TTL

Summary

TTL (tubulin tyrosine ligase, HGNC:21586) is a protein-coding gene on chromosome 2q14.1, encoding Tubulin–tyrosine ligase (Q8NG68). Catalyzes the post-translational addition of a tyrosine to the C-terminal end of detyrosinated alpha-tubulin.

TTL is a cytosolic enzyme involved in the posttranslational modification of alpha-tubulin (see MIM 602529). Alpha-tubulin within assembled microtubules is detyrosinated over time at the C terminus. After microtubule disassembly, TTL restores the tyrosine residues and consequently participates in a cycle of tubulin detyrosination and tyrosination (Erck et al., 2003 [PubMed 14571137]).

Source: NCBI Gene 150465 — RefSeq curated summary.

At a glance

• Gene–disease (curated): complex neurodevelopmental disorder (Moderate, GenCC) — +1 more curated relationship
• Clinical variants (ClinVar): 51 total — 1 likely-pathogenic
• GTEx eGene: eQTL in 25 tissues, sQTL in 14 (q < 0.05)
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.42 (moderately constrained)
• MANE Select transcript: NM_153712
• Notable: 51 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21586
Approved symbol	TTL
Name	tubulin tyrosine ligase
Location	2q14.1
Locus type	gene with protein product
Status	Approved
Aliases	MGC46235
Ensembl gene	ENSG00000114999
Ensembl biotype	protein_coding
OMIM	608291
Entrez	150465

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 11 protein_coding, 9 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined, 1 retained_intron

MANE Select: ENST00000233336

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 1, TSL 3: 2

ENST00000233336, ENST00000460450, ENST00000476615, ENST00000485537, ENST00000901134, ENST00000920102, ENST00000961587, ENST00000961588, ENST00001014341, ENST00001014342, ENST00001014343, ENST00001014344, ENST00001014345, ENST00001014346, ENST00001068540, ENST00001127858, ENST00001127859, ENST00001127860, ENST00001127861, ENST00001127862, ENST00001127863, ENST00001127864, ENST00001142757

RefSeq mRNA: 2 — MANE Select: NM_153712 NM_001371712, NM_153712

CCDS: CCDS2096

Canonical transcript exons

ENST00000233336 — 7 exons

Exon	Start	End
ENSE00000773823	112501206	112501341
ENSE00001128757	112520282	112520425
ENSE00001181380	112494143	112494375
ENSE00001181382	112485917	112485995
ENSE00001249738	112482156	112482501
ENSE00001366598	112528681	112541739
ENSE00003583817	112502912	112503181

Expression profiles

Bgee: expression breadth ubiquitous, 255 present calls, max score 96.82.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.0598 / max 135.6369, expressed in 1812 samples.

Highest expression (Bgee): dorsal root ganglion, cortical plate, ventricle myocardium, trigeminal ganglion, ganglionic eminence.

Genetic regulation across tissues (GTEx eQTL / sQTL)

TTL is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 25 tissues and its splicing (sQTL) in 14 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 39 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Skin Sun Exposed Lower leg	eqtl	2.8e-23	-0.32	2:112513832:C:A
Skin Not Sun Exposed Suprapubic	eqtl	1.0e-17	-0.26	2:112497637:T:G
Muscle Skeletal	eqtl	1.6e-15	-0.19	2:112482606:T:C
Cells Cultured fibroblasts	sqtl	8.5e-12	-0.53	2:112520372:T:C
Muscle Skeletal	sqtl	6.4e-11	-0.58	2:112520372:T:C
Esophagus Muscularis	sqtl	8.5e-09	-0.48	2:112536721:C:T
Heart Atrial Appendage	eqtl	1.7e-08	-0.23	2:112482606:T:C
Esophagus Gastroesophageal Junction	eqtl	4.4e-08	-0.22	2:112501339:C:T
Nerve Tibial	eqtl	1.0e-07	-0.70	2:112526988:G:T
Esophagus Muscularis	eqtl	3.3e-07	-0.19	2:112513832:C:A
Heart Left Ventricle	eqtl	1.5e-06	-0.17	2:112476739:C:T
Brain Spinal cord cervical c-1	eqtl	3.9e-05	-0.23	2:112520613:T:TTGTA
Brain Caudate basal ganglia	eqtl	6.6e-05	+0.16	2:112526767:T:A
Brain Cortex	sqtl	8.5e-05	-0.63	2:112520734:C:A
Thyroid	sqtl	8.7e-05	-0.36	2:112536721:C:T
Brain Hippocampus	eqtl	9.0e-05	+0.18	2:112564323:T:C
Brain Putamen basal ganglia	eqtl	9.3e-05	-0.19	2:112495675:G:A
Thyroid	eqtl	1.3e-04	-0.17	2:112531455:A:G
Artery Tibial	eqtl	4.8e-04	-0.10	2:112513832:C:A
Colon Transverse	eqtl	1.1e-03	-0.14	2:112476739:C:T

FANTOM5 promoters

5 alternative TSS:

Promoter ID	TPM avg	Samples expressed
21982	14.4992	1805
21983	3.2875	1519
21981	1.9987	1281
202348	0.2529	90
21984	0.0216	7

Top tissues by expression

showing 100 of 256 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
dorsal root ganglion	UBERON:0000044	96.82	gold quality
cortical plate	UBERON:0005343	95.69	gold quality
left ventricle myocardium	UBERON:0006566	95.50	gold quality
trigeminal ganglion	UBERON:0001675	94.93	gold quality
ganglionic eminence	UBERON:0004023	94.49	gold quality
medial globus pallidus	UBERON:0002477	94.41	gold quality
globus pallidus	UBERON:0001875	93.46	gold quality
middle temporal gyrus	UBERON:0002771	93.41	gold quality
ventricular zone	UBERON:0003053	92.97	gold quality
deltoid	UBERON:0001476	92.89	gold quality
cardiac muscle of right atrium	UBERON:0003379	92.51	silver quality
tendon of biceps brachii	UBERON:0008188	92.42	gold quality
vastus lateralis	UBERON:0001379	92.26	gold quality
tibialis anterior	UBERON:0001385	92.26	silver quality
quadriceps femoris	UBERON:0001377	92.24	gold quality
Brodmann (1909) area 46	UBERON:0006483	92.16	gold quality
gastrocnemius	UBERON:0001388	92.03	gold quality
upper arm skin	UBERON:0004263	91.96	gold quality
muscle of leg	UBERON:0001383	91.80	gold quality
body of tongue	UBERON:0011876	91.55	gold quality
stromal cell of endometrium	CL:0002255	91.45	gold quality
prefrontal cortex	UBERON:0000451	91.35	gold quality
skeletal muscle tissue	UBERON:0001134	91.25	gold quality
corpus callosum	UBERON:0002336	91.19	gold quality
putamen	UBERON:0001874	91.04	gold quality
cartilage tissue	UBERON:0002418	91.02	gold quality
muscle tissue	UBERON:0002385	90.63	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	90.15	gold quality
superior vestibular nucleus	UBERON:0007227	90.08	gold quality
myocardium	UBERON:0002349	90.04	gold quality
biceps brachii	UBERON:0001507	89.95	gold quality
frontal cortex	UBERON:0001870	89.92	gold quality
secondary oocyte	CL:0000655	89.80	gold quality
tongue	UBERON:0001723	89.70	gold quality
Ammon’s horn	UBERON:0001954	89.67	gold quality
amygdala	UBERON:0001876	89.61	gold quality
caudate nucleus	UBERON:0001873	89.57	gold quality
hindlimb stylopod muscle	UBERON:0004252	89.57	gold quality
neocortex	UBERON:0001950	89.51	gold quality
medulla oblongata	UBERON:0001896	89.48	gold quality
temporal lobe	UBERON:0001871	89.46	gold quality
cerebral cortex	UBERON:0000956	89.43	gold quality
Brodmann (1909) area 23	UBERON:0013554	89.34	gold quality
dorsal plus ventral thalamus	UBERON:0001897	89.23	gold quality
lateral globus pallidus	UBERON:0002476	89.11	gold quality
nucleus accumbens	UBERON:0001882	89.09	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	88.92	gold quality
gingival epithelium	UBERON:0001949	88.82	gold quality
superior frontal gyrus	UBERON:0002661	88.76	gold quality
inferior vagus X ganglion	UBERON:0005363	88.75	gold quality
parietal lobe	UBERON:0001872	88.58	gold quality
entorhinal cortex	UBERON:0002728	88.54	gold quality
visceral pleura	UBERON:0002401	88.37	gold quality
occipital lobe	UBERON:0002021	88.34	gold quality
substantia nigra	UBERON:0002038	88.26	gold quality
saphenous vein	UBERON:0007318	88.26	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	88.20	gold quality
forebrain	UBERON:0001890	88.19	gold quality
midbrain	UBERON:0001891	88.08	gold quality
right frontal lobe	UBERON:0002810	88.06	gold quality
gingiva	UBERON:0001828	88.01	gold quality
epithelial cell of pancreas	CL:0000083	88.00	gold quality
substantia nigra pars reticulata	UBERON:0001966	87.99	gold quality
islet of Langerhans	UBERON:0000006	87.93	gold quality
postcentral gyrus	UBERON:0002581	87.87	gold quality
parietal pleura	UBERON:0002400	87.74	gold quality
subthalamic nucleus	UBERON:0001906	87.68	gold quality
superior surface of tongue	UBERON:0007371	87.67	gold quality
anterior cingulate cortex	UBERON:0009835	87.65	gold quality
synovial joint	UBERON:0002217	87.63	gold quality
substantia nigra pars compacta	UBERON:0001965	87.59	gold quality
cardiac ventricle	UBERON:0002082	87.49	gold quality
heart left ventricle	UBERON:0002084	87.46	gold quality
layer of synovial tissue	UBERON:0007616	87.45	gold quality
Brodmann (1909) area 9	UBERON:0013540	87.41	gold quality
heart right ventricle	UBERON:0002080	87.38	gold quality
primary visual cortex	UBERON:0002436	87.34	gold quality
brain	UBERON:0000955	87.30	gold quality
monocyte	CL:0000576	87.28	gold quality
ventral tegmental area	UBERON:0002691	87.16	gold quality
leukocyte	CL:0000738	86.99	gold quality
lateral nuclear group of thalamus	UBERON:0002736	86.88	gold quality
pharyngeal mucosa	UBERON:0000355	86.80	gold quality
heart	UBERON:0000948	86.69	gold quality
tendon	UBERON:0000043	86.54	gold quality
kidney epithelium	UBERON:0004819	86.54	silver quality
thymus	UBERON:0002370	86.11	gold quality
skin of hip	UBERON:0001554	86.08	gold quality
smooth muscle tissue	UBERON:0001135	86.02	gold quality
apex of heart	UBERON:0002098	86.01	gold quality
germinal epithelium of ovary	UBERON:0001304	85.92	gold quality
hypothalamus	UBERON:0001898	85.84	gold quality
lung	UBERON:0002048	85.72	gold quality
right lung	UBERON:0002167	85.47	gold quality
cardiac atrium	UBERON:0002081	85.46	gold quality
upper lobe of lung	UBERON:0008948	85.40	gold quality
upper lobe of left lung	UBERON:0008952	85.39	gold quality
esophagus squamous epithelium	UBERON:0006920	85.30	gold quality
right coronary artery	UBERON:0001625	85.15	gold quality
endometrium	UBERON:0001295	85.11	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.40
E-MTAB-6911	no	119.84
E-GEOD-76312	no	97.53

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 70 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Cerebral cortex	tissue	42.5
Somatosensory cortex	tissue	42.5
Occipital cortex	tissue	41.3
Frontal cortex	tissue	38.0
Basal ganglia	tissue	37.4
Caudate putamen	tissue	37.4
Retrosplenial and cingulate cortex	tissue	31.5
Ventral forebrain	tissue	29.5
Amygdala	tissue	28.0
Entorhinal cortex	tissue	27.5
Hippocampal formation	tissue	22.6
Corpus callosum	tissue	17.8
Pons	tissue	17.3
Thalamus	tissue	16.5
Septum	tissue	16.2
Midbrain	tissue	16.1
Hypothalamus	tissue	15.6
Olfactory bulb	tissue	14.9
Cerebellum	tissue	13.3
Putamen	tissue	13.0
Postcentral gyrus	tissue	12.6
Nucleus accumbens	tissue	12.1
Retrosplenial cortex	tissue	12.0
Hippocampus	tissue	11.0
Substantia nigra	tissue	10.9
Medulla oblongata	tissue	10.8
Locus coeruleus	tissue	10.7
Spinal cord	tissue	9.4
Choroid plexus	tissue	7.8
Skeletal muscle	tissue	3.5
Tongue	tissue	3.5
Bone marrow	tissue	1.6
Heart muscle	tissue	1.5
Skin 1	tissue	1.3
Lung	tissue	1.3
Retina	tissue	1.2
Smooth muscle	tissue	1.2
Placenta	tissue	1.1
Esophagus	tissue	1.0
Gallbladder	tissue	1.0
Lymph node	tissue	0.9
Adipose tissue	tissue	0.9
Urinary bladder	tissue	0.9
Endometrium 1	tissue	0.9
Thymus	tissue	0.9
Appendix	tissue	0.9
Parathyroid gland	tissue	0.8
Epididymis	tissue	0.8
Thyroid gland	tissue	0.8
Spleen	tissue	0.8
Rectum	tissue	0.7
Pancreas	tissue	0.7
Kidney	tissue	0.7
Adrenal gland	tissue	0.7
Tonsil	tissue	0.7
Seminal vesicle	tissue	0.6
Colon	tissue	0.6
Small intestine	tissue	0.6
Duodenum	tissue	0.6
Cervix	tissue	0.5

Brain sub-regions (HPA Brain Atlas): detected in 185; highest nTPM — White matter (17.8), Temporal white matter (14.4), Somatosensory cortex, postcentral gyrus, ventral (white matter) (13.7), Claustrum (13.4), Area striata (white matter) (13.3).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting TTL by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 144 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-12136	99.98	72.81	5713
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-4725-3P	99.96	69.53	2520

Functional genomics

gnomAD constraint: pLI 0.999, LOEUF 0.423, missense Z 1.78 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000233336 — one region, missense o/e 0.80.

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	ttl	ENSDARG00000062418
mus_musculus	Ttl	ENSMUSG00000027394
rattus_norvegicus	Ttl	ENSRNOG00000018205

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1916987) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 12 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal telencephalon development	1
ataxia	1
decreased exploration in new environment	1
edema	1
abnormal breathing pattern	1
abnormal forebrain development	1
abnormal bone structure	1
absent brain internal capsule	1
abnormal neuron differentiation	1
neonatal lethality, complete penetrance	1
preweaning lethality, complete penetrance	1
disorganized cerebral cortex lamination	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Bos taurus	Q0VC71	97.2%	Diamond
Pongo abelii	Q5R978	96.8%	Diamond
Chlorocebus aethiops	Q6EEF3	94.1%	Diamond
Sus scrofa	P38160	93.1%	Diamond
Xenopus tropicalis	B2GUB3	58.6%	Diamond
Tetrahymena thermophila SB210	Q23K29	47.8%	Diamond
Schizosaccharomyces pombe 972h-	Q10438	46.9%	Diamond
Drosophila melanogaster	Q9VM91	37.0%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
POLR1B	protein-coding	84172
CHCHD5	protein-coding	84269
RGPD8	protein-coding	727851
ZC3H6	protein-coding	376940

Protein

Protein identifiers

Tubulin–tyrosine ligase — Q8NG68 (reviewed: Q8NG68)

All UniProt accessions (1): Q8NG68

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the post-translational addition of a tyrosine to the C-terminal end of detyrosinated alpha-tubulin.

Subunit / interactions. Monomer.

Similarity. Belongs to the tubulin–tyrosine ligase family.

RefSeq proteins (2): NP_001358641, NP_714923* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004344	TTL/TTLL_fam	Family
IPR052492	Tubulin-tyrosine_ligase	Family

Pfam: PF03133

Enzyme classification (BRENDA)

• EC 6.3.2.25 — tubulin-tyrosine ligase (BRENDA: 11 organisms, 35 substrates, 25 inhibitors, 12 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

9 substrates with measured Km, best-characterized 9. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
L-TYR	0.017–0.045	3
L-PHE	0.432–2.9	2
ALPHA-TUBULIN	0.002	1
ATP	0.014	1
L-DOPA	0.186	1
L-HYDROXYPHENYLALANINE	0.16	1
L-TYROSINE	0.0068	1
TYRAMINE	8	1
UNTYROSINATED TUBULIN	0.0019	1

Catalyzed reactions (Rhea)

• C-terminal L-alpha-aminoacyl-L-glutamyl-L-glutamyl-[tubulin] + L-tyrosine + ATP = C-terminal L-alpha-aminoacyl-L-glutamyl-L-glutamyl-L-tyrosyl-[tubulin] + ADP + phosphate + H(+) (RHEA:17605)

UniProt features (42 total): strand 20, helix 15, turn 4, chain 1, domain 1, sequence conflict 1

Structure

Experimental structures (PDB)

1 structures by resolution:

PDB	Title	Method	Resolution (Å)
8ASN	Crystal structure of the apo human TTL in complex with tubulin-stathmin	X-RAY DIFFRACTION	2.57

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NG68-F1	93.13	0.85

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Ligase, Metabolic proteins, Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): vesicles; nucleoplasm

Antibody reliability (HPA): IF approved

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 3; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

3 pathways:

ID	Pathway	Evidence
R-HSA-8955332	Carboxyterminal post-translational modifications of tubulin	electronic
R-HSA-392499	Metabolism of proteins	—
R-HSA-597592	Post-translational protein modification	—

MSigDB gene sets: 184 (showing top): FXR_IR1_Q6, GCM_MAP4K4, GCM_PTPRD, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_NEURON_PROJECTION_EXTENSION, RORA1_01, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH, GOBP_CHROMOSOME_LOCALIZATION, GOBP_POSITIVE_REGULATION_OF_MITOTIC_CELL_CYCLE, GOBP_GROWTH, GOBP_NEUROGENESIS, TGACCTY_ERR1_Q2, GTGCCTT_MIR506, WEI_MYCN_TARGETS_WITH_E_BOX, GOBP_REGULATION_OF_ANATOMICAL_STRUCTURE_SIZE

GO Biological Process (5): microtubule cytoskeleton organization (GO:0000226), post-translational protein modification (GO:0043687), positive regulation of mitotic cell cycle (GO:0045931), regulation of metaphase plate congression (GO:0090235), protein modification process (GO:0036211)

GO Molecular Function (4): tubulin-tyrosine ligase activity (GO:0004835), ATP binding (GO:0005524), nucleotide binding (GO:0000166), ligase activity (GO:0016874)

GO Cellular Component (2): spindle microtubule (GO:0005876), microtubule (GO:0005874)

Reactome top-level categories

2 top-level categories:

Category	Pathways
Post-translational protein modification	1
Metabolism of proteins	1

GO top-level categories

22 GO namespaces:

Category	Terms
cytoskeleton organization	1
microtubule-based process	1
protein modification process	1
mitotic cell cycle	1
regulation of mitotic cell cycle	1
positive regulation of cell cycle	1
regulation of localization	1
metaphase chromosome alignment	1
protein metabolic process	1
macromolecule modification	1
acid-amino acid ligase activity	1
catalytic activity, acting on a protein	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
anion binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
catalytic activity	1
spindle	1
microtubule	1
microtubule cytoskeleton	1
polymeric cytoskeletal fiber	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 5 of 11 annotations. The rest are phylogenetic / computational / electronic (IEA).

5 experimentally-supported GO terms:

GO term	NS	Evidence
positive regulation of mitotic cell cycle	BP	mutant phenotype
post-translational protein modification	BP	mutant phenotype
regulation of metaphase plate congression	BP	mutant phenotype
spindle microtubule	CC	direct assay
tubulin-tyrosine ligase activity	MF	mutant phenotype

Protein interactions and networks

STRING

showing 15 of 480 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TTL	CLIP1	P30622	850
TTL	SVBP	Q8N300	836
TTL	VASH1	Q7L8A9	742
TTL	VASH2	Q86V25	711
TTL	TTLL12	Q14166	656
TTL	AGBL4	Q5VU57	614
TTL	AGTPBP1	Q9UPW5	610
TTL	ATAT1	Q5SQI0	609
TTL	AGBL5	Q8NDL9	585
TTL	TTLL5	Q6EMB2	536
TTL	TTLL4	Q14679	498
TTL	CPXM2	Q8N436	497
TTL	CCSAP	Q6IQ19	477
TTL	CCDC81	Q6ZN84	456
TTL	ZNF142	P52746	444

IntAct

Human interaction partners of TTL in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

2 partners by confidence:

Partner	Interaction type	MIscore	Records
SLC2A1	physical association	0.400	1
CST4	association	0.350	1

BioGRID (25 interactions; top human partners by supporting records): TSC22D4 (Affinity Capture-MS; 3 records), LCP1 (Affinity Capture-MS; 2 records), MARVELD2 (Affinity Capture-MS; 2 records), POMC (Affinity Capture-MS; 2 records), ALOX15B (Co-fractionation), AMY1C (Affinity Capture-MS), CST4 (Affinity Capture-MS), ELAVL1 (Affinity Capture-RNA), GNA11 (Co-fractionation), IL17B (Affinity Capture-MS), NUDT21 (Affinity Capture-RNA), NXF1 (Affinity Capture-RNA), RCL1 (Affinity Capture-MS), RPA1 (Proximity Label-MS), RPA2 (Proximity Label-MS)

SIGNOR signaling

9 signaling interactions:

A	Effect	B	Mechanism
TTL	down-regulates	TUBA1A	tyrosination
TTL	down-regulates	TUBA1B	tyrosination
TTL	down-regulates	TUBA1C	tyrosination
TTL	down-regulates	“TUBAC Family”	tyrosination
TTL	down-regulates	TUBA3E	tyrosination
TTL	down-regulates	TUBA4A	tyrosination
TTL	down-regulates	TUBA8	tyrosination
STMN1	down-regulates	TTL	binding
TTL	down-regulates	Tubulin	tyrosination

Disease & clinical

Genetic variants

Variant evidence for TTL: 51 ClinVar records (1 pathogenic / likely pathogenic). Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	32
Likely benign	1
Benign	4

Top pathogenic / likely-pathogenic (1)

Showing all 1 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
226183	GRCh37/hg19 2q13(chr2:111186302-113273657)	Likely pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore TTL’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 36 predictions of 961):

Position(s)	Effect	Δscore	Sites
2:112482502–112482503	donor_loss	1.0000	5
2:112520280–112520281	acceptor_loss	1.0000	6
2:112482503	donor_loss	0.9900
2:112501204–112501205	acceptor_loss	0.9900	6
2:112501342–112501344	donor_loss	0.9900	8
2:112503068	donor_gain	0.9900
2:112503145	donor_gain	0.9900
2:112483075	donor_gain	0.9800
2:112483087	donor_gain	0.9800
2:112485996–112485997	donor_loss	0.9800	6

AlphaMissense

1,190 missense substitutions predicted likely pathogenic (of 2,480 scored), across 255 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
D200	8	0.999	0.999
D318	8	0.999	1.000
N242	8	0.996	1.000
N333	8	0.991	0.999
N63	8	0.985	1.000
H239	8	0.984	0.998
F199	8	0.975	0.999
H243	8	0.975	0.997
N260	8	0.971	0.998
F312	8	0.970	0.998
D126	8	0.954	0.992
F37	8	0.948	0.999
F49	8	0.944	0.999
D208	8	0.943	0.996
F317	8	0.942	0.998
F319	8	0.937	0.998
F131	8	0.935	0.998
D8	8	0.934	0.986
F315	8	0.931	0.997
F359	8	0.923	0.995

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Disease associations

OMIM: gene MIM:608291 | disease phenotypes:

GenCC curated gene-disease

2 curated gene-disease records:

Disease	Classification	Inheritance	Records
complex neurodevelopmental disorder	Moderate	Autosomal recessive
hypertrophic cardiomyopathy	Limited	Autosomal dominant

Mondo (2): hypertrophic cardiomyopathy (MONDO:0005045), complex neurodevelopmental disorder (MONDO:0100038)

MeSH disease descriptors

1 disease descriptors:

Descriptor	Name	Tree numbers
D002312	Cardiomyopathy, Hypertrophic	C14.280.238.100; C14.280.484.048.750.070.160

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5549 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

22 measured of 24 human assays (24 total across all organisms); most potent 22 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
6alpha,8alpha-dihydroxy-23-carbossi-labd-13(14),17-dien-16,19-olide	KD	7 nM
6alpha,8alpha,23-trihydroxy-labd-13(14),17-dien-16(R),19-olide	KD	72 nM
8alpha-hydroxy,23alpha-O-ethyl-23,6alpha-epoxy-labd-13(14),17-dien-16(R),19-olide	KD	73 nM
6alpha,8alpha-dihydroxy-23-carbossi-labd-13(14),15,17-trien-16,19-olide	KD	93 nM
6alpha,8alpha,23-trihydroxy-labd-13(14),15,17-trien-16,19-olide	KD	110 nM
8alpha-hydroxylabd-13(14),15,17-trien-6alpha,23-16,19-diolide	KD	150 nM
6alpha,8alpha-dihydroxy-23-oxo-13(14),15,17-trien-16,19-olide	KD	200 nM
8alpha-23-dihydroxy-23,6alpha-epoxy-labd-13(14),15,17-trien-16,19-olide	KD	480 nM
6alpha,8alpha-dihydroxy-23-oxo-labd-13(14),17-dien-16(R),19-olide	KD	810 nM
8alpha,15(S)-dihydroxy,23alpha-O-ethyl-23,6alpha-epoxy-labd-13(14),17-dien-16(S),19-olide	KD	960 nM
6alpha,15(S),23-trihydroxy-labd-8(22),13(14),17-trien-16(S),19-olide	KD	2000 nM
6alpha,8alpha,15(S)-trihydroxy-23-oxo-labd-13(14),17-dien-16(S),19-olide	KD	3000 nM
6alpha,8alpha,15(S)-trihydroxy-23-carbossi-labd-13(14),17-dien-16(S),19-olide	KD	3000 nM
6alpha,15(S)-dihydroxy-23-oxo-labd-8(22),13(14),17-trien-16(S),19-olide	KD	3300 nM
6alpha,8alpha,15(S),23-tetrahydroxy-labd-13(14),17-dien-16(S),19-olide	KD	4700 nM
6alpha,8alpha,15(S)-trihydroxy-23-carbossimethyllabd-13(14),17-dien-16(S),19-olide	KD	6200 nM
23,6alpha-epoxy-labd-8,13(14),17-trien-16(R),19-olide	KD	8700 nM
(2S)-2-amino-3-(4-hydroxyphenyl)propanoic acid	IC50	100000 nM	US-20240415800
3-Aminotyrosine	KI	200000 nM
3-Azidotyrosine	KI	200000 nM
3-Formyltyrosine	KI	300000 nM
3-Nitrotyrosine	KI	400000 nM

ChEMBL bioactivities

17 potent at pChembl≥5 of 17 total, top 17 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.15	Kd	7	nM	CHEMBL525164
7.14	Kd	72	nM	CHEMBL497827
7.14	Kd	73	nM	CHEMBL483883
7.03	Kd	93	nM	CHEMBL496193
6.96	Kd	110	nM	CHEMBL524070
6.82	Kd	150	nM	CHEMBL496195
6.70	Kd	200	nM	CHEMBL496194
6.32	Kd	480	nM	CHEMBL495805
6.09	Kd	810	nM	CHEMBL497036
6.02	Kd	960	nM	CHEMBL519500
5.70	Kd	2000	nM	CHEMBL523078
5.52	Kd	3000	nM	CHEMBL497233
5.52	Kd	3000	nM	CHEMBL497633
5.48	Kd	3300	nM	CHEMBL497037
5.33	Kd	4700	nM	CHEMBL484080
5.21	Kd	6200	nM	CHEMBL497636
5.06	Kd	8700	nM	CHEMBL496050

PubChem BioAssay actives

17 with measured affinity, of 31 total; 17 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
(1R,4aS,5R,6R,8S,8aR)-6,8-dihydroxy-1,4a,6-trimethyl-5-[(E)-3-methyl-5-(3-methyl-5-oxo-2H-furan-2-yl)pent-3-enyl]-3,4,5,7,8,8a-hexahydro-2H-naphthalene-1-carboxylic acid	371851: Binding affinity to TTL by surface plasmon resonance	kd	0.0070	uM
(2R)-2-[(E)-5-[(1R,2R,4S,4aR,5R,8aS)-2,4-dihydroxy-5-(hydroxymethyl)-2,5,8a-trimethyl-3,4,4a,6,7,8-hexahydro-1H-naphthalen-1-yl]-3-methylpent-2-enyl]-3-methyl-2H-furan-5-one	371851: Binding affinity to TTL by surface plasmon resonance	kd	0.0720	uM
(2R)-2-[(E)-5-[(1S,3S,4R,8S,9R,10R,12R)-3-ethoxy-10-hydroxy-4,8,10-trimethyl-2-oxatricyclo[6.3.1.04,12]dodecan-9-yl]-3-methylpent-2-enyl]-3-methyl-2H-furan-5-one	371851: Binding affinity to TTL by surface plasmon resonance	kd	0.0730	uM
(1R,4aS,5R,6R,8S,8aR)-6,8-dihydroxy-1,4a,6-trimethyl-5-[(E,5Z)-3-methyl-5-(3-methyl-5-oxofuran-2-ylidene)pent-3-enyl]-3,4,5,7,8,8a-hexahydro-2H-naphthalene-1-carboxylic acid	371851: Binding affinity to TTL by surface plasmon resonance	kd	0.0930	uM
(5Z)-5-[(E)-5-[(1R,2R,4S,4aR,5R,8aS)-2,4-dihydroxy-5-(hydroxymethyl)-2,5,8a-trimethyl-3,4,4a,6,7,8-hexahydro-1H-naphthalen-1-yl]-3-methylpent-2-enylidene]-4-methylfuran-2-one	371851: Binding affinity to TTL by surface plasmon resonance	kd	0.1100	uM
(1S,4R,8S,9R,10R,12R)-10-hydroxy-4,8,10-trimethyl-9-[(E,5Z)-3-methyl-5-(3-methyl-5-oxofuran-2-ylidene)pent-3-enyl]-2-oxatricyclo[6.3.1.04,12]dodecan-3-one	371851: Binding affinity to TTL by surface plasmon resonance	kd	0.1500	uM
(1R,4aS,5R,6R,8S,8aR)-6,8-dihydroxy-1,4a,6-trimethyl-5-[(E,5Z)-3-methyl-5-(3-methyl-5-oxofuran-2-ylidene)pent-3-enyl]-3,4,5,7,8,8a-hexahydro-2H-naphthalene-1-carbaldehyde	371851: Binding affinity to TTL by surface plasmon resonance	kd	0.2000	uM
(5Z)-5-[(E)-5-[(1S,4R,8S,9R,10R,12R)-3,10-dihydroxy-4,8,10-trimethyl-2-oxatricyclo[6.3.1.04,12]dodecan-9-yl]-3-methylpent-2-enylidene]-4-methylfuran-2-one	371851: Binding affinity to TTL by surface plasmon resonance	kd	0.4800	uM
(1R,4aS,5R,6R,8S,8aR)-6,8-dihydroxy-1,4a,6-trimethyl-5-[(E)-3-methyl-5-[(2R)-3-methyl-5-oxo-2H-furan-2-yl]pent-3-enyl]-3,4,5,7,8,8a-hexahydro-2H-naphthalene-1-carbaldehyde	371851: Binding affinity to TTL by surface plasmon resonance	kd	0.8100	uM
(2S)-2-[(E,1S)-5-[(1S,3S,4R,8S,9R,10R,12R)-3-ethoxy-10-hydroxy-4,8,10-trimethyl-2-oxatricyclo[6.3.1.04,12]dodecan-9-yl]-1-hydroxy-3-methylpent-2-enyl]-3-methyl-2H-furan-5-one	371851: Binding affinity to TTL by surface plasmon resonance	kd	0.9600	uM
(2S)-2-[(E,1S)-5-[(1S,4S,4aR,5R,8aR)-4-hydroxy-5-(hydroxymethyl)-5,8a-dimethyl-2-methylidene-3,4,4a,6,7,8-hexahydro-1H-naphthalen-1-yl]-1-hydroxy-3-methylpent-2-enyl]-3-methyl-2H-furan-5-one	371851: Binding affinity to TTL by surface plasmon resonance	kd	2.0000	uM
(1R,4aS,5R,6R,8S,8aR)-6,8-dihydroxy-5-[(E,5S)-5-hydroxy-3-methyl-5-[(2S)-3-methyl-5-oxo-2H-furan-2-yl]pent-3-enyl]-1,4a,6-trimethyl-3,4,5,7,8,8a-hexahydro-2H-naphthalene-1-carboxylic acid	371851: Binding affinity to TTL by surface plasmon resonance	kd	3.0000	uM
(1R,4aS,5R,6R,8S,8aR)-6,8-dihydroxy-5-[(E,5S)-5-hydroxy-3-methyl-5-[(2S)-3-methyl-5-oxo-2H-furan-2-yl]pent-3-enyl]-1,4a,6-trimethyl-3,4,5,7,8,8a-hexahydro-2H-naphthalene-1-carbaldehyde	371851: Binding affinity to TTL by surface plasmon resonance	kd	3.0000	uM
(1R,4aR,5S,8S,8aR)-8-hydroxy-5-[(E,5S)-5-hydroxy-3-methyl-5-[(2S)-3-methyl-5-oxo-2H-furan-2-yl]pent-3-enyl]-1,4a-dimethyl-6-methylidene-3,4,5,7,8,8a-hexahydro-2H-naphthalene-1-carbaldehyde	371851: Binding affinity to TTL by surface plasmon resonance	kd	3.3000	uM
(2S)-2-[(E,1S)-5-[(1R,2R,4S,4aR,5R,8aS)-2,4-dihydroxy-5-(hydroxymethyl)-2,5,8a-trimethyl-3,4,4a,6,7,8-hexahydro-1H-naphthalen-1-yl]-1-hydroxy-3-methylpent-2-enyl]-3-methyl-2H-furan-5-one	371851: Binding affinity to TTL by surface plasmon resonance	kd	4.7000	uM
methyl (1R,4aS,5R,6R,8S,8aR)-6,8-dihydroxy-5-[(E,5S)-5-hydroxy-3-methyl-5-[(2S)-3-methyl-5-oxo-2H-furan-2-yl]pent-3-enyl]-1,4a,6-trimethyl-3,4,5,7,8,8a-hexahydro-2H-naphthalene-1-carboxylate	371851: Binding affinity to TTL by surface plasmon resonance	kd	6.2000	uM
(2R)-2-[(E)-5-[(1S,4R,8R,9S,12R)-4,8-dimethyl-10-methylidene-2-oxatricyclo[6.3.1.04,12]dodecan-9-yl]-3-methylpent-2-enyl]-3-methyl-2H-furan-5-one	371851: Binding affinity to TTL by surface plasmon resonance	kd	8.7000	uM

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Acetaminophen	increases expression	3
Benzo(a)pyrene	affects methylation, increases expression	3
bisphenol F	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects expression	1
cobaltous chloride	decreases expression	1
perfluorooctanoic acid	decreases expression	1
2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine	increases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
2-palmitoylglycerol	increases expression	1
perfluorohexanesulfonic acid	decreases expression	1
ICG 001	increases expression	1
abrine	decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Bortezomib	decreases expression	1
Diazinon	increases methylation	1
Doxorubicin	decreases expression	1
Estradiol	affects expression	1
Lead	affects splicing	1
Smoke	decreases expression	1
Tretinoin	decreases expression	1
Valproic Acid	increases expression	1
Okadaic Acid	increases expression	1
Copper Sulfate	increases expression	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2406639	Binding	Inhibition of TTL (unknown origin)	Phosphinic acid-based inhibitors of tubulin polyglutamylases. — *Bioorg Med Chem Lett*

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E0SF	Ubigene HeLa TTL KO	Cancer cell line	Female
CVCL_XU82	HAP1 TTL (-)	Cancer cell line	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 235 trials:

NCT	Phase	Status	Title
NCT00879060	Phase 4	COMPLETED	Clinical and Therapeutic Implications of Fibrosis in Hypertrophic Cardiomyopathy
NCT01721967	Phase 4	COMPLETED	Ranolazine for the Treatment of Chest Pain in HCM Patients
NCT02948998	Phase 4	UNKNOWN	Evaluating the Effect of Spironolactone on Hypertrophic Cardiomyopathy
NCT03249272	Phase 4	TERMINATED	Microvascular Dysfunction in Nonischemic Cardiomyopathy: Insights From CMR Assessment of Coronary Flow Reserve
NCT04133532	Phase 4	COMPLETED	Effect of Metoprolol in Post Alcohol Septal Ablation Patients With Hypertrophic Cardiomyopathy
NCT06401343	Phase 4	UNKNOWN	Use of SGLT2i in noHCM With HFpEF
NCT07103655	Phase 4	ENROLLING_BY_INVITATION	The Therapeutic Value of Mavacamten in Hypertrophic Cardiomyopathy With Mid-to-Apical Left Ventricular Obstruction
NCT07600177	Phase 4	RECRUITING	Mavacamten to Aficamten Transition in Patients With Obstructive Hypertrophic Cardiomyopathy
NCT07807384	Phase 4	NOT_YET_RECRUITING	Efficacy and Safety of an LVEF-Guided Mavacamten Dose Up-Titration Strategy in Chinese Patients With Symptomatic Obstructive Hypertrophic Cardiomyopathy
NCT00317967	Phase 3	COMPLETED	Study to Determine if Atorvastatin Reduces Size and Stiffness of Muscle in the Left Ventricle of the Heart
NCT00698074	Phase 3	UNKNOWN	Diastolic Ventricular Interaction and the Effects of Biventricular Pacing in Hypertrophic Cardiomyopathy
NCT00821353	Phase 3	COMPLETED	Antiarrhythmic Therapy Versus Catheter Ablation for Atrial Fibrillation in Hypertrophic Cardiomyopathy
NCT02431221	Phase 3	WITHDRAWN	Efficacy, Safety, and Tolerability of Perhexiline in Subjects With Hypertrophic Cardiomyopathy and Heart Failure
NCT03470545	Phase 3	COMPLETED	Clinical Study to Evaluate Mavacamten (MYK-461) in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy
NCT05174416	Phase 3	COMPLETED	A Study to Evaluate the Efficacy and Safety of Mavacamten in Chinese Adults With Symptomatic Obstructive HCM
NCT05182658	Phase 3	ACTIVE_NOT_RECRUITING	Empagliflozin in Hypertrophic Cardiomyopathy
NCT05186818	Phase 3	COMPLETED	Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Placebo in Adults With Symptomatic oHCM
NCT05767346	Phase 3	COMPLETED	Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Metoprolol Succinate in Adults With Symptomatic oHCM
NCT06116968	Phase 3	COMPLETED	An Open-Label Study of Aficamten for Chinese Patients With Symptomatic oHCM
NCT06873828	Phase 3	NOT_YET_RECRUITING	Evaluation of the Efficacy and Safety of Wearable ECG (AT-Patch) in Patients With Hypertrophic Cardiomyopathy Requiring 48-Hour Holter MonitoringEvaluation of the Efficacy and Safety of Wearable ECG (AT-Patch) in Patients With Hypertrophic Cardiomyopathy Requiring 48-Hour Holter Monitoring
NCT07021976	Phase 3	ACTIVE_NOT_RECRUITING	A Phase III Trial of HRS-1893 in Patients With Obstructive Hypertrophic Cardiomyopathy
NCT07023341	Phase 3	ACTIVE_NOT_RECRUITING	A Study to Learn More About How Well Aficamten Works in Japanese Participants With Symptomatic Obstructive Hypertrophic Cardiomyopathy
NCT07202897	Phase 3	RECRUITING	LA-HCM Study : Rivaroxaban for Antithrombotic Prevention in Hypertrophic Cardiomyopathy Patients With Abnormal Left Atrial Strain.
NCT00001631	Phase 2	COMPLETED	Study of Blood Flow in Heart Muscle
NCT00001894	Phase 2	COMPLETED	A Comparison of Two Treatments: Pacemaker and Percutaneous Transluminal Septal Ablation for Hypertrophic Cardiomyopathy
NCT00001960	Phase 2	COMPLETED	Studying the Effectiveness of Pacemaker Therapy in Children Who Have Thickened Heart Muscle
NCT00011076	Phase 2	COMPLETED	Pirfenidone to Treat Hypertrophic Cardiomyopathy
NCT00035386	Phase 2	COMPLETED	Alcohol Septal Ablation in Obstructive Hypertrophic Cardiomyopathy: A Pilot Study
NCT00430833	Phase 2	UNKNOWN	CHANCE - Candesartan in Hypertrophic Cardiomyopathy
NCT00500552	Phase 2	COMPLETED	Perhexiline Therapy in Patients With Hypertrophic Cardiomyopathy
NCT01150461	Phase 2	COMPLETED	Effect of Losartan in Patients With Nonobstructive Hypertrophic Cardiomyopathy
NCT01230918	Phase 2	TERMINATED	Study to Develop a Non-invasive Marker for Monitoring Myocardial Fibrosis
NCT01447654	Phase 2	COMPLETED	Inhibition of the Renin Angiotensin System With Losartan in Patients With Hypertrophic Cardiomyopathy
NCT01696370	Phase 2	UNKNOWN	Trimetazidine Therapy in Hypertrophic Cardiomyopathy
NCT01912534	Phase 2	COMPLETED	Valsartan for Attenuating Disease Evolution In Early Sarcomeric HCM
NCT02590809	Phase 2	COMPLETED	Hypertrophic Cardiomyopathy Symptom Release by BX1514M
NCT03496168	Phase 2	COMPLETED	Extension Study of Mavacamten (MYK-461) in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy Previously Enrolled in PIONEER
NCT03532802	Phase 2	COMPLETED	The Effect of Metoprolol in Patients With Hypertrophic Obstructive Cardiomyopathy.
NCT03832660	Phase 2	COMPLETED	Sacubitril/Valsartan vs Lifestyle in Hypertrophic Cardiomyopathy
NCT04219826	Phase 2	COMPLETED	Dose-finding Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of CK-3773274 in Adults With Hypertrophic Cardiomyopathy
NCT04426578	Phase 2	UNKNOWN	Role of Perhexiline in Hypertrophic Cardiomyopathy
NCT04706429	Phase 2	COMPLETED	The Efficacy and Mechanism of Trientine in Patients With Hypertrophic Cardiomyopathy
NCT06347159	Phase 2	ACTIVE_NOT_RECRUITING	A Study of EDG-7500 in Adults With Hypertrophic Cardiomyopathy (CIRRUS-HCM)
NCT06516068	Phase 2	ACTIVE_NOT_RECRUITING	A Trial of HRS-1893 in Patients With Obstructive Hypertrophic Cardiomyopathy
NCT07021963	Phase 2	RECRUITING	A Clinical Study to Evaluate the Long-term Safety of HRS-1893 in Hypertrophic Cardiomyopathy
NCT07367724	Phase 2	RECRUITING	Ademetionine in Obstructive Hypertrophic Cardiomyopathy
NCT07675668	Phase 2	NOT_YET_RECRUITING	Aom0304 in Adult Patients With Symptomatic Hypertrophic Cardiomyopathy
NCT00001396	Phase 1	COMPLETED	Natural History and Results of Dual Chamber (DDD) Pacemaker Therapy of Children With Obstructive Hypertrophic Cardiomyop…
NCT00504647	Phase 1	UNKNOWN	Biventricular Pacing in Hypertrophic Cardiomyopathy
NCT01537926	Phase 1	COMPLETED	Hypertrophic Regression With N-Acetylcysteine in HCM
NCT02329184	Phase 1	COMPLETED	Study Evaluating the Safety, Tolerability and Preliminary Pharmacokinetics and Pharmacodynamics of MYK-461
NCT04783766	Phase 1	COMPLETED	Safety, Tolerability and Pharmacokinetics Study of CK-3773274
NCT05135871	Phase 1	COMPLETED	Study Evaluating the Pharmacokinetics of Mavacamten in Healthy Adult Chinese Subjects
NCT05879523	Phase 1	COMPLETED	A Trial of HRS-1893 in Healthy Volunteers and Patients With Obstructive Hypertrophic Cardiomyopathy
NCT06210607	Phase 1	UNKNOWN	A Trial of HS-10511 in Healthy Subjects
NCT06354556	Phase 1	COMPLETED	Effect of Verapamil Tablets on the Pharmacokinetic of HRS-1893 Tablets in Healthy Subjects
NCT06775834	Phase 1	COMPLETED	Safety and Pharmacokinetics Study of HRS-1893 Tablets in Healthy Subjects and Those With Impaired Kidney Function
NCT00319982	Phase 2/3	COMPLETED	Treatment of Preclinical Hypertrophic Cardiomyopathy With Diltiazem
NCT02291237	Phase 2/3	TERMINATED	Effect of Eleclazine (GS-6615) on Exercise Capacity in Subjects With Symptomatic Hypertrophic Cardiomyopathy
NCT03723655	Phase 2/3	COMPLETED	A Long-Term Safety Extension Study of Mavacamten in Adults Who Have Completed MAVERICK-HCM or EXPLORER-HCM

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for TTL across ~30M SureChEMBL compounds — explore on Sugi Predict.