CRYAB

Summary

CRYAB (crystallin alpha B, HGNC:2389) is a protein-coding gene on chromosome 11q23.1, encoding Alpha-crystallin B chain (P02511). May contribute to the transparency and refractive index of the lens.

Mammalian lens crystallins are divided into alpha, beta, and gamma families. Alpha crystallins are composed of two gene products: alpha-A and alpha-B, for acidic and basic, respectively. Alpha crystallins can be induced by heat shock and are members of the small heat shock protein (HSP20) family. They act as molecular chaperones although they do not renature proteins and release them in the fashion of a true chaperone; instead they hold them in large soluble aggregates. These heterogeneous aggregates consist of 30-40 subunits; the alpha-A and alpha-B subunits have a 3:1 ratio, respectively. Two additional functions of alpha crystallins are an autokinase activity and participation in the intracellular architecture. The encoded protein has been identified as a moonlighting protein based on its ability to perform mechanistically distinct functions. Alpha-A and alpha-B gene products are differentially expressed; alpha-A is preferentially restricted to the lens and alpha-B is expressed widely in many tissues and organs. Elevated expression of alpha-B crystallin occurs in many neurological diseases; a missense mutation cosegregated in a family with a desmin-related myopathy. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 1410 — RefSeq curated summary.

At a glance

• Gene–disease (curated): myofibrillar myopathy 2 (Definitive, GenCC) — +7 more curated relationships
• GWAS associations: 4
• Clinical variants (ClinVar): 376 total — 16 pathogenic, 5 likely-pathogenic
• Phenotypes (HPO): 60
• Druggable target: yes
• MANE Select transcript: NM_001289808

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2389
Approved symbol	CRYAB
Name	crystallin alpha B
Location	11q23.1
Locus type	gene with protein product
Status	Approved
Aliases	HSPB5
Ensembl gene	ENSG00000109846
Ensembl biotype	protein_coding
OMIM	123590
Entrez	1410

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 19 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000227251, ENST00000524660, ENST00000525823, ENST00000526167, ENST00000526180, ENST00000527899, ENST00000527950, ENST00000528628, ENST00000528961, ENST00000529647, ENST00000531198, ENST00000533280, ENST00000533475, ENST00000533879, ENST00000533971, ENST00000616970, ENST00000650687, ENST00000651164, ENST00000651650, ENST00000652223, ENST00000652606, ENST00000858791

RefSeq mRNA: 6 — MANE Select: NM_001289808 NM_001289807, NM_001289808, NM_001330379, NM_001368245, NM_001368246, NM_001885

CCDS: CCDS81626, CCDS8351

Canonical transcript exons

ENST00000650687 — 3 exons

Exon	Start	End
ENSE00002175177	111911524	111911770
ENSE00003759983	111910327	111910449
ENSE00003892258	111908564	111908967

Expression profiles

Bgee: expression breadth ubiquitous, 289 present calls, max score 99.95.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 446.4261 / max 32202.3878, expressed in 1192 samples.

FANTOM5 promoters (17 alternative TSS)

Promoter ID	TPM avg	Samples expressed
122295	386.2922	1054
206448	21.8253	805
122298	14.5154	854
206447	8.1665	534
122296	6.1693	683
122291	5.8711	320
122290	0.6469	102
122299	0.6422	371
122289	0.5475	91
122287	0.5422	93

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
middle frontal gyrus	UBERON:0002702	99.95	gold quality
left ventricle myocardium	UBERON:0006566	99.95	gold quality
cardiac ventricle	UBERON:0002082	99.94	gold quality
heart left ventricle	UBERON:0002084	99.94	gold quality
right atrium auricular region	UBERON:0006631	99.94	gold quality
cardiac atrium	UBERON:0002081	99.93	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	99.93	gold quality
apex of heart	UBERON:0002098	99.92	gold quality
olfactory bulb	UBERON:0002264	99.92	gold quality
cranial nerve II	UBERON:0000941	99.91	gold quality
gastrocnemius	UBERON:0001388	99.91	gold quality
heart right ventricle	UBERON:0002080	99.91	gold quality
spinal cord	UBERON:0002240	99.91	gold quality
hindlimb stylopod muscle	UBERON:0004252	99.91	gold quality
inferior vagus X ganglion	UBERON:0005363	99.91	gold quality
myocardium	UBERON:0002349	99.90	gold quality
cardiac muscle of right atrium	UBERON:0003379	99.88	gold quality
tibialis anterior	UBERON:0001385	99.87	gold quality
medial globus pallidus	UBERON:0002477	99.86	gold quality
body of tongue	UBERON:0011876	99.86	gold quality
muscle of leg	UBERON:0001383	99.85	gold quality
globus pallidus	UBERON:0001875	99.85	gold quality
metanephros cortex	UBERON:0010533	99.83	gold quality
tibial nerve	UBERON:0001323	99.82	gold quality
diaphragm	UBERON:0001103	99.81	gold quality
muscle organ	UBERON:0001630	99.81	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	99.81	gold quality
skeletal muscle organ	UBERON:0014892	99.81	gold quality
biceps brachii	UBERON:0001507	99.78	gold quality
vena cava	UBERON:0004087	99.78	gold quality

Single-cell (SCXA)

Detected in 30 experiment(s), a significant marker in 28.

Experiment	Marker?	Max mean expression
E-MTAB-9435	yes	11122.19
E-CURD-126	yes	8933.11
E-MTAB-8142	yes	7781.15
E-GEOD-135922	yes	7545.43
E-HCAD-11	yes	6916.81
E-GEOD-84465	yes	5209.23
E-MTAB-8410	yes	5084.18
E-CURD-46	yes	3911.17
E-GEOD-180759	yes	3753.33
E-HCAD-31	yes	3629.92
E-HCAD-25	yes	3369.98
E-MTAB-6701	yes	2528.78
E-HCAD-13	yes	2517.80
E-HCAD-35	yes	2163.59
E-MTAB-10290	yes	1580.38

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AHR, ARNT, ESR1, ETS1, GATA3, HMGA1, HSF1, HSF2, HSF4, MAF, MAFA, MAFB, NR3C1, PAX6, RARB, RXRA, RXRB, SMARCA1, SOX17, SP1, SRF, TFAP2A, TFAP2B, TP53, TP73

miRNA regulators (miRDB)

12 targeting CRYAB, 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-9718	99.94	68.91	918
HSA-MIR-383-3P	99.85	65.84	1359
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-1179	99.71	68.70	1040
HSA-MIR-578	99.46	68.36	1787
HSA-MIR-100-3P	99.20	67.33	672
HSA-MIR-3145-3P	98.85	69.07	2031
HSA-MIR-367-5P	98.84	67.18	902
HSA-MIR-628-5P	98.36	67.74	844
HSA-MIR-653-3P	98.31	67.71	1542
HSA-MIR-938	97.41	68.28	656
HSA-MIR-5579-3P	97.00	68.81	1111

Literature-anchored findings (GeneRIF, showing 40)

• Alpha crystallin is a moonlighting protein that functions as a heat shock protein as well as a lens crystallin. (PMID:10217480)
• mutation causes dominant congenital posterior polar cataract (PMID:11577372)
• Of the 24 genes regulated during osteoblastic differentiation, only one, the alpha B crystalline gene, showed evidence of linkage. (PMID:11771659)
• HSP27 and alphaB-crystallin are increased, phosphorylated and localized in aggresomes when proteasome activity is inhibited (PMID:11926998)
• suppression of dithiothreitol-induced aggregation of abrin by alpha B-crystallin (PMID:12095619)
• These findings indicate that alpha B-crystallin is a novel negative regulator of myogenic apoptosis that directly links the differentiation program to apoptosis resistance. (PMID:12140279)
• the involvement of alphaB-crystallin in the ubiquitin/proteasome pathway in a phosphorylation- and cell cycle-dependent manner (PMID:12468532)
• The regions of alpha B crystallin most affected by interaction with ATP are near putative substrate binding regions and in the C-terminal extension, as identified by hydrogen-deuterium exchange. (PMID:12501218)
• CRYAB shows increased transcript levels in Alzheimer’s disease brains. (PMID:12600716)
• The results indicate that Hsp27 promotes stability of alpha B-crystallin. (PMID:12646227)
• CRYAB is a nuclear speckle component in unstressed cells in tissue culture. (PMID:12837281)
• The peripheral response towards the myelin antigen alpha B-crystallin is neither quantitatively nor qualitatively peculiar to multiple sclerosis (MS) and is not a prerequisite for MS induction in this Sardininan population. (PMID:12940843)
• Alpha B-crystallin peptide 1-16, generated as a remnant epitope following digestion with natural gelatinase B, provokes a significant T cell response in alpha B-crystallin knockout mice. (PMID:12965253)
• the protective effect of alphaB-crystallin requires synthesis of the endogenous heat shock proteins (PMID:14523008)
• the SRLFDQFFG sequence region contributes to the oligomer dynamics in addition to the higher order assembly and structural stability, and is one of the critical motifs in structure-function regulation of alpha A- and alpha B-crystallin (PMID:14532291)
• alphaB-crystallin bound in the position of the N2B region of titin, but not to PEVK region (PMID:14676215)
• A truncating mutation in the C-terminal region of alphaB-crystallin was determined in 2 patients with adult-onset myofibrillar myopathy; the region is crucial for the solubilization and chaperone functions of the molecule. (PMID:14681890)
• Autoreactive alpha B-crystallin-specific T helper type 1 (Th1) cells may have the potential to contribute to the pathogenesis of multiple sclerosis. (PMID:14743435)
• accumulation and abnormal modification of alpha-crystallins might be implicated in the pathogenic mechanism of anterior polar cataracts. (PMID:15004872)
• Phosphorylation of alphaB-crystallin alters chaperone function through loss of dimeric substructure (PMID:15117944)
• CRYAB was expressed in vivo in lungs containing metastasized MDA-MB-435 cells but not in normal lung tissue of athymic mice, suggesting that it is an important cellular protein that is down regulated through BRMS1 mediated metastasis suppression. (PMID:15168732)
• alpha-synuclein and alphaB-crystallin interact readily with each other and affect each other’s properties, in particular alpha-synuclein fibril formation and alphaB-crystallin chaperone action (PMID:15236975)
• presence of WT-alphaB in the alpha-crystallin heteroaggregate leads to packing-induced structural changes which influences the oligomerization and modulate chaperone activity (PMID:15284238)
• HSF4 binds to alphaB-crystallin, Hsp70, and Hsp82 promoters and has a role in interacting with the canonical heat shock element of the alphaB-crystallin gene (PMID:15308659)
• Alpha-B-crystallin associates with the perinuclear Golgi in a cell cycle-dependent fashion in U373 human glioblastoma cells. It appears in the nascent Golgi immediately following cytokinesis. (PMID:15339919)
• Studies with synchronized human glioblastoma cell line U373MG suggest association of aB-crystallin with cell cycle-dependent Golgi reorganization. (PMID:15339919)
• structure activity relationship (PMID:15382236)
• Using a cross-linker, close proximity of C termini of alpha B and alpha C crystallins was demonstrated. (PMID:15388868)
• alphaB-crystallin has a phosphorylation-dependent role in the ubiquitination of a component of SC35 speckles (PMID:15511225)
• Alpha B-crystallin is a major chaperone in multiple system atrophy. A role for this protein in the formation of inclusion bodies in glial cells is suggested. (PMID:15639800)
• alpha B-crystallin is a novel inhibitor of TRAIL-induced apoptosis that suppresses the activation of caspase-3. (PMID:15653686)
• isothermal titration calorimetric analysis of hydrophobicity and the chaperone-like function of alphaA- and alphaB-crystallin (PMID:15817465)
• The role of CRYAB in the reactivation of denaturant-inactivated G6PD is reported. (PMID:15952936)
• role of CRYA2 in protein conformational diseases, particularly in Alzheimer’s disease (PMID:16053447)
• establish the importance of residues 60-71 in oligomerization of alphaB-crystallin and subunit interaction between alphaB- and alphaA-crystallins (PMID:16142923)
• Our results suggest that a variety of oligomers composed of different proportions of different sHSPs may form in cell types expressing multiple sHSPs. (PMID:16225851)
• Identification of protein domains of alphaB crystallin that are needed for chaperone activity. (PMID:16274233)
• alphaB-crystallin is a novel oncoprotein expressed in basal-like breast carcinomas that independently predicts shorter survival. (PMID:16395408)
• role of pH, Ca2+, and ATP in regulating the subunit dynamics of alphaB crystallin was investigated; a model for the relationship between the subunit dynamics and chaperone activity of alphaB crystallin was established (PMID:16480679)
• Arg157His mutation of alphaB crystallin may be involved in the pathogenesis of dilated cardiomyopathy via impaired accommodation to the heart-specific N2B domain of titin/connectin. (PMID:16483541)

Cross-species orthologs

22 orthologs

Organism	Symbol	Gene ID
danio_rerio	cryaba	ENSDARG00000042621
danio_rerio	cryabb	ENSDARG00000101380
mus_musculus	Cryab	ENSMUSG00000032060
rattus_norvegicus	Cryab	ENSRNOG00000010524
drosophila_melanogaster	Hsp22	FBGN0001223
drosophila_melanogaster	Hsp23	FBGN0001224
drosophila_melanogaster	Hsp26	FBGN0001225
drosophila_melanogaster	Hsp67Ba	FBGN0001227
drosophila_melanogaster	Hsp67Bc	FBGN0001229
drosophila_melanogaster	l(2)efl	FBGN0011296
drosophila_melanogaster	CG14207	FBGN0031037
caenorhabditis_elegans		WBGENE00002011
caenorhabditis_elegans		WBGENE00002015
caenorhabditis_elegans		WBGENE00002016
caenorhabditis_elegans		WBGENE00002017
caenorhabditis_elegans		WBGENE00002018
caenorhabditis_elegans		WBGENE00002019
caenorhabditis_elegans		WBGENE00002020
caenorhabditis_elegans		WBGENE00002023
caenorhabditis_elegans		WBGENE00008591
caenorhabditis_elegans		WBGENE00008592
caenorhabditis_elegans	hsp-12.1	WBGENE00011906

Paralogs (8): HSPB6 (ENSG00000004776), HSPB1 (ENSG00000106211), HSPB8 (ENSG00000152137), CRYAA (ENSG00000160202), HSPB3 (ENSG00000169271), HSPB2 (ENSG00000170276), HSPB7 (ENSG00000173641), HSPB9 (ENSG00000260325)

Protein

Protein identifiers

Alpha-crystallin B chain — P02511 (reviewed: P02511)

Alternative names: Alpha(B)-crystallin, Heat shock protein beta-5, Heat shock protein family B member 5, Renal carcinoma antigen NY-REN-27, Rosenthal fiber component

All UniProt accessions (7): P02511, A0A024R3B9, E9PJL7, E9PNH7, E9PRA8, E9PS12, V9HW27

UniProt curated annotations — full annotation on UniProt →

Function. May contribute to the transparency and refractive index of the lens. Has chaperone-like activity, preventing aggregation of various proteins under a wide range of stress conditions. In lens epithelial cells, stabilizes the ATP6V1A protein, preventing its degradation by the proteasome.

Subunit / interactions. Heteromer composed of three CRYAA and one CRYAB subunits. Aggregates with homologous proteins, including the small heat shock protein HSPB1, to form large heteromeric complexes. Inter-subunit bridging via zinc ions enhances stability, which is crucial as there is no protein turn over in the lens. Interacts with HSPBAP1 and TTN/titin. Interacts with TMEM109; in the cellular response to DNA damage. Interacts with DES; binds rapidly during early stages of DES filament assembly and a reduced binding seen in the later stages. Interacts with TMED10; the interaction mediates the translocation from the cytoplasm into the ERGIC (endoplasmic reticulum-Golgi intermediate compartment) and thereby secretion. Interacts with ATP6V1A and with MTOR, forming a ternary complex.

Subcellular location. Cytoplasm. Nucleus. Secreted. Lysosome.

Tissue specificity. Lens as well as other tissues. Expressed in myocardial tissue.

Disease relevance. Myopathy, myofibrillar, 2A, adult-onset (MFM2A) [MIM:608810] A form of myofibrillar myopathy, a group of chronic neuromuscular disorders characterized at ultrastructural level by disintegration of the sarcomeric Z disk and myofibrils, and replacement of the normal myofibrillar markings by small dense granules, or larger hyaline masses, or amorphous material. MFM2A is an autosomal dominant form characterized by weakness of the proximal and distal limb muscles, weakness of the neck, velopharynx and trunk muscles, respiratory insufficiency, hypertrophic cardiomyopathy, and cataract. The disease is caused by variants affecting the gene represented in this entry. Cataract 16, multiple types (CTRCT16) [MIM:613763] An opacification of the crystalline lens of the eye that frequently results in visual impairment or blindness. Opacities vary in morphology, are often confined to a portion of the lens, and may be static or progressive. In general, the more posteriorly located and dense an opacity, the greater the impact on visual function. CTRCT16 includes posterior polar cataract, among others. Posterior polar cataract is a subcapsular opacity, usually disk-shaped, located at the back of the lens. The disease is caused by variants affecting the gene represented in this entry. CRYAB mutations may be involved in restrictive cardiomyopathy (RCM), a rare non-ischemic myocardial disease. RCM is characterized by restrictive ventricular-filling physiology in the presence of normal or reduced diastolic and/or systolic volumes (of 1 or both ventricles), biatrial enlargement, and normal ventricular wall thickness. Myopathy, myofibrillar, 2B, infantile-onset (MFM2B) [MIM:613869] A form of myofibrillar myopathy, a group of chronic neuromuscular disorders characterized at ultrastructural level by disintegration of the sarcomeric Z disk and myofibrils, and replacement of the normal myofibrillar markings by small dense granules, or larger hyaline masses, or amorphous material. MFM2B is an autosomal recessive form characterized by onset in the first weeks of life after a normal neonatal period. Affected infants show rapidly progressive muscular rigidity of the trunk and limbs associated with increasing respiratory difficulty resulting in death before age 3 years. The disease is caused by variants affecting the gene represented in this entry. Cardiomyopathy, dilated, 1II (CMD1II) [MIM:615184] A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the small heat shock protein (HSP20) family.

RefSeq proteins (6): NP_001276736, NP_001276737, NP_001317308, NP_001355174, NP_001355175, NP_001876 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001436	Alpha-crystallin/sHSP_animal	Family
IPR002068	A-crystallin/Hsp20_dom	Domain
IPR003090	Alpha-crystallin_N	Domain
IPR008978	HSP20-like_chaperone	Homologous_superfamily
IPR037882	ACD_alphaB-crystallin	Domain
IPR055269	Alpha-crystallin/HSP_16	Family

Pfam: PF00011, PF00525

UniProt features (43 total): strand 10, sequence variant 9, modified residue 6, binding site 5, site 3, glycosylation site 2, sequence conflict 2, helix 2, chain 1, domain 1, region of interest 1, turn 1

Structure

Experimental structures (PDB)

21 structures.

PDB	Method	Resolution (Å)
4M5S	X-RAY DIFFRACTION	1.37
3SGP	X-RAY DIFFRACTION	1.4
7ROJ	X-RAY DIFFRACTION	1.6
3SGM	X-RAY DIFFRACTION	1.7
3SGS	X-RAY DIFFRACTION	1.7
2Y1Y	X-RAY DIFFRACTION	2
4M5T	X-RAY DIFFRACTION	2
3SGR	X-RAY DIFFRACTION	2.17
2Y1Z	X-RAY DIFFRACTION	2.5
3SGO	X-RAY DIFFRACTION	2.56
2WJ7	X-RAY DIFFRACTION	2.63
5VVV	X-RAY DIFFRACTION	2.8
3SGN	X-RAY DIFFRACTION	2.81
3L1G	X-RAY DIFFRACTION	3.32
9BEE	ELECTRON MICROSCOPY	3.4
2Y22	X-RAY DIFFRACTION	3.7
2YGD	ELECTRON MICROSCOPY	9.4
3J07	SOLID-STATE NMR, SOLUTION SCATTERING, ELECTRON MICROSCOPY	20
2KLR	SOLID-STATE NMR
2N0K	SOLUTION NMR
6BP9	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P02511-F1	75.42	0.39

Functional residue map

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

Catalytic / active sites (3): 68 (susceptible to oxidation); 48 (susceptible to oxidation); 60 (susceptible to oxidation)

Ligand- & substrate-binding residues (5): 83; 104; 106; 111; 119

Post-translational modifications (6): 1, 19, 45, 59, 92, 166

Glycosylation sites (2): 41, 170

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-3371571	HSF1-dependent transactivation

MSigDB gene sets: 491 (showing top): GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_ASSEMBLY, GOBP_RESPONSE_TO_IONIZING_RADIATION, GRUETZMANN_PANCREATIC_CANCER_DN, GOBP_RESPONSE_TO_ESTRADIOL, PEREZ_TP63_TARGETS, ENK_UV_RESPONSE_KERATINOCYTE_UP, GOBP_NEGATIVE_REGULATION_OF_CELL_GROWTH, GOBP_NEGATIVE_REGULATION_OF_REACTIVE_OXYGEN_SPECIES_METABOLIC_PROCESS, ASTON_MAJOR_DEPRESSIVE_DISORDER_DN, GOBP_GROWTH, GOCC_CELL_SURFACE, GOBP_CELLULAR_RESPONSE_TO_GAMMA_RADIATION, GAUSSMANN_MLL_AF4_FUSION_TARGETS_E_UP, KYNG_DNA_DAMAGE_DN, MODULE_329

GO Biological Process (27): response to hypoxia (GO:0001666), lens development in camera-type eye (GO:0002088), protein folding (GO:0006457), glutathione metabolic process (GO:0006749), muscle contraction (GO:0006936), tubulin complex assembly (GO:0007021), muscle organ development (GO:0007517), response to heat (GO:0009408), negative regulation of gene expression (GO:0010629), negative regulation of cell growth (GO:0030308), microtubule polymerization or depolymerization (GO:0031109), negative regulation of protein-containing complex assembly (GO:0031333), response to estradiol (GO:0032355), negative regulation of intracellular transport (GO:0032387), protein refolding (GO:0042026), response to hydrogen peroxide (GO:0042542), negative regulation of apoptotic process (GO:0043066), regulation of programmed cell death (GO:0043067), negative regulation of DNA-templated transcription (GO:0045892), protein stabilization (GO:0050821), stress-activated MAPK cascade (GO:0051403), apoptotic process involved in morphogenesis (GO:0060561), cellular response to gamma radiation (GO:0071480), negative regulation of amyloid fibril formation (GO:1905907), negative regulation of reactive oxygen species metabolic process (GO:2000378), negative regulation of metabolic process (GO:0009892), camera-type eye development (GO:0043010)

GO Molecular Function (11): amyloid-beta binding (GO:0001540), structural molecule activity (GO:0005198), structural constituent of eye lens (GO:0005212), microtubule binding (GO:0008017), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), protein-containing complex binding (GO:0044877), metal ion binding (GO:0046872), obsolete unfolded protein binding (GO:0051082), protein binding (GO:0005515), cytoskeletal protein binding (GO:0008092)

GO Cellular Component (21): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), mitochondrion (GO:0005739), lysosome (GO:0005764), cytosol (GO:0005829), cell surface (GO:0009986), Z disc (GO:0030018), axon (GO:0030424), M band (GO:0031430), actin filament bundle (GO:0032432), protein-containing complex (GO:0032991), dendritic spine (GO:0043197), perikaryon (GO:0043204), extracellular exosome (GO:0070062), synaptic membrane (GO:0097060), cardiac myofibril (GO:0097512), extracellular region (GO:0005576), plasma membrane (GO:0005886), I band (GO:0031674), contractile muscle fiber (GO:0043292)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Cellular response to heat stress	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	10
response to stress	2
protein-containing complex assembly	2
negative regulation of cellular process	2
protein binding	2
binding	2
intracellular membrane-bounded organelle	2
cytoplasm	2
response to decreased oxygen levels	1
camera-type eye development	1
anatomical structure development	1
cellular process	1
protein maturation	1
modified amino acid metabolic process	1
sulfur compound metabolic process	1
muscle system process	1
animal organ development	1
muscle structure development	1
response to temperature stimulus	1
gene expression	1
regulation of gene expression	1
negative regulation of macromolecule biosynthetic process	1
regulation of cell growth	1
cell growth	1
negative regulation of growth	1
microtubule cytoskeleton organization	1
regulation of protein-containing complex assembly	1
negative regulation of cellular component organization	1
response to lipid	1
response to oxygen-containing compound	1
regulation of intracellular transport	1
intracellular transport	1
negative regulation of transport	1
protein folding	1
response to reactive oxygen species	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
programmed cell death	1
regulation of cellular process	1

Protein interactions and networks

STRING

2826 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CRYAB	BAG3	O95817	875
CRYAB	MYOT	Q9UBF9	851
CRYAB	CRYBB2	P43320	836
CRYAB	CRYBB1	P53674	824
CRYAB	CRYBB3	P26998	814
CRYAB	CRYGS	P22914	809
CRYAB	CRYBA4	P53673	808
CRYAB	CRYBA1	P05813	756
CRYAB	CRYGD	P07320	736
CRYAB	LDB3	O75112	724
CRYAB	CRYBA2	P53672	720
CRYAB	TTN	Q8WZ42	707
CRYAB	GJA8	P48165	685
CRYAB	UBB	P02248	685
CRYAB	FLNC	Q14315	684

IntAct

201 interactions, top by confidence:

A	B	Type	Score
CRYAB	CRYAB	psi-mi:“MI:0915”(physical association)	0.980
CRYAB	CRYAB	psi-mi:“MI:0407”(direct interaction)	0.980
CRYAB	CRYAB	psi-mi:“MI:0403”(colocalization)	0.980

BioGRID (341): CRYAB (Two-hybrid), HSPB1 (Two-hybrid), CRYAB (Two-hybrid), CRYAB (Two-hybrid), ACOT7 (Two-hybrid), TNPO2 (Two-hybrid), MRPL11 (Two-hybrid), TRAPPC6A (Two-hybrid), KRTAP8-1 (Two-hybrid), KRTAP19-5 (Two-hybrid), NYNRIN (Affinity Capture-MS), DDX20 (Affinity Capture-MS), SEH1L (Affinity Capture-MS), GEMIN4 (Affinity Capture-MS), IQGAP3 (Affinity Capture-MS)

ESM2 similar proteins: A5JV83, O93591, P02487, P02497, P02500, P02506, P02507, P02508, P02509, P02510, P02511, P02512, P04792, P05811, P06904, P09887, P14602, P15990, P15991, P23927, P23928, P24622, P24623, P30218, P30219, P35385, P41316, P42929, P42930, P42931, Q00649, Q05557, Q05713, Q3T149, Q5EAC9, Q5ENY9, Q5R9K0, Q5RAB0, Q5S1U1, Q60HG8

Diamond homologs: A5JV83, O14558, P02487, P02488, P02489, P02507, P02510, P02511, P02512, P04120, P04792, P05811, P06581, P06582, P14602, P15991, P23927, P23928, P30218, P30219, P34696, P35385, P41316, P42929, P42930, P42931, P82147, P97541, Q00649, Q04757, Q05557, Q05713, Q148F8, Q1RI96, Q3T149, Q5EAC9, Q5ENY9, Q5R9K0, Q5RAB0, Q5S1U1

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
TFAP2A	“up-regulates quantity by expression”	CRYAB	“transcriptional regulation”
TFAP2B	“up-regulates quantity by expression”	CRYAB	“transcriptional regulation”
TP53	“up-regulates quantity by expression”	CRYAB	“transcriptional regulation”
CRYAB	“up-regulates activity”	CRYGD	binding
CRYAB	“up-regulates activity”	CRYGC	binding
CRYAB	“up-regulates activity”	CRYGS	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 119 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
lens development in camera-type eye	5	18.2×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	16
Likely pathogenic	5
Uncertain significance	221
Likely benign	101
Benign	8

Top pathogenic / likely-pathogenic (21)

Variant ID	HGVS	Classification
1070020	NC_000011.9:g.(?111779478)(111782458_?)del	Pathogenic
1322163	NM_001289808.2(CRYAB):c.76C>T (p.Gln26Ter)	Pathogenic
1392460	NM_001289808.2(CRYAB):c.145del (p.Leu49fs)	Pathogenic
1455522	NC_000011.9:g.(?111779488)(111780026_?)del	Pathogenic
16953	NM_001289808.2(CRYAB):c.358A>G (p.Arg120Gly)	Pathogenic
16954	NM_001289808.2(CRYAB):c.450del (p.Lys150fs)	Pathogenic
1710339	NM_001289808.2(CRYAB):c.466del (p.Glu156fs)	Pathogenic
2424297	NC_000011.9:g.(?111779488)(111782448_?)del	Pathogenic
29669	NM_001289808.2(CRYAB):c.60del (p.Ser21fs)	Pathogenic
41927	NM_001289808.2(CRYAB):c.418G>A (p.Asp140Asn)	Pathogenic
41928	NM_001289808.2(CRYAB):c.58C>T (p.Pro20Ser)	Pathogenic
41930	NM_001289808.2(CRYAB):c.325G>C (p.Asp109His)	Pathogenic
4709887	NM_001289808.2(CRYAB):c.59C>G (p.Pro20Arg)	Pathogenic
4721629	NM_001289808.2(CRYAB):c.32_33del (p.Arg11fs)	Pathogenic
4736669	NM_001289808.2(CRYAB):c.101del (p.Glu34fs)	Pathogenic
804222	NM_001289808.2(CRYAB):c.514del (p.Ala172fs)	Pathogenic
1184448	NM_001289808.2(CRYAB):c.525del (p.Lys175fs)	Likely pathogenic
1677720	NM_001289808.2(CRYAB):c.119del (p.Thr40fs)	Likely pathogenic
2630615	NM_001289808.2(CRYAB):c.100dup (p.Glu34fs)	Likely pathogenic
265829	NM_001289808.2(CRYAB):c.326A>G (p.Asp109Gly)	Likely pathogenic
4687943	NM_001289808.2(CRYAB):c.527A>G (p.Ter176Trp)	Likely pathogenic

SpliceAI

551 predictions. Top by Δscore:

Variant	Effect	Δscore
11:111910324:TA:T	donor_loss	1.0000
11:111910325:A:AC	donor_gain	1.0000
11:111910325:AC:A	donor_gain	1.0000
11:111910326:C:CT	donor_gain	1.0000
11:111910326:CC:C	donor_gain	1.0000
11:111910326:CCTG:C	donor_gain	1.0000
11:111910326:CCTGG:C	donor_gain	1.0000
11:111910445:CGCAT:C	acceptor_gain	1.0000
11:111910447:CAT:C	acceptor_gain	1.0000
11:111910448:AT:A	acceptor_gain	1.0000
11:111910449:TCT:T	acceptor_loss	1.0000
11:111910450:C:CC	acceptor_gain	1.0000
11:111910456:A:AC	acceptor_gain	1.0000
11:111910456:A:C	acceptor_gain	1.0000
11:111910460:CAAGG:C	acceptor_gain	1.0000
11:111910461:A:T	acceptor_gain	1.0000
11:111910464:G:C	acceptor_gain	1.0000
11:111910464:G:GC	acceptor_gain	1.0000
11:111908974:C:CT	acceptor_gain	0.9900
11:111908974:C:T	acceptor_gain	0.9900
11:111910326:CCT:C	donor_gain	0.9900
11:111910446:GCAT:G	acceptor_gain	0.9900
11:111910447:CATC:C	acceptor_gain	0.9900
11:111911519:CTCA:C	donor_loss	0.9900
11:111911520:TCA:T	donor_loss	0.9900
11:111911521:CA:C	donor_loss	0.9900
11:111911522:A:AC	donor_gain	0.9900
11:111911523:C:CC	donor_gain	0.9900
11:111911523:C:CG	donor_loss	0.9900
11:111913438:TAG:T	acceptor_loss	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000403837 (11:111918856 A>G,T), RS1000792864 (11:111912487 G>A,C), RS1001245516 (11:111924842 G>A,C), RS1001320644 (11:111925123 A>G), RS1002278304 (11:111911708 T>A,C), RS1002509286 (11:111917044 A>G), RS1002610421 (11:111910209 C>A,T), RS1003261138 (11:111921478 A>G,T), RS1003292118 (11:111921761 T>A,C), RS1003949256 (11:111916264 C>T), RS1004123270 (11:111909729 G>C), RS1004407909 (11:111922254 C>A,T), RS1004813728 (11:111921113 G>A), RS1005927969 (11:111912862 G>A,T), RS1006212047 (11:111908088 G>A)

Disease associations

OMIM: gene MIM:123590 | disease phenotypes: MIM:615184, MIM:608810, MIM:613763, MIM:613869, MIM:115210, MIM:192600, MIM:278730

GenCC curated gene-disease

Disease	Classification	Inheritance
myofibrillar myopathy 2	Definitive	Autosomal dominant
fatal infantile hypertonic myofibrillar myopathy	Strong	Autosomal recessive
cataract 16 multiple types	Strong	Autosomal dominant
familial isolated dilated cardiomyopathy	Supportive	Autosomal dominant
early-onset lamellar cataract	Supportive	Autosomal dominant
early-onset nuclear cataract	Supportive	Autosomal dominant
early-onset posterior polar cataract	Supportive	Autosomal dominant
dilated cardiomyopathy 1II	Limited	Autosomal dominant

Mondo (15): dilated cardiomyopathy 1II (MONDO:0014073), myofibrillar myopathy 2 (MONDO:0012130), cataract 16 multiple types (MONDO:0013411), fatal infantile hypertonic myofibrillar myopathy (MONDO:0013472), dilated cardiomyopathy (MONDO:0005021), cardiomyopathy, familial restrictive, 1 (MONDO:0007270), cardiomyopathy (MONDO:0004994), congestive heart failure (MONDO:0005009), hypertrophic cardiomyopathy (MONDO:0005045), familial hypertrophic cardiomyopathy (MONDO:0024573), xeroderma pigmentosum group D (MONDO:0010212), (MONDO:0015470), early-onset lamellar cataract (MONDO:0018611), early-onset nuclear cataract (MONDO:0020376), early-onset posterior polar cataract (MONDO:0020378)

Orphanet (14): Familial isolated dilated cardiomyopathy (Orphanet:154), Fatal infantile hypertonic myofibrillar myopathy (Orphanet:280553), Alpha-B crystallin-related late-onset myopathy (Orphanet:399058), Early onset non-syndromic cataract (Orphanet:91492), Early-onset partial cataract (Orphanet:98992), Early-onset posterior polar cataract (Orphanet:98993), Early-onset zonular cataract (Orphanet:98995), Dilated cardiomyopathy (Orphanet:217604), Familial isolated restrictive cardiomyopathy (Orphanet:75249), Rare cardiomyopathy (Orphanet:167848), Rare hypertrophic cardiomyopathy (Orphanet:217569), Rare familial disorder with hypertrophic cardiomyopathy (Orphanet:99739), NON RARE IN EUROPE: Familial isolated hypertrophic cardiomyopathy (Orphanet:155), OBSOLETE: Xeroderma pigmentosum complementation group D (Orphanet:276258)

HPO phenotypes

60 total (30 of 60 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000407	Sensorineural hearing impairment
HP:0000467	Neck muscle weakness
HP:0000518	Cataract
HP:0000519	Developmental cataract
HP:0000556	Retinal dystrophy
HP:0000969	Edema
HP:0001115	Posterior polar cataract
HP:0001142	Lenticonus
HP:0001265	Hyporeflexia
HP:0001276	Hypertonia
HP:0001288	Gait disturbance
HP:0001349	Facial diplegia
HP:0001522	Death in infancy
HP:0001612	Weak cry
HP:0001618	Dysphonia
HP:0001635	Congestive heart failure
HP:0001638	Cardiomyopathy
HP:0001644	Dilated cardiomyopathy
HP:0001653	Mitral regurgitation
HP:0001727	Thromboembolic stroke
HP:0002015	Dysphagia
HP:0002063	Rigidity
HP:0002093	Respiratory insufficiency
HP:0002104	Apnea
HP:0002747	Respiratory insufficiency due to muscle weakness
HP:0002875	Exertional dyspnea
HP:0002878	Respiratory failure
HP:0003198	Myopathy

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST008362_43	Birth weight	1.000000e-08
GCST010320_3	PR interval	2.000000e-11
GCST010321_68	PR interval	3.000000e-13
GCST012227_630	Hip circumference adjusted for BMI	4.000000e-08

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004344	birth weight
EFO:0004462	PR interval
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors (9)

Descriptor	Name	Tree numbers
D009202	Cardiomyopathies	C14.280.238
D002311	Cardiomyopathy, Dilated	C14.280.195.160; C14.280.238.070; C16.320.488.750
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
C563848	Alpha-B Crystallinopathy (supp.)
C566168	Cardiomyopathy, Familial Restrictive, 1 (supp.)
C563333	Cataract, Age-Related Nuclear (supp.)
C565134	Cataract, Posterior Polar, 2 (supp.)
C562591	Xeroderma Pigmentosum, Complementation Group D (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3621022 (SINGLE PROTEIN)

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

ChEMBL bioactivities

8 potent at pChembl≥5 of 9 total, top 8 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.75	EC50	18	nM	CHEMBL4204376
7.58	EC50	26	nM	CHEMBL4209249
7.24	EC50	57	nM	CHEMBL4203007
7.19	EC50	64	nM	CHEMBL4218328
6.97	EC50	106	nM	CHEMBL4205794
6.50	EC50	320	nM	CHEMBL169046
5.85	EC50	1420	nM	LANOSTEROL
5.51	EC50	3116	nM	CHEMBL4203007

PubChem BioAssay actives

8 with measured affinity, of 131 total; 7 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
(2R,3R,5R,10S,13R,14R,17R)-2-fluoro-17-[(2R)-6-hydroxy-6-methylheptan-2-yl]-4,4,10,13,14-pentamethyl-2,3,5,6,7,11,12,15,16,17-decahydro-1H-cyclopenta[a]phenanthren-3-ol	1386480: Inhibition of alpha-crystallin B R120G mutant (unknown origin)-induced intracellular protein aggregation expressed in human HeLa cells or HLE-B3 cells incubated for 6 to 8 hrs by fluorescence microscopy relative to untreated control	ec50	0.0180	uM
(2R,3S,5R,10S,13R,14R,17R)-2-fluoro-17-[(2R)-6-hydroxy-6-methylheptan-2-yl]-4,4,10,13,14-pentamethyl-2,3,5,6,7,11,12,15,16,17-decahydro-1H-cyclopenta[a]phenanthren-3-ol	1386480: Inhibition of alpha-crystallin B R120G mutant (unknown origin)-induced intracellular protein aggregation expressed in human HeLa cells or HLE-B3 cells incubated for 6 to 8 hrs by fluorescence microscopy relative to untreated control	ec50	0.0260	uM
(3S,5R,10S,13R,14R,17R)-17-[(2R)-6-hydroxy-6-methylheptan-2-yl]-4,4,10,13,14-pentamethyl-2,3,5,6,7,11,12,15,16,17-decahydro-1H-cyclopenta[a]phenanthren-3-ol	1386480: Inhibition of alpha-crystallin B R120G mutant (unknown origin)-induced intracellular protein aggregation expressed in human HeLa cells or HLE-B3 cells incubated for 6 to 8 hrs by fluorescence microscopy relative to untreated control	ec50	0.0570	uM
(3S,5R,10S,13R,14R,17R)-17-[(2R)-6-hydroxy-6-methylheptan-2-yl]-4,4,10,13,14-pentamethyl-2,3,5,6,12,15,16,17-octahydro-1H-cyclopenta[a]phenanthren-3-ol	1386480: Inhibition of alpha-crystallin B R120G mutant (unknown origin)-induced intracellular protein aggregation expressed in human HeLa cells or HLE-B3 cells incubated for 6 to 8 hrs by fluorescence microscopy relative to untreated control	ec50	0.0640	uM
(5R,10S,13R,14R,17R)-17-[(2R)-6-hydroxy-6-methylheptan-2-yl]-4,4,10,13,14-pentamethyl-1,2,5,6,7,11,12,15,16,17-decahydrocyclopenta[a]phenanthren-3-one	1386480: Inhibition of alpha-crystallin B R120G mutant (unknown origin)-induced intracellular protein aggregation expressed in human HeLa cells or HLE-B3 cells incubated for 6 to 8 hrs by fluorescence microscopy relative to untreated control	ec50	0.1060	uM
(3S,8S,9S,10R,13R,14S,17R)-17-[(2R)-6-hydroxy-6-methylheptan-2-yl]-10,13-dimethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-ol	1386480: Inhibition of alpha-crystallin B R120G mutant (unknown origin)-induced intracellular protein aggregation expressed in human HeLa cells or HLE-B3 cells incubated for 6 to 8 hrs by fluorescence microscopy relative to untreated control	ec50	0.3200	uM
(3S,5R,10S,13R,14R,17R)-4,4,10,13,14-pentamethyl-17-[(2R)-6-methylhept-5-en-2-yl]-2,3,5,6,7,11,12,15,16,17-decahydro-1H-cyclopenta[a]phenanthren-3-ol	1386480: Inhibition of alpha-crystallin B R120G mutant (unknown origin)-induced intracellular protein aggregation expressed in human HeLa cells or HLE-B3 cells incubated for 6 to 8 hrs by fluorescence microscopy relative to untreated control	ec50	1.4200	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression	5
monomethylarsonous acid	decreases expression, increases expression	4
Silicon Dioxide	decreases expression, increases expression	4
Benzo(a)pyrene	increases expression, increases methylation	3
Cadmium	increases abundance, increases expression	3
Copper	increases expression, affects binding, decreases expression	3
Doxorubicin	decreases response to substance, affects expression, decreases expression	3
Cadmium Chloride	decreases expression, increases abundance, increases expression	3
chloropicrin	increases expression	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	2
dimethylarsinous acid	increases expression	2
Rosiglitazone	affects expression, affects cotreatment, increases expression	2
Troglitazone	decreases reaction, affects cotreatment, increases expression	2
Acetaminophen	decreases expression, increases expression	2
Carbon Tetrachloride	increases expression	2
Cisplatin	affects cotreatment, increases expression	2
Dexamethasone	increases expression, increases reaction	2
Estradiol	increases expression, affects cotreatment	2
Tobacco Smoke Pollution	increases expression	2
Tretinoin	decreases expression, increases expression	2
Valproic Acid	affects cotreatment, increases expression	2
Aflatoxin B1	affects expression, increases expression, increases methylation	2
tert-Butylhydroperoxide	affects cotreatment, increases expression, decreases reaction, decreases expression	2
FR900359	increases phosphorylation	1
methylmercuric chloride	increases expression	1
bisphenol A	increases expression	1
lead acetate	increases expression	1
methylselenic acid	increases expression	1
pyrogallol 1,3-dimethyl ether	increases expression, affects cotreatment, affects localization	1
pyrithione zinc	increases expression	1

ChEMBL screening assays

13 unique, capped per target: 13 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3626191	Binding	Binding affinity to CRYAB (unknown origin) assessed as reduction in CRYAB-VEGFA protein interaction	Rational design of proteinprotein interaction inhibitors — Medchemcomm

Cellosaurus cell lines

5 cell lines: 5 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_C9HF	UKEi001-A-1	Induced pluripotent stem cell	Female
CVCL_D6JS	UMCUi001-A	Induced pluripotent stem cell	Female
CVCL_D6JT	UMCUi002-A	Induced pluripotent stem cell	Male
CVCL_D6JU	UMCUi003-A	Induced pluripotent stem cell	Male
CVCL_D6NU	ICSSUi004-A	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
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
NCT07241104	PHASE1	RECRUITING	A Study of AZD4063 in PLN R14del Dilated Cardiomyopathy