DHX34

Summary

DHX34 (DExH-box helicase 34, HGNC:16719) is a protein-coding gene on chromosome 19q13.32, encoding Probable ATP-dependent RNA helicase DHX34 (Q14147). Probable ATP-binding RNA helicase required for nonsense-mediated decay (NMD) degradation of mRNA transcripts containing premature stop codons.

DEAD box proteins, characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), are putative RNA helicases. They are implicated in a number of cellular processes involving alteration of RNA secondary structure such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly. Based on their distribution patterns, some members of this DEAD box protein family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. This gene encodes a member of this family. It is mapped to the glioma 19q tumor suppressor region and is a tumor suppressor candidate gene.

Source: NCBI Gene 9704 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder (Limited, GenCC) — +1 more curated relationship
• Clinical variants (ClinVar): 335 total — 1 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 1
• MANE Select transcript: NM_014681

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16719
Approved symbol	DHX34
Name	DExH-box helicase 34
Location	19q13.32
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0134
Ensembl gene	ENSG00000134815
Ensembl biotype	protein_coding
OMIM	615475
Entrez	9704

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 5 protein_coding, 3 retained_intron, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000328771, ENST00000460681, ENST00000471451, ENST00000486327, ENST00000718251, ENST00000718252, ENST00000718253, ENST00000924268, ENST00000924269, ENST00000965089

RefSeq mRNA: 1 — MANE Select: NM_014681 NM_014681

CCDS: CCDS12700

Canonical transcript exons

ENST00000328771 — 17 exons

Exon	Start	End
ENSE00000916236	47362476	47362693
ENSE00000916238	47355039	47355350
ENSE00001048978	47352754	47353735
ENSE00001330659	47376443	47376560
ENSE00001366052	47375924	47376097
ENSE00001377598	47357866	47358120
ENSE00001837966	47349315	47349352
ENSE00002501465	47381980	47382704
ENSE00003501006	47375466	47375708
ENSE00003509661	47359968	47360070
ENSE00003522832	47373599	47373700
ENSE00003594444	47377100	47377206
ENSE00003606930	47379710	47379985
ENSE00003611638	47372730	47372923
ENSE00003619833	47381186	47381324
ENSE00003635484	47380816	47380992
ENSE00003691284	47366981	47367155

Expression profiles

Bgee: expression breadth ubiquitous, 217 present calls, max score 90.21.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.5495 / max 432.3689, expressed in 1757 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
176676	5.2857	1652
176677	2.4476	1153
176678	2.3377	690
176680	0.2835	59
176681	0.1029	33
176679	0.0921	24

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right testis	UBERON:0004534	90.21	gold quality
blood	UBERON:0000178	90.19	gold quality
left testis	UBERON:0004533	89.93	gold quality
granulocyte	CL:0000094	88.90	gold quality
testis	UBERON:0000473	86.84	gold quality
spleen	UBERON:0002106	85.36	gold quality
right uterine tube	UBERON:0001302	85.17	gold quality
right lobe of liver	UBERON:0001114	85.12	gold quality
adenohypophysis	UBERON:0002196	84.56	gold quality
lower esophagus mucosa	UBERON:0035834	83.92	gold quality
pituitary gland	UBERON:0000007	83.85	gold quality
endocervix	UBERON:0000458	83.46	gold quality
right hemisphere of cerebellum	UBERON:0014890	83.34	gold quality
left ovary	UBERON:0002119	83.33	gold quality
tendon of biceps brachii	UBERON:0008188	83.31	silver quality
right ovary	UBERON:0002118	83.26	gold quality
apex of heart	UBERON:0002098	83.25	gold quality
right lobe of thyroid gland	UBERON:0001119	82.99	gold quality
mucosa of transverse colon	UBERON:0004991	82.57	gold quality
body of uterus	UBERON:0009853	82.44	gold quality
ectocervix	UBERON:0012249	82.44	gold quality
cortical plate	UBERON:0005343	82.42	gold quality
left lobe of thyroid gland	UBERON:0001120	82.25	gold quality
cerebellar hemisphere	UBERON:0002245	82.10	gold quality
left uterine tube	UBERON:0001303	82.03	gold quality
cerebellar cortex	UBERON:0002129	81.99	gold quality
upper lobe of left lung	UBERON:0008952	81.64	gold quality
right adrenal gland	UBERON:0001233	81.57	gold quality
metanephros cortex	UBERON:0010533	81.37	gold quality
thyroid gland	UBERON:0002046	81.35	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.52

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

18 targeting DHX34, 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-4481	100.00	66.42	1669
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-4302	99.89	67.94	1187
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-516B-5P	99.56	66.33	1495
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-4316	99.37	65.75	1360
HSA-MIR-3619-5P	99.00	68.87	2308
HSA-MIR-4742-5P	98.89	68.41	1542
HSA-MIR-214-3P	98.71	68.12	2128
HSA-MIR-761	98.71	68.07	2051
HSA-MIR-7973	96.48	65.54	502
HSA-MIR-193A-5P	95.70	65.33	613

Literature-anchored findings (GeneRIF, showing 6)

• DHX34 and NBAS act in concert with core nonsense-mediated mRNA decay factors to co-regulate a large number of endogenous RNA targets. (PMID:23828042)
• DHX34 promotes mRNP remodeling and triggers the conversion from the SURF complex to the DECID complex resulting in NMD activation. (PMID:25220460)
• DHX34 activates nonsense-mediated mRNA decay by functioning as a scaffold for SMG1-mediated UPF1 phosphorylation via complex formation with SMG1 and UPF1. (PMID:26841701)
• Missense mutation in DHX34 gene is associated with neurodevelopmental disorder. (PMID:31256877)
• Regulation of RUVBL1-RUVBL2 AAA-ATPases by the nonsense-mediated mRNA decay factor DHX34, as evidenced by Cryo-EM. (PMID:33205750)
• A dual role for the RNA helicase DHX34 in NMD and pre-mRNA splicing and its function in hematopoietic differentiation. (PMID:35768279)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	dhx34	ENSDARG00000061168
mus_musculus	Dhx34	ENSMUSG00000006019
rattus_norvegicus	Dhx34	ENSRNOG00000047575
drosophila_melanogaster	CG32533	FBGN0052533
caenorhabditis_elegans		WBGENE00021365

Paralogs (18): DHX33 (ENSG00000005100), YTHDC2 (ENSG00000047188), DHX29 (ENSG00000067248), DHX8 (ENSG00000067596), DHX32 (ENSG00000089876), DHX35 (ENSG00000101452), DHX40 (ENSG00000108406), DHX15 (ENSG00000109606), HELB (ENSG00000127311), DHX30 (ENSG00000132153), DHX9 (ENSG00000135829), DHX38 (ENSG00000140829), DQX1 (ENSG00000144045), DHX37 (ENSG00000150990), TDRD9 (ENSG00000156414), DHX57 (ENSG00000163214), DHX36 (ENSG00000174953), DHX16 (ENSG00000204560)

Protein

Protein identifiers

Probable ATP-dependent RNA helicase DHX34 — Q14147 (reviewed: Q14147)

Alternative names: DEAH box protein 34, DExH-box helicase 34

All UniProt accessions (2): Q14147, H7C504

UniProt curated annotations — full annotation on UniProt →

Function. Probable ATP-binding RNA helicase required for nonsense-mediated decay (NMD) degradation of mRNA transcripts containing premature stop codons. Promotes the phosphorylation of UPF1 along with its interaction with key NMD pathway proteins UPF2 and EIF4A3. Interaction with the RUVBL1-RUVBL2 complex results in loss of nucleotide binding ability and ATP hydrolysis of the complex. Negatively regulates the nucleotide binding ability and ATP hydrolysis of the RUVBL1-RUVBL2 complex via induction of N-terminus conformation changes of the RUVBL2 subunits.

Subunit / interactions. Forms a complex with RUVBL1 and RUVBL2. Part of a complex composed of SMG1, DHX34 and UPF1; within the complex DHX34 acts as a scaffolding protein to facilitate SMG1 phosphorylation of UPF1. Interacts with UPF1, MOV10, EIF4A3, XRN2, SMG6, SMG7, SMG9, UPF3A, UPF3B, CASC3/MLN51, XRN1, DIS3 and DCP1A; the interactions are RNA-independent. Interacts with NCBP1/CPB80; the interaction is RNA-dependent. Interacts (via C-terminus) with SMG1; the interaction is RNA-independent.

Tissue specificity. Expressed in whole blood, testis and spleen. Also expressed in the brain.

Similarity. Belongs to the DEAD box helicase family. DEAH subfamily.

RefSeq proteins (1): NP_055496* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001650	Helicase_C-like	Domain
IPR007502	Helicase-assoc_dom	Domain
IPR011545	DEAD/DEAH_box_helicase_dom	Domain
IPR011709	DEAD-box_helicase_OB_fold	Domain
IPR014001	Helicase_ATP-bd	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR048333	HA2_WH	Domain
IPR056382	DHX34_Znf-C2H2	Domain

Pfam: PF00270, PF00271, PF04408, PF07717, PF21010, PF24485

Enzyme classification (BRENDA):

• EC 3.6.4.13 — RNA helicase (BRENDA: 3 organisms, 3 substrates, 0 inhibitors, 0 Km, 0 kcat entries)

Catalyzed reactions (Rhea), 1 shown:

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

UniProt features (21 total): region of interest 6, sequence variant 5, domain 2, modified residue 2, mutagenesis site 2, chain 1, compositionally biased region 1, binding site 1, short sequence motif 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14147-F1	80.85	0.42

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 (1): 185–192

Post-translational modifications (2): 749, 750

Mutagenesis-validated functional residues (2):

Position	Phenotype
191	results in interaction with etf1/erf1, gspt1/erf3a and gspt2/erf3b. reduces upf1 phosphorylation. no effect on mrna bind
279	results in interaction with etf1/erf1, gspt1/erf3a and gspt2/erf3b. increases mrna binding. reduces upf1 phosphorylation

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 100 (showing top): GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_REGULATION_OF_CATABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_PHOSPHORUS_METABOLIC_PROCESS, BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_UP, GOBP_NUCLEAR_TRANSCRIBED_MRNA_CATABOLIC_PROCESS_NONSENSE_MEDIATED_DECAY, GOBP_REGULATION_OF_PHOSPHORUS_METABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_CATABOLIC_PROCESS, MODULE_192, GOMF_HYDROLASE_ACTIVITY_ACTING_ON_ACID_ANHYDRIDES, GOMF_ATP_HYDROLYSIS_ACTIVITY, GOMF_ADENYL_NUCLEOTIDE_BINDING, GOMF_ISOMERASE_ACTIVITY, GOBP_NUCLEAR_TRANSCRIBED_MRNA_CATABOLIC_PROCESS

GO Biological Process (4): nuclear-transcribed mRNA catabolic process, nonsense-mediated decay (GO:0000184), nuclear-transcribed mRNA catabolic process (GO:0000956), positive regulation of phosphorylation (GO:0042327), negative regulation of nuclear-transcribed mRNA catabolic process, nonsense-mediated decay (GO:2000623)

GO Molecular Function (10): RNA binding (GO:0003723), RNA helicase activity (GO:0003724), helicase activity (GO:0004386), ATP binding (GO:0005524), ATP hydrolysis activity (GO:0016887), protein-containing complex binding (GO:0044877), nucleotide binding (GO:0000166), nucleic acid binding (GO:0003676), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (1): membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	3
ATP-dependent activity	2
nuclear-transcribed mRNA catabolic process	1
mRNA catabolic process	1
phosphorylation	1
regulation of phosphorylation	1
positive regulation of phosphate metabolic process	1
nuclear-transcribed mRNA catabolic process, nonsense-mediated decay	1
negative regulation of mRNA catabolic process	1
regulation of nuclear-transcribed mRNA catabolic process, nonsense-mediated decay	1
nucleic acid binding	1
helicase activity	1
ATP-dependent activity, acting on RNA	1
catalytic activity, acting on RNA	1
nucleic acid conformation isomerase activity	1
catalytic activity, acting on a nucleic acid	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
ribonucleoside triphosphate phosphatase activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
catalytic activity	1
cellular anatomical structure	1

Protein interactions and networks

STRING

2440 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DHX34	SMG9	Q9H0W8	856
DHX34	UPF2	Q9HAU5	854
DHX34	UPF1	Q92900	850
DHX34	UPF3A	Q9H1J1	846
DHX34	SMG1	Q96Q15	845
DHX34	SMG8	Q8ND04	841
DHX34	SMG5	Q9UPR3	656
DHX34	SMG6	Q86US8	644
DHX34	UPF3B	Q9BZI7	641
DHX34	SMG7	Q92540	638
DHX34	EIF4A3	P38919	544
DHX34	SRSF1	Q07955	527
DHX34	SEC13	P55735	517
DHX34	NBAS	A2RRP1	509
DHX34	PABPC1	P11940	507

IntAct

24 interactions, top by confidence:

A	B	Type	Score
KIF3A	KIF3B	psi-mi:“MI:0914”(association)	0.840
N	RBM47	psi-mi:“MI:0914”(association)	0.530
CDPF1	DHX34	psi-mi:“MI:0915”(physical association)	0.500
GSK3B	DHX34	psi-mi:“MI:0915”(physical association)	0.370
DHX34	RPS6KA6	psi-mi:“MI:0915”(physical association)	0.370
Isy1	PFDN6	psi-mi:“MI:0914”(association)	0.350
Septin6	SEPTIN10	psi-mi:“MI:0914”(association)	0.350
MAPK6		psi-mi:“MI:0914”(association)	0.350
MAPK6	MYO9A	psi-mi:“MI:0914”(association)	0.350
N	RBM47	psi-mi:“MI:0914”(association)	0.350
S100A2	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
PTGES3	SBNO1	psi-mi:“MI:0914”(association)	0.350
DNAJA2	DENND11	psi-mi:“MI:0914”(association)	0.350
DHX34	ARG2	psi-mi:“MI:0914”(association)	0.350
CDPF1	USP4	psi-mi:“MI:0914”(association)	0.350
RBM15	ILVBL	psi-mi:“MI:2364”(proximity)	0.270
DHX34	POLA2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (37): DHX34 (Affinity Capture-MS), DHX34 (Affinity Capture-MS), DHX34 (Affinity Capture-MS), DHX34 (Affinity Capture-RNA), DHX34 (Affinity Capture-MS), DHX34 (Affinity Capture-MS), POLA2 (Two-hybrid), DHX34 (Affinity Capture-MS), DHX34 (Affinity Capture-MS), DHX34 (Affinity Capture-MS), CSTF2T (Affinity Capture-MS), DHX34 (Affinity Capture-MS), FAM172A (Affinity Capture-MS), ARG2 (Affinity Capture-MS), FBXO38 (Affinity Capture-MS)

ESM2 similar proteins: A0A250YGJ5, A0A2K5TU92, A9SDL4, B2RZ55, B8ARK7, D3ZU57, D4ACP5, E1BRE2, E2RDZ6, F7EZ75, O94762, P23249, P38935, P40694, P52824, P59941, Q0P595, Q14147, Q1HG60, Q25337, Q2KHU5, Q3ZBQ0, Q4R834, Q5R6G3, Q5RBF1, Q5RJQ4, Q60560, Q68FX9, Q6DHI5, Q7XWV4, Q80SX8, Q8BKJ9, Q8IXJ6, Q8K2C6, Q8N6T7, Q8N8A6, Q8R104, Q8R216, Q8VDQ8, Q922B1

Diamond homologs: A1Z9L3, A2A4P0, B4GEU5, B4JT42, B4K5R2, B4RC48, D4A2Z8, F4HYJ7, F4IE66, F4IJV4, F4ILR7, F4IM84, F4JMJ3, F4JRJ6, F4K2E9, F4KGU4, O17438, O22243, O22899, O35286, O42643, O42945, O43143, O45244, O46072, O51767, O60114, O60231, O70133, O94536, P0C7L7, P0CE10, P15938, P20095, P24384, P34305, P34498, P36009, P37024, P43329

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	2
Uncertain significance	251
Likely benign	24
Benign	29

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
691942	NM_014681.6(DHX34):c.2327G>C (p.Arg776Pro)	Pathogenic
691940	NM_014681.6(DHX34):c.1322A>G (p.Asn441Ser)	Likely pathogenic
691941	NM_014681.6(DHX34):c.466C>T (p.Gln156Ter)	Likely pathogenic

SpliceAI

2320 predictions. Top by Δscore:

Variant	Effect	Δscore
19:47349348:GTGTG:G	donor_gain	1.0000
19:47349350:GTG:G	donor_gain	1.0000
19:47349353:G:GG	donor_gain	1.0000
19:47349353:GTA:G	donor_loss	1.0000
19:47349354:T:A	donor_loss	1.0000
19:47353732:ACAGG:A	donor_loss	1.0000
19:47353733:CAGGT:C	donor_loss	1.0000
19:47353734:AGGT:A	donor_loss	1.0000
19:47353735:GGTG:G	donor_loss	1.0000
19:47353736:GTG:G	donor_loss	1.0000
19:47353737:T:A	donor_loss	1.0000
19:47355032:A:AG	acceptor_gain	1.0000
19:47355036:CA:C	acceptor_loss	1.0000
19:47355037:A:AG	acceptor_gain	1.0000
19:47355037:AG:A	acceptor_gain	1.0000
19:47355037:AGGTC:A	acceptor_gain	1.0000
19:47355038:G:A	acceptor_gain	1.0000
19:47355038:G:GT	acceptor_gain	1.0000
19:47355038:GGT:G	acceptor_gain	1.0000
19:47355038:GGTC:G	acceptor_gain	1.0000
19:47355038:GGTCG:G	acceptor_gain	1.0000
19:47355346:TCACG:T	donor_gain	1.0000
19:47355348:ACG:A	donor_gain	1.0000
19:47355349:CG:C	donor_gain	1.0000
19:47355349:CGG:C	donor_loss	1.0000
19:47355350:GG:G	donor_gain	1.0000
19:47355351:G:GG	donor_gain	1.0000
19:47355352:T:A	donor_loss	1.0000
19:47358075:G:GA	donor_gain	1.0000
19:47358118:AAGG:A	donor_loss	1.0000

AlphaMissense

7408 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:47362561:G:C	Q487H	1.000
19:47362561:G:T	Q487H	1.000
19:47353599:G:A	G190D	0.999
19:47353605:C:T	S192F	0.999
19:47357998:T:C	F384L	0.999
19:47358000:C:A	F384L	0.999
19:47358000:C:G	F384L	0.999
19:47360023:C:A	A443D	0.999
19:47360035:T:A	V447D	0.999
19:47362541:A:C	S481R	0.999
19:47362543:T:A	S481R	0.999
19:47362543:T:G	S481R	0.999
19:47362553:G:C	A485P	0.999
19:47362563:G:C	R488P	0.999
19:47362578:G:A	G493D	0.999
19:47362580:C:A	R494S	0.999
19:47362600:C:G	C500W	0.999
19:47353599:G:T	G190V	0.998
19:47353601:A:C	K191Q	0.998
19:47353605:C:A	S192Y	0.998
19:47353677:C:A	A216D	0.998
19:47355168:G:C	D279H	0.998
19:47355169:A:T	D279V	0.998
19:47355172:A:T	E280V	0.998
19:47355268:C:A	A312D	0.998
19:47357993:T:C	L382P	0.998
19:47357999:T:C	F384S	0.998
19:47358070:T:A	W408R	0.998
19:47358070:T:C	W408R	0.998
19:47359971:T:C	F426L	0.998

dbSNP variants (sampled 300 via entrez): RS1000183111 (19:47362888 C>T), RS1000239821 (19:47364505 G>C), RS1000273276 (19:47365495 G>A), RS1000286981 (19:47359378 C>A), RS1000481843 (19:47354372 A>G), RS1000675331 (19:47364720 A>G), RS1000721507 (19:47367244 G>C), RS1000847165 (19:47355743 T>C,G), RS1000977782 (19:47368035 T>G), RS1000988384 (19:47350497 C>A), RS1001098253 (19:47383016 T>C,G), RS1001100128 (19:47380705 C>T), RS1001217429 (19:47355553 G>C), RS1001221739 (19:47379919 T>C), RS1001315236 (19:47380159 G>A)

Disease associations

OMIM: gene MIM:615475 | disease phenotypes: MIM:173900, MIM:174200

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder	Limited	Autosomal dominant
intellectual disability	Limited	Autosomal recessive

Mondo (7): intellectual disability (MONDO:0001071), microcephaly (MONDO:0001149), renal agenesis, unilateral (MONDO:0019636), pulmonary emphysema (MONDO:0004849), polycystic kidney disease (MONDO:0020642), postaxial polydactyly (MONDO:0020927), neurodevelopmental disorder (MONDO:0700092)

Orphanet (2): Renal agenesis, unilateral (Orphanet:93100), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0000252	Microcephaly

GWAS associations

0 associations (top):

MeSH disease descriptors (6)

Descriptor	Name	Tree numbers
D004646	Emphysema	C23.550.325
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
D065886	Neurodevelopmental Disorders	F03.625
D007690	Polycystic Kidney Diseases	C12.050.351.968.419.403.875; C12.200.777.419.403.875; C12.950.419.403.875; C16.131.077.717; C16.320.184.625
D011656	Pulmonary Emphysema	C08.381.495.389.750; C23.550.291.500.875.875

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Acetaminophen	decreases expression, increases expression	2
FR900359	increases phosphorylation	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
zinc chromate	decreases expression, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
CGP 52608	affects binding, increases reaction	1
abrine	increases expression	1
Air Pollutants	affects expression, increases abundance	1
Atrazine	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Estradiol	increases expression	1
Hydrogen Peroxide	affects expression	1
Ozone	affects expression, increases abundance	1
Smoke	decreases expression	1
Tetrachlorodibenzodioxin	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Cyclosporine	increases expression	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
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
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
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
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
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
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
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)
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays