TRMT5

Summary

TRMT5 (tRNA methyltransferase 5, HGNC:23141) is a protein-coding gene on chromosome 14q23.1, encoding tRNA (guanine(37)-N(1))-methyltransferase (Q32P41). Involved in mitochondrial tRNA methylation. It is a selective cancer dependency (DepMap: 71.4% of cell lines).

tRNAs contain as many as 13 or 14 nucleotides that are modified posttranscriptionally by enzymes that are highly specific for particular nucleotides in the tRNA structure. TRMT5 methylates the N1 position of guanosine-37 (G37) in selected tRNAs using S-adenosyl methionine (Brule et al., 2004 [PubMed 15248782]).

Source: NCBI Gene 57570 — RefSeq curated summary.

At a glance

• Gene–disease (curated): mitochondrial disease (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 1
• Clinical variants (ClinVar): 269 total — 1 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 42
• Cancer dependency (DepMap): dependent in 71.4% of screened cell lines
• MANE Select transcript: NM_020810

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23141
Approved symbol	TRMT5
Name	tRNA methyltransferase 5
Location	14q23.1
Locus type	gene with protein product
Status	Approved
Aliases	TRM5
Ensembl gene	ENSG00000126814
Ensembl biotype	protein_coding
OMIM	611023
Entrez	57570

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000261249, ENST00000553903, ENST00000555420, ENST00000928589

RefSeq mRNA: 3 — MANE Select: NM_020810 NM_001350253, NM_001350254, NM_020810

CCDS: CCDS32092

Canonical transcript exons

ENST00000261249 — 5 exons

Exon	Start	End
ENSE00000392738	60975475	60976126
ENSE00000658240	60977514	60977638
ENSE00000867516	60971441	60975194
ENSE00000867517	60979231	60979886
ENSE00002437566	60980963	60981079

Expression profiles

Bgee: expression breadth ubiquitous, 244 present calls, max score 96.01.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 14.7468 / max 303.9640, expressed in 1782 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
143522	12.6904	1772
143524	1.3266	169
143523	0.6051	118
143525	0.1247	44

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	96.01	gold quality
secondary oocyte	CL:0000655	95.66	gold quality
oocyte	CL:0000023	95.38	gold quality
calcaneal tendon	UBERON:0003701	88.30	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.99	gold quality
cartilage tissue	UBERON:0002418	83.44	gold quality
tibialis anterior	UBERON:0001385	82.49	silver quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.29	gold quality
islet of Langerhans	UBERON:0000006	81.32	gold quality
right testis	UBERON:0004534	81.11	gold quality
cortical plate	UBERON:0005343	81.01	gold quality
ganglionic eminence	UBERON:0004023	80.71	gold quality
embryo	UBERON:0000922	80.70	gold quality
testis	UBERON:0000473	80.50	gold quality
left testis	UBERON:0004533	80.37	gold quality
tendon	UBERON:0000043	79.81	gold quality
ventricular zone	UBERON:0003053	79.58	gold quality
gastrocnemius	UBERON:0001388	79.18	gold quality
smooth muscle tissue	UBERON:0001135	79.05	gold quality
muscle of leg	UBERON:0001383	79.03	gold quality
adrenal tissue	UBERON:0018303	78.84	gold quality
stromal cell of endometrium	CL:0002255	78.39	gold quality
hindlimb stylopod muscle	UBERON:0004252	78.06	gold quality
pancreas	UBERON:0001264	78.04	gold quality
skeletal muscle organ	UBERON:0014892	77.50	gold quality
nasopharynx	UBERON:0001728	77.49	gold quality
epithelium of nasopharynx	UBERON:0001951	77.48	gold quality
body of pancreas	UBERON:0001150	77.15	gold quality
rectum	UBERON:0001052	77.01	gold quality
deltoid	UBERON:0001476	76.95	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.34

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

152 targeting TRMT5, 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-3163	100.00	77.23	8605
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-6793-5P	99.97	65.95	758
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 71.4% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 4)

• comparison of human TRM5 and E Coli TrmD activities, requirements for optimal activity, and tRNA methylation sites (PMID:15248782)
• Conservation of structure and mechanism by Trm5 enzymes (PMID:23887145)
• TRMT5 mutations cause a defect in post-transcriptional modification of mitochondrial tRNA associated with multiple respiratory-chain deficiencies. (PMID:26189817)
• A novel TRMT5 mutation causes a complex inherited neuropathy syndrome: The role of nerve pathology in defining a demyelinating neuropathy. (PMID:35342985)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	trmt5	ENSDARG00000069278
mus_musculus	Trmt5	ENSMUSG00000034442
rattus_norvegicus	Trmt5	ENSRNOG00000007785
drosophila_melanogaster	CG32281	FBGN0052281
caenorhabditis_elegans		WBGENE00194707

Paralogs (2): TYW3 (ENSG00000162623), TRMT12 (ENSG00000183665)

Protein

Protein identifiers

tRNA (guanine(37)-N(1))-methyltransferase — Q32P41 (reviewed: Q32P41)

Alternative names: M1G-methyltransferase, tRNA [GM37] methyltransferase, tRNA methyltransferase 5 homolog

All UniProt accessions (3): Q32P41, G3V494, G3V5X1

UniProt curated annotations — full annotation on UniProt →

Function. Involved in mitochondrial tRNA methylation. Specifically methylates the N1 position of guanosine-37 in various tRNAs. Methylation is not dependent on the nature of the nucleoside 5’ of the target nucleoside. This is the first step in the biosynthesis of wybutosine (yW), a modified base adjacent to the anticodon of tRNAs and required for accurate decoding.

Subunit / interactions. Monomer.

Subcellular location. Mitochondrion matrix. Nucleus. Cytoplasm.

Disease relevance. Peripheral neuropathy with variable spasticity, exercise intolerance, and developmental delay (PNSED) [MIM:616539] An autosomal recessive mitochondrial disorder with multisystemic and highly variable manifestations. Affected individuals suffer from a peripheral neuropathy, with distal muscle weakness and atrophy, and distal sensory impairment. Additional variable features include early-onset hypotonia and global developmental delay, poor or absent motor skills, exercise intolerance, poor growth, cerebellar signs, spasticity, and seizures. Biochemical analysis may show deficiencies in mitochondrial respiratory complex. Lactic acidosis is frequently observed. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the class I-like SAM-binding methyltransferase superfamily. TRM5/TYW2 family.

RefSeq proteins (3): NP_001337182, NP_001337183, NP_065861* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR025792	tRNA_Gua_MeTrfase_euk	Family
IPR029063	SAM-dependent_MTases_sf	Homologous_superfamily
IPR030382	MeTrfase_TRM5/TYW2	Domain
IPR056743	TRM5-TYW2-like_MTfase	Domain
IPR056744	TRM5/TYW2-like_N	Domain

Pfam: PF02475, PF25133

Enzyme classification (BRENDA):

• EC 2.1.1.228 — tRNA (guanine37-N1)-methyltransferase (BRENDA: 18 organisms, 109 substrates, 186 inhibitors, 79 Km, 42 kcat entries)

Substrate kinetics (BRENDA)

38 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
GUANINE37 IN METHANOCALDOCOCCUS JANNASCHII TRNAC	0.0007–0.0083	9
GUANINE37 IN TRNALEU	0.0024–0.0625	7
S-ADENOSYL-L-METHIONINE	0.0004–0.003	5
GUANINE37 IN TRNAGLNCUG	0.0008–0.067	4
GUANINE37 IN ESCHERICHIA COLI TRNA1LEU	0.0001–0.0057	2
GUANINE37 IN HUMAN MITOCHONDRIAL TRNAPRO	0.0055–0.0086	2
GUANINE37 IN METHANOCALDOCOCCUS JANNASCHII TRNAP	0.0012–0.0073	2
GUANINE37 IN YEAST TRNAASP POSSESSING A G36G37 S	0.0002–0.019	2
GUANINE37 IN YEAST TRNAASP POSSESSING AN A36G37	0.0006–0.046	2
GUANINE37 IN AQUIFEX AEOLICUS TRNAARG(ACG)	0.0006	1
GUANINE37 IN AQUIFEX AEOLICUS TRNAARG(CCG)	0.0008	1
GUANINE37 IN AQUIFEX AEOLICUS TRNAGLN(UUG)	0.0004	1
GUANINE37 IN AQUIFEX AEOLICUS TRNAHIS(GUG)	0.0006	1
GUANINE37 IN AQUIFEX AEOLICUS TRNALEU(CAG)	0.0009	1
GUANINE37 IN AQUIFEX AEOLICUS TRNAPRO(GGG)	0.0007	1

Catalyzed reactions (Rhea), 1 shown:

• guanosine(37) in tRNA + S-adenosyl-L-methionine = N(1)-methylguanosine(37) in tRNA + S-adenosyl-L-homocysteine + H(+) (RHEA:36899)

UniProt features (12 total): sequence variant 5, binding site 4, chain 1, region of interest 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q32P41-F1	80.50	0.64

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 (4): 289; 327–328; 355–356; 387

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-6782861	Synthesis of wybutosine at G37 of tRNA(Phe)

MSigDB gene sets: 236 (showing top): RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_TRNA_METABOLIC_PROCESS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_RNA_METHYLATION, GOBP_RNA_MODIFICATION, GOBP_MITOCHONDRIAL_RNA_PROCESSING, GOBP_TRNA_METHYLATION, GOBP_MITOCHONDRIAL_RNA_METABOLIC_PROCESS, GARY_CD5_TARGETS_DN, chr14q23, GOBP_TRNA_THREONYLCARBAMOYLADENOSINE_METABOLIC_PROCESS, GGTGAAG_MIR412, GOBP_METHYLATION, GOBP_TRNA_PROCESSING

GO Biological Process (5): tRNA N1-guanine methylation (GO:0002939), mitochondrial tRNA methylation (GO:0070901), tRNA processing (GO:0008033), tRNA methylation (GO:0030488), methylation (GO:0032259)

GO Molecular Function (4): tRNA methyltransferase activity (GO:0008175), tRNA (guanine(37)-N1)-methyltransferase activity (GO:0052906), methyltransferase activity (GO:0008168), transferase activity (GO:0016740)

GO Cellular Component (4): nucleus (GO:0005634), cytoplasm (GO:0005737), mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
tRNA modification in the nucleus and cytosol	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
tRNA methylation	2
mitochondrion	2
intracellular membrane-bounded organelle	2
mitochondrial tRNA modification	1
RNA processing	1
tRNA metabolic process	1
RNA methylation	1
tRNA modification	1
metabolic process	1
RNA methyltransferase activity	1
catalytic activity, acting on a tRNA	1
tRNA (guanine) methyltransferase activity	1
transferase activity, transferring one-carbon groups	1
catalytic activity	1
intracellular anatomical structure	1
cellular anatomical structure	1
cytoplasm	1
intracellular organelle lumen	1

Protein interactions and networks

STRING

1522 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TRMT5	TYW1	Q9NV66	858
TRMT5	TYW2	Q53H54	845
TRMT5	TYW3	Q6IPR3	839
TRMT5	LCMT2	O60294	807
TRMT5	TRMT10A	Q8TBZ6	791
TRMT5	TRIT1	Q9H3H1	774
TRMT5	FTSJ1	Q9UET6	733
TRMT5	TRMT6	Q9UJA5	718
TRMT5	TRMT61A	Q96FX7	710
TRMT5	TRMT10B	Q6PF06	709
TRMT5	TRMT11	Q7Z4G4	693
TRMT5	TRMT10C	Q7L0Y3	684
TRMT5	ADAT3	Q96EY9	680
TRMT5	PUS1	Q9Y606	678
TRMT5	YRDC	Q86U90	666

IntAct

14 interactions, top by confidence:

A	B	Type	Score
TRMT5	PCBP3	psi-mi:“MI:0915”(physical association)	0.400
SSB	RPS3A	psi-mi:“MI:0914”(association)	0.350
SELENBP1	ZNF24	psi-mi:“MI:0914”(association)	0.350
FAHD1	VWA8	psi-mi:“MI:0914”(association)	0.350
SELENBP1	TRMT5	psi-mi:“MI:0914”(association)	0.350
MRPL49	UBA6	psi-mi:“MI:0914”(association)	0.350
VENTX	UBA6	psi-mi:“MI:0914”(association)	0.350
	VWA8	psi-mi:“MI:2364”(proximity)	0.270
HSPD1	VWA8	psi-mi:“MI:2364”(proximity)	0.270
MGST3	VWA8	psi-mi:“MI:2364”(proximity)	0.270
PDK1	VWA8	psi-mi:“MI:2364”(proximity)	0.270
TRMT61B	VWA8	psi-mi:“MI:2364”(proximity)	0.270
NPM1	SBNO1	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (51): TRMT5 (Negative Genetic), TRMT5 (Negative Genetic), TRMT5 (Proximity Label-MS), TRMT5 (Proximity Label-MS), TRMT5 (Proximity Label-MS), TRMT5 (Proximity Label-MS), TRMT5 (Proximity Label-MS), TRMT5 (Proximity Label-MS), TRMT5 (Proximity Label-MS), TRMT5 (Proximity Label-MS), TRMT5 (Proximity Label-MS), TRMT5 (Proximity Label-MS), TRMT5 (Proximity Label-MS), TRMT5 (Proximity Label-MS), TRMT5 (Proximity Label-MS)

ESM2 similar proteins: A2AV36, A2VD33, A4IG53, A4QP75, A6QQV6, B2RXZ1, B8A5G9, C5XX79, F1QCV2, F6VSS6, F6ZFR0, F7GSQ4, Q05B89, Q32P41, Q32PX9, Q3MHN8, Q3T0H0, Q4KLT3, Q4KMK0, Q4V7D6, Q5M7E3, Q5RFM7, Q5U4E8, Q5ZIB9, Q5ZKG3, Q63276, Q66KI9, Q6NS23, Q6NTR1, Q6NUA1, Q6P4Z6, Q6PCI6, Q7TS68, Q80Y81, Q8BQJ6, Q8CGS5, Q8QHA5, Q8TEA1, Q8WV93, Q922X9

Diamond homologs: A0CC46, A2E5K9, A5K6L0, A8B4Q0, A8N339, A8WHT1, B3L2G0, B5DPF1, B7FTW3, B7G5J1, B8A5G9, B8BQY5, C0H537, C4M572, C4YH95, D0NLC2, D3BT31, E0VLV0, E3KWE1, E3WPP8, F4NUJ6, F6H2F8, F6VSS6, F7A355, F7GSQ4, O58523, P38793, Q16VC0, Q32P41, Q3MHN8, Q4PHW2, Q4WX30, Q54WD6, Q58293, Q58952, Q59TN1, Q6NQ64, Q7Q5Z3, Q8IRE4, Q8SVV3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	2
Uncertain significance	145
Likely benign	86
Benign	12

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
372248	NM_020810.3(TRMT5):c.1156A>G (p.Met386Val)	Pathogenic
1878258	NM_020810.3(TRMT5):c.267_270delinsCTG (p.Ala89_Phe90insTer)	Likely pathogenic
3892730	NM_020810.3(TRMT5):c.259A>T (p.Arg87Ter)	Likely pathogenic

SpliceAI

700 predictions. Top by Δscore:

Variant	Effect	Δscore
14:60977634:CTGGC:C	acceptor_gain	1.0000
14:60977639:C:CC	acceptor_gain	1.0000
14:60975067:C:CT	donor_gain	0.9900
14:60975068:T:TT	donor_gain	0.9900
14:60977636:GGC:G	acceptor_gain	0.9900
14:60979227:GTAC:G	donor_loss	0.9900
14:60979228:TACCA:T	donor_loss	0.9900
14:60979230:C:CT	donor_loss	0.9900
14:60981025:T:TA	donor_gain	0.9900
14:60981026:C:A	donor_gain	0.9900
14:60976124:AACC:A	acceptor_loss	0.9800
14:60976125:ACCT:A	acceptor_loss	0.9800
14:60976127:C:T	acceptor_loss	0.9800
14:60976128:T:C	acceptor_loss	0.9800
14:60977511:TACCT:T	donor_loss	0.9800
14:60977635:TGGC:T	acceptor_gain	0.9800
14:60977640:T:C	acceptor_loss	0.9800
14:60979229:A:AC	donor_gain	0.9800
14:60979230:C:CC	donor_gain	0.9800
14:60979888:T:C	acceptor_gain	0.9800
14:60980954:C:CT	donor_gain	0.9700
14:60979225:ACGT:A	donor_loss	0.9600
14:60979887:C:CC	acceptor_gain	0.9600
14:60980955:C:CT	donor_gain	0.9600
14:60980980:T:TA	donor_gain	0.9600
14:60972588:T:TC	acceptor_gain	0.9500
14:60976129:G:C	acceptor_loss	0.9500
14:60977637:GC:G	acceptor_gain	0.9500
14:60977638:CC:C	acceptor_gain	0.9500
14:60979886:CCT:C	acceptor_gain	0.9500

AlphaMissense

3369 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:60979298:A:C	F200L	0.994
14:60979298:A:T	F200L	0.994
14:60979300:A:G	F200L	0.994
14:60976047:C:G	R291P	0.992
14:60976078:A:G	W281R	0.991
14:60976078:A:T	W281R	0.991
14:60979336:C:G	A188P	0.991
14:60975912:A:G	L336P	0.990
14:60979287:C:A	G204V	0.990
14:60975561:C:G	R453T	0.989
14:60975656:A:C	F421L	0.989
14:60975656:A:T	F421L	0.989
14:60975658:A:G	F421L	0.989
14:60975945:G:T	A325D	0.989
14:60976073:A:C	N282K	0.989
14:60976073:A:T	N282K	0.989
14:60977638:C:T	G223D	0.989
14:60979287:C:T	G204E	0.989
14:60979295:G:C	S201R	0.989
14:60979295:G:T	S201R	0.989
14:60979297:T:G	S201R	0.989
14:60975941:A:C	N326K	0.988
14:60975941:A:T	N326K	0.988
14:60975560:T:A	R453S	0.987
14:60975560:T:G	R453S	0.987
14:60976065:A:G	L285P	0.987
14:60979272:A:G	L209P	0.987
14:60979628:A:C	F90L	0.987
14:60979628:A:T	F90L	0.987
14:60979629:A:G	F90S	0.987

dbSNP variants (sampled 300 via entrez): RS1000353823 (14:60982994 A>G), RS1000468631 (14:60983320 A>G), RS1000478677 (14:60970960 G>T), RS1000757090 (14:60977758 G>A,C), RS1000787377 (14:60971406 G>A), RS1001040315 (14:60983392 T>C), RS1001393094 (14:60972677 T>C), RS1001471385 (14:60983144 T>C), RS1001474341 (14:60983492 T>C), RS1001530692 (14:60980359 A>T), RS1001882035 (14:60972520 G>A,T), RS1002152586 (14:60978895 C>T), RS1002439956 (14:60978522 A>G), RS1002541850 (14:60973549 G>T), RS1002546569 (14:60981298 C>G,T)

Disease associations

OMIM: gene MIM:611023 | disease phenotypes: MIM:616539

GenCC curated gene-disease

Disease	Classification	Inheritance
combined oxidative phosphorylation defect type 26	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
mitochondrial disease	Definitive	AR

Mondo (2): combined oxidative phosphorylation defect type 26 (MONDO:0014684), intellectual disability (MONDO:0001071)

Orphanet (2): Combined oxidative phosphorylation defect type 26 (Orphanet:477684), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

42 total (30 of 42 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000124	Renal tubular dysfunction
HP:0000160	Narrow mouth
HP:0000325	Triangular face
HP:0000592	Blue sclerae
HP:0000737	Irritability
HP:0001252	Hypotonia
HP:0001257	Spasticity
HP:0001263	Global developmental delay
HP:0001265	Hyporeflexia
HP:0001276	Hypertonia
HP:0001324	Muscle weakness
HP:0001337	Tremor
HP:0001347	Hyperreflexia
HP:0001394	Cirrhosis
HP:0001508	Failure to thrive
HP:0001639	Hypertrophic cardiomyopathy
HP:0001738	Exocrine pancreatic insufficiency
HP:0001952	Glucose intolerance
HP:0002017	Nausea and vomiting
HP:0002024	Malabsorption
HP:0002094	Dyspnea
HP:0002151	Increased circulating lactate concentration
HP:0002188	Delayed CNS myelination
HP:0002465	Poor speech
HP:0002875	Exertional dyspnea
HP:0003076	Glycosuria
HP:0003128	Lactic acidosis
HP:0003487	Babinski sign
HP:0003546	Exercise intolerance

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST008473_49	Visceral fat	2.000000e-06

MeSH disease descriptors (1)

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

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, decreases methylation	2
Particulate Matter	affects cotreatment, increases abundance, increases expression	2
FR900359	increases phosphorylation	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	decreases expression	1
sodium arsenite	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
erucylphospho-N,N,N-trimethylpropylammonium	decreases expression	1
Temozolomide	increases expression	1
Decitabine	affects expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	increases response to substance	1
Cisplatin	affects expression	1
Coumestrol	increases expression	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Dimethyl Sulfoxide	increases expression	1
Doxorubicin	decreases expression	1
Gasoline	increases expression, affects cotreatment, increases abundance	1
Mustard Gas	decreases expression	1
Polycyclic Aromatic Hydrocarbons	increases abundance, increases expression, affects cotreatment	1
Rotenone	decreases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Vinblastine	affects response to substance	1
Cyclosporine	increases expression	1
Aflatoxin B1	decreases methylation	1
Cadmium Chloride	decreases expression	1

Clinical trials (associated diseases)

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

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