMIM	614584
Entrez	54681

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 18 protein_coding, 3 protein_coding_CDS_not_defined, 3 retained_intron

ENST00000343546, ENST00000383729, ENST00000444213, ENST00000468374, ENST00000472301, ENST00000472796, ENST00000475629, ENST00000484115, ENST00000485210, ENST00000486817, ENST00000491739, ENST00000609406, ENST00000867725, ENST00000867726, ENST00000867727, ENST00000867728, ENST00000867729, ENST00000867730, ENST00000918330, ENST00000942774, ENST00000942775, ENST00000942776, ENST00000942777, ENST00000942778

RefSeq mRNA: 2 — MANE Select: NM_177939 NM_177938, NM_177939

CCDS: CCDS2781, CCDS43089

Canonical transcript exons

ENST00000383729 — 9 exons

Exon	Start	End
ENSE00001435457	49006687	49007153
ENSE00001498336	49005777	49005867
ENSE00001498338	49004861	49005046
ENSE00001956630	48990241	48990610
ENSE00003488880	49004098	49004260
ENSE00003565151	49001438	49001628
ENSE00003633534	49006064	49006187
ENSE00003706354	48990833	48990914
ENSE00003709152	49002500	49002596

Expression profiles

Bgee: expression breadth ubiquitous, 280 present calls, max score 97.95.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 21.6556 / max 163.6504, expressed in 1722 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
36595	15.0977	1687
36593	5.2970	1509
36592	0.8059	448
36594	0.3503	183
36597	0.1047	53

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	97.95	gold quality
bronchial epithelial cell	CL:0002328	97.83	gold quality
epithelium of bronchus	UBERON:0002031	97.80	gold quality
pituitary gland	UBERON:0000007	97.69	gold quality
adenohypophysis	UBERON:0002196	97.62	gold quality
bronchus	UBERON:0002185	97.50	gold quality
prefrontal cortex	UBERON:0000451	96.58	gold quality
right frontal lobe	UBERON:0002810	96.45	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.25	gold quality
Brodmann (1909) area 9	UBERON:0013540	96.15	gold quality
nucleus accumbens	UBERON:0001882	96.10	gold quality
frontal cortex	UBERON:0001870	95.97	gold quality
cerebellar hemisphere	UBERON:0002245	95.81	gold quality
cerebellar cortex	UBERON:0002129	95.80	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	95.65	gold quality
anterior cingulate cortex	UBERON:0009835	95.65	gold quality
cingulate cortex	UBERON:0003027	95.64	gold quality
neocortex	UBERON:0001950	95.57	gold quality
postcentral gyrus	UBERON:0002581	95.53	gold quality
lateral nuclear group of thalamus	UBERON:0002736	95.48	gold quality
caudate nucleus	UBERON:0001873	95.47	gold quality
cerebellum	UBERON:0002037	95.46	gold quality
hypothalamus	UBERON:0001898	95.40	gold quality
middle temporal gyrus	UBERON:0002771	95.31	gold quality
parietal lobe	UBERON:0001872	95.16	gold quality
superior frontal gyrus	UBERON:0002661	95.03	gold quality
forebrain	UBERON:0001890	95.02	gold quality
cerebral cortex	UBERON:0000956	95.01	gold quality
putamen	UBERON:0001874	94.97	gold quality
telencephalon	UBERON:0001893	94.82	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-7303	no	840.53
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

7 targeting P4HTM, 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-5692A	100.00	74.40	6850
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-3619-5P	99.00	68.87	2308
HSA-MIR-214-3P	98.71	68.12	2128
HSA-MIR-10398-3P	93.46	63.62	70

Literature-anchored findings (GeneRIF, showing 11)

• Data suggest that PH-4 is a novel hypoxia-inducible factor-prolyl hydroxylase that may be involved in the degradation of hypoxia-inducible transcription factors under normoxia. (PMID:12163023)
• the longest and shortest isoenzymes have major transcripts encoding inactive polypeptides, which suggest novel regulation by alternative splicing. (PMID:12788921)
• crystal structure of the peptide-substrate-binding domain (PMID:15456751)
• This review summarizes recent progress in elucidating the molecular mechanisms of hypoxia-inducible factor (HIF)-1 activation, focusing on the role of oxygen-dependent asparaginyl hydroxylase in hypoxia signal transduction. (PMID:16154531)
• Results suggest that increased expression of prolyl hydroxylase (PH) might play an role in the physiology of uterine leiomyoma during the menstrual cycle. (PMID:23241241)
• This review will expand our knowledge of biology of HIFs, PHDs, PHD inhibitors, and bone regeneration, and it may also aid the design of novel therapies for accelerating bone repair and regeneration or inhibiting bone tumours. [review] (PMID:24895555)
• The results suggest that SESN2 increases degradation of HIF-1A via AMPK-PHD regulation that contributes to inhibition of in vitro and in vivo tumorigenesis. (PMID:27840318)
• Further delineation of HIDEA syndrome. (PMID:32965080)
• Structure of transmembrane prolyl 4-hydroxylase reveals unique organization of EF and dioxygenase domains. (PMID:33334883)
• Biallelic Mutations in P4HTM Cause Syndromic Obesity. (PMID:37083980)
• A pathogenic P4HTM gene variant in two brothers with autism spectrum disorder. (PMID:38441145)

Cross-species orthologs

34 orthologs

Organism	Symbol	Gene ID
danio_rerio	p4htma	ENSDARG00000071233
danio_rerio	p4htmb	ENSDARG00000075209
mus_musculus	P4htm	ENSMUSG00000006675
rattus_norvegicus	P4htm	ENSRNOG00000020249
drosophila_melanogaster	PH4alphaMP	FBGN0026190
drosophila_melanogaster	CG4174	FBGN0036793
drosophila_melanogaster	CG18233	FBGN0036795
drosophila_melanogaster	CG18231	FBGN0036796
drosophila_melanogaster	CG11828	FBGN0039616
drosophila_melanogaster	PH4alphaEFB	FBGN0039776
drosophila_melanogaster	PH4alphaSG2	FBGN0039779
drosophila_melanogaster	PH4alphaNE1	FBGN0039780
drosophila_melanogaster	CG15539	FBGN0039782
drosophila_melanogaster	PH4alphaNE2	FBGN0039783
drosophila_melanogaster	CG9698	FBGN0039784
drosophila_melanogaster	CG15864	FBGN0040528
drosophila_melanogaster	CG18749	FBGN0042182
drosophila_melanogaster	CG31013	FBGN0051013
drosophila_melanogaster	PH4alphaSG1	FBGN0051014
drosophila_melanogaster	PH4alphaPV	FBGN0051015
drosophila_melanogaster	CG31016	FBGN0051016
drosophila_melanogaster	PH4alphaNE3	FBGN0051017
drosophila_melanogaster	CG31021	FBGN0051021
drosophila_melanogaster	CG31371	FBGN0051371
drosophila_melanogaster	CG31524	FBGN0051524
drosophila_melanogaster	CG32199	FBGN0052199
drosophila_melanogaster	CG32201	FBGN0052201
drosophila_melanogaster	CG34041	FBGN0054041
drosophila_melanogaster	CG34345	FBGN0085374
drosophila_melanogaster	CG18234	FBGN0265268
caenorhabditis_elegans		WBGENE00004025
caenorhabditis_elegans		WBGENE00004026
caenorhabditis_elegans		WBGENE00015773
caenorhabditis_elegans		WBGENE00077688

Paralogs (3): P4HA2 (ENSG00000072682), P4HA1 (ENSG00000122884), P4HA3 (ENSG00000149380)

Protein

Protein identifiers

Transmembrane prolyl 4-hydroxylase — Q9NXG6 (reviewed: Q9NXG6)

Alternative names: Hypoxia-inducible factor prolyl hydroxylase 4

All UniProt accessions (5): A0A0C4DGS7, Q9NXG6, H7C153, V9GY20, V9GYK5

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the post-translational formation of 4-hydroxyproline in hypoxia-inducible factor (HIF) alpha proteins. Hydroxylates HIF1A at ‘Pro-402’ and ‘Pro-564’. May function as a cellular oxygen sensor and, under normoxic conditions, may target HIF through the hydroxylation for proteasomal degradation via the von Hippel-Lindau ubiquitination complex.

Subunit / interactions. Homodimer.

Subcellular location. Endoplasmic reticulum membrane.

Tissue specificity. Widely expressed with highest levels in adult pancreas, heart, skeletal muscle, brain, placenta, kidney and adrenal gland. Expressed at lower levels in epiphyseal cartilage and in fibroblasts.

Post-translational modifications. Glycosylated.

Disease relevance. Hypotonia, hyperventilation, impaired intellectual development, dysautonomia, epilepsy, and eye abnormalities (HIDEA) [MIM:618493] An autosomal recessive neurodevelopmental disorder characterized by global developmental delay, poor or absent speech, hypotonia, variable ocular movement and visual abnormalities, and respiratory difficulties. Disease onset is in infancy and death due to respiratory insufficiency may occur. The disease is caused by variants affecting the gene represented in this entry.

Cofactor. Binds 1 Fe(2+) ion per subunit.

Induction. By hypoxia in many cultured cell lines.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9NXG6-1	1	yes
Q9NXG6-2	2, b
Q9NXG6-3	3

RefSeq proteins (2): NP_808807, NP_808808* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002048	EF_hand_dom	Domain
IPR005123	Oxoglu/Fe-dep_dioxygenase_dom	Domain
IPR006620	Pro_4_hyd_alph	Domain
IPR011992	EF-hand-dom_pair	Homologous_superfamily
IPR018247	EF_Hand_1_Ca_BS	Binding_site
IPR044862	Pro_4_hyd_alph_FE2OG_OXY	Domain
IPR045054	P4HA-like	Family

Pfam: PF13499, PF13640

Catalyzed reactions (Rhea), 1 shown:

• L-prolyl-[hypoxia-inducible factor alpha subunit] + 2-oxoglutarate + O2 = trans-4-hydroxy-L-prolyl-[hypoxia-inducible factor alpha subunit] + succinate + CO2 (RHEA:48400)

UniProt features (69 total): strand 20, helix 14, binding site 13, turn 4, glycosylation site 3, domain 3, topological domain 2, splice variant 2, sequence variant 2, sequence conflict 2, region of interest 2, chain 1, transmembrane region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
6TP5	X-RAY DIFFRACTION	2.25

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NXG6-F1	81.94	0.56

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 (13): 200; 202; 204; 209; 237; 239; 241; 248; 328; 330; 374; 451 …

Glycosylation sites (3): 348, 368, 382

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 246 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_MYELOID_CELL_HOMEOSTASIS, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_PAIRED_DONORS_WITH_INCORPORATION_OR_REDUCTION_OF_MOLECULAR_OXYGEN, GOBP_ERYTHROCYTE_HOMEOSTASIS, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_UP, CAIRO_HEPATOBLASTOMA_CLASSES_DN, GOBP_REGULATION_OF_HEMOPOIESIS, INAMURA_LUNG_CANCER_SCC_SUBTYPES_UP, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, GOBP_REGULATION_OF_ERYTHROCYTE_DIFFERENTIATION, GOBP_MULTICELLULAR_ORGANISMAL_LEVEL_HOMEOSTASIS, BASAKI_YBX1_TARGETS_DN, CCCNNGGGAR_OLF1_01, TGCCTTA_MIR124A, AACTGGA_MIR145

GO Biological Process (1): regulation of erythrocyte differentiation (GO:0045646)

GO Molecular Function (10): procollagen-proline 4-dioxygenase activity (GO:0004656), iron ion binding (GO:0005506), calcium ion binding (GO:0005509), 2-oxoglutarate-dependent dioxygenase activity (GO:0016706), L-ascorbic acid binding (GO:0031418), hypoxia-inducible factor-proline dioxygenase activity (GO:0160082), oxidoreductase activity (GO:0016491), oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen (GO:0016705), metal ion binding (GO:0046872), dioxygenase activity (GO:0051213)

GO Cellular Component (3): endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
peptidyl-proline 4-dioxygenase activity	2
oxidoreductase activity	2
erythrocyte differentiation	1
regulation of myeloid cell differentiation	1
procollagen-proline dioxygenase activity	1
transition metal ion binding	1
metal ion binding	1
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen	1
dioxygenase activity	1
vitamin binding	1
carboxylic acid binding	1
monosaccharide binding	1
heterocyclic compound binding	1
catalytic activity	1
cation binding	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1050 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
P4HTM	PAX6	P26367	858
P4HTM	PHC3	Q8NDX5	825
P4HTM	DCAF7	P61962	651
P4HTM	EGLN2	Q96KS0	644
P4HTM	EGLN3	Q9H6Z9	627
P4HTM	EGLN1	Q9GZT9	599
P4HTM	LY86	O95711	546
P4HTM	SFT2D2	O95562	543
P4HTM	KMT2C	Q8NEZ4	495
P4HTM	UQCC5	Q8WVI0	475
P4HTM	H4C7	Q99525	449
P4HTM	H4C16	P02304	446
P4HTM	LY96	Q9Y6Y9	434
P4HTM	AKT1	P31749	427
P4HTM	MFAP3L	O75121	406

IntAct

34 interactions, top by confidence:

A	B	Type	Score
GLP1R	P4HTM	psi-mi:“MI:0915”(physical association)	0.510
P4HTM	F2RL1	psi-mi:“MI:0915”(physical association)	0.370
P4HTM	GPR37	psi-mi:“MI:0915”(physical association)	0.370
P4HTM	LTB4R2	psi-mi:“MI:0915”(physical association)	0.370
	VPS37C	psi-mi:“MI:0914”(association)	0.350
TMEM106A	QSOX1	psi-mi:“MI:0914”(association)	0.350
TMEM106A	TMEM131L	psi-mi:“MI:0914”(association)	0.350
HLA-G	TMEM131L	psi-mi:“MI:0914”(association)	0.350
SFTPC	TMEM131L	psi-mi:“MI:0914”(association)	0.350
IL5RA	POTEF	psi-mi:“MI:0914”(association)	0.350
NCR3	POTEF	psi-mi:“MI:0914”(association)	0.350
DNAJB9	POTEF	psi-mi:“MI:0914”(association)	0.350
CFC1	POTEF	psi-mi:“MI:0914”(association)	0.350
PRG2	QSOX1	psi-mi:“MI:0914”(association)	0.350
SDF2L1	MANBA	psi-mi:“MI:0914”(association)	0.350
GGH	MANBA	psi-mi:“MI:0914”(association)	0.350
CBLN4	AGRN	psi-mi:“MI:0914”(association)	0.350
ALPP	MAN2B1	psi-mi:“MI:0914”(association)	0.350
LPAR1	GOSR2	psi-mi:“MI:0914”(association)	0.350
LIPG	TOR1B	psi-mi:“MI:0914”(association)	0.350
ADAM30	ADAM10	psi-mi:“MI:0914”(association)	0.350
GXYLT1	CLGN	psi-mi:“MI:0914”(association)	0.350
FCGR3B	CLGN	psi-mi:“MI:0914”(association)	0.350
TM2D3	SPINT1	psi-mi:“MI:0914”(association)	0.350
AIFM1	HSPA12A	psi-mi:“MI:0914”(association)	0.350
ADAMTS12	LRP6	psi-mi:“MI:0914”(association)	0.350
HSD17B13	HARS2	psi-mi:“MI:0914”(association)	0.350
SLC1A3	DDX11L8	psi-mi:“MI:0914”(association)	0.350
SLC35F3	TMEM223	psi-mi:“MI:0914”(association)	0.350

BioGRID (44): P4HTM (Reconstituted Complex), P4HTM (Affinity Capture-MS), P4HTM (Two-hybrid), P4HTM (Two-hybrid), P4HTM (Two-hybrid), P4HTM (Affinity Capture-Western), P4HTM (Affinity Capture-MS), P4HTM (Affinity Capture-MS), P4HTM (Affinity Capture-MS), P4HTM (Affinity Capture-MS), P4HTM (Affinity Capture-MS), P4HTM (Affinity Capture-MS), P4HTM (Affinity Capture-MS), P4HTM (Affinity Capture-MS), P4HTM (Affinity Capture-MS)

ESM2 similar proteins: A0A0D3QS98, A0A0D3QS99, A2A5I3, O19010, O19011, O42596, P01137, P04202, P04629, P07200, P09533, P16562, P17246, P18341, P35739, P50414, P54108, P54831, P57110, Q01974, Q38HS2, Q3KPV7, Q3UFB7, Q505J3, Q5R7Y0, Q5T4F7, Q60477, Q658N2, Q6UWX4, Q7T141, Q7TSQ1, Q80XH4, Q8BG58, Q91009, Q99JR5, Q9CXM0, Q9D2G9, Q9EQT5, Q9GZM7, Q9H3Y0

Diamond homologs: F4ILF8, F4J0A8, F4JAU3, F4JNU8, F4JZ24, O15460, P0DUB0, P13674, P16924, P54001, Q10576, Q19673, Q1RMU3, Q20065, Q24JN5, Q5RAG8, Q5UP57, Q5ZLK5, Q60715, Q60716, Q6W3E9, Q6W3F0, Q75UG4, Q7Z4N8, Q8BG58, Q8GXT7, Q8L970, Q8LAN3, Q8VZJ7, Q9LN20, Q9NXG6, Q9SZT0, Q9ZW86

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	7
Uncertain significance	73
Likely benign	12
Benign	1

Top pathogenic / likely-pathogenic (12)

Variant ID	HGVS	Classification
1254369	NM_177939.3(P4HTM):c.659G>A (p.Trp220Ter)	Pathogenic
2074552	NM_177939.3(P4HTM):c.1074-11del	Pathogenic
2156633	NM_177939.3(P4HTM):c.649G>T (p.Gly217Ter)	Pathogenic
635794	NM_177939.3(P4HTM):c.1073G>A (p.Arg358His)	Pathogenic
635797	NM_177939.3(P4HTM):c.1411C>T (p.Gln471Ter)	Pathogenic
1303426	NM_177939.3(P4HTM):c.1228C>A (p.Arg410Ser)	Likely pathogenic
2503452	NM_177939.3(P4HTM):c.819dup (p.Asn274fs)	Likely pathogenic
2585134	NM_177939.3(P4HTM):c.1165_1166del	Likely pathogenic
4278352	NM_177939.3(P4HTM):c.1274T>C (p.Leu425Pro)	Likely pathogenic
4532793	NM_177939.3(P4HTM):c.436+1G>T	Likely pathogenic
4532794	NM_177939.3(P4HTM):c.934G>A (p.Glu312Lys)	Likely pathogenic
981901	NM_177939.3(P4HTM):c.1238C>T (p.Pro413Leu)	Likely pathogenic

SpliceAI

2214 predictions. Top by Δscore:

Variant	Effect	Δscore
3:48997962:G:GT	donor_gain	1.0000
3:48997962:G:T	donor_gain	1.0000
3:49001435:CAGAA:C	acceptor_loss	1.0000
3:49001436:A:G	acceptor_loss	1.0000
3:49001437:GA:G	acceptor_gain	1.0000
3:49001437:GAA:G	acceptor_gain	1.0000
3:49001619:GCTCC:G	donor_gain	1.0000
3:49001641:GGACC:G	donor_gain	1.0000
3:49001642:GACC:G	donor_gain	1.0000
3:49002595:CGGTG:C	donor_loss	1.0000
3:49002597:G:GG	donor_gain	1.0000
3:49002598:T:G	donor_loss	1.0000
3:49002599:G:GG	donor_loss	1.0000
3:49004097:GGA:G	acceptor_gain	1.0000
3:49006062:A:AG	acceptor_gain	1.0000
3:49006063:G:GG	acceptor_gain	1.0000
3:49006063:GA:G	acceptor_gain	1.0000
3:49006184:CAAGG:C	donor_loss	1.0000
3:49006186:AGGT:A	donor_loss	1.0000
3:49006189:T:A	donor_loss	1.0000
3:49006682:TCTA:T	acceptor_loss	1.0000
3:49006683:CTA:C	acceptor_loss	1.0000
3:49006684:TA:T	acceptor_loss	1.0000
3:49006685:AGGT:A	acceptor_loss	1.0000
3:49006686:GGTT:G	acceptor_gain	1.0000
3:49001432:T:TA	acceptor_gain	0.9900
3:49001433:G:A	acceptor_gain	0.9900
3:49001436:A:AG	acceptor_gain	0.9900
3:49001437:G:GG	acceptor_gain	0.9900
3:49001437:GAAA:G	acceptor_gain	0.9900

AlphaMissense

3285 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:49004991:T:A	C340S	1.000
3:49004991:T:C	C340R	1.000
3:49004992:G:A	C340Y	1.000
3:49004992:G:C	C340S	1.000
3:49004993:C:G	C340W	1.000
3:49004904:A:C	S311R	0.999
3:49004905:G:T	S311I	0.999
3:49004906:C:A	S311R	0.999
3:49004906:C:G	S311R	0.999
3:49004920:T:A	V316D	0.999
3:49004955:C:G	H328D	0.999
3:49004962:A:T	D330V	0.999
3:49004964:A:C	S331R	0.999
3:49004966:T:A	S331R	0.999
3:49004966:T:G	S331R	0.999
3:49004992:G:T	C340F	0.999
3:49005043:G:A	C357Y	0.999
3:49005044:C:G	C357W	0.999
3:49005785:C:T	T361I	0.999
3:49005832:T:C	F377L	0.999
3:49005833:T:C	F377S	0.999
3:49005833:T:G	F377C	0.999
3:49005834:C:A	F377L	0.999
3:49005834:C:G	F377L	0.999
3:49006151:G:C	A418P	0.999
3:49006152:C:A	A418E	0.999
3:49006155:T:A	V419D	0.999
3:49006160:T:A	W421R	0.999
3:49006160:T:C	W421R	0.999
3:49006168:C:A	N423K	0.999

dbSNP variants (sampled 300 via entrez): RS1000043222 (3:49002863 C>G), RS1000294746 (3:48994909 C>T), RS1000318609 (3:48995884 C>A,T), RS1000603771 (3:49001074 T>G), RS1000791676 (3:49000187 T>C), RS1001239731 (3:48996765 A>G), RS1001242840 (3:49002362 G>A), RS1001292310 (3:48996545 A>G,T), RS1001370119 (3:49003443 T>A), RS1001726791 (3:48994945 A>C,G), RS1001754587 (3:48995253 T>A,G), RS1001798607 (3:49003775 C>G,T), RS1002652482 (3:49000508 A>G), RS1002729886 (3:48992964 G>C), RS1002782747 (3:48993241 G>A)

Disease associations

OMIM: gene MIM:614584 | disease phenotypes: MIM:618493, MIM:618732

GenCC curated gene-disease

Disease	Classification	Inheritance
hypotonia, hypoventilation, impaired intellectual development, dysautonomia, epilepsy, and eye abnormalities	Definitive	Autosomal recessive

Mondo (3): hypotonia, hypoventilation, impaired intellectual development, dysautonomia, epilepsy, and eye abnormalities (MONDO:0032780), Poirier-Bienvenu neurodevelopmental syndrome (MONDO:0032889), intellectual disability (MONDO:0001071)

Orphanet (3): Poirier-Bienvenu neurodevelopmental syndrome (Orphanet:689397), OBSOLETE: Hypotonia-hypoventilation-intellectual disability-dysautonomia-epilepsy-eye abnormalities syndrome (Orphanet:656273), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

11 total (11 of 11 shown, HPO-id order):

HPO	Term
HP:0000280	Coarse facial features
HP:0000486	Strabismus
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001288	Gait disturbance
HP:0001513	Obesity
HP:0002360	Sleep disturbance
HP:0002857	Genu valgum
HP:0003028	Abnormality of the ankle
HP:0006094	Finger joint hypermobility
HP:0010864	Severe intellectual disability

GWAS associations

14 associations (top):

Study	Trait	p-value
GCST004131_23	Inflammatory bowel disease	1.000000e-33
GCST004132_17	Crohn’s disease	3.000000e-23
GCST004133_11	Ulcerative colitis	8.000000e-20
GCST007294_107	Body fat distribution (trunk fat ratio)	9.000000e-06
GCST007294_72	Body fat distribution (trunk fat ratio)	1.000000e-18
GCST007294_98	Body fat distribution (trunk fat ratio)	3.000000e-15
GCST007295_21	Body fat distribution (leg fat ratio)	8.000000e-06
GCST007295_45	Body fat distribution (leg fat ratio)	1.000000e-10
GCST007295_80	Body fat distribution (leg fat ratio)	1.000000e-14
GCST010698_80	Subcortical volume (min-P)	3.000000e-24
GCST010699_110	Brain morphology (min-P)	4.000000e-08
GCST010701_52	Cortical surface area (MOSTest)	1.000000e-16
GCST010702_36	Subcortical volume (MOSTest)	1.000000e-10
GCST010703_262	Brain morphology (MOSTest)	2.000000e-13

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004341	body fat distribution
EFO:0004346	neuroimaging measurement

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: yes

ChEMBL targets (2): CHEMBL3047 (SINGLE PROTEIN), CHEMBL3831261 (PROTEIN FAMILY)

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

Binding affinities (BindingDB)

9 measured of 28 human assays (28 total across all organisms); most potent 9 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
1-[2-[6-(3,3-difluoroazetidin-1-yl)pyrimidin-4-yl]-3-oxo-1H-pyrazol-4-yl]triazole-4-carbonitrile	IC50	70 nM	US-8580778: Substituted dihydropyrazolones and their use
1-[2-[6-(3,3-difluoroazetidin-1-yl)pyrimidin-4-yl]-3-oxo-1H-pyrazol-4-yl]imidazole-4-carbonitrile	IC50	90 nM	US-8580778: Substituted dihydropyrazolones and their use
1-[2-[6-(3,3-difluoropyrrolidin-1-yl)pyrimidin-4-yl]-3-oxo-1H-pyrazol-4-yl]triazole-4-carbonitrile	IC50	130 nM	US-8580778: Substituted dihydropyrazolones and their use
1-[2-[6-(oxazinan-2-yl)pyrimidin-4-yl]-3-oxo-1H-pyrazol-4-yl]triazole-4-carbonitrile	IC50	170 nM	US-8580778: Substituted dihydropyrazolones and their use
1-[2-[6-(1,4-oxazepan-4-yl)pyrimidin-4-yl]-3-oxo-1H-pyrazol-4-yl]imidazole-4-carbonitrile	IC50	180 nM	US-8580778: Substituted dihydropyrazolones and their use
1-[2-[6-(1,4-oxazepan-4-yl)pyrimidin-4-yl]-3-oxo-1H-pyrazol-4-yl]triazole-4-carbonitrile	IC50	380 nM	US-8580778: Substituted dihydropyrazolones and their use
1-[6-(4-imidazol-1-yl-3-oxo-1H-pyrazol-2-yl)pyrimidin-4-yl]azetidine-3-carboxylic acid	IC50	540 nM	US-8580778: Substituted dihydropyrazolones and their use
2-[6-[3-(dimethylamino)azetidin-1-yl]pyrimidin-4-yl]-4-(triazol-1-yl)-1H-pyrazol-3-one	IC50	760 nM	US-8580778: Substituted dihydropyrazolones and their use
2-[6-(4-cyclobutylpiperazin-1-yl)pyrimidin-4-yl]-4-(triazol-1-yl)-1H-pyrazol-3-one	IC50	880 nM	US-8580778: Substituted dihydropyrazolones and their use

ChEMBL bioactivities

68 potent at pChembl≥5 of 99 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.40	IC50	4	nM	CHEMBL5922741
8.35	IC50	4.5	nM	CHEMBL5854473
8.22	IC50	6	nM	CHEMBL5867395
7.96	IC50	11	nM	CHEMBL5814965
7.82	IC50	15	nM	CHEMBL5916377
7.60	IC50	25	nM	CHEMBL5842146
7.16	IC50	70	nM	CHEMBL3115317
7.05	IC50	90	nM	CHEMBL3640646
6.89	IC50	130	nM	CHEMBL3640645
6.77	IC50	170	nM	CHEMBL3642645
6.75	IC50	180	nM	CHEMBL3651449
6.75	IC50	180	nM	CHEMBL3642643
6.73	IC50	185	nM	CHEMBL332005
6.72	IC50	190	nM	CHEMBL332005
6.58	IC50	260	nM	CHEMBL3640754
6.50	IC50	320	nM	CHEMBL124527
6.42	IC50	380	nM	CHEMBL3642644
6.32	IC50	480	nM	CHEMBL3651450
6.27	IC50	540	nM	CHEMBL3640643
6.16	IC50	700	nM	CHEMBL3651451
6.12	IC50	760	nM	CHEMBL3640644
6.06	IC50	880	nM	CHEMBL3651452
6.06	IC50	880	nM	CHEMBL3640642
6.05	IC50	890	nM	CHEMBL3651453
6.05	IC50	900	nM	CHEMBL3640757
6.04	IC50	910	nM	CHEMBL3640755
6.03	IC50	930	nM	CHEMBL3651454
6.00	IC50	1000	nM	CHEMBL1744254
5.96	IC50	1100	nM	CHEMBL166568
5.95	IC50	1120	nM	CHEMBL3651455
5.80	IC50	1600	nM	CHEMBL3640758
5.80	IC50	1600	nM	CHEMBL1203805
5.77	IC50	1700	nM	CHEMBL3651456
5.75	IC50	1800	nM	CHEMBL1203806
5.75	IC50	1800	nM	CHEMBL1744252
5.62	EC50	2400	nM	CHEMBL4463388
5.62	IC50	2400	nM	CHEMBL1744251
5.58	EC50	2600	nM	CHEMBL4464252
5.57	IC50	2700	nM	CHEMBL3651457
5.55	IC50	2800	nM	CHEMBL3651458
5.52	IC50	3000	nM	CHEMBL355500
5.50	EC50	3200	nM	CHEMBL4459542
5.49	IC50	3240	nM	CHEMBL3640756
5.43	IC50	3700	nM	CHEMBL3640759
5.42	EC50	3800	nM	CHEMBL4519581
5.40	IC50	4000	nM	CHEMBL3651459
5.39	IC50	4100	nM	CHEMBL355389
5.36	IC50	4400	nM	CHEMBL166658
5.32	EC50	4800	nM	CHEMBL4514184
5.30	EC50	5000	nM	CHEMBL4589866

PubChem BioAssay actives

34 with measured affinity, of 128 total; 31 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
6-(5-carboxy-2-pyridinyl)pyridine-3-carboxylic acid	226111: Inhibition of prolyl 4-hydroxylase by chromatographic determination of [14C]-succinic acid on ion-exchange minicolumna	ic50	0.1850	uM
6-[5-[(4-ethoxyphenyl)carbamoyl]-2-pyridinyl]pyridine-3-carboxylic acid	226111: Inhibition of prolyl 4-hydroxylase by chromatographic determination of [14C]-succinic acid on ion-exchange minicolumna	ic50	0.3200	uM
sodium 5-[(4-methoxyphenyl)sulfonylcarbamoyl]pyridine-2-carboxylate	160197: Inhibition of prolyl 4-hydroxylase	ic50	1.0000	uM
5-(benzenesulfonylcarbamoyl)pyridine-2-carboxylic acid	160197: Inhibition of prolyl 4-hydroxylase	ic50	1.1000	uM
5-(propan-2-ylsulfonylcarbamoyl)pyridine-2-carboxylic acid;hydrochloride	160197: Inhibition of prolyl 4-hydroxylase	ic50	1.6000	uM
5-(methylsulfonylcarbamoyl)pyridine-2-carboxylic acid;hydrochloride	160197: Inhibition of prolyl 4-hydroxylase	ic50	1.8000	uM
disodium;5-[(Z)-C-oxido-N-quinolin-8-ylsulfonylcarbonimidoyl]pyridine-2-carboxylate;hydrate	160197: Inhibition of prolyl 4-hydroxylase	ic50	1.8000	uM
(1R,2R,10R,13R,14R,17S,20R,21S)-N-hydroxy-2,9,9,13,14-pentamethyl-20-prop-1-en-2-yl-6,7-diazahexacyclo[11.11.0.02,10.04,8.014,22.017,21]tetracosa-4(8),5-diene-17-carboxamide	1612308: Inhibition of PHD (unknown origin) expressed in mouse NIH/3T3 cells harboring HRE-driven luciferase gene assessed as transactivation of HIF1alpha after 6 hrs by luciferase reporter gene assay	ec50	2.4000	uM
disodium;5-[(Z)-N-(5-chlorothiophen-2-yl)sulfonyl-C-oxidocarbonimidoyl]pyridine-2-carboxylate;hydrate	160197: Inhibition of prolyl 4-hydroxylase	ic50	2.4000	uM
(1R,2R,10R,13R,14R,17S,20R,21S)-N-hydroxy-2,9,9,13,14-pentamethyl-20-prop-1-en-2-yl-7-oxa-6-azahexacyclo[11.11.0.02,10.04,8.014,22.017,21]tetracosa-4(8),5-diene-17-carboxamide	1612308: Inhibition of PHD (unknown origin) expressed in mouse NIH/3T3 cells harboring HRE-driven luciferase gene assessed as transactivation of HIF1alpha after 6 hrs by luciferase reporter gene assay	ec50	2.6000	uM
5-(benzylsulfonylcarbamoyl)pyridine-2-carboxylic acid	160197: Inhibition of prolyl 4-hydroxylase	ic50	3.0000	uM
(1R,3aS,5aR,5bR,7aS,11aS,11bR,13bS)-N-hydroxy-5a,5b,8,8,11a-pentamethyl-1-prop-1-en-2-yl-1,2,3,4,5,6,7,7a,11,11b,12,13,13a,13b-tetradecahydrocyclopenta[a]chrysene-3a-carboxamide	1612308: Inhibition of PHD (unknown origin) expressed in mouse NIH/3T3 cells harboring HRE-driven luciferase gene assessed as transactivation of HIF1alpha after 6 hrs by luciferase reporter gene assay	ec50	3.2000	uM
(4aS,6aR,6aS,6bR,8aR,10E,12aR,14bS)-N-hydroxy-10-hydroxyimino-2,2,6a,6b,9,9,12a-heptamethyl-3,4,5,6,6a,7,8,8a,11,12,13,14b-dodecahydro-1H-picene-4a-carboxamide	1612308: Inhibition of PHD (unknown origin) expressed in mouse NIH/3T3 cells harboring HRE-driven luciferase gene assessed as transactivation of HIF1alpha after 6 hrs by luciferase reporter gene assay	ec50	3.8000	uM
5-[[4-(dimethylamino)phenyl]carbamoyl]pyridine-2-carboxylic acid	160194: Inhibition of prolyl 4-hydroxylase activity by an indirect assay	ic50	4.1000	uM
5-(naphthalen-1-ylsulfonylcarbamoyl)pyridine-2-carboxylic acid	160197: Inhibition of prolyl 4-hydroxylase	ic50	4.4000	uM
(1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13bR)-N,9-dihydroxy-5a,5b,8,8,11a-pentamethyl-1-prop-1-en-2-yl-1,2,3,4,5,6,7,7a,9,10,11,11b,12,13,13a,13b-hexadecahydrocyclopenta[a]chrysene-3a-carboxamide	1612308: Inhibition of PHD (unknown origin) expressed in mouse NIH/3T3 cells harboring HRE-driven luciferase gene assessed as transactivation of HIF1alpha after 6 hrs by luciferase reporter gene assay	ec50	4.8000	uM
(4aS,6aR,6aS,6bR,8aS,12aS,14bS)-N-hydroxy-2,2,6a,6b,9,9,12a-heptamethyl-1,3,4,5,6,6a,7,8,8a,12,13,14b-dodecahydropicene-4a-carboxamide	1612308: Inhibition of PHD (unknown origin) expressed in mouse NIH/3T3 cells harboring HRE-driven luciferase gene assessed as transactivation of HIF1alpha after 6 hrs by luciferase reporter gene assay	ec50	5.0000	uM
5-[(4-ethoxyphenyl)carbamoyl]pyridine-2-carboxylic acid	160194: Inhibition of prolyl 4-hydroxylase activity by an indirect assay	ic50	5.0000	uM
N-(benzenesulfonyl)-6-[5-(benzenesulfonylcarbamoyl)-2-pyridinyl]pyridine-3-carboxamide	226111: Inhibition of prolyl 4-hydroxylase by chromatographic determination of [14C]-succinic acid on ion-exchange minicolumna	ic50	5.0400	uM
pyridine-2,5-dicarboxylic acid	226111: Inhibition of prolyl 4-hydroxylase by chromatographic determination of [14C]-succinic acid on ion-exchange minicolumna	ic50	5.1800	uM
methyl (1S,2S,4aR,4bS,6aS,10aS,12aR)-1-[3-(hydroxyamino)-3-oxopropyl]-1,4a,4b,9,9-pentamethyl-2-prop-1-en-2-yl-3,4,5,6,7,8,10,10a,12,12a-decahydro-2H-chrysene-6a-carboxylate	1612308: Inhibition of PHD (unknown origin) expressed in mouse NIH/3T3 cells harboring HRE-driven luciferase gene assessed as transactivation of HIF1alpha after 6 hrs by luciferase reporter gene assay	ec50	5.8000	uM
disodium;5-[(Z)-N-[4-(4,7-dichloroquinolin-2-yl)phenyl]sulfonyl-C-oxidocarbonimidoyl]pyridine-2-carboxylate	160197: Inhibition of prolyl 4-hydroxylase	ic50	6.6000	uM
(1R,3aS,5aR,5bR,7aR,9E,11aR,11bR,13bR)-N-hydroxy-9-hydroxyimino-5a,5b,8,8,11a-pentamethyl-1-prop-1-en-2-yl-2,3,4,5,6,7,7a,10,11,11b,12,13,13a,13b-tetradecahydro-1H-cyclopenta[a]chrysene-3a-carboxamide	1612308: Inhibition of PHD (unknown origin) expressed in mouse NIH/3T3 cells harboring HRE-driven luciferase gene assessed as transactivation of HIF1alpha after 6 hrs by luciferase reporter gene assay	ec50	6.8000	uM
(4aS,6aR,6aS,6bR,8aR,10R,11R,12aR,14bS)-N,10,11-trihydroxy-2,2,6a,6b,9,9,12a-heptamethyl-1,3,4,5,6,6a,7,8,8a,10,11,12,13,14b-tetradecahydropicene-4a-carboxamide	1612308: Inhibition of PHD (unknown origin) expressed in mouse NIH/3T3 cells harboring HRE-driven luciferase gene assessed as transactivation of HIF1alpha after 6 hrs by luciferase reporter gene assay	ec50	7.1000	uM
(1R,2S,5S,10S,14R,15R,21R)-N-hydroxy-1,2,8,8,15,20,20-heptamethyl-18-oxo-19-oxapentacyclo[12.9.0.02,11.05,10.015,21]tricos-11-ene-5-carboxamide	1612308: Inhibition of PHD (unknown origin) expressed in mouse NIH/3T3 cells harboring HRE-driven luciferase gene assessed as transactivation of HIF1alpha after 6 hrs by luciferase reporter gene assay	ec50	7.5000	uM
(1S,2R,4aS,6aR,6aS,6bR,8aR,10S,12aR,14bS)-N,10-dihydroxy-1,2,6a,6b,9,9,12a-heptamethyl-2,3,4,5,6,6a,7,8,8a,10,11,12,13,14b-tetradecahydro-1H-picene-4a-carboxamide	1612308: Inhibition of PHD (unknown origin) expressed in mouse NIH/3T3 cells harboring HRE-driven luciferase gene assessed as transactivation of HIF1alpha after 6 hrs by luciferase reporter gene assay	ec50	7.7000	uM
5-[(4-methylphenyl)carbamoyl]pyridine-2-carboxylic acid	160194: Inhibition of prolyl 4-hydroxylase activity by an indirect assay	ic50	8.3000	uM
disodium;5-[(Z)-N-(4,5-dibromothiophen-2-yl)sulfonyl-C-oxidocarbonimidoyl]pyridine-2-carboxylate	160197: Inhibition of prolyl 4-hydroxylase	ic50	8.5000	uM
(1S,2R,4aS,6aR,6aS,6bR,8aR,10E,12aR,14bS)-N-hydroxy-10-hydroxyimino-1,2,6a,6b,9,9,12a-heptamethyl-1,2,3,4,5,6,6a,7,8,8a,11,12,13,14b-tetradecahydropicene-4a-carboxamide	1612308: Inhibition of PHD (unknown origin) expressed in mouse NIH/3T3 cells harboring HRE-driven luciferase gene assessed as transactivation of HIF1alpha after 6 hrs by luciferase reporter gene assay	ec50	8.9000	uM
5-(carboxymethyl)pyridine-2-carboxylic acid	160197: Inhibition of prolyl 4-hydroxylase	ic50	9.6000	uM
5-(2-carboxyethyl)pyridine-2-carboxylic acid	160197: Inhibition of prolyl 4-hydroxylase	ic50	9.6000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression, increases methylation	6
sodium arsenite	affects cotreatment, decreases expression	2
Air Pollutants	affects expression, increases abundance, increases expression	2
Smoke	decreases expression, increases abundance, increases expression	2
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, increases expression	1
lead acetate	affects cotreatment, decreases expression	1
cypermethrin	increases expression	1
cobaltous chloride	decreases expression	1
butyraldehyde	decreases expression	1
manganese chloride	decreases reaction, decreases degradation, decreases hydroxylation, decreases activity	1
ferrous chloride	affects cotreatment, increases activity	1
coumarin	increases phosphorylation	1
perfluorooctane sulfonic acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
bisphenol S	decreases methylation, affects cotreatment	1
picoxystrobin	decreases expression	1
Temozolomide	decreases expression	1
Sunitinib	decreases expression	1
Arsenic Trioxide	decreases response to substance	1
Fulvestrant	affects cotreatment, decreases methylation	1
Vorinostat	decreases expression	1
Ascorbic Acid	affects cotreatment, increases activity	1
Dexamethasone	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Estradiol	decreases expression, affects cotreatment	1
Ethyl Methanesulfonate	increases expression	1
Indomethacin	increases expression, affects cotreatment	1

ChEMBL screening assays

28 unique, capped per target: 28 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2394605	Binding	Binding affinity to human P4H expressed in Escherichia coli at 13 mM after 30 mins by SDS-PAGE analysis	Bioavailable affinity label for collagen prolyl 4-hydroxylase. — Bioorg Med Chem

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
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