FHL1

Summary

FHL1 (four and a half LIM domains 1, HGNC:3702) is a protein-coding gene on chromosome Xq26.3, encoding Four and a half LIM domains protein 1 (Q13642). May have an involvement in muscle development or hypertrophy.

This gene encodes a member of the four-and-a-half-LIM-only protein family. Family members contain two highly conserved, tandemly arranged, zinc finger domains with four highly conserved cysteines binding a zinc atom in each zinc finger. Expression of these family members occurs in a cell- and tissue-specific mode and these proteins are involved in many cellular processes. Mutations in this gene have been found in patients with Emery-Dreifuss muscular dystrophy. Multiple alternately spliced transcript variants which encode different protein isoforms have been described.

Source: NCBI Gene 2273 — RefSeq curated summary.

At a glance

• Gene–disease (curated): X-linked myopathy with postural muscle atrophy (Definitive, GenCC) — +5 more curated relationships
• Clinical variants (ClinVar): 673 total — 75 pathogenic, 22 likely-pathogenic
• Phenotypes (HPO): 120
• MANE Select transcript: NM_001159699

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3702
Approved symbol	FHL1
Name	four and a half LIM domains 1
Location	Xq26.3
Locus type	gene with protein product
Status	Approved
Aliases	SLIM1, KYO-T, bA535K18.1, FHL1B, XMPMA, FLH1A, MGC111107
Ensembl gene	ENSG00000022267
Ensembl biotype	protein_coding
OMIM	300163
Entrez	2273

Gene structure

Transcript identifiers

Ensembl transcripts: 41 — 36 protein_coding, 3 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000370674, ENST00000370676, ENST00000370683, ENST00000394153, ENST00000394155, ENST00000420362, ENST00000434885, ENST00000449474, ENST00000452016, ENST00000456445, ENST00000458357, ENST00000477080, ENST00000477204, ENST00000535737, ENST00000539015, ENST00000543669, ENST00000618438, ENST00000625935, ENST00000626004, ENST00000627383, ENST00000627578, ENST00000627812, ENST00000628032, ENST00000628443, ENST00000628568, ENST00000628919, ENST00000629039, ENST00000630084, ENST00000630278, ENST00000630677, ENST00000630684, ENST00000651089, ENST00000651256, ENST00000651929, ENST00000652457, ENST00000652745, ENST00000862283, ENST00000862284, ENST00000862285, ENST00000862286, ENST00000952767

RefSeq mRNA: 15 — MANE Select: NM_001159699 NM_001159699, NM_001159700, NM_001159701, NM_001159702, NM_001159703, NM_001159704, NM_001167819, NM_001330659, NM_001369326, NM_001369327, NM_001369328, NM_001369329, NM_001369330, NM_001369331, NM_001449

CCDS: CCDS14655, CCDS55505, CCDS55506, CCDS55507, CCDS76036, CCDS83493

Canonical transcript exons

ENST00000370683 — 6 exons

Exon	Start	End
ENSE00000676980	136208455	136208641
ENSE00000890595	136207016	136207190
ENSE00000890598	136207792	136207961
ENSE00001453299	136197047	136197134
ENSE00003570762	136206407	136206588
ENSE00003764342	136209871	136211354

Expression profiles

Bgee: expression breadth ubiquitous, 291 present calls, max score 99.99.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 58.5651 / max 5480.9512, expressed in 1571 samples.

FANTOM5 promoters (29 alternative TSS)

Promoter ID	TPM avg	Samples expressed
197669	19.8255	424
197652	13.1920	1391
197651	8.8957	1480
197671	6.3772	279
197668	3.8050	250
197650	1.7176	1020
197653	0.9799	480
197649	0.4247	201
209826	0.4000	161
197659	0.3955	166

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	99.99	gold quality
biceps brachii	UBERON:0001507	99.98	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	99.96	gold quality
body of tongue	UBERON:0011876	99.96	gold quality
vastus lateralis	UBERON:0001379	99.95	gold quality
deltoid	UBERON:0001476	99.95	gold quality
diaphragm	UBERON:0001103	99.94	gold quality
skeletal muscle tissue	UBERON:0001134	99.94	gold quality
quadriceps femoris	UBERON:0001377	99.94	gold quality
urethra	UBERON:0000057	99.93	gold quality
tibialis anterior	UBERON:0001385	99.93	gold quality
triceps brachii	UBERON:0001509	99.93	gold quality
synovial joint	UBERON:0002217	99.92	gold quality
hindlimb stylopod muscle	UBERON:0004252	99.92	gold quality
gastrocnemius	UBERON:0001388	99.90	gold quality
muscle organ	UBERON:0001630	99.90	gold quality
gluteal muscle	UBERON:0002000	99.89	gold quality
blood vessel layer	UBERON:0004797	99.89	gold quality
saphenous vein	UBERON:0007318	99.89	gold quality
muscle of leg	UBERON:0001383	99.88	gold quality
heart right ventricle	UBERON:0002080	99.87	gold quality
mucosa of stomach	UBERON:0001199	99.84	gold quality
right coronary artery	UBERON:0001625	99.83	gold quality
vena cava	UBERON:0004087	99.82	gold quality
skin of hip	UBERON:0001554	99.80	gold quality
ascending aorta	UBERON:0001496	99.79	gold quality
thoracic aorta	UBERON:0001515	99.79	gold quality
aorta	UBERON:0000947	99.78	gold quality
popliteal artery	UBERON:0002250	99.78	gold quality
tibial artery	UBERON:0007610	99.78	gold quality

Single-cell (SCXA)

Detected in 15 experiment(s), a significant marker in 15.

Experiment	Marker?	Max mean expression
E-HCAD-13	yes	1407.22
E-GEOD-135922	yes	894.95
E-HCAD-1	yes	80.14
E-MTAB-10287	yes	67.38
E-MTAB-8410	yes	52.42
E-HCAD-11	yes	43.89
E-HCAD-10	yes	36.57
E-CURD-46	yes	25.25
E-GEOD-84465	yes	22.27
E-HCAD-5	yes	16.78
E-CURD-112	yes	10.65
E-MTAB-10553	yes	6.14
E-HCAD-9	yes	5.03
E-GEOD-130148	yes	4.19
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

72 targeting FHL1, 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-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-544A	99.84	68.66	1965
HSA-MIR-8080	99.82	67.52	1342
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-4517	99.76	69.19	1867
HSA-MIR-8084	99.73	69.57	1760
HSA-MIR-1197	99.70	67.75	1027
HSA-MIR-3059-5P	99.70	69.93	2491
HSA-MIR-1208	99.70	68.28	1533
HSA-MIR-1205	99.65	66.76	1826
HSA-MIR-10394-5P	99.65	66.83	1852
HSA-MIR-4666B	99.64	68.69	1282
HSA-MIR-298	99.63	67.56	1916
HSA-MIR-5003-5P	99.61	69.13	1624
HSA-MIR-3682-3P	99.58	67.63	865
HSA-MIR-4649-3P	99.56	66.90	1783
HSA-MIR-7844-5P	99.55	68.56	1428
HSA-MIR-105-5P	99.54	69.24	2060
HSA-MIR-7853-5P	99.54	69.30	2055
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-6081	99.48	66.07	1446
HSA-MIR-4728-3P	99.47	68.94	981

Literature-anchored findings (GeneRIF, showing 40)

• SLIM1 may play an important role during the early stages of skeletal muscle differentiation, specifically in alpha5beta1-integrin-mediated signaling pathways (PMID:12917103)
• FHL1 is a novel regulator of myosin-binding protein C activity that may have a role in sarcomere assembly (PMID:16407297)
• Fasting insulin and insulin sensitivity index responses to exercise training were associated with DNA sequence variation in FHL1 in white men. (PMID:17589823)
• These results characterize TLX1 as a dual function regulator whose activity in respect to FHL1 is critically dependent upon its cellular concentration, as well as cell type and promoter context. (PMID:18073142)
• Study characterized a new disorder, X-linked myopathy with postural muscle atrophy (XMPMA), and identified FHL1 as the causative gene. (PMID:18179888)
• In a large Italian-American pedigree with dominant Scapuloperoneal syndrome all of the affected individuals have a missense change (c.365G–>C) in the FHL1 gene encoding FHL1. (PMID:18179901)
• The results shows that HOXD13 gene mutation was not involved in outbreak in idiopathic congenital talipes equinovarus, but changes of HOXD13 and FHL1 gene expression related to the development of talipes equinovarus malformation. (PMID:18244901)
• a novel laser microdissection/proteomics approach has helped identify both inherited and de novo mutations in FHL1, thereby defining a new X-linked protein aggregation disorder of muscle. (PMID:18274675)
• Results support a role of FHL1 as a key molecular component in the I(Kur) complex in human atrium, where it likely regulates functional expression of KCNA5. (PMID:18281375)
• Fhl1 gene was underexpressed in clinical gastric cancer. (PMID:18465173)
• upregulated in various forms of PH, including idiopathic pulmonary arterial hypertension (PMID:18725486)
• Hoxd13 and Fhl1 were expressed in the interdigital tissues of E12.5 rat embryo. Luciferase assay and EMSA identified a novel promoter region of Fhl1 that directly interacts with Hoxd13 (PMID:18758158)
• FHL1 appears to modulate muscle mass and strength enhancement. (PMID:19075112)
• Human four-and-a-half LIM family members suppress tumor cell growth through a TGF-beta-like signaling pathway. (PMID:19139564)
• Four novel mutations are identified in FHL1: heterozygous missense mutations in patients 1 and 2 (fatal infantile form), in-frame deletion in patient 3, and hemizygous mutation in patient 4. All mutations are located in the second LIM domain of FHL1. (PMID:19171836)
• The mutations detected were exclusive to the second LIM domain of FHL1 and were found in both sporadic as well as familial cases of reducing body myopathy. (PMID:19181672)
• The results presented here suggested the cooperative transcriptional regulation of estrogen signaling by FHL1 and RIP140. (PMID:19401155)
• As a consequence of C terminal FHL1 gene mutations, the X-linked myopathy characterized by postural muscle atrophy (XMPMA) phenotype and morphotype with cytoplasmic bodies are found. (PMID:19687455)
• FHL1 should be considered as a gene associated with the X-linked Emery-Dreifuss muscular dystrophy phenotype, as well as with hypertrophic cardiomyopathy. (PMID:19716112)
• The pH-regulated antigen 1 (Pra1) protein was identified as a novel Factor H and FHL-1 binding protein. (PMID:19850343)
• Our finding expands the phenotypic spectrum of the recently identified FHL1-associated myopathies and widens the differential diagnosis of Emery-Dreifuss-like syndromes. (PMID:20186852)
• This study reported a novel LIM2 domain mutation in FHL1 in a family with Reducing body myopathy with cytoplasmic bodies and spinal rigidity. (PMID:20571991)
• Expression levels of FHL1 mRNA increased in all cell lines tested, as shown by RT-PCR. The methylation index of FHL1 in our samples was significantly higher in 70 BC specimens than in 10 normal bladder epithelium specimens. (PMID:20596604)
• A novel missense mutation in the LIM2 domain of FHL1 co-segregated with X-linked scapuloperoneal myopathy in the family (PMID:20633900)
• FHL1B/PP2A(Cbeta) interaction may illustrate a novel cell-cycle regulatory pathway. (PMID:20969868)
• FHL1 protein expression is downregulated in thoracic aortic dissection. (PMID:21126853)
• These results indicate that USP15 is involved in the regulation of hypertrophic responses in cardiac muscle through transcriptional and post-translational modulation of SLIM1. (PMID:21219870)
• This review will profile each of the FHL1, with a comprehensive analysis of mutations, a comparison of the clinical and histopathological features and will present several hypotheses for the possible disease mechanism(s)–{REVIEW} (PMID:21310615)
• We report on three British families with a heterogeneous myopathy clinical presentation segregating a single FHL1 gene mutation and haplotype, suggesting that this represents a founder mutation. (PMID:21629301)
• reduced expression of FHL1 may play an important role in the development and progression of lung cancer. (PMID:21702045)
• In order to substantiate a possible relation between K(v1.5) and FHL1C, a pull-down assay was performed. (PMID:22053194)
• FHL-1 may regulate estrogen receptor signaling function through regulation of AKT activation besides the physical and functional interaction with Estrogen receptor alpha. (PMID:22094188)
• FHL1 dystrophies are associated with myofibrillar myopathies pathology; mutations in the LIM2 domain are associated with reducing bodies composed of distinct tubulofilaments. (PMID:22094483)
• The decrease in or loss of FHL1 expression may be related to the incidence, progression, invasiveness, and metastatic potential of gastric cancer. (PMID:22143536)
• FHL1-3 inhibit HIF-1 transcriptional activity and HIF-1alpha transactivation domain function by oxygen-independent mechanisms. (PMID:22219185)
• FHL1 is a novel disease gene for hypertrophic cardiomyopathy. (PMID:22523091)
• A mother, daughter, and son suffering from FHL1 myopathy have a mutation in the second LIM domain of fhl1 with musculoskeletal involvement. (PMID:22541254)
• FHL1 is a methylation-silenced tumor-suppressor gene on chromosome X in gastrointestinal cancers, and that its silencing contributes to the formation of an epigenetic field for cancerization. (PMID:22689052)
• A novel mechanism involving four-and-a-half LIM domain protein-1 and extracellular signal-regulated kinase-2 regulates titin phosphorylation and mechanics. (PMID:22778266)
• C224W mutation of FHLi protein had slightly elevated pulmonary artery pressure (PMID:22923418)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	fhl1b	ENSDARG00000056653
danio_rerio	fhl1a	ENSDARG00000071498
mus_musculus	Fhl1	ENSMUSG00000023092
mus_musculus	Fhl4	ENSMUSG00000050035
rattus_norvegicus	Fhl4	ENSRNOG00000006998

Paralogs (20): LMO3 (ENSG00000048540), LHX5 (ENSG00000089116), ZFHX4 (ENSG00000091656), LHX2 (ENSG00000106689), LHX6 (ENSG00000106852), LHX3 (ENSG00000107187), LHX4 (ENSG00000121454), LMO2 (ENSG00000135363), ZFHX2 (ENSG00000136367), LMX1B (ENSG00000136944), ZFHX3 (ENSG00000140836), LMO4 (ENSG00000143013), LHX9 (ENSG00000143355), CRIP3 (ENSG00000146215), LHX8 (ENSG00000162624), LMX1A (ENSG00000162761), LMO1 (ENSG00000166407), CRIP2 (ENSG00000182809), CRIP1 (ENSG00000213145), LHX1 (ENSG00000273706)

Protein

Protein identifiers

Four and a half LIM domains protein 1 — Q13642 (reviewed: Q13642)

Alternative names: Skeletal muscle LIM-protein 1

All UniProt accessions (18): A0A0D9SEY7, A0A0D9SFB0, A0A0D9SFI6, A0A0D9SFZ9, A0A0D9SGB2, A0A0D9SGC5, A0A0D9SGD1, A0A494C0D6, A0A494C0J3, A0A494C1G1, Q13642, Q5JXH7, Q5JXH8, Q5JXH9, Q5JXI0, Q5JXI2, Q5JXI3, Q5JXI8

UniProt curated annotations — full annotation on UniProt →

Function. May have an involvement in muscle development or hypertrophy.

Subunit / interactions. (Microbial infection) Interacts (via LIM domain 1) with Chikungunya virus non-structural protein 3 (via C-terminus); this interaction is required for viral RNA replication.

Subcellular location. Cytoplasm Cytoplasm. Nucleus Nucleus. Cytoplasm. Cytosol.

Tissue specificity. Isoform 1 is highly expressed in skeletal muscle and to a lesser extent in heart, placenta, ovary, prostate, testis, small intestine, colon and spleen. Expression is barely detectable in brain, lung, liver, kidney, pancreas, thymus and peripheral blood leukocytes. Isoform 2 is expressed in brain, skeletal muscle and to a lesser extent in heart, colon, prostate and small intestine. Isoform 3 is expressed in testis, heart and skeletal muscle.

Disease relevance. Emery-Dreifuss muscular dystrophy 6, X-linked (EDMD6) [MIM:300696] A form of Emery-Dreifuss muscular dystrophy, a degenerative myopathy characterized by weakness and atrophy of muscle without involvement of the nervous system, early contractures of the elbows, Achilles tendons and spine, and cardiomyopathy associated with cardiac conduction defects. The disease is caused by variants affecting distinct genetic loci, including the gene represented in this entry. Scapuloperoneal myopathy, X-linked dominant (SPM) [MIM:300695] A disease characterized by progressive muscle weakness and wasting, upper and lower limbs weakness, foot drop, scapular winging, and myopathic changes on muscle biopsy. Most affected individuals become wheelchair-bound. The disease is caused by variants affecting the gene represented in this entry. Myopathy, X-linked, with postural muscle atrophy (XMPMA) [MIM:300696] A progressive muscular dystrophy with onset in adulthood. Affected individuals develop a proximal myopathy characterized by specific atrophy of postural muscles, limited neck flexion, bent spine, contractures of the Achilles tendon, respiratory problems, and cardiomyopathy. Patients may show muscle hypertrophy in the early stages of the disorder. The disease is caused by variants affecting the gene represented in this entry. Reducing body myopathy, X-linked 1A, severe, with infantile or early childhood onset (RBMX1A) [MIM:300717] A rare myopathy clinically characterized by rapidly progressive muscular weakness, and pathologically by the presence of intracytoplasmic inclusion bodies strongly stained by menadione-linked alpha-glycerophosphate dehydrogenase in the absence of substrate, alpha-glycerophosphate. The term ‘reducing body’ refers to the reducing activity of the inclusions to nitroblue tetrazolium in the absence of substrate. This condition is also commonly associated with rimmed vacuoles and cytoplasmic bodies. Death in childhood is frequent in the severe form of the disease, due to respiratory failure. The disease is caused by variants affecting the gene represented in this entry. Reducing body myopathy, X-linked 1B, with late childhood or adult onset (RBMX1B) [MIM:300718] A rare myopathy clinically characterized by rapidly progressive muscular weakness, and pathologically by the presence of intracytoplasmic inclusion bodies strongly stained by menadione-linked alpha-glycerophosphate dehydrogenase in the absence of substrate, alpha-glycerophosphate. The term ‘reducing body’ refers to the reducing activity of the inclusions to nitroblue tetrazolium in the absence of substrate. This condition is also commonly associated with rimmed vacuoles and cytoplasmic bodies. The disease is caused by variants affecting the gene represented in this entry. Uruguay faciocardiomusculoskeletal syndrome (FCMSU) [MIM:300280] An X-linked recessive syndrome characterized by brachyturricephaly, pugilistic coarse facies, a muffled voice, cardiomyopathy, muscular hypertrophy, broad hands, wide feet with progressive pes cavus deformities, dislocation of toes, variable congenital hip dislocation, and scoliosis. The disease is caused by variants affecting the gene represented in this entry.

Isoforms (5)

UniProt ID	Names	Canonical?
Q13642-2	2, FHL1B, SLIMMER	yes
Q13642-1	1, FHL1, FHL1A, SLIM1
Q13642-3	3, FHL1C
Q13642-4	4
Q13642-5	5

RefSeq proteins (15): NP_001153171, NP_001153172, NP_001153173, NP_001153174, NP_001153175, NP_001153176, NP_001161291, NP_001317588, NP_001356255, NP_001356256, NP_001356257, NP_001356258, NP_001356259, NP_001356260, NP_001440 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001781	Znf_LIM	Domain
IPR042997	Fhl1	Family
IPR056807	LIM_FHL1/2/3/5_N	Domain

Pfam: PF00412, PF25076

UniProt features (63 total): sequence variant 20, strand 19, sequence conflict 5, splice variant 4, turn 4, domain 3, helix 3, initiator methionine 1, chain 1, zinc finger region 1, modified residue 1, cross-link 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
1X63	SOLUTION NMR
2CUP	SOLUTION NMR
2CUR	SOLUTION NMR
2EGQ	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13642-F1	73.11	0.40

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (2): 4, 86

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 594 (showing top): GOBP_POTASSIUM_ION_TRANSPORT, VERHAAK_AML_WITH_NPM1_MUTATED_DN, GOBP_MEMBRANE_DEPOLARIZATION, ZHAN_LATE_DIFFERENTIATION_GENES_UP, CHIARADONNA_NEOPLASTIC_TRANSFORMATION_KRAS_DN, TSENG_IRS1_TARGETS_UP, BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_DN, CHIARETTI_T_ALL_REFRACTORY_TO_THERAPY, GOBP_NEGATIVE_REGULATION_OF_CELL_GROWTH, GOBP_CELL_CYCLE_PHASE_TRANSITION, GOBP_GROWTH, HSIAO_HOUSEKEEPING_GENES, MCBRYAN_PUBERTAL_TGFB1_TARGETS_UP, TGACCTY_ERR1_Q2, GOBP_REGULATION_OF_MEMBRANE_DEPOLARIZATION

GO Biological Process (8): muscle organ development (GO:0007517), animal organ morphogenesis (GO:0009887), negative regulation of G2/M transition of mitotic cell cycle (GO:0010972), cell differentiation (GO:0030154), negative regulation of cell growth (GO:0030308), regulation of atrial cardiac muscle cell membrane depolarization (GO:0060371), positive regulation of potassium ion transmembrane transport (GO:1901381), negative regulation of G1/S transition of mitotic cell cycle (GO:2000134)

GO Molecular Function (6): zinc ion binding (GO:0008270), transmembrane transporter binding (GO:0044325), channel activator activity (GO:0099103), potassium channel activator activity (GO:0099104), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (5): nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), focal adhesion (GO:0005925)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
animal organ development	2
negative regulation of mitotic cell cycle phase transition	2
cellular anatomical structure	2
muscle structure development	1
anatomical structure morphogenesis	1
G2/M transition of mitotic cell cycle	1
regulation of G2/M transition of mitotic cell cycle	1
negative regulation of cell cycle G2/M phase transition	1
cellular developmental process	1
regulation of cell growth	1
cell growth	1
negative regulation of growth	1
negative regulation of cellular process	1
regulation of membrane depolarization	1
positive regulation of potassium ion transport	1
potassium ion transmembrane transport	1
regulation of potassium ion transmembrane transport	1
positive regulation of cation transmembrane transport	1
G1/S transition of mitotic cell cycle	1
negative regulation of cell cycle G1/S phase transition	1
regulation of G1/S transition of mitotic cell cycle	1
transition metal ion binding	1
protein binding	1
channel activity	1
channel regulator activity	1
transporter activator activity	1
potassium channel activity	1
potassium channel regulator activity	1
channel activator activity	1
binding	1
cation binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cytoplasm	1
membrane	1
cell periphery	1
cell-substrate junction	1

Protein interactions and networks

STRING

1092 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FHL1	RBPJ	Q06330	846
FHL1	INPP5A	Q14642	762
FHL1	EMD	P50402	707
FHL1	MYBPC3	Q14896	690
FHL1	TTN	Q8WZ42	688
FHL1	MYBPC2	Q14324	591
FHL1	IGFBP5	P24593	588
FHL1	ENO1	P06733	500
FHL1	MYOD1	P15172	496
FHL1	FHL2	Q14192	480
FHL1	DCUN1D5	Q9BTE7	461
FHL1	MYOT	Q9UBF9	450
FHL1	GRIN2D	O15399	433
FHL1	TMEM43	Q9BTV4	417
FHL1	PXN	P49023	411

IntAct

94 interactions, top by confidence:

A	B	Type	Score
PDLIM7	BAG3	psi-mi:“MI:0914”(association)	0.800
MAPK14	OBSL1	psi-mi:“MI:0914”(association)	0.790
CNOT3	CNOT1	psi-mi:“MI:0914”(association)	0.740
RHOA	CTSA	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
AKAP12	FHL1	psi-mi:“MI:0915”(physical association)	0.670
FHL1	NRIP1	psi-mi:“MI:0915”(physical association)	0.630
NRIP1	FHL1	psi-mi:“MI:0407”(direct interaction)	0.630
NRIP1	FHL1	psi-mi:“MI:0915”(physical association)	0.630
AKAP12	HSPA12A	psi-mi:“MI:0914”(association)	0.530
ZNF71	DKC1	psi-mi:“MI:0914”(association)	0.530
GPS1	PXDNL	psi-mi:“MI:0914”(association)	0.530
MANSC1	SMPD2	psi-mi:“MI:0914”(association)	0.530
FHL1	SRPK1	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
FHL1	ESR1	psi-mi:“MI:0915”(physical association)	0.400
FHL1	ZNF16	psi-mi:“MI:0915”(physical association)	0.370
FHL1	DBN1	psi-mi:“MI:0915”(physical association)	0.370
FHL1	DEAF1	psi-mi:“MI:0915”(physical association)	0.370
EED	FHL1	psi-mi:“MI:0915”(physical association)	0.370
HES1	FHL1	psi-mi:“MI:0915”(physical association)	0.370
PDE4DIP	FHL1	psi-mi:“MI:0915”(physical association)	0.370
TXNIP	FHL1	psi-mi:“MI:0915”(physical association)	0.370
C	FHL1	psi-mi:“MI:0915”(physical association)	0.370
RBPJ	SAMD1	psi-mi:“MI:0914”(association)	0.350
RBPJ	RPA2	psi-mi:“MI:0914”(association)	0.350
JUN		psi-mi:“MI:0914”(association)	0.350
JUN	TPM3	psi-mi:“MI:0914”(association)	0.350
TANK	CNOT1	psi-mi:“MI:0914”(association)	0.350

BioGRID (245): SRF (Reconstituted Complex), EP300 (Affinity Capture-Western), CREBBP (Affinity Capture-Western), Nfatc1 (Reconstituted Complex), Nfatc1 (Affinity Capture-Western), Nfatc1 (Co-localization), TTN (Two-hybrid), FHL1 (Two-hybrid), MYBPC1 (Two-hybrid), MYBPC1 (Affinity Capture-Western), FHL1 (Reconstituted Complex), ESR1 (Affinity Capture-Western), AKT1 (Affinity Capture-Western), FHL1 (Affinity Capture-MS), FHL1 (Affinity Capture-MS)

ESM2 similar proteins: A0M8R4, O04193, O35115, O70433, O80839, P21291, P29675, P47875, P50238, P50461, P50462, P50463, P50464, P53777, P63254, P63255, P67966, P67967, P97315, P97447, Q07DY3, Q07DZ4, Q09YI0, Q13642, Q13643, Q14192, Q16527, Q1ECF5, Q2IBA3, Q2KI95, Q2QLF4, Q2YDK0, Q32LE9, Q3MHY1, Q3ZBI6, Q4R7A4, Q4U0T9, Q500W4, Q56K04, Q5RC52

Diamond homologs: A0A1L8F1M4, A0M8R4, A0M8S5, A0M8U6, A1Z6W3, A8WH69, O35115, O43294, O43900, O60711, O70433, O94929, P47226, P48059, P49023, P49024, P50464, P97447, Q00PK1, Q07DW1, Q07DX3, Q07DY3, Q07DZ4, Q07E27, Q07E40, Q07E51, Q09476, Q09YI0, Q09YJ2, Q09YK3, Q09YL5, Q09YN8, Q108U9, Q13642, Q13643, Q14192, Q174I2, Q17QE2, Q28FG2, Q292U2

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
RING1	up-regulates	FHL1	binding
PIAS1	down-regulates	FHL1	sumoylation
SRC	“up-regulates activity”	FHL1	phosphorylation
FHL1	down-regulates	RBPJ	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	75
Likely pathogenic	22
Uncertain significance	263
Likely benign	186
Benign	17

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1071343	NM_001159699.2(FHL1):c.243C>A (p.Cys81Ter)	Pathogenic
1071860	NC_000023.10:g.(?135288556)(135293528_?)del	Pathogenic
1074316	NM_001159699.2(FHL1):c.590G>A (p.Trp197Ter)	Pathogenic
11547	NM_001159699.2(FHL1):c.413G>C (p.Trp138Ser)	Pathogenic
11549	NM_001159699.2(FHL1):c.428_430dup (p.Phe143_Thr144insIle)	Pathogenic
11550	NM_001159699.2(FHL1):c.415C>T (p.His139Tyr)	Pathogenic
11551	NM_001159699.2(FHL1):c.443G>T (p.Cys148Phe)	Pathogenic
11554	NM_001159699.2(FHL1):c.497G>A (p.Cys166Tyr)	Pathogenic
11555	NM_001159699.2(FHL1):c.358T>C (p.Cys120Arg)	Pathogenic
11556	NM_001159699.2(FHL1):c.889T>G (p.Ter297Glu)	Pathogenic
11557	NM_001159699.2(FHL1):c.673T>C (p.Cys225Arg)	Pathogenic
11558	NM_001159699.2(FHL1):c.865dup (p.Cys289fs)	Pathogenic
11559	NM_001159702.3(FHL1):c.838G>A (p.Val280Met)	Pathogenic
11560	NM_001159699.2(FHL1):c.736+1G>A	Pathogenic
11561	NM_001159699.2(FHL1):c.416A>T (p.His139Leu)	Pathogenic
11562	NM_001159699.2(FHL1):c.417C>G (p.His139Gln)	Pathogenic
11563	NM_001159699.2(FHL1):c.499_507del (p.Val167_Cys169del)	Pathogenic
1184470	NM_001159699.2(FHL1):c.708_736+22del	Pathogenic
1322915	NM_001159699.2(FHL1):c.519dup (p.Phe174fs)	Pathogenic
1359487	NM_001159699.2(FHL1):c.55G>T (p.Glu19Ter)	Pathogenic
1363228	NM_001159699.2(FHL1):c.414del (p.Trp138fs)	Pathogenic
1392309	NM_001159699.2(FHL1):c.417C>A (p.His139Gln)	Pathogenic
1404846	NM_001159699.2(FHL1):c.505T>A (p.Cys169Ser)	Pathogenic
1457116	NM_001159699.2(FHL1):c.618del (p.Cys207fs)	Pathogenic
1457827	NM_001159699.2(FHL1):c.288del (p.Phe96fs)	Pathogenic
1458011	NM_001159699.2(FHL1):c.441del (p.Cys148fs)	Pathogenic
1459000	NM_001159699.2(FHL1):c.875G>A (p.Cys292Tyr)	Pathogenic
1500210	NM_001159699.2(FHL1):c.736+1G>C	Pathogenic
1506742	NM_001159699.2(FHL1):c.863_864dup (p.Cys289fs)	Pathogenic
1958260	NM_001159699.2(FHL1):c.801delinsAA (p.His267fs)	Pathogenic

SpliceAI

1036 predictions. Top by Δscore:

Variant	Effect	Δscore
X:136206404:CAGGT:C	acceptor_loss	1.0000
X:136206405:A:AG	acceptor_gain	1.0000
X:136206405:A:C	acceptor_loss	1.0000
X:136206406:G:GA	acceptor_gain	1.0000
X:136206406:GGT:G	acceptor_gain	1.0000
X:136206406:GGTC:G	acceptor_gain	1.0000
X:136206588:GGTA:G	donor_loss	1.0000
X:136206589:GTA:G	donor_loss	1.0000
X:136206590:T:A	donor_loss	1.0000
X:136207006:T:TA	acceptor_gain	1.0000
X:136207007:G:A	acceptor_gain	1.0000
X:136207011:TCCA:T	acceptor_loss	1.0000
X:136207014:A:AG	acceptor_gain	1.0000
X:136207014:AG:A	acceptor_gain	1.0000
X:136207014:AGGAG:A	acceptor_gain	1.0000
X:136207015:G:GT	acceptor_gain	1.0000
X:136207015:GG:G	acceptor_gain	1.0000
X:136207015:GGA:G	acceptor_gain	1.0000
X:136207015:GGAGG:G	acceptor_gain	1.0000
X:136207188:CAG:C	donor_loss	1.0000
X:136207189:AG:A	donor_loss	1.0000
X:136207191:G:GA	donor_loss	1.0000
X:136207192:T:A	donor_loss	1.0000
X:136207787:T:TA	acceptor_gain	1.0000
X:136207788:GCA:G	acceptor_loss	1.0000
X:136207789:CA:C	acceptor_loss	1.0000
X:136207790:A:AC	acceptor_loss	1.0000
X:136207790:A:AG	acceptor_gain	1.0000
X:136207791:G:GT	acceptor_gain	1.0000
X:136207791:GGA:G	acceptor_gain	1.0000

AlphaMissense

1998 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:136206552:T:G	C40W	1.000
X:136208515:T:C	C188R	1.000
X:136208517:T:G	C188W	1.000
X:136208551:T:C	F200L	1.000
X:136208553:C:A	F200L	1.000
X:136208553:C:G	F200L	1.000
X:136206451:T:A	C7S	0.999
X:136206451:T:C	C7R	0.999
X:136206452:G:C	C7S	0.999
X:136206453:C:G	C7W	0.999
X:136206514:T:C	C28R	0.999
X:136206523:T:A	C31S	0.999
X:136206523:T:C	C31R	0.999
X:136206524:G:C	C31S	0.999
X:136206525:C:G	C31W	0.999
X:136206526:T:C	F32L	0.999
X:136206528:T:A	F32L	0.999
X:136206528:T:G	F32L	0.999
X:136206550:T:A	C40S	0.999
X:136206550:T:C	C40R	0.999
X:136206551:G:A	C40Y	0.999
X:136206551:G:C	C40S	0.999
X:136206551:G:T	C40F	0.999
X:136206559:T:A	C43S	0.999
X:136206559:T:C	C43R	0.999
X:136206560:G:C	C43S	0.999
X:136207040:T:A	W61R	0.999
X:136207040:T:C	W61R	0.999
X:136207052:T:C	C65R	0.999
X:136207053:G:A	C65Y	0.999

dbSNP variants (sampled 300 via entrez): RS1000001684 (X:136167626 T>G), RS1000063544 (X:136150756 C>T), RS1000095235 (X:136160748 A>C,G), RS1000169066 (X:136160299 C>T), RS1000224196 (X:136173751 T>G), RS1000246296 (X:136186274 C>G), RS1000284030 (X:136171945 C>T), RS1000365223 (X:136178034 T>A,G), RS1000369998 (X:136182935 A>G), RS1000419246 (X:136177568 T>C), RS1000552873 (X:136147686 C>T), RS1000596854 (X:136186669 A>G), RS1000637400 (X:136196279 C>T), RS1000689875 (X:136195430 G>A), RS1000736016 (X:136169269 G>A)

Disease associations

OMIM: gene MIM:300163 | disease phenotypes: MIM:300696, MIM:300280, MIM:300695, MIM:300717, MIM:300718, MIM:300243, MIM:160150, MIM:267700, MIM:192600, MIM:310300

GenCC curated gene-disease

Disease	Classification	Inheritance
X-linked myopathy with postural muscle atrophy	Definitive	X-linked
myopathy, reducing body, X-linked, early-onset, severe	Strong	X-linked
FHL1-related myopathy	Strong	X-linked
X-linked scapuloperoneal muscular dystrophy	Supportive	X-linked
reducing body myopathy	Supportive	X-linked
X-linked Emery-Dreifuss muscular dystrophy	Supportive	X-linked

Mondo (15): X-linked myopathy with postural muscle atrophy (MONDO:0010401), Uruguay Faciocardiomusculoskeletal syndrome (MONDO:0010292), X-linked scapuloperoneal muscular dystrophy (MONDO:0010400), myopathy, reducing body, X-linked, early-onset, severe (MONDO:0010414), myopathy, reducing body, X-linked, childhood-onset (MONDO:0010415), Christianson syndrome (MONDO:0010278), centronuclear myopathy (MONDO:0018947), Emery-Dreifuss muscular dystrophy 6, X-linked (MONDO:0800318), familial hemophagocytic lymphohistiocytosis type 1 (MONDO:0009974), familial hypertrophic cardiomyopathy (MONDO:0024573), Emery-Dreifuss muscular dystrophy (MONDO:0016830), hypertrophic cardiomyopathy (MONDO:0005045), reducing body myopathy (MONDO:0019948), X-linked Emery-Dreifuss muscular dystrophy (MONDO:0010680), FHL1-related myopathy (MONDO:0800462)

Orphanet (10): X-linked myopathy with postural muscle atrophy (Orphanet:178461), X-linked scapuloperoneal muscular dystrophy (Orphanet:431272), Reducing body myopathy (Orphanet:97239), Christianson syndrome (Orphanet:85278), Centronuclear myopathy (Orphanet:595), Familial hemophagocytic lymphohistiocytosis (Orphanet:540), Rare familial disorder with hypertrophic cardiomyopathy (Orphanet:99739), Emery-Dreifuss muscular dystrophy (Orphanet:261), Rare hypertrophic cardiomyopathy (Orphanet:217569), NON RARE IN EUROPE: Familial isolated hypertrophic cardiomyopathy (Orphanet:155)

HPO phenotypes

120 total (30 of 120 shown, HPO-id order):

HPO	Term
HP:0000232	Everted lower lip vermilion
HP:0000244	Brachyturricephaly
HP:0000278	Retrognathia
HP:0000336	Prominent supraorbital ridges
HP:0000339	Pugilistic facies
HP:0000358	Posteriorly rotated ears
HP:0000369	Low-set ears
HP:0000445	Wide nose
HP:0000448	Prominent nose
HP:0000470	Short neck
HP:0000475	Broad neck
HP:0000494	Downslanted palpebral fissures
HP:0000508	Ptosis
HP:0000574	Thick eyebrow
HP:0000664	Synophrys
HP:0000767	Pectus excavatum
HP:0000912	Sprengel anomaly
HP:0001169	Broad palm
HP:0001249	Intellectual disability
HP:0001252	Hypotonia
HP:0001265	Hyporeflexia
HP:0001284	Areflexia
HP:0001288	Gait disturbance
HP:0001315	Reduced tendon reflexes
HP:0001371	Flexion contracture
HP:0001374	Congenital hip dislocation
HP:0001387	Joint stiffness
HP:0001417	X-linked inheritance
HP:0001419	X-linked recessive inheritance
HP:0001423	X-linked dominant inheritance

GWAS associations

0 associations (top):

MeSH disease descriptors (8)

Descriptor	Name	Tree numbers
D002312	Cardiomyopathy, Hypertrophic	C14.280.238.100; C14.280.484.048.750.070.160
D024741	Cardiomyopathy, Hypertrophic, Familial	C14.280.238.100.500; C14.280.484.048.750.070.160.500; C16.320.160
D020389	Muscular Dystrophy, Emery-Dreifuss	C05.651.534.500.350; C10.668.491.175.500.350; C16.320.322.625; C16.320.577.350
D000083143	X-Linked Emery-Dreifuss Muscular Dystrophy	C05.651.534.500.350.500; C10.668.491.175.500.350.500; C16.320.322.625.500; C16.320.577.350.500
C567484	Mental Retardation, X-Linked, Syndromic, Christianson Type (supp.)
C567468	Myopathy, Reducing Body, X-Linked, Childhood-Onset (supp.)
C567469	Myopathy, Reducing Body, X-Linked, Early-Onset, Severe (supp.)
C564544	Uruguay Faciocardiomusculoskeletal Syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

79 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases methylation	4
Valproic Acid	affects expression, decreases methylation, increases expression	4
bisphenol S	decreases methylation, increases expression	2
Doxorubicin	decreases expression, affects expression	2
Estradiol	affects cotreatment, decreases expression, increases expression, decreases reaction	2
Nickel	decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
2,4,6-tribromophenol	decreases expression	1
triphenyl phosphate	affects expression	1
6-hydroxy-5-((p- sulfophenyl)azo)-2-naphthalenesulfonic acid disodium salt	affects cotreatment, increases expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
decabromobiphenyl ether	decreases expression	1
beta-lapachone	increases expression	1
sulforaphane	decreases expression	1
tetrabromobisphenol A	decreases expression	1
perfluorooctanoic acid	increases expression	1
doxifluridine	decreases response to substance	1
manganese chloride	decreases expression	1
potassium chromate(VI)	decreases expression	1
1-UFT protocol	decreases response to substance	1
S-(1,2-dichlorovinyl)cysteine	decreases expression, affects cotreatment	1
S 1 (combination)	decreases response to substance	1
CGP 52608	increases reaction, affects binding	1
chloropicrin	decreases expression	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
bisphenol B	increases expression	1
abrine	decreases expression	1

Cellosaurus cell lines

7 cell lines: 4 cancer cell line, 2 induced pluripotent stem cell, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1S4	Abcam HeLa FHL1 KO	Cancer cell line	Female
CVCL_C9LI	INEUi003-A	Induced pluripotent stem cell	Male
CVCL_C9LJ	INEUi004-A	Induced pluripotent stem cell	Female
CVCL_D7PW	Ubigene A-549 FHL1 KO	Cancer cell line	Male
CVCL_D8LE	Ubigene HCT 116 FHL1 KO	Cancer cell line	Male
CVCL_D9EW	Ubigene HEK293 FHL1 KO	Transformed cell line	Female
CVCL_E0D3	Ubigene HeLa FHL1 KO	Cancer cell line	Female

Clinical trials (associated diseases)

243 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.
NCT00368355	PHASE2	COMPLETED	T Cell Depletion for Recipients of HLA Haploidentical Related Donor Stem Cell Grafts
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