TAFAZZIN

Summary

TAFAZZIN (tafazzin, phospholipid-lysophospholipid transacylase, HGNC:11577) is a protein-coding gene on chromosome Xq28, encoding Tafazzin (Q16635). Acyltransferase required to remodel newly synthesized phospholipid cardiolipin (1’,3’-bis-[1,2-diacyl-sn-glycero-3-phospho]-glycerol or CL), a key component of the mitochondrial inner membrane, with tissue specific acyl chains necessary for adequate mitochondrial function. It is a selective cancer dependency (DepMap: 33.9% of cell lines).

This gene encodes a protein that is expressed at high levels in cardiac and skeletal muscle. Mutations in this gene have been associated with a number of clinical disorders including Barth syndrome, dilated cardiomyopathy (DCM), hypertrophic DCM, endocardial fibroelastosis, and left ventricular noncompaction (LVNC). Multiple transcript variants encoding different isoforms have been described. A long form and a short form of each of these isoforms is produced; the short form lacks a hydrophobic leader sequence and may exist as a cytoplasmic protein rather than being membrane-bound. Other alternatively spliced transcripts have been described but the full-length nature of all these transcripts is not known.

Source: NCBI Gene 6901 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Barth syndrome (Definitive, ClinGen)
• Clinical variants (ClinVar): 567 total — 47 pathogenic, 43 likely-pathogenic
• Phenotypes (HPO): 49
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 33.9% of screened cell lines
• MANE Select transcript: NM_000116

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11577
Approved symbol	TAFAZZIN
Name	tafazzin, phospholipid-lysophospholipid transacylase
Location	Xq28
Locus type	gene with protein product
Status	Approved
Aliases	BTHS, G4.5, TAZ1
Ensembl gene	ENSG00000102125
Ensembl biotype	protein_coding
OMIM	300394
Entrez	6901

Gene structure

Transcript identifiers

Ensembl transcripts: 39 — 19 retained_intron, 15 protein_coding, 5 nonsense_mediated_decay

ENST00000369776, ENST00000426231, ENST00000439735, ENST00000470127, ENST00000475699, ENST00000476679, ENST00000476800, ENST00000479875, ENST00000483674, ENST00000483780, ENST00000494912, ENST00000498029, ENST00000601016, ENST00000612012, ENST00000612460, ENST00000613002, ENST00000613634, ENST00000614595, ENST00000615658, ENST00000615986, ENST00000616020, ENST00000617701, ENST00000620808, ENST00000621647, ENST00000651139, ENST00000652354, ENST00000652358, ENST00000652390, ENST00000652476, ENST00000652644, ENST00000652682, ENST00000652685, ENST00000698234, ENST00000698235, ENST00000698317, ENST00000698318, ENST00000698319, ENST00000698320, ENST00000965099

RefSeq mRNA: 6 — MANE Select: NM_000116 NM_000116, NM_001303465, NM_001410698, NM_181311, NM_181312, NM_181313

CCDS: CCDS14748, CCDS14749, CCDS14750, CCDS35450, CCDS94701, CCDS94702

Canonical transcript exons

ENST00000601016 — 11 exons

Exon	Start	End
ENSE00003017673	154413482	154413567
ENSE00003022330	154411539	154411952
ENSE00003050674	154414101	154414190
ENSE00003127263	154412086	154412214
ENSE00003154518	154419543	154419623
ENSE00003158525	154419705	154419746
ENSE00003627163	154420903	154421726
ENSE00003724812	154420212	154420264
ENSE00003736420	154413207	154413252
ENSE00003736683	154420658	154420735
ENSE00003787276	154420032	154420094

Expression profiles

Bgee: expression breadth ubiquitous, 238 present calls, max score 97.10.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 16.5869 / max 146.6726, expressed in 1803 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
198153	16.4428	1803
198154	0.1440	75

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	97.10	gold quality
granulocyte	CL:0000094	96.07	gold quality
lower esophagus mucosa	UBERON:0035834	95.83	gold quality
right hemisphere of cerebellum	UBERON:0014890	95.16	gold quality
right atrium auricular region	UBERON:0006631	95.03	gold quality
right lobe of thyroid gland	UBERON:0001119	94.73	gold quality
cerebellar hemisphere	UBERON:0002245	94.59	gold quality
spleen	UBERON:0002106	94.37	gold quality
cerebellar cortex	UBERON:0002129	94.32	gold quality
mucosa of transverse colon	UBERON:0004991	94.28	gold quality
left lobe of thyroid gland	UBERON:0001120	94.19	gold quality
tibial nerve	UBERON:0001323	94.01	gold quality
small intestine Peyer’s patch	UBERON:0003454	93.99	gold quality
endocervix	UBERON:0000458	93.98	gold quality
metanephros cortex	UBERON:0010533	93.86	gold quality
ectocervix	UBERON:0012249	93.68	gold quality
right lung	UBERON:0002167	93.60	gold quality
right ovary	UBERON:0002118	93.49	gold quality
body of uterus	UBERON:0009853	93.37	gold quality
cardiac atrium	UBERON:0002081	93.26	gold quality
heart left ventricle	UBERON:0002084	93.23	gold quality
left ovary	UBERON:0002119	93.23	gold quality
upper lobe of left lung	UBERON:0008952	93.22	gold quality
adenohypophysis	UBERON:0002196	93.20	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	93.20	gold quality
mucosa of stomach	UBERON:0001199	93.14	gold quality
hindlimb stylopod muscle	UBERON:0004252	93.14	gold quality
left uterine tube	UBERON:0001303	93.09	gold quality
skin of abdomen	UBERON:0001416	92.99	gold quality
right frontal lobe	UBERON:0002810	92.98	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.16
E-MTAB-6142	no	91.35

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOXC1, PPARG, RELA, RUNX2, SSRP1, TTF1

miRNA regulators (miRDB)

35 targeting TAFAZZIN, 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-4692	100.00	67.32	2066
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-6752-3P	99.72	66.71	1587
HSA-MIR-670-5P	99.67	69.94	1565
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-2392	99.43	67.50	708
HSA-MIR-125A-5P	99.36	70.59	1640
HSA-MIR-125B-5P	99.36	70.36	1662
HSA-MIR-6731-5P	99.28	67.42	2375
HSA-MIR-8085	99.28	67.56	2362
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-4667-3P	99.26	65.45	1608
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-544B	99.18	67.41	1632
HSA-MIR-4434	99.10	67.01	1984
HSA-MIR-5703	99.10	67.09	2053
HSA-MIR-455-3P	98.94	67.68	878
HSA-MIR-3190-5P	98.87	64.89	1345
HSA-MIR-548S	98.50	67.17	1213
HSA-MIR-1910-3P	98.44	67.51	1695
HSA-MIR-1233-5P	98.19	66.71	1201
HSA-MIR-6778-5P	98.19	66.59	1239
HSA-MIR-6511A-5P	98.13	67.47	1770

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 33.9% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• Mutations in the Xq28 gene G4.5 lead to dilated cardiomyopathy associated with ultrastructural changes in mitochodria of heart, liver and skeletal muscle. (PMID:11896212)
• one splice variant of TAZ most likely represents the only physiologically important mRNA, at least with regard to cardiolipin metabolism (PMID:12930833)
• human TAZ has a role in mitochondrial dysfunction in Barth syndrome (PMID:15304507)
• Motif, critical for the glycerolphosphate acyltransferase family, was observed in human tafazzin. The presence of a mutation in this region in Barth syndrome patients indicates that this motif is essential for tafazzin function. (PMID:15499385)
• Data show that the tafazzin 1 interactome defined here provides novel insight into the variable respiratory defects and morphological abnormalities observed in mitochondria of BTHS patients. (PMID:18799610)
• A 5.5-month old boy with Barth’s syndrome phenotype had a novel missense T43P mutation in exon 2 of the TAZ gene. His mother was heterozygous for this mutation. (PMID:19261493)
• the characteristic fatty acid profile of cardiolipin is not determined by the substrate specificity of tafazzin (PMID:19700766)
• A novel, hemizygous nonsense mutation in TAZ exon 7 (c.583G>T, p.Gly195X) was detected in an infant with Barth syndrome with dilated cardiomyopathy and heart failure and in his great-uncle with left ventricular noncompaction. (PMID:23031367)
• Tafazzin activity is critical for the differentiation of cardiomyocytes. (Review) (PMID:23200781)
• The identification of TAZ mutation has major impact on their medical care as the surveillance needs to be expanded to cover for the Barth syndrome, a severe metabolic phenotype also caused by TAZ mutation, in addition to DCM. (PMID:23345479)
• data suggest that genes other than G4.5 are responsible for the familial form of noncompaction of the ventricular myocardium (PMID:23359024)
• study reports five new TAZ gene mutations in six unrelated Barth Syndrome patients, including two new gross gene rearrangements (PMID:23409742)
• The underlying molecular defects in Barth syndrome are truncation, deletion or substitution mutations in the TAZ gene, resulting in loss-of-function of tafazzin. Review. (PMID:23432031)
• Basal levels of superoxide anion production were slightly higher in patients’ cells than in control cells as previously evidenced via an increased protein carbonylation in the taz1Delta mutant in the yeast. (PMID:23523468)
• Three novel hemizygous mutations in the TAZ gene were found (c.584G>T; c.109+6T>C; c.86G>A). We conclude that Barth syndrome should be included in differential diagnosis of cardiomyopathy in childhood. (PMID:24093814)
• Results show that in both healthy controls and in Barth syndrome patients, a greater variety of alternatively spliced forms than previously described was found. It includes a sizeable proportion of minor splice variants besides the four dominant isoforms. (PMID:24342716)
• Strong expression of TAZ protein seems to be related to rectal cancer development and RT response, it can be a predictive biomarker of distant recurrence in patients with preoperative RT. (PMID:24858921)
• mitochondria-targeted antioxidant prevents cardiac dysfunction induced by tafazzin gene knockdown in cardiac myocytes (PMID:25247053)
• novel mutation in exon 1 of the TAZ gene and female mosaicism in three generations of a Polish family with Barth syndrome (PMID:25776009)
• two novel and non-identical TAZ gene rearrangements were found in the offspring of a single female carrier of Barth syndrome. (PMID:25782672)
• Tafazzin deficiency in mouse embryonic fibroblasts also led to impaired oxidative phosphorylation and severe oxidative stress (PMID:25919711)
• ability of CL-ND to elicit a physiological response was examined in an HL60 cell culture model of Barth Syndrome neutropenia. siRNA knockdown of the phospholipid transacylase, tafazzin (TAZ), induced apoptosis in these cells (PMID:26164234)
• TAZ mutation-confirmed diagnosis of Barth syndrome (BTHS) was available for 39/42 of the participants. Of 39 patients, 13 have a missense mutation, 6 have a nonsense mutation, 8 have a splicing mutation, 6 have a small out-of-frame insertion or deletion, 2 have a small in-frame insertion, and 4 have a large deletion encompassing several exons (PMID:26845103)
• Molecular analysis of at risk female family members identified the patient’s sister and mother as heterozygous carriers. Apparently harmless synonymous variants in the TAZ gene can damage gene expression. Such findings widen our knowledge of molecular heterogeneity in Barth syndrome. (PMID:26853223)
• TAZ mutation is associated with Barth syndrome. (PMID:26908608)
• This is the first report of systematic mutation screening of TAZ in a large cohort of pediatric patients with primary cardiomyopathy using the NGS approach. TAZ mutations were found in 4/114 (3.5%) male patients with primary cardiomyopathy. Our findings indicate that the inclusion of TAZ gene testing in cardiomyopathy genetic testing panels may contribute to the early diagnosis of BTHS. (PMID:28183324)
• TAZ is overexpressed in cervical cancer and may promote tumorigenicity of cervical cancer cells and inhibit apoptosis. (PMID:28489874)
• intrinsic mitochondrial localization sequences in the human TAZ protein, were identified. (PMID:29129703)
• Report left ventricular non-compaction associated with Barth Syndrome due to triple mutations in TAZ, DTNA, and SDHA genes in multiple members of one family. (PMID:29508483)
• we show that TAZ is abundant in human aRMS tumor samples, and that TAZ suppression decreases proliferation, promotes differentiation, and inhibits cancer cell stemness. TAZ-deficient aRMS cells are also enriched in G2-M, suggesting that TAZ may be important for G2-M cell-cycle progression. (PMID:29514840)
• Impact of Tafazzin Variants on Dilated Cardiomyopathy Phenotype in Left Ventricular Non-Compaction Patients in Early Infancy. (PMID:30122738)
• We report a novel TAZ gene mutation in male and female siblings with left ventricular noncompaction and hypotonia. Additionally, the brother presented an intermittent neutropenia and increased urinary levels of 3-methylglutaconic and 3-methylglutaric acid. The molecular genetic testing showed that both siblings carry the mutation: c.253insC, p.(Arg85Profs*54) in exon 3 of the TAZ gene. Normal karyotype female. (PMID:30226969)
• Study characterized structural and metabolic adaptations in Barth syndrome patients primary skin fibroblasts and provided novel insights into the molecular details of supercomplex destabilization, aberrant cristae morphology and metabolic changes resulting from TAZ mutations. (PMID:30251684)
• Tafazzin deficiency is associated with defective remodeling of the mitochondrial phospholipid cardiolipin causing cardiomyopathy in Barth syndrome. (PMID:30332638)
• This study demonstrated that overexpression of TAZ caused by downregulation of miR-125b promoted resistance of glioma cells to TRAIL. MiR-125b/TAZ axis may represent a potential strategy to reverse the TRAIL in glioma. (PMID:31056533)
• Truncated TEAD-binding protein of TAZ inhibits glioma survival through the induction of apoptosis and repression of epithelial-mesenchymal transition. (PMID:31209945)
• This is the first case of the association of Barth syndrome with cystic fibrosis. Pedigree analysis revealed similar sudden infant deaths in close relatives. Further analysis revealed that the patient had exon 1 mutation c51.G> C (p.Trp17X); TAZ gene mutation was also detected in our patient as previously described in his cousin. (PMID:31559736)
• Barth syndrome due to the c.481G>A mutation of the TAZ gene probably underlies the recurrent hydrops fetalis and fetal dilated cardiomyopathy in this family. (PMID:31598953)
• Delayed appearance of 3-methylglutaconic aciduria in neonates with early onset metabolic cardiomyopathies: A potential pitfall for the diagnosis. (PMID:31729175)
• The Function of Tafazzin, a Mitochondrial Phospholipid-Lysophospholipid Acyltransferase. (PMID:32234310)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	tafazzin	ENSDARG00000041421
mus_musculus	Tafazzin	ENSMUSG00000009995
rattus_norvegicus	Tafazzin	ENSRNOG00000053023
drosophila_melanogaster	Taz	FBGN0026619
caenorhabditis_elegans		WBGENE00006491

Protein

Protein identifiers

Tafazzin — Q16635 (reviewed: Q16635)

Alternative names: Protein G4.5

All UniProt accessions (18): Q16635, A0A087WWD5, A0A0S2Z4E6, A0A0S2Z4F4, A0A0S2Z4K0, A0A0S2Z4K9, A0A494C004, A0A494C0C5, A0A494C0D2, A0A494C0V5, A0A494C141, A0A494C1B0, A0A494C1C6, A0A499FJ53, A6XNE1, C9J699, F6Y2X3, H7C2I9

UniProt curated annotations — full annotation on UniProt →

Function. Acyltransferase required to remodel newly synthesized phospholipid cardiolipin (1’,3’-bis-[1,2-diacyl-sn-glycero-3-phospho]-glycerol or CL), a key component of the mitochondrial inner membrane, with tissue specific acyl chains necessary for adequate mitochondrial function. Its role in cellular physiology is to improve mitochondrial performance. CL is critical for the coassembly of lipids and proteins in mitochondrial membranes, for instance, remodeling of the acyl groups of CL in the mitochondrial inner membrane affects the assembly and stability of respiratory chain complex IV and its supercomplex forms. Catalyzes the transacylation between phospholipids and lysophospholipids, with the highest rate being between phosphatidylcholine (1,2-diacyl-sn-glycero-3-phosphocholine or PC) and CL. Catalyzes both 1-acyl-sn-glycero-3-phosphocholine (lysophosphatidylcholine or LPC) reacylation and PC-CL transacylation, that means, it exchanges acyl groups between CL and PC by a combination of forward and reverse transacylations. Also catalyzes transacylations between other phospholipids such as phosphatidylethanolamine (1,2-diacyl-sn-glycero-3-phosphoethanolamine or PE) and CL, between PC and PE, and between PC and phosphatidate (1,2-diacyl-sn-glycero-3-phosphate or PA), although at lower rate. Not regiospecific, it transfers acyl groups into any of the sn-1 and sn-2 positions of the monolysocardiolipin (MLCL), which is an important prerequisite for uniformity and symmetry in CL acyl distribution. Cannot transacylate dilysocardiolipin (DLCL), thus, the role of MLCL is limited to that of an acyl acceptor. CoA-independent, it can reshuffle molecular species within a single phospholipid class. Redistributes fatty acids between MLCL, CL, and other lipids, which prolongs the half-life of CL. Its action is completely reversible, which allows for cyclic changes, such as fission and fusion or bending and flattening of the membrane. Hence, by contributing to the flexibility of the lipid composition, it plays an important role in the dynamics of mitochondria membranes. Essential for the final stage of spermatogenesis, spermatid individualization. Required for the initiation of mitophagy. Required to ensure progression of spermatocytes through meiosis. Exon 7 of human tafazzin is essential for catalysis. Catalyzes the transacylation between lysophosphatidate (such as 1-acyl-sn-glycero-3-phosphate) and phosphatidylglycerol (1,2-diacyl-sn-glycero-3-phospho-(1’-sn-glycerol)). Contributes to cardiolipin (1’,3’-bis-[1,2-diacyl-sn-glycero-3-phospho]-glycerol or CL) remodeling. Catalyzes the transacylation between lysophospholipids and phospholipids, and plays a fundamental role in cardiolipin (1’,3’-bis-[1,2-diacyl-sn-glycero-3-phospho]-glycerol or CL) metabolism and remodeling. Catalytically inactive. Catalytically inactive.

Subunit / interactions. Associates with multiple protein complexes.

Subcellular location. Mitochondrion outer membrane. Mitochondrion inner membrane Mitochondrion membrane Cytoplasm Mitochondrion membrane Mitochondrion membrane Cytoplasm Mitochondrion membrane Cytoplasm Cytoplasm.

Tissue specificity. High levels in cardiac and skeletal muscle. Up to 10 isoforms can be present in different amounts in different tissues. Most isoforms are ubiquitous. Isoforms that lack the N-terminus are found in leukocytes and fibroblasts, but not in heart and skeletal muscle. Some forms appear restricted to cardiac and skeletal muscle or to leukocytes.

Disease relevance. Barth syndrome (BTHS) [MIM:302060] An X-linked disease characterized by dilated cardiomyopathy with endocardial fibroelastosis, a predominantly proximal skeletal myopathy, growth retardation, neutropenia, and organic aciduria, particularly excess of 3-methylglutaconic acid. Additional features include hypertrophic cardiomyopathy, isolated left ventricular non-compaction, ventricular arrhythmia, motor delay, poor appetite, fatigue and exercise intolerance, hypoglycemia, lactic acidosis, hyperammonemia, and dramatic late catch-up growth after growth delay throughout childhood. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The HXXXXD motif is essential for acyltransferase activity.

Pathway. Phospholipid metabolism.

Miscellaneous. The enzyme was named after a masochistic character Tafazzi, once popular on Italian television, apparently due to the difficulty encountered for its identification and characterization.

Similarity. Belongs to the taffazin family.

Isoforms (9)

UniProt ID	Names	Canonical?
Q16635-3	3, Del_exon_5, TAZ-delta5, Exon-5-deleted	yes
Q16635-1	1, TAZ-FL, Full-length
Q16635-2	2, Short
Q16635-4	4, Del_exon_6
Q16635-5	5, Del_exon_7, TAZ-delta7, Exon-7-deleted
Q16635-6	6
Q16635-7	7, TAZ-delta5-delta7, Exons-5+7-deleted
Q16635-8	8
Q16635-9	9

RefSeq proteins (6): NP_000107, NP_001290394, NP_001397627, NP_851828, NP_851829, NP_851830 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000872	Tafazzin	Family
IPR002123	Plipid/glycerol_acylTrfase	Domain

Pfam: PF01553

Catalyzed reactions (Rhea), 5 shown:

• 1’-[1,2-diacyl-sn-glycero-3-phospho],3’-[1-acyl-sn-glycero-3-phospho]-glycerol + a 1,2-diacyl-sn-glycero-3-phosphocholine = a cardiolipin + a 1-acyl-sn-glycero-3-phosphocholine (RHEA:33731)
• 1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine + 1-hexadecanoyl-sn-glycero-3-phosphocholine = 1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine + 1-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine (RHEA:43816)
• a 1-acyl-sn-glycero-3-phosphate + a 1,2-diacyl-sn-glycero-3-phospho-(1’-sn-glycerol) = 1-acyl-sn-glycero-3-phospho-(1’-sn-glycerol) + a 1,2-diacyl-sn-glycero-3-phosphate (RHEA:67748)
• 1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phospho-(1’-sn-glycerol) + 1-(9Z-octadecenoyl)-sn-glycero-3-phosphate = 1-(9Z)-octadecenoyl-2-(9Z,12Z)-octadecadienoyl-sn-glycero-3-phosphate + 1-hexadecanoyl-sn-glycero-3-phospho-(1’-sn-glycerol) (RHEA:67752)
• 1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine + 1-hexadecanoyl-sn-glycero-3-phosphocholine = 2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine + 1,2-dihexadecanoyl-sn-glycero-3-phosphocholine (RHEA:68988)

UniProt features (22 total): sequence variant 11, splice variant 4, topological domain 2, region of interest 2, chain 1, intramembrane region 1, short sequence motif 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q16635-F1	94.87	0.91

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-1268020	Mitochondrial protein import
R-HSA-1482798	Acyl chain remodeling of CL
R-HSA-1430728	Metabolism
R-HSA-1483206	Glycerophospholipid biosynthesis
R-HSA-1483257	Phospholipid metabolism
R-HSA-556833	Metabolism of lipids
R-HSA-9609507	Protein localization

MSigDB gene sets: 322 (showing top): CREL_01, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GCANCTGNY_MYOD_Q6, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, TGACCTY_ERR1_Q2, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, FOXO1_01, MODULE_308, GGGTGGRR_PAX4_03, GOBP_PHOSPHATIDYLGLYCEROL_METABOLIC_PROCESS, CAGCTG_AP4_Q5, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_REGULATION_OF_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_CRISTAE_FORMATION, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS

GO Biological Process (7): inner mitochondrial membrane organization (GO:0007007), cardiolipin acyl-chain remodeling (GO:0035965), cristae formation (GO:0042407), positive regulation of cardiolipin metabolic process (GO:1900210), positive regulation of ATP biosynthetic process (GO:2001171), lipid metabolic process (GO:0006629), phospholipid metabolic process (GO:0006644)

GO Molecular Function (6): 1-acylglycerol-3-phosphate O-acyltransferase activity (GO:0003841), obsolete O-acyltransferase activity (GO:0008374), 1-acylglycerophosphocholine O-acyltransferase activity (GO:0047184), protein binding (GO:0005515), transferase activity (GO:0016740), acyltransferase activity (GO:0016746)

GO Cellular Component (7): mitochondrion (GO:0005739), mitochondrial outer membrane (GO:0005741), mitochondrial inner membrane (GO:0005743), mitochondrial intermembrane space (GO:0005758), mitochondrial membrane (GO:0031966), cytoplasm (GO:0005737), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Protein localization	1
Glycerophospholipid biosynthesis	1
Phospholipid metabolism	1
Metabolism of lipids	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cardiolipin metabolic process	2
mitochondrial membrane	2
mitochondrial envelope	2
cellular anatomical structure	2
mitochondrial membrane organization	1
inner mitochondrial membrane organization	1
regulation of cardiolipin metabolic process	1
positive regulation of phospholipid metabolic process	1
ATP biosynthetic process	1
positive regulation of purine nucleotide biosynthetic process	1
positive regulation of ATP metabolic process	1
regulation of ATP biosynthetic process	1
primary metabolic process	1
lipid metabolic process	1
organophosphate metabolic process	1
acylglycerol O-acyltransferase activity	1
lysophosphatidic acid acyltransferase activity	1
acyltransferase activity, transferring groups other than amino-acyl groups	1
binding	1
catalytic activity	1
transferase activity	1
cytoplasm	1
intracellular membrane-bounded organelle	1
organelle outer membrane	1
organelle inner membrane	1
organelle envelope lumen	1
mitochondrion	1
organelle membrane	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1356 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TAFAZZIN	DNAJC19	Q96DA6	893
TAFAZZIN	AUH	Q13825	843
TAFAZZIN	LDB3	O75112	819
TAFAZZIN	LCLAT1	Q6UWP7	758
TAFAZZIN	DTNA	Q9Y4J8	753
TAFAZZIN	RUNX2	Q13950	727
TAFAZZIN	TAMM41	Q96BW9	722
TAFAZZIN	CRLS1	Q9UJA2	710
TAFAZZIN	DMD	P11532	653
TAFAZZIN	TMEM214	Q6NUQ4	649
TAFAZZIN	EXD2	Q9NVH0	649
TAFAZZIN	ACTC1	P04270	622
TAFAZZIN	PTPMT1	Q8WUK0	621
TAFAZZIN	TNNT2	P45379	616
TAFAZZIN	PLA2G6	O60733	604

IntAct

41 interactions, top by confidence:

A	B	Type	Score
HSPD1	NUDT19	psi-mi:“MI:0914”(association)	0.710
SLC15A1	METTL15	psi-mi:“MI:0914”(association)	0.530
APLNR	METTL15	psi-mi:“MI:0914”(association)	0.530
LRRTM1	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
PLAUR	XRCC3	psi-mi:“MI:0914”(association)	0.530
NAPSA	CTSD	psi-mi:“MI:0914”(association)	0.530
TAFAZZIN	H3-4	psi-mi:“MI:0915”(physical association)	0.400
DVL2	TAFAZZIN	psi-mi:“MI:0915”(physical association)	0.400
TAFAZZIN	CFTR	psi-mi:“MI:0915”(physical association)	0.370
CFTR	TAFAZZIN	psi-mi:“MI:0915”(physical association)	0.370
NS3	C15orf61	psi-mi:“MI:0914”(association)	0.350
PDGFRA	GXYLT2	psi-mi:“MI:0914”(association)	0.350
CLEC12B	GXYLT2	psi-mi:“MI:0914”(association)	0.350
OSTM1	ILVBL	psi-mi:“MI:0914”(association)	0.350
UQCRFS1	VWA8	psi-mi:“MI:0914”(association)	0.350
NAAA	POTEF	psi-mi:“MI:0914”(association)	0.350
CPA5	RAP1BL	psi-mi:“MI:0914”(association)	0.350
GPR182	METTL15	psi-mi:“MI:0914”(association)	0.350
PTH2R	METTL15	psi-mi:“MI:0914”(association)	0.350
ST14	LIPT2	psi-mi:“MI:0914”(association)	0.350
RLN1	RTL8C	psi-mi:“MI:0914”(association)	0.350
SCGB2A2	RTL8C	psi-mi:“MI:0914”(association)	0.350
SLC22A4	RTL8C	psi-mi:“MI:0914”(association)	0.350
NIT1	NUDT19	psi-mi:“MI:0914”(association)	0.350
CEACAM8	PRRT4	psi-mi:“MI:0914”(association)	0.350
DPEP2	GET1	psi-mi:“MI:0914”(association)	0.350
TAFAZZIN	MANBA	psi-mi:“MI:0914”(association)	0.350
TMEM25	NME4	psi-mi:“MI:0914”(association)	0.350
LY86	PLXNB2	psi-mi:“MI:0914”(association)	0.350
LYZL2	ZZEF1	psi-mi:“MI:0914”(association)	0.350

BioGRID (357): TAZ (Affinity Capture-RNA), TAZ (Affinity Capture-RNA), TAZ (Protein-peptide), HSPD1 (Affinity Capture-MS), CACNA2D2 (Affinity Capture-MS), KDELC1 (Affinity Capture-MS), TMEM132A (Affinity Capture-MS), LRP5 (Affinity Capture-MS), LRP6 (Affinity Capture-MS), LRP1B (Affinity Capture-MS), PAM (Affinity Capture-MS), HLA-F (Affinity Capture-MS), FREM2 (Affinity Capture-MS), MBTPS1 (Affinity Capture-MS), ITGAV (Affinity Capture-MS)

ESM2 similar proteins: A2ADU8, A2ADU9, A6QP72, F6ZFR0, O74850, O94361, P51658, Q08650, Q16635, Q22267, Q32LS6, Q3UN02, Q41745, Q4V8A1, Q4V9F0, Q502J0, Q54GC1, Q58HT5, Q58NB6, Q5F3X0, Q62730, Q6CF02, Q6E1M8, Q6E213, Q6IV76, Q6IV77, Q6IV78, Q6IV82, Q6IV83, Q6IV84, Q6IWY1, Q6P342, Q6PAZ3, Q6ZPD8, Q7TQA3, Q8LG50, Q8N3Y7, Q8TC12, Q8VD48, Q91WF0

Diamond homologs: F1QCP6, Q16635, Q54DX7, Q6IV76, Q6IV77, Q6IV78, Q6IV82, Q6IV83, Q6IV84, Q91WF0, Q9V6G5, Q9ZV87, Q06510

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
CDK1	“down-regulates quantity by destabilization”	TAZ	phosphorylation
LATS1	“down-regulates activity”	TAZ	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	47
Likely pathogenic	43
Uncertain significance	182
Likely benign	186
Benign	8

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1070847	NC_000023.10:g.(?153640161)(153649363_?)del	Pathogenic
1070848	NC_000023.10:g.(?153639844)(153642537_?)del	Pathogenic
1070849	NC_000023.10:g.(?153647872)(153650075_?)del	Pathogenic
1072332	NM_000116.5(TAFAZZIN):c.129del (p.Val44fs)	Pathogenic
1075571	NM_000116.5(TAFAZZIN):c.293_294insTTAGGACCCC (p.Ala98_Ala99insTer)	Pathogenic
11100	NM_000116.5(TAFAZZIN):c.239-1G>A	Pathogenic
11102	NM_000116.5(TAFAZZIN):c.239-1G>C	Pathogenic
11103	NM_000116.5(TAFAZZIN):c.580dup (p.Trp194fs)	Pathogenic
11104	NM_000116.5(TAFAZZIN):c.634del (p.Leu212fs)	Pathogenic
11107	NM_000116.5(TAFAZZIN):c.284+110G>A	Pathogenic
11109	NM_000116.5(TAFAZZIN):c.110-2A>G	Pathogenic
11110	NM_000116.5(TAFAZZIN):c.280C>A (p.Arg94Ser)	Pathogenic
11111	NM_000116.5(TAFAZZIN):c.605_608del (p.Glu202fs)	Pathogenic
11112	NM_000116.5(TAFAZZIN):c.647-1G>C	Pathogenic
1704478	NM_000116.5(TAFAZZIN):c.517del (p.Asp173fs)	Pathogenic
177908	NM_000116.5(TAFAZZIN):c.710_711del (p.Val237fs)	Pathogenic
1800451	NM_000116.5(TAFAZZIN):c.489dup (p.Phe164fs)	Pathogenic
1922509	NM_000116.5(TAFAZZIN):c.586del (p.Ile196fs)	Pathogenic
1966105	NM_000116.5(TAFAZZIN):c.238+1del	Pathogenic
202091	NM_000116.5(TAFAZZIN):c.154G>T (p.Glu52Ter)	Pathogenic
202093	NM_000116.5(TAFAZZIN):c.582G>A (p.Trp194Ter)	Pathogenic
202100	NM_000116.5(TAFAZZIN):c.526C>T (p.His176Tyr)	Pathogenic
2112174	NM_000116.5(TAFAZZIN):c.153C>A (p.Tyr51Ter)	Pathogenic
2127122	NM_000116.5(TAFAZZIN):c.575del (p.Phe192fs)	Pathogenic
2138791	NM_000116.5(TAFAZZIN):c.536del (p.Pro179fs)	Pathogenic
234475	NM_000116.5(TAFAZZIN):c.461-2A>G	Pathogenic
2506887	NM_000116.5(TAFAZZIN):c.703dup (p.Ile235fs)	Pathogenic
2506891	NM_000116.5(TAFAZZIN):c.497T>A (p.Leu166Ter)	Pathogenic
2506894	NM_000116.5(TAFAZZIN):c.868_872dup (p.Arg292fs)	Pathogenic
2506921	NM_000116.5(TAFAZZIN):c.236G>A (p.Trp79Ter)	Pathogenic

SpliceAI

2132 predictions. Top by Δscore:

Variant	Effect	Δscore
X:154411948:GACCA:G	donor_gain	1.0000
X:154411953:G:GG	donor_gain	1.0000
X:154412085:GA:G	acceptor_gain	1.0000
X:154412196:G:GT	donor_gain	1.0000
X:154413337:G:GT	donor_gain	1.0000
X:154420025:T:TA	acceptor_gain	1.0000
X:154420026:G:A	acceptor_gain	1.0000
X:154420091:GTCG:G	donor_gain	1.0000
X:154420732:GGCT:G	donor_gain	1.0000
X:154420733:GCT:G	donor_gain	1.0000
X:154420733:GCTG:G	donor_gain	1.0000
X:154420736:G:GG	donor_gain	1.0000
X:154412082:CCAG:C	acceptor_gain	0.9900
X:154412084:A:AG	acceptor_gain	0.9900
X:154412085:G:GG	acceptor_gain	0.9900
X:154412196:G:T	donor_gain	0.9900
X:154412212:GGG:G	donor_gain	0.9900
X:154412213:GGG:G	donor_gain	0.9900
X:154413480:A:AG	acceptor_gain	0.9900
X:154413480:A:C	acceptor_loss	0.9900
X:154413480:AG:A	acceptor_gain	0.9900
X:154413481:G:GG	acceptor_gain	0.9900
X:154413481:GG:G	acceptor_gain	0.9900
X:154413481:GGA:G	acceptor_gain	0.9900
X:154413481:GGACC:G	acceptor_gain	0.9900
X:154413545:C:T	donor_gain	0.9900
X:154413564:CGAG:C	donor_loss	0.9900
X:154413568:G:GA	donor_loss	0.9900
X:154419621:AAG:A	donor_loss	0.9900
X:154419622:AGGT:A	donor_loss	0.9900

AlphaMissense

1940 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:154412180:T:A	N68K	1.000
X:154412180:T:G	N68K	1.000
X:154412181:C:G	H69D	1.000
X:154412196:G:C	D74H	1.000
X:154412196:G:T	D74Y	1.000
X:154412197:A:T	D74V	1.000
X:154412211:T:A	W79R	1.000
X:154412211:T:C	W79R	1.000
X:154413248:C:A	R94S	1.000
X:154413507:T:C	F104L	1.000
X:154413509:C:A	F104L	1.000
X:154413509:C:G	F104L	1.000
X:154419588:T:C	L169P	1.000
X:154419602:T:A	W174R	1.000
X:154419602:T:C	W174R	1.000
X:154419743:T:A	W194R	1.000
X:154419743:T:C	W194R	1.000
X:154419745:G:C	W194C	1.000
X:154419745:G:T	W194C	1.000
X:154420037:G:T	G197W	1.000
X:154411928:G:C	G29R	0.999
X:154411929:G:A	G29D	0.999
X:154411937:A:C	S32R	0.999
X:154411939:C:A	S32R	0.999
X:154411939:C:G	S32R	0.999
X:154412164:T:A	L63H	0.999
X:154412164:T:C	L63P	0.999
X:154412167:T:A	I64N	0.999
X:154412175:T:C	S67P	0.999
X:154412181:C:A	H69N	0.999

dbSNP variants (sampled 300 via entrez): RS1000334088 (X:154410379 C>A,T), RS1000448721 (X:154410845 C>T), RS1000608589 (X:154420336 T>C), RS1000899842 (X:154419923 G>T), RS1001117878 (X:154415749 C>T), RS1001234126 (X:154416144 A>G), RS1002233472 (X:154417930 C>T), RS1004469259 (X:154416585 G>A), RS1004777145 (X:154416197 A>G), RS1005349467 (X:154421569 G>A), RS1005488594 (X:154411574 G>C), RS1006187280 (X:154414467 C>T), RS1006862123 (X:154409911 G>A,C), RS1006905025 (X:154413952 T>A,C), RS1007026402 (X:154419290 G>A)

Disease associations

OMIM: gene MIM:300394 | disease phenotypes: MIM:302060, MIM:226000, MIM:192600, MIM:604169, MIM:115200

GenCC curated gene-disease

Disease	Classification	Inheritance
Barth syndrome	Definitive	X-linked

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
Barth syndrome	Definitive	XL

Mondo (8): Barth syndrome (MONDO:0010543), dilated cardiomyopathy (MONDO:0005021), endocardial fibroelastosis (MONDO:0009169), familial hypertrophic cardiomyopathy (MONDO:0024573), cardiomyopathy (MONDO:0004994), left ventricular noncompaction (MONDO:0018901), familial dilated cardiomyopathy (MONDO:0016333), dilated cardiomyopathy 1A (MONDO:0007269)

Orphanet (9): Barth syndrome (Orphanet:111), Endocardial fibroelastosis (Orphanet:2022), Dilated cardiomyopathy (Orphanet:217604), Rare familial disorder with hypertrophic cardiomyopathy (Orphanet:99739), Rare cardiomyopathy (Orphanet:167848), Left ventricular noncompaction (Orphanet:54260), Familial dilated cardiomyopathy (Orphanet:217607), Familial dilated cardiomyopathy with conduction defect due to LMNA mutation (Orphanet:300751), NON RARE IN EUROPE: Familial isolated hypertrophic cardiomyopathy (Orphanet:155)

HPO phenotypes

49 total (30 of 49 shown, HPO-id order):

HPO	Term
HP:0000293	Full cheeks
HP:0000303	Mandibular prognathia
HP:0000307	Pointed chin
HP:0000311	Round face
HP:0000337	Broad forehead
HP:0000348	High forehead
HP:0000400	Macrotia
HP:0000407	Sensorineural hearing impairment
HP:0000490	Deeply set eye
HP:0000969	Edema
HP:0001263	Global developmental delay
HP:0001270	Motor delay
HP:0001288	Gait disturbance
HP:0001419	X-linked recessive inheritance
HP:0001508	Failure to thrive
HP:0001510	Growth delay
HP:0001635	Congestive heart failure
HP:0001639	Hypertrophic cardiomyopathy
HP:0001644	Dilated cardiomyopathy
HP:0001706	Endocardial fibroelastosis
HP:0001727	Thromboembolic stroke
HP:0001762	Talipes equinovarus
HP:0001874	Abnormality of neutrophils
HP:0001875	Decreased total neutrophil count
HP:0001913	Decreased total granulocyte count
HP:0002058	Myopathic facies
HP:0002286	Fair hair
HP:0002837	Recurrent bronchitis
HP:0002875	Exertional dyspnea
HP:0003198	Myopathy

GWAS associations

0 associations (top):

MeSH disease descriptors (6)

Descriptor	Name	Tree numbers
D056889	Barth Syndrome	C14.240.400.172; C14.280.400.172; C16.131.077.121; C16.131.240.400.172; C16.320.322.068; C16.320.565.398.224; C18.452.584.563.224; C18.452.648.398.224
D009202	Cardiomyopathies	C14.280.238
D002311	Cardiomyopathy, Dilated	C14.280.195.160; C14.280.238.070; C16.320.488.750
D024741	Cardiomyopathy, Hypertrophic, Familial	C14.280.238.100.500; C14.280.484.048.750.070.160.500; C16.320.160
D004695	Endocardial Fibroelastosis	C14.280.238.281
C536231	familial dilated cardiomyopathy (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5291574 (SINGLE PROTEIN)

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

Binding affinities (BindingDB)

104 measured of 110 human assays (110 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
US12083101, Example 71b	IC50	1 nM	US-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 110	IC50	1 nM	US-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 112	IC50	1 nM	US-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 147	IC50	1 nM	US-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 170	IC50	1 nM	US-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 12	IC50	1.5 nM	US-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 38	IC50	2 nM	US-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 56b	IC50	2 nM	US-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 66a	IC50	2 nM	US-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 66b	IC50	2 nM	US-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 67a	IC50	2 nM	US-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 71a	IC50	2 nM	US-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 94a	IC50	2 nM	US-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 99	IC50	2 nM	US-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 100a	IC50	2 nM	US-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 104b	IC50	2 nM	US-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 108	IC50	2 nM	US-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 113	IC50	2 nM	US-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 115a	IC50	2 nM	US-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 115b	IC50	2 nM	US-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 121	IC50	2 nM	US-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 126	IC50	2 nM	US-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 151	IC50	2 nM	US-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 152	IC50	2 nM	US-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 171	IC50	2 nM	US-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 31	IC50	3 nM	US-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 33	IC50	3 nM	US-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 51	IC50	3 nM	US-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 57b	IC50	3 nM	US-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 86	IC50	3 nM	US-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 94b	IC50	3 nM	US-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 102a	IC50	3 nM	US-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 120	IC50	3 nM	US-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 143	IC50	3 nM	US-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 146	IC50	3 nM	US-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 8	IC50	4 nM	US-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 58b	IC50	4 nM	US-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 69b	IC50	4 nM	US-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 85a	IC50	4 nM	US-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 97	IC50	4 nM	US-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 111	IC50	4 nM	US-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 140a	IC50	4 nM	US-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 150	IC50	4 nM	US-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 164	IC50	4 nM	US-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 49	IC50	5 nM	US-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 69a	IC50	5 nM	US-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 96	IC50	5 nM	US-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 98	IC50	5 nM	US-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 103	IC50	5 nM	US-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors
US12083101, Example 141	IC50	5 nM	US-12083101: Biaryl derivatives as YAP/TAZ-TEAD protein-protein interaction inhibitors

CTD chemical–gene interactions

16 total (human), top 16 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	decreases expression	1
napabucasin	decreases expression	1
ceric oxide	decreases expression	1
beta-glycerophosphoric acid	affects cotreatment, increases expression	1
(+)-JQ1 compound	decreases expression	1
Sunitinib	increases expression	1
Acetaminophen	increases expression	1
Amiodarone	increases expression	1
Ascorbic Acid	affects cotreatment, increases expression	1
Atrazine	increases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Cholecalciferol	increases expression, affects cotreatment	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Okadaic Acid	decreases expression	1
Acrylamide	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5249657	Binding	Inhibition of TAZ (unknown origin) phosporylation relative to control	Advances of targeting the YAP/TAZ-TEAD complex in the hippo pathway for the treatment of cancers. — Eur J Med Chem

Cellosaurus cell lines

31 cell lines: 15 transformed cell line, 9 induced pluripotent stem cell, 6 cancer cell line, 1 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A1YS	UMGi054-A.3	Induced pluripotent stem cell	Male
CVCL_A1YT	UMGi054-A.4	Induced pluripotent stem cell	Male
CVCL_A1YU	UMGi055-A.3	Induced pluripotent stem cell	Male
CVCL_A1YW	UMGi056-A.1	Induced pluripotent stem cell	Male
CVCL_A1YX	UMGi056-A.5	Induced pluripotent stem cell	Male
CVCL_A1YY	UMGi056-A.8	Induced pluripotent stem cell	Male
CVCL_B8QH	Abcam HCT 116 TAFFAZIN KO	Cancer cell line	Male
CVCL_B9C5	Abcam MCF-7 TAFFAZIN KO	Cancer cell line	Female
CVCL_B9SY	Abcam A-549 TAFAZZIN KO	Cancer cell line	Male
CVCL_BU12	GM22128	Transformed cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT07531251	PHASE4	NOT_YET_RECRUITING	Clinical Trial in Patients With Barth Syndrome- 4TAZPower
NCT00374465	PHASE4	UNKNOWN	Therapy With Verapamil or Carvedilol in Chronic Heart Failure
NCT01293903	PHASE4	COMPLETED	Study of Qiliqiangxin Capsule to Treat Dilated Cardiomyopathy
NCT01557140	PHASE4	COMPLETED	A Randomized Trial of Carvedilol in Chronic Chagas Cardiomyopathy
NCT01917149	PHASE4	COMPLETED	Supramaximal Titrated Inhibition of RAAS in Dilated Cardiomyopathy
NCT02115581	PHASE4	COMPLETED	Coenzyme Q10 Supplementation in Children With Idiopathic Dilated Cardiomyopathy
NCT06236022	PHASE4	RECRUITING	The Effects of Sirolimus in Patients With Dilated Cardiomyopathy Infected With Kaposi Sarcoma-associated Virus
NCT00333827	PHASE3	COMPLETED	Cell Therapy In Dilated Cardiomyopathy
NCT00505154	PHASE3	COMPLETED	Effect of Rosuvastatin on Left Ventricular Remodeling
NCT01223703	PHASE3	COMPLETED	PUFAs and Left Ventricular Function in Heart Failure
NCT01583114	PHASE3	TERMINATED	PREclinical Mutation CARriers From Families With DIlated Cardiomyopathy and ACE Inhibitors
NCT01914081	PHASE3	UNKNOWN	Resveratrol: A Potential Anti- Remodeling Agent in Heart Failure, From Bench to Bedside
NCT02989181	PHASE3	UNKNOWN	Continues Positive Airway Pressure Treatment for Patients With Dilated Cardiomyopathy and Obstructive Sleep Apnea
NCT03439514	PHASE3	TERMINATED	A Study of ARRY-371797 (PF-07265803) in Patients With Symptomatic Dilated Cardiomyopathy Due to a Lamin A/C Gene Mutation
NCT05237323	PHASE3	COMPLETED	Micophenolate Mofetil Versus Azathioprine in Myocarditis
NCT05849766	PHASE3	COMPLETED	Effect of Dapagliflozin on Cardiac Structure, Function and Secondary Mitral Regurgitation in Patients with Left Ventricle Dysfunction
NCT06250257	PHASE3	RECRUITING	Bromocriptine in Dilated Cardiomyopathy Among Women of Reproductive Age
NCT00629018	PHASE2	COMPLETED	Safety and Efficacy Study of Stem Cell Transplantation to Treat Dilated Cardiomyopathy
NCT00629096	PHASE2	COMPLETED	Intracoronary Infusion of Autologous Bone Marrow Cells for Treatment of Idiopathic Dilated Cardiomyopathy
NCT00765518	PHASE2	COMPLETED	Use of Ixmyelocel-T (Formerly Cardiac Repair Cell [CRC] Treatment) in Patients With Heart Failure Due to Dilated Cardiomyopathy (IMPACT-DCM)
NCT00847964	PHASE2	COMPLETED	Safety and Feasibility of Algisyl-LVR™ as a Method of Left Ventricular Restoration in Patients With DCM Undergoing Open-heart Surgery
NCT01020968	PHASE2	COMPLETED	Use of Ixmyelocel-T (Formerly Catheter-based Cardiac Repair Cell [CRC]) Treatment in Patients With Heart Failure Due to Dilated Cardiomyopathy
NCT01302171	PHASE2	COMPLETED	Bone Marrow Derived Adult Stem Cells for Dilated Cardiomyopathy
NCT01350310	PHASE2	COMPLETED	Safety and Efficacy Study of Intramyocardial Stem Cell Therapy in Patients With Dilated Cardiomyopathy
NCT02133911	PHASE2	COMPLETED	A Pilot Trial of Ranolazine to Treat Patients With Dilated Cardiomyopathy
NCT03071653	PHASE2	SUSPENDED	Left Cardiac Sympathetic Denervation for Cardiomyopathy Feasibility Pilot Study
NCT03572660	PHASE2	ACTIVE_NOT_RECRUITING	Use of Bone Marrow Derived Stem Cell and G-CSF With Circulatory Assistance in the Treatment of DCM
NCT03775070	PHASE2	COMPLETED	Simvastatin Therapy in Patients With Dilated Cardiomyopathy.
NCT04405804	PHASE2	UNKNOWN	Early Administration of Ivabradine in Children With Heart Failure
NCT05410873	PHASE2	COMPLETED	Examining the Effects of Mitochondrial Oxidative Stress in DCM
NCT06632834	PHASE2	RECRUITING	Outcome-targeted Therapy: Principle and Outcome Evaluation: Clinical Study and Phenotype-genotype Correlation
NCT00585546	PHASE1	TERMINATED	Harefield Recovery Protocol Study for Patients With Refractory Chronic Heart Failure
NCT02293603	PHASE1	UNKNOWN	Dilated cardiomYopathy iNtervention With Allogeneic MyocardIally-regenerative Cells (DYNAMIC)
NCT03062956	PHASE1	COMPLETED	A Single Ascending Dose Study Assessing the Safety, Tolerability, PK and PD of MYK-491
NCT03129568	PHASE1	COMPLETED	Transcoronary Infusion of Cardiac Progenitor Cells in Pediatric Dilated Cardiomyopathy
NCT04982081	PHASE1	UNKNOWN	Treating Congestive HF With hiPSC-CMs Through Endocardial Injection
NCT06381466	PHASE1	TERMINATED	A Study to Investigate Safety, Tolerability, and Pharmacokinetics of Oral AZD0233 Compared With Placebo in Healthy Adult Participants.
NCT06464588	PHASE1	RECRUITING	A Phase 1 Open-Label Study of the Safety of Intravenous Allogeneic Neonatal Mesenchymal Cells (nMSCs) in Young Adult (1A) and Pediatric (1B) Patients With Dilated Cardiomyopathy (DCM)
NCT06902896	PHASE1	COMPLETED	Safety and Efficacy of FAP iCDC in End-stage Dilated Cardiomyopathy
NCT07137338	PHASE1	RECRUITING	A Phase 1 AAV Gene Therapy Trial Evaluating Safety and Preliminary Efficacy of RP-A701 in Subjects With BAG3 Dilated Cardiomyopathy