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
• Druggable target: yes
• MANE Select transcript: NM_153712

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: 8 — 5 protein_coding, 2 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000233336, ENST00000460450, ENST00000476615, ENST00000485537, ENST00000901134, ENST00000920102, ENST00000961587, ENST00000961588

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.

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

256 total, 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

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

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

144 targeting TTL, 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-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

Cross-species orthologs

3 orthologs

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

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), 1 shown:

• 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 (41 total): strand 20, helix 14, turn 4, chain 1, domain 1, sequence conflict 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
8ASN	X-RAY DIFFRACTION	2.57

Predicted structure (AlphaFold)

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

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-8955332	Carboxyterminal post-translational modifications of tubulin

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 (6): microtubule cytoskeleton organization (GO:0000226), regulation of axon extension (GO:0030516), 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

Rollup of top-1 pathways:

Category	Pathways
Post-translational protein modification	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoskeleton organization	1
microtubule-based process	1
regulation of developmental growth	1
axon extension	1
regulation of extent of cell growth	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
nucleoside phosphate binding	1
heterocyclic compound binding	1
catalytic activity	1
spindle	1
microtubule	1
microtubule cytoskeleton	1
polymeric cytoskeletal fiber	1

Protein interactions and networks

STRING

562 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TTL	CLIP1	P30622	846
TTL	SVBP	Q8N300	775
TTL	STMN1	P16949	696
TTL	AGBL4	Q5VU57	653
TTL	AGTPBP1	Q9UPW5	650
TTL	VASH1	Q7L8A9	648
TTL	VASH2	Q86V25	607
TTL	TTLL12	Q14166	586
TTL	ATAT1	Q5SQI0	585
TTL	STMN4	Q9H169	577
TTL	AGBL5	Q8NDL9	575
TTL	TTLL4	Q14679	570
TTL	CPXM2	Q8N436	541
TTL	TUBA1B	P04687	478
TTL	TTLL5	Q6EMB2	442

IntAct

15 interactions, top by confidence:

A	B	Type	Score
RCL1	BMS1	psi-mi:“MI:0914”(association)	0.690
LCP1	PLS3	psi-mi:“MI:0914”(association)	0.640
POMC	AMD1	psi-mi:“MI:0914”(association)	0.530
MARVELD2	GAP43	psi-mi:“MI:0914”(association)	0.530
TTL	SLC2A1	psi-mi:“MI:0915”(physical association)	0.400
TSC22D4	TBL1X	psi-mi:“MI:0914”(association)	0.350
MARVELD2	RAP2A	psi-mi:“MI:0914”(association)	0.350
TUBB4B	TUBA1B	psi-mi:“MI:0914”(association)	0.350
IL17B	DCTN6	psi-mi:“MI:0914”(association)	0.350
TSC22D4	PSMA7	psi-mi:“MI:0914”(association)	0.350
SPMAP2	PRICKLE3	psi-mi:“MI:0914”(association)	0.350
TTL	CST4	psi-mi:“MI:0914”(association)	0.350

BioGRID (25): TTL (Affinity Capture-RNA), TTL (Affinity Capture-MS), TTL (Affinity Capture-MS), TTL (Affinity Capture-MS), TTL (Affinity Capture-MS), TTL (Affinity Capture-MS), TTL (Proximity Label-MS), TTL (Affinity Capture-MS), TTL (Affinity Capture-MS), TTL (Affinity Capture-MS), TTL (Affinity Capture-MS), TTL (Affinity Capture-MS), TTL (Affinity Capture-MS), CST4 (Affinity Capture-MS), TTL (Affinity Capture-MS)

ESM2 similar proteins: A0A0G2K344, A2APC3, A4Q9E4, A8X9V4, B0XDC4, G5EF51, H2KZM9, O43314, O95922, P17569, P20807, P24135, P32871, P36859, P38160, P38584, P38585, P42336, P42337, P42338, P43368, P47047, P51186, P92006, Q09647, Q0VC71, Q10438, Q16JS8, Q21279, Q23SI8, Q3SXZ7, Q3SZH6, Q4KWH5, Q4KWH8, Q564U4, Q5PPI9, Q5REW0, Q641W7, Q6DNF4, Q6PF93

Diamond homologs: A2APC3, A4Q9E4, A4Q9E5, A4Q9E8, A4Q9F0, A4Q9F1, A4Q9F4, A4Q9F6, A6NNM8, A6PVC2, A8CVX7, A8X9V4, B2GUB3, E9P886, F7E540, H2KZM9, O95922, P38160, P38584, Q09647, Q0VC71, Q14679, Q1ECV4, Q23AS2, Q23K29, Q23MT7, Q23SI8, Q3SXZ7, Q3SZH6, Q564U4, Q5PPI9, Q5R978, Q641W7, Q6EEF3, Q6EMB2, Q6ZT98, Q80UG8, Q8CHB8, Q8N841, Q8NG68

SIGNOR signaling

9 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

Clinical variants and AI predictions

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)

Variant ID	HGVS	Classification
226183	GRCh37/hg19 2q13(chr2:111186302-113273657)	Likely pathogenic

SpliceAI

1782 predictions. Top by Δscore:

Variant	Effect	Δscore
2:112482498:CTGGG:C	donor_loss	1.0000
2:112482499:TGGG:T	donor_loss	1.0000
2:112482500:GG:G	donor_gain	1.0000
2:112482500:GGGTG:G	donor_loss	1.0000
2:112482501:GG:G	donor_gain	1.0000
2:112482502:G:GG	donor_gain	1.0000
2:112482502:GTGA:G	donor_loss	1.0000
2:112482503:T:G	donor_loss	1.0000
2:112485991:GTGAA:G	donor_gain	1.0000
2:112485993:GAA:G	donor_gain	1.0000
2:112485996:G:GG	donor_gain	1.0000
2:112503113:G:GG	donor_gain	1.0000
2:112503149:T:TG	donor_gain	1.0000
2:112503150:A:AA	donor_gain	1.0000
2:112518573:GCC:G	donor_gain	1.0000
2:112520276:TCATA:T	acceptor_loss	1.0000
2:112520277:CATAG:C	acceptor_loss	1.0000
2:112520279:TAGGA:T	acceptor_loss	1.0000
2:112520280:AGGA:A	acceptor_loss	1.0000
2:112520421:GCTC:G	donor_gain	1.0000
2:112520421:GCTCA:G	donor_gain	1.0000
2:112520426:G:GG	donor_gain	1.0000
2:112482476:G:GT	donor_gain	0.9900
2:112482494:GAGAC:G	donor_gain	0.9900
2:112483075:G:GT	donor_gain	0.9900
2:112501203:TA:T	acceptor_loss	0.9900
2:112501338:TCCGG:T	donor_loss	0.9900
2:112501339:CCG:C	donor_loss	0.9900
2:112501340:CGGT:C	donor_loss	0.9900
2:112501341:GG:G	donor_loss	0.9900

AlphaMissense

2480 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:112482460:T:C	L39P	1.000
2:112482469:G:A	G42E	1.000
2:112485948:T:A	N63K	1.000
2:112485948:T:G	N63K	1.000
2:112485980:A:T	K74I	1.000
2:112485981:A:C	K74N	1.000
2:112485981:A:T	K74N	1.000
2:112494345:T:A	W147R	1.000
2:112494345:T:C	W147R	1.000
2:112494354:A:G	K150E	1.000
2:112494356:G:C	K150N	1.000
2:112494356:G:T	K150N	1.000
2:112494375:G:C	G157R	1.000
2:112501284:A:C	Q183P	1.000
2:112501325:C:A	R197S	1.000
2:112501326:G:C	R197P	1.000
2:112501328:A:G	K198E	1.000
2:112501330:G:C	K198N	1.000
2:112501330:G:T	K198N	1.000
2:112502916:T:A	W204R	1.000
2:112502916:T:C	W204R	1.000
2:112502971:G:C	R222P	1.000
2:112503032:T:A	N242K	1.000
2:112503032:T:G	N242K	1.000
2:112520353:G:A	G316D	1.000
2:112520359:A:C	D318A	1.000
2:112520359:A:T	D318V	1.000
2:112520360:C:A	D318E	1.000
2:112520360:C:G	D318E	1.000
2:112520398:A:T	E331V	1.000

dbSNP variants (sampled 300 via entrez): RS1000002196 (2:112520692 T>C,G), RS1000245041 (2:112529036 A>G), RS1000324775 (2:112514346 C>G,T), RS1000393507 (2:112490369 G>A), RS1000453765 (2:112502443 C>T), RS1000485460 (2:112524045 T>A), RS1000585796 (2:112515714 G>A), RS1000588064 (2:112516804 G>A,C), RS1000747652 (2:112503751 C>T), RS1000800061 (2:112510772 C>T), RS1000820381 (2:112509670 G>A,C,T), RS1000959318 (2:112493269 G>A), RS1000965063 (2:112492070 T>A), RS1000999740 (2:112535645 A>G), RS1001047933 (2:112515978 A>C)

Disease associations

OMIM: gene MIM:608291 | disease phenotypes:

GenCC curated gene-disease

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

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

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

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 (VIP=true, CPIC=false)

Binding affinities (BindingDB)

5 measured of 6 human assays (6 total across all organisms); most potent 5 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
(2S)-2-amino-3-(4-hydroxyphenyl)propanoic acid	KI	25000 nM
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)

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

Trial	Phase	Status	Title
NCT00879060	PHASE4	COMPLETED	Clinical and Therapeutic Implications of Fibrosis in Hypertrophic Cardiomyopathy
NCT01721967	PHASE4	COMPLETED	Ranolazine for the Treatment of Chest Pain in HCM Patients
NCT02948998	PHASE4	UNKNOWN	Evaluating the Effect of Spironolactone on Hypertrophic Cardiomyopathy
NCT03249272	PHASE4	TERMINATED	Microvascular Dysfunction in Nonischemic Cardiomyopathy: Insights From CMR Assessment of Coronary Flow Reserve
NCT04133532	PHASE4	COMPLETED	Effect of Metoprolol in Post Alcohol Septal Ablation Patients With Hypertrophic Cardiomyopathy
NCT06401343	PHASE4	RECRUITING	Use of SGLT2i in noHCM With HFpEF
NCT07103655	PHASE4	NOT_YET_RECRUITING	The Therapeutic Value of Mavacamten in Hypertrophic Cardiomyopathy With Mid-to-Apical Left Ventricular Obstruction
NCT07600177	PHASE4	RECRUITING	Mavacamten to Aficamten Transition in Patients With Obstructive Hypertrophic Cardiomyopathy
NCT00317967	PHASE3	COMPLETED	Study to Determine if Atorvastatin Reduces Size and Stiffness of Muscle in the Left Ventricle of the Heart
NCT00698074	PHASE3	UNKNOWN	Diastolic Ventricular Interaction and the Effects of Biventricular Pacing in Hypertrophic Cardiomyopathy
NCT00821353	PHASE3	COMPLETED	Antiarrhythmic Therapy Versus Catheter Ablation for Atrial Fibrillation in Hypertrophic Cardiomyopathy
NCT02431221	PHASE3	WITHDRAWN	Efficacy, Safety, and Tolerability of Perhexiline in Subjects With Hypertrophic Cardiomyopathy and Heart Failure
NCT03470545	PHASE3	COMPLETED	Clinical Study to Evaluate Mavacamten (MYK-461) in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy
NCT05174416	PHASE3	COMPLETED	A Study to Evaluate the Efficacy and Safety of Mavacamten in Chinese Adults With Symptomatic Obstructive HCM
NCT05182658	PHASE3	ACTIVE_NOT_RECRUITING	Empagliflozin in Hypertrophic Cardiomyopathy
NCT05186818	PHASE3	COMPLETED	Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Placebo in Adults With Symptomatic oHCM
NCT05767346	PHASE3	COMPLETED	Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Metoprolol Succinate in Adults With Symptomatic oHCM
NCT06116968	PHASE3	COMPLETED	An Open-Label Study of Aficamten for Chinese Patients With Symptomatic oHCM
NCT06873828	PHASE3	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	PHASE3	RECRUITING	A Phase III Trial of HRS-1893 in Patients With Obstructive Hypertrophic Cardiomyopathy
NCT07023341	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Learn More About How Well Aficamten Works in Japanese Participants With Symptomatic Obstructive Hypertrophic Cardiomyopathy
NCT07202897	PHASE3	NOT_YET_RECRUITING	LA-HCM Study : Rivaroxaban for Antithrombotic Prevention in Hypertrophic Cardiomyopathy Patients With Abnormal Left Atrial Strain.
NCT00001631	PHASE2	COMPLETED	Study of Blood Flow in Heart Muscle
NCT00001894	PHASE2	COMPLETED	A Comparison of Two Treatments: Pacemaker and Percutaneous Transluminal Septal Ablation for Hypertrophic Cardiomyopathy
NCT00001960	PHASE2	COMPLETED	Studying the Effectiveness of Pacemaker Therapy in Children Who Have Thickened Heart Muscle
NCT00011076	PHASE2	COMPLETED	Pirfenidone to Treat Hypertrophic Cardiomyopathy
NCT00035386	PHASE2	COMPLETED	Alcohol Septal Ablation in Obstructive Hypertrophic Cardiomyopathy: A Pilot Study
NCT00430833	PHASE2	UNKNOWN	CHANCE - Candesartan in Hypertrophic Cardiomyopathy
NCT00500552	PHASE2	COMPLETED	Perhexiline Therapy in Patients With Hypertrophic Cardiomyopathy
NCT01150461	PHASE2	COMPLETED	Effect of Losartan in Patients With Nonobstructive Hypertrophic Cardiomyopathy
NCT01230918	PHASE2	TERMINATED	Study to Develop a Non-invasive Marker for Monitoring Myocardial Fibrosis
NCT01447654	PHASE2	COMPLETED	Inhibition of the Renin Angiotensin System With Losartan in Patients With Hypertrophic Cardiomyopathy
NCT01696370	PHASE2	UNKNOWN	Trimetazidine Therapy in Hypertrophic Cardiomyopathy
NCT01912534	PHASE2	COMPLETED	Valsartan for Attenuating Disease Evolution In Early Sarcomeric HCM
NCT02590809	PHASE2	COMPLETED	Hypertrophic Cardiomyopathy Symptom Release by BX1514M
NCT03496168	PHASE2	COMPLETED	Extension Study of Mavacamten (MYK-461) in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy Previously Enrolled in PIONEER
NCT03532802	PHASE2	COMPLETED	The Effect of Metoprolol in Patients With Hypertrophic Obstructive Cardiomyopathy.
NCT03832660	PHASE2	COMPLETED	Sacubitril/Valsartan vs Lifestyle in Hypertrophic Cardiomyopathy
NCT04219826	PHASE2	COMPLETED	Dose-finding Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of CK-3773274 in Adults With Hypertrophic Cardiomyopathy
NCT04426578	PHASE2	UNKNOWN	Role of Perhexiline in Hypertrophic Cardiomyopathy