CAPN3

Summary

CAPN3 (calpain 3, HGNC:1480) is a protein-coding gene on chromosome 15q15.1, encoding Calpain-3 (P20807). Calcium-regulated non-lysosomal thiol-protease.

Calpain, a heterodimer consisting of a large and a small subunit, is a major intracellular protease, although its function has not been well established. This gene encodes a muscle-specific member of the calpain large subunit family that specifically binds to titin. Mutations in this gene are associated with limb-girdle muscular dystrophies type 2A. Alternate promoters and alternative splicing result in multiple transcript variants encoding different isoforms and some variants are ubiquitously expressed.

Source: NCBI Gene 825 — RefSeq curated summary.

At a glance

• Gene–disease (curated): muscular dystrophy, limb-girdle, autosomal dominant (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 28
• Clinical variants (ClinVar): 2,151 total — 280 pathogenic, 180 likely-pathogenic
• Phenotypes (HPO): 42
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_000070

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1480
Approved symbol	CAPN3
Name	calpain 3
Location	15q15.1
Locus type	gene with protein product
Status	Approved
Aliases	CANP3, p94, nCL-1
Ensembl gene	ENSG00000092529
Ensembl biotype	protein_coding
OMIM	114240
Entrez	825

Gene structure

Transcript identifiers

Ensembl transcripts: 58 — 33 protein_coding, 10 nonsense_mediated_decay, 8 retained_intron, 7 protein_coding_CDS_not_defined

ENST00000318023, ENST00000337571, ENST00000349748, ENST00000357568, ENST00000397163, ENST00000397200, ENST00000397204, ENST00000466222, ENST00000561817, ENST00000562199, ENST00000564503, ENST00000565173, ENST00000565274, ENST00000565559, ENST00000567071, ENST00000567817, ENST00000568153, ENST00000569136, ENST00000569827, ENST00000638141, ENST00000673646, ENST00000673658, ENST00000673684, ENST00000673687, ENST00000673692, ENST00000673705, ENST00000673743, ENST00000673750, ENST00000673771, ENST00000673774, ENST00000673813, ENST00000673839, ENST00000673851, ENST00000673854, ENST00000673886, ENST00000673890, ENST00000673893, ENST00000673928, ENST00000673936, ENST00000673939, ENST00000673950, ENST00000673978, ENST00000673987, ENST00000674011, ENST00000674012, ENST00000674018, ENST00000674027, ENST00000674041, ENST00000674052, ENST00000674064, ENST00000674093, ENST00000674119, ENST00000674130, ENST00000674135, ENST00000674139, ENST00000674140, ENST00000674146, ENST00000674149

RefSeq mRNA: 6 — MANE Select: NM_000070 NM_000070, NM_024344, NM_173087, NM_173088, NM_173089, NM_173090

CCDS: CCDS10085, CCDS10086, CCDS32207, CCDS45245, CCDS45246

Canonical transcript exons

ENST00000397163 — 24 exons

Exon	Start	End
ENSE00002204882	42359501	42360114
ENSE00003460877	42409303	42409380
ENSE00003464872	42394256	42394341
ENSE00003476707	42384483	42384552
ENSE00003483545	42403741	42403777
ENSE00003487304	42389953	42390096
ENSE00003507856	42409931	42409995
ENSE00003508111	42401641	42401810
ENSE00003511177	42405926	42405943
ENSE00003515072	42409787	42409844
ENSE00003522315	42410588	42410666
ENSE00003543631	42399492	42399652
ENSE00003560501	42411287	42411345
ENSE00003563229	42386167	42386285
ENSE00003573344	42387753	42387886
ENSE00003589768	42411747	42412317
ENSE00003600997	42396800	42396877
ENSE00003606999	42410428	42410496
ENSE00003617374	42388928	42389096
ENSE00003639224	42402124	42402135
ENSE00003656165	42410884	42411000
ENSE00003687541	42408211	42408324
ENSE00003688077	42392639	42392722
ENSE00003760241	42402794	42403002

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 99.41.

FANTOM5 (CAGE): breadth broad, TPM avg 15.8251 / max 1248.3055, expressed in 347 samples.

FANTOM5 promoters (22 alternative TSS)

Promoter ID	TPM avg	Samples expressed
146262	6.0968	211
146245	2.9350	68
146263	2.2170	149
146265	1.4619	132
146261	0.8524	149
146264	0.6783	127
146266	0.4513	115
146257	0.3432	52
146246	0.3306	32
146260	0.1222	54

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
hindlimb stylopod muscle	UBERON:0004252	99.41	gold quality
skeletal muscle tissue	UBERON:0001134	99.33	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	99.31	gold quality
gastrocnemius	UBERON:0001388	98.98	gold quality
corpus callosum	UBERON:0002336	98.98	gold quality
muscle of leg	UBERON:0001383	98.30	gold quality
substantia nigra	UBERON:0002038	98.19	gold quality
putamen	UBERON:0001874	98.10	gold quality
Ammon’s horn	UBERON:0001954	97.64	gold quality
primary visual cortex	UBERON:0002436	97.18	gold quality
caudate nucleus	UBERON:0001873	96.98	gold quality
temporal lobe	UBERON:0001871	96.61	gold quality
amygdala	UBERON:0001876	96.61	gold quality
hypothalamus	UBERON:0001898	95.41	gold quality
left testis	UBERON:0004533	94.99	gold quality
right testis	UBERON:0004534	94.92	gold quality
nucleus accumbens	UBERON:0001882	94.83	gold quality
Brodmann (1909) area 9	UBERON:0013540	94.80	gold quality
muscle tissue	UBERON:0002385	94.62	gold quality
right frontal lobe	UBERON:0002810	93.98	gold quality
right lobe of liver	UBERON:0001114	93.82	gold quality
adult mammalian kidney	UBERON:0000082	93.66	gold quality
sural nerve	UBERON:0015488	93.61	gold quality
frontal cortex	UBERON:0001870	93.32	gold quality
skin of abdomen	UBERON:0001416	93.22	gold quality
cerebral cortex	UBERON:0000956	93.21	gold quality
brain	UBERON:0000955	93.17	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	93.16	gold quality
testis	UBERON:0000473	93.14	gold quality
zone of skin	UBERON:0000014	93.13	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-8142	yes	968.39
E-GEOD-135922	yes	19.88
E-GEOD-84465	yes	11.85
E-ANND-3	yes	4.05

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

3 targets.

Target	Regulation
BCL2	Activation
CFLAR	Activation
MYOD1	Repression

miRNA regulators (miRDB)

27 targeting CAPN3, 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-3119	99.92	71.34	2390
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-4760-5P	99.80	69.88	1619
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-671-5P	99.52	67.11	1277
HSA-MIR-6797-3P	99.17	66.94	668
HSA-MIR-4738-3P	98.98	67.98	1846
HSA-MIR-4802-5P	98.97	66.26	833
HSA-MIR-181A-2-3P	98.91	67.60	1168
HSA-MIR-6076	98.61	65.69	637
HSA-MIR-4691-5P	98.41	66.77	1343
HSA-MIR-6792-3P	98.41	66.86	1359
HSA-MIR-6804-5P	98.39	65.77	1084
HSA-MIR-6509-3P	98.32	67.33	1343
HSA-MIR-7156-3P	98.25	67.66	859
HSA-MIR-6881-5P	98.16	67.38	665
HSA-MIR-4475	97.36	66.95	761
HSA-MIR-3116	97.07	65.78	1324
HSA-MIR-4690-3P	97.02	64.72	981
HSA-MIR-5685	97.02	64.34	1004
HSA-MIR-6856-3P	96.47	66.27	781
HSA-MIR-6782-5P	96.45	64.42	612
HSA-MIR-6835-5P	95.81	64.27	500
HSA-MIR-571	95.38	66.54	671
HSA-MIR-6732-5P	93.97	64.65	422
HSA-MIR-4765	93.11	66.17	737
HSA-MIR-29C-5P	87.36	66.96	29

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• reduced expression of calpain 3 was associated with phenotypes related to obesity and insulin resistance (PMID:12075569)
• effects of type of mutation, amount of calpain in the muscle, gender and ethnicity of affected patients on clinical course (age of onset and ascertainment) were analysed (PMID:12461690)
• reaction analysis of calpain p94 autolysis and domains (PMID:12482600)
• The enzyme is preferentially expressed in B- and T-lymphocytes, whereas it is poorly expressed in natural killer cells and almost undetectable in polymorphonuclear cells. (PMID:12882647)
• The 550delA mutation was present on 76% of CAPN3 (calpain 3) chromosomes that led us to screen general population for this mutation (PMID:14981715)
• Insertion sequence 1 of p94 acts as internal autoinhibitory propeptide, blocking the active site of p94 from substrates and inhibitors. (PMID:15073171)
• Ten novel CAPN3 mutations found in concentrated in several exons in Muscular Dystrophies patients (PMID:15221789)
• This study found that three novel mutations of calpain 3 gene in limb girdle muscular dystrophy type 2A (LGMD2A, calpainopathy). (PMID:15351423)
• the time- and concentration-dependent changes in [Ca2+]i that occurred during concentric exercise fall near but below the level necessary to cause autolysis of calpains in vivo (PMID:16107503)
• Efficient and stable CAPN3 transgene expression in mouse muscle restores enzyme proteolytic activity without evident toxicity in a calpain 3-deficient mouse model of limb-girdle muscular dystrophy type 2A. (PMID:16290124)
• Thus, the proteolytic activity of the core of p94 and its deletion mutant lacking NS and IS1 was shown to be strictly Ca(2+)-dependent. We propose a two-stage model of activation of the proteolytic core of p94. (PMID:16533054)
• the importance of p94-connectin interaction in the control of p94 functions by regulating autolytic decay of p94 (PMID:16627476)
• This review summarizes the known biochemical and physiological features of calpain 3 and the mechanisms of the mutations that result in disease. (PMID:16934440)
• Study provides evidence of the pathogenetic effect of specific CAPN3 gene mutations on protein function in limb girdle muscular dystrophy type 2A muscle and offers insights into the protein regions that are crucial for the autolytic activity of calpain-3. (PMID:16971480)
• CAPN3 mRNAs which contain frame-shift mutations are degraded by nonsense-mediated mRNA decay in cells of limb girdle muscular dystrophy type 2A patients (PMID:17157502)
• Three novel and six recurrent mutations are identified in Limb-girdle muscular dystrophy type 2A. (PMID:17318636)
• amount of autolyzed calpain-3 unchanged immediately and 3 h after eccentric exercise but increased markedly 24 h after (PMID:17585039)
• CAPN3 mutations may have a role in limb-girdle muscular dystrophy (PMID:17596655)
• The c.550delA mutation in CAPN3 was found in 8.1% of limb girdle muscular dystrophy and 1.9% of hyperCKemia patients. Two mutations (Val509Phe and Gln565Stop) have not been reported before. (PMID:17702496)
• nonsense-mediated messenger RNA decay as a mechanism for under-expression of CAPN3 associated to some specific variations (PMID:17979987)
• IkappaB alpha is expressed following NF-kappaB activation independent of the CAPN3 status, whereas expression of c-FLIP is obtained only when CAPN3 is present. (PMID:18073330)
• These results highlight the importance of conserved amino acids in domain IIb as well as in the p94-specific IS2 region. (PMID:18258189)
• A mutation analysis of the CAPN3 gene (Athena Diagnostics) was performed and revealed a C > T transition at nucleotide position 551 leading to a Thr184Met substitution, a known disease-causing mutation. (PMID:18299526)
• implicate the dynamic nature of connectin molecule as a regulatory scaffold of p94 functions (PMID:18310072)
• AHNAK accumulates when calpain 3 is defective in skeletal muscle of calpainopathy patients; moreover, AHNAK fragments cleaved by CAPN3 have lost their affinity for dysferlin. (PMID:18334579)
• CAPN3 mutation is associated with limb-girdle muscular dystrophy type 2A (PMID:18337726)
• CAPN3 alternative splicing isoforms in white blood cells in limb-girdle muscular dystrophy 2A (PMID:18563459)
• CAPN3 degraded AldoA; however, no accumulation of AldoA was observed in total extracts from CAPN3-deficient muscles suggesting that AldoA is not an in vivo substrate of CAPN3 (PMID:18676612)
• Data show a high predictive value for reduced-absent calpain-3 or lost autolytic activity, and the biochemical assays are powerful tools for otherwise laborious genetic screening of cases with a high probability of being primary calpainopathy. (PMID:18854869)
• Data show that loss of function of the full-length isoform of CAPN3, also known as p94, as the pathogenic isoform can explain the “progressive” development of muscular dystrophy. (PMID:18974005)
• Finding its mutation is useful for genetic diagnosis of type2 limb-gardle muscular dystrophies. (PMID:19048948)
• calpain 3 variants can play a proapoptotic role in melanoma cells and its downregulation, as observed in highly aggressive lesions, could contribute to melanoma progression. (PMID:19386580)
• Immunohistochemistry with Calp3-2C4 has a similar pickup rate of LGMD2A as immunoblot and it may therefore be useful for distinguishing the majority of genuine CAPN3 defects from secondary protein reduction. (PMID:19556129)
• calpain 3 participates in the establishment of the pool of reserve cells by decreasing the transcriptional activity of the key myogenic regulator MyoD via proteolysis independently of the ubiquitin-proteasome degradation pathway. (PMID:20139084)
• Limb-girdle muscular dystrophy patients carried a new splicing site mutation (c.1536+1G>T) in the CAPN3 gene, which leads to complete retention of intron 12 of the CAPN3 gene and total calpain3 deficiency. (PMID:20477750)
• The major c.550delA mutation in the CAPN3 gene was identified in 70% of Russian patients. (PMID:20517216)
• The findings suggest that mutation analysis of the CAPN3 cDNA should use skeletal muscle tissue as materials instead of peripheral blood. (PMID:20533264)
• Interactions with M-band titin and calpain 3 link myospryn (CMYA5) to tibial and limb-girdle muscular dystrophies. (PMID:20634290)
• 5 different intronic variants (one novel) in CAPN3 that bioinformatic tools predicted would affect RNA splicing, underwent comprehensive studies which were designed to prove they are disease-causing. (PMID:20635405)
• CARP and its regulator calpain 3 appear to occupy a central position in the important cell fate-governing NF-kappaB pathway in skeletal muscle (PMID:20860623)

Cross-species orthologs

13 orthologs

Organism	Symbol	Gene ID
danio_rerio	capn3a	ENSDARG00000041864
danio_rerio	capn3b	ENSDARG00000043035
mus_musculus	Capn3	ENSMUSG00000079110
rattus_norvegicus	Capn3	ENSRNOG00000008609
caenorhabditis_elegans		WBGENE00000542
caenorhabditis_elegans	clp-3	WBGENE00000544
caenorhabditis_elegans		WBGENE00000546
caenorhabditis_elegans		WBGENE00000547
caenorhabditis_elegans		WBGENE00006606
caenorhabditis_elegans	clp-8	WBGENE00009695
caenorhabditis_elegans	clpr-3	WBGENE00010417
caenorhabditis_elegans	clpr-1	WBGENE00012233
caenorhabditis_elegans	clpr-3	WBGENE00013184

Paralogs (20): CAPN1 (ENSG00000014216), SRI (ENSG00000075142), CAPN6 (ENSG00000077274), CAPN15 (ENSG00000103326), GCA (ENSG00000115271), ADGB (ENSG00000118492), CAPNS1 (ENSG00000126247), CAPN7 (ENSG00000131375), CAPN9 (ENSG00000135773), CAPN11 (ENSG00000137225), CAPN10 (ENSG00000142330), CAPN5 (ENSG00000149260), PEF1 (ENSG00000162517), CAPN2 (ENSG00000162909), CAPN13 (ENSG00000162949), CAPN12 (ENSG00000182472), CAPN8 (ENSG00000203697), CAPN14 (ENSG00000214711), PDCD6 (ENSG00000249915), CAPNS2 (ENSG00000256812)

Protein

Protein identifiers

Calpain-3 — P20807 (reviewed: P20807)

Alternative names: Calcium-activated neutral proteinase 3, Calpain L3, Calpain p94, Muscle-specific calcium-activated neutral protease 3, New calpain 1

All UniProt accessions (22): P20807, A0A0S2Z3E1, A0A0S2Z3E6, A0A669KAB9, A0A669KAU4, A0A669KAU6, A0A669KAX6, A0A669KB02, A0A669KB08, A0A669KB11, A0A669KB98, A0A669KBA3, A0A669KBE1, F8W8F5, H3BMH1, H3BNN7, H3BS30, H3BS77, H3BSA2, H3BUR3, H3BUZ3, H3BV08

UniProt curated annotations — full annotation on UniProt →

Function. Calcium-regulated non-lysosomal thiol-protease. Proteolytically cleaves CTBP1 at ‘His-409’. Mediates, with UTP25, the proteasome-independent degradation of p53/TP53.

Subunit / interactions. Homodimer; via EF-hand domain 4. Interacts with TTN/titin. Interacts with CMYA5; this interaction, which results in CMYA5 proteolysis, may protect CAPN3 from autolysis. Interacts with SIMC1. Interacts with UTP25; the interaction is required for CAPN3 translocation to the nucleolus.

Subcellular location. Cytoplasm. Nucleus. Nucleolus.

Tissue specificity. Isoform I is skeletal muscle specific.

Disease relevance. Muscular dystrophy, limb-girdle, autosomal recessive 1 (LGMDR1) [MIM:253600] An autosomal recessive degenerative myopathy characterized by progressive symmetrical atrophy and weakness of the proximal limb muscles and elevated serum creatine kinase. The symptoms usually begin during the first two decades of life, and the disease gradually worsens, often resulting in loss of walking ability 10 or 20 years after onset. The disease is caused by variants affecting the gene represented in this entry. Muscular dystrophy, limb-girdle, autosomal dominant 4 (LGMDD4) [MIM:618129] A form of autosomal dominant limb-girdle muscular dystrophy, a myopathy characterized by proximal and/or distal muscle weakness and atrophy. The age at onset is variable and can range from the first to the sixth decade, although later onset is less common. LGMDD4 is characterized by onset of proximal muscle weakness in young adulthood, gait difficulties, increased serum creatine kinase, myalgia, and back pain. Some patients may have upper limb involvement. Disease severity and expressivity are highly variable. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Activated by micromolar concentrations of calcium and inhibited by calpastatin.

Similarity. Belongs to the peptidase C2 family.

Isoforms (5)

UniProt ID	Names	Canonical?
P20807-1	I	yes
P20807-2	II
P20807-3	III
P20807-4	IV
P20807-5	V

RefSeq proteins (6): NP_000061, NP_077320, NP_775110, NP_775111, NP_775112, NP_775113 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000169	Pept_cys_AS	Active_site
IPR001300	Peptidase_C2_calpain_cat	Domain
IPR002048	EF_hand_dom	Domain
IPR011992	EF-hand-dom_pair	Homologous_superfamily
IPR018247	EF_Hand_1_Ca_BS	Binding_site
IPR022682	Calpain_domain_III	Domain
IPR022683	Calpain_III	Domain
IPR022684	Calpain_cysteine_protease	Family
IPR029531	CAPN3_PEF	Domain
IPR032100	Calpain_u2	Domain
IPR033883	C2_III	Domain
IPR036213	Calpain_III_sf	Homologous_superfamily
IPR038765	Papain-like_cys_pep_sf	Homologous_superfamily
IPR054069	CAPN3/13-like_C_EFh	Domain

Pfam: PF00648, PF01067, PF13833, PF16648, PF21875

Enzyme classification (BRENDA):

• EC 3.4.22.54 — calpain-3 (BRENDA: 10 organisms, 105 substrates, 12 inhibitors, 0 Km, 0 kcat entries)
• EC 3.4.22.56 — caspase-3 (BRENDA: 15 organisms, 215 substrates, 504 inhibitors, 53 Km, 35 kcat entries)

Substrate kinetics (BRENDA)

33 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ACETYL-DEVD-7-AMIDO-4-METHYLCOUMARIN	0.005–10.7	10
ACETYL-L-ASP-L-GLU-L-VAL-L-ASP-7-AMIDO-4-METHYLC	0.0048–0.0335	6
BENZOYL-L-ASP-L-GLU-L-VAL-L-ASP-7-AMIDO-4-METHYL	0.002–0.0255	6
5’-TETRAMETHYLRHODAMINE-5(6)-CARBOXAMIDE-DEVD-CY	0.0016	1
AC-DEVD-4-METHYLCOUMARIN 7-AMIDE	0.0337	1
ACETYL-DEVD-4-NITROANILIDE	0.011	1
ACETYL-DQMD-4-NITROANILIDE	0.044	1
ACETYL-L-ASP-L-GLU-L-VAL-L-ASP-4-NITROANILIDE	0.067	1
ACETYL-L-ASP-L-MET-L-GLN-L-ASP-4-NITROANILIDE	1.6	1
ACETYL-L-ASP-L-VAL-L-ALA-L-ASP-4-NITROANILIDE	0.222	1
ACETYL-L-LEU-L-ASP-L-VAL-L-ALA-L-ASP-4-NITROANIL	0.147	1
ACETYL-L-VAL-L-ASP-L-VAL-L-ALA-L-ASP-4-NITROANIL	0.164	1
ACETYL-VDQMDGW-AMIDE	0.2	1
ACETYL-VDVAD-4-NITROANILIDE	0.067	1
ACETYL-VEID-4-NITROANILIDE	0.25	1

UniProt features (148 total): sequence variant 65, helix 22, strand 20, binding site 18, domain 5, region of interest 5, splice variant 5, active site 3, compositionally biased region 2, chain 1, mutagenesis site 1, turn 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
6BDT	X-RAY DIFFRACTION	2.3
4OKH	X-RAY DIFFRACTION	2.45
6BGP	X-RAY DIFFRACTION	2.75
6BJD	X-RAY DIFFRACTION	2.8
6BKJ	X-RAY DIFFRACTION	3.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P20807-F1	79.18	0.44

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): 129; 334; 358

Ligand- & substrate-binding residues (18): 662; 665; 667; 672; 705; 707; 709; 711; 716; 735; 737; 739 …

Mutagenesis-validated functional residues (1):

Position	Phenotype
129	loss of activity. no effect on cmya5-binding. does not degradate p53/tp53.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-1474228	Degradation of the extracellular matrix
R-HSA-1474244	Extracellular matrix organization

MSigDB gene sets: 417 (showing top): GOBP_POSITIVE_REGULATION_OF_CALCIUM_ION_TRANSPORT, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_SKELETAL_MUSCLE_TISSUE_REGENERATION, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH, PEREZ_TP63_TARGETS, GOBP_REGULATION_OF_PROTEIN_SUMOYLATION, GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, ASTON_MAJOR_DEPRESSIVE_DISORDER_DN, KENNY_CTNNB1_TARGETS_UP, GOBP_GROWTH, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION, GOBP_REGENERATION, MEF2_02

GO Biological Process (28): proteolysis (GO:0006508), apoptotic process (GO:0006915), muscle organ development (GO:0007517), positive regulation of satellite cell activation involved in skeletal muscle regeneration (GO:0014718), response to muscle activity (GO:0014850), protein catabolic process (GO:0030163), myofibril assembly (GO:0030239), protein destabilization (GO:0031648), negative regulation of protein sumoylation (GO:0033234), negative regulation of apoptotic process (GO:0043066), regulation of canonical NF-kappaB signal transduction (GO:0043122), sarcomere organization (GO:0045214), regulation of myoblast differentiation (GO:0045661), positive regulation of proteolysis (GO:0045862), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of DNA-templated transcription (GO:0045893), muscle cell cellular homeostasis (GO:0046716), positive regulation of release of sequestered calcium ion into cytosol (GO:0051281), response to calcium ion (GO:0051592), muscle structure development (GO:0061061), protein-containing complex assembly (GO:0065003), G1 to G0 transition involved in cell differentiation (GO:0070315), cellular response to calcium ion (GO:0071277), cellular response to salt stress (GO:0071472), protein localization to membrane (GO:0072657), self proteolysis (GO:0097264), calcium-dependent self proteolysis (GO:1990092), programmed cell death (GO:0012501)

GO Molecular Function (14): catalytic activity (GO:0003824), calcium-dependent cysteine-type endopeptidase activity (GO:0004198), calcium ion binding (GO:0005509), peptidase activity (GO:0008233), cysteine-type peptidase activity (GO:0008234), structural constituent of muscle (GO:0008307), sodium ion binding (GO:0031402), titin binding (GO:0031432), identical protein binding (GO:0042802), molecular adaptor activity (GO:0060090), protein binding (GO:0005515), hydrolase activity (GO:0016787), metal ion binding (GO:0046872), ligase regulator activity (GO:0055103)

GO Cellular Component (10): nucleus (GO:0005634), nucleolus (GO:0005730), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), myofibril (GO:0030016), Z disc (GO:0030018), T-tubule (GO:0030315), protein-containing complex (GO:0032991), endomembrane system (GO:0012505)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Extracellular matrix organization	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
protein metabolic process	2
actomyosin structure organization	2
DNA-templated transcription	2
regulation of DNA-templated transcription	2
molecular_function	2
binding	2
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
animal organ development	1
muscle structure development	1
regulation of satellite cell activation involved in skeletal muscle regeneration	1
satellite cell activation involved in skeletal muscle regeneration	1
positive regulation of skeletal muscle tissue regeneration	1
positive regulation of cell activation	1
response to activity	1
macromolecule catabolic process	1
cellular component assembly involved in morphogenesis	1
striated muscle cell development	1
supramolecular fiber organization	1
membraneless organelle assembly	1
regulation of protein stability	1
protein sumoylation	1
regulation of protein sumoylation	1
negative regulation of protein modification by small protein conjugation or removal	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
canonical NF-kappaB signal transduction	1
regulation of intracellular signal transduction	1
myofibril assembly	1
myoblast differentiation	1
regulation of cell differentiation	1
proteolysis	1
regulation of proteolysis	1
positive regulation of protein metabolic process	1
negative regulation of RNA biosynthetic process	1
positive regulation of RNA biosynthetic process	1
cellular homeostasis	1

Protein interactions and networks

STRING

1887 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CAPN3	TTN	Q8WZ42	997
CAPN3	DYSF	O75923	985
CAPN3	FKRP	Q9H9S5	859
CAPN3	TRIM32	Q13049	858
CAPN3	CAST	P20810	857
CAPN3	SGCG	Q13326	852
CAPN3	TRIM71	Q2Q1W2	844
CAPN3	TCAP	O15273	843
CAPN3	FLNC	Q14315	820
CAPN3	SGCB	Q16585	819
CAPN3	PARVB	Q9HBI1	801
CAPN3	MYPN	Q86TC9	799
CAPN3	DMD	P11532	794
CAPN3	AHNAK	Q09666	786
CAPN3	CAV3	P56539	778

IntAct

36 interactions, top by confidence:

A	B	Type	Score
OSGIN1	CAPN3	psi-mi:“MI:0915”(physical association)	0.670
CAPN3	OSGIN1	psi-mi:“MI:0915”(physical association)	0.670
NTAQ1	CAPN3	psi-mi:“MI:0915”(physical association)	0.560
CAPN3	TTN	psi-mi:“MI:0915”(physical association)	0.550
CAPN3	CAPN3	psi-mi:“MI:0407”(direct interaction)	0.440
TRIM63	CAPN3	psi-mi:“MI:0915”(physical association)	0.400
TRIM54	CAPN3	psi-mi:“MI:0915”(physical association)	0.400
	GNAT3	psi-mi:“MI:0915”(physical association)	0.400
CAPN3	HSP90B2P	psi-mi:“MI:0915”(physical association)	0.400
espY1	CAPN3	psi-mi:“MI:0915”(physical association)	0.370
CAPN3	E7	psi-mi:“MI:0915”(physical association)	0.370
CAPN3	FXR1	psi-mi:“MI:0915”(physical association)	0.370
CAPN3	UBE3A	psi-mi:“MI:0915”(physical association)	0.370
CAPN3	Ankrd1	psi-mi:“MI:0915”(physical association)	0.370
ATG16L1	ESYT2	psi-mi:“MI:0914”(association)	0.350
CRYAB	CAPN3	psi-mi:“MI:0915”(physical association)	0.000
POMP	CAPN3	psi-mi:“MI:0915”(physical association)	0.000
CAPN3	TTN	psi-mi:“MI:0915”(physical association)	0.000
CAPN3	AMOT	psi-mi:“MI:0915”(physical association)	0.000
CAPN3	C1QTNF9	psi-mi:“MI:0915”(physical association)	0.000
CAPN3	CMYA5	psi-mi:“MI:0915”(physical association)	0.000
FNDC3B	CAPN3	psi-mi:“MI:0915”(physical association)	0.000
CAPN3	MMP2	psi-mi:“MI:0915”(physical association)	0.000
MYBPC1	CAPN3	psi-mi:“MI:0915”(physical association)	0.000
MYBPH	CAPN3	psi-mi:“MI:0915”(physical association)	0.000
CAPN3	PREPL	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (54): OSGIN1 (Two-hybrid), WDYHV1 (Two-hybrid), NECAB2 (Two-hybrid), YARS2 (Co-fractionation), CAPN3 (Two-hybrid), TFCP2 (Two-hybrid), CEP76 (Two-hybrid), CAPN3 (Affinity Capture-MS), CAPN3 (Synthetic Lethality), CAPN3 (Two-hybrid), CAPN3 (Two-hybrid), EXOC8 (Two-hybrid), GTPBP3 (Two-hybrid), CCDC102B (Two-hybrid), WDYHV1 (Two-hybrid)

ESM2 similar proteins: A0A0G2K344, A0A3Q1N1R0, E1BKH1, G3GTP0, G5EF51, O13728, O70481, P06814, P16259, P16885, P20807, P24135, P32871, P34529, P35875, P42336, P42337, P43368, P49917, P51186, P97393, Q09879, Q11208, Q13017, Q32TF8, Q32TG3, Q4V8Q1, Q5JST6, Q5JVL4, Q5R6L3, Q64691, Q6GL75, Q6GQ76, Q6J756, Q6NU25, Q758X6, Q803R5, Q8BTF7, Q8BTI9, Q8CIH5

Diamond homologs: A6NHC0, A8MX76, G3V7W1, O08529, O08688, O14815, O15484, O23184, O35350, O35646, O35920, O75808, O88456, O88501, P00789, P04574, P04632, P05044, P06813, P06814, P06815, P07384, P13135, P16259, P17655, P20807, P27398, P27730, P28676, P30626, P34308, P35750, P43367, P43368, P51186, P97571, Q07009, Q11002, Q22036, Q27970

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
CAPN3	“up-regulates activity”	CDK5/CDK5R1	cleavage
CAST	“down-regulates activity”	CAPN3	binding
CAPN3	“up-regulates activity”	CDK5R1	cleavage
CAPN3	“down-regulates activity”	MAPT	cleavage
CAPN3	“up-regulates activity”	GSK3A	cleavage
CAPN3	“up-regulates activity”	GSK3B	cleavage

Disease & clinical

Clinical variants and AI predictions

ClinVar

2151 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	280
Likely pathogenic	180
Uncertain significance	690
Likely benign	654
Benign	73

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1067511	NM_000070.3(CAPN3):c.2380+1G>A	Pathogenic
1068828	NM_000070.3(CAPN3):c.389G>A (p.Trp130Ter)	Pathogenic
1069050	NM_000070.3(CAPN3):c.1788_1791del (p.Lys598fs)	Pathogenic
1069199	NM_000070.3(CAPN3):c.60del (p.Pro22fs)	Pathogenic
1069414	NM_000070.3(CAPN3):c.1985del (p.Ala662fs)	Pathogenic
1071203	NM_000070.3(CAPN3):c.2048_2051del (p.Lys683fs)	Pathogenic
1071335	NM_000070.3(CAPN3):c.1590dup (p.Lys531fs)	Pathogenic
1071948	NM_000070.3(CAPN3):c.1999G>T (p.Glu667Ter)	Pathogenic
1072494	NM_000070.3(CAPN3):c.1977_1978delinsCT (p.Lys659_Gln660delinsAsnTer)	Pathogenic
1074226	NM_000070.3(CAPN3):c.1740_1743del (p.Ser581fs)	Pathogenic
1075864	NM_000070.3(CAPN3):c.286C>T (p.Gln96Ter)	Pathogenic
1076334	NC_000015.9:g.(?42701491)(42703981_?)del	Pathogenic
1076819	NM_000070.3(CAPN3):c.2019dup (p.Lys674fs)	Pathogenic
1192502	NM_000070.3(CAPN3):c.2217C>G (p.Ser739=)	Pathogenic
1285364	NM_000070.3(CAPN3):c.2257delinsAA (p.Asp753fs)	Pathogenic
128570	NM_000070.3(CAPN3):c.2243G>A (p.Arg748Gln)	Pathogenic
1299546	NM_000070.3(CAPN3):c.1363T>C (p.Trp455Arg)	Pathogenic
1321461	NM_000070.3(CAPN3):c.347C>A (p.Ala116Asp)	Pathogenic
1325395	NM_000070.3(CAPN3):c.966T>A (p.Tyr322Ter)	Pathogenic
1325397	NM_000070.3(CAPN3):c.743T>G (p.Met248Arg)	Pathogenic
1325401	NM_000070.3(CAPN3):c.703_704insA (p.Val235fs)	Pathogenic
1352662	NM_000070.3(CAPN3):c.1895_1913dup (p.Pro639fs)	Pathogenic
1358312	NM_000070.3(CAPN3):c.2050+1G>C	Pathogenic
1370170	NM_000070.3(CAPN3):c.193del (p.His65fs)	Pathogenic
1376842	NM_000070.3(CAPN3):c.648C>G (p.Tyr216Ter)	Pathogenic
1382408	NM_000070.3(CAPN3):c.1012_1013del (p.Val338fs)	Pathogenic
1398928	NM_000070.3(CAPN3):c.1800+2T>C	Pathogenic
1451907	NC_000015.9:g.(?42676661)(42684940_?)del	Pathogenic
1452007	NM_000070.3(CAPN3):c.2050+1dup	Pathogenic
1453063	NM_000070.3(CAPN3):c.1515_1518dup (p.Tyr507fs)	Pathogenic

SpliceAI

4494 predictions. Top by Δscore:

Variant	Effect	Δscore
15:42360112:CCGG:C	donor_loss	1.0000
15:42360113:CGGT:C	donor_loss	1.0000
15:42360115:G:C	donor_loss	1.0000
15:42360116:T:A	donor_loss	1.0000
15:42384549:C:G	donor_gain	1.0000
15:42387887:G:GG	donor_gain	1.0000
15:42388925:A:AG	acceptor_gain	1.0000
15:42388925:AAG:A	acceptor_gain	1.0000
15:42388926:A:G	acceptor_gain	1.0000
15:42389093:TGATG:T	donor_loss	1.0000
15:42389094:GAT:G	donor_gain	1.0000
15:42389095:AT:A	donor_gain	1.0000
15:42389095:ATG:A	donor_loss	1.0000
15:42389096:TGT:T	donor_loss	1.0000
15:42389097:G:GA	donor_loss	1.0000
15:42389097:G:GG	donor_gain	1.0000
15:42389934:A:AG	acceptor_gain	1.0000
15:42399482:A:AG	acceptor_gain	1.0000
15:42399483:A:G	acceptor_gain	1.0000
15:42399484:C:G	acceptor_gain	1.0000
15:42399489:CAG:C	acceptor_loss	1.0000
15:42399490:A:AG	acceptor_gain	1.0000
15:42399490:AG:A	acceptor_gain	1.0000
15:42399490:AGGAT:A	acceptor_gain	1.0000
15:42399491:G:GG	acceptor_gain	1.0000
15:42399491:GG:G	acceptor_gain	1.0000
15:42399491:GGA:G	acceptor_gain	1.0000
15:42399491:GGAT:G	acceptor_gain	1.0000
15:42399491:GGATG:G	acceptor_gain	1.0000
15:42401630:T:A	acceptor_gain	1.0000

AlphaMissense

5519 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:42399610:T:A	W438R	1.000
15:42399610:T:C	W438R	1.000
15:42399612:G:C	W438C	1.000
15:42399612:G:T	W438C	1.000
15:42401737:T:C	L484P	1.000
15:42360100:T:A	W99R	0.999
15:42360100:T:C	W99R	0.999
15:42386175:T:A	W130R	0.999
15:42386175:T:C	W130R	0.999
15:42387756:T:A	W168R	0.999
15:42387756:T:C	W168R	0.999
15:42387771:T:A	W173R	0.999
15:42387771:T:C	W173R	0.999
15:42387852:T:C	F200L	0.999
15:42387854:C:A	F200L	0.999
15:42387854:C:G	F200L	0.999
15:42387855:T:A	W201R	0.999
15:42387855:T:C	W201R	0.999
15:42387868:T:C	L205P	0.999
15:42387883:C:A	A210D	0.999
15:42388930:T:C	L212P	0.999
15:42388951:T:C	L219P	0.999
15:42388983:G:C	D230H	0.999
15:42388984:A:C	D230A	0.999
15:42388984:A:T	D230V	0.999
15:42392706:T:A	V338D	0.999
15:42394296:G:C	R357P	0.999
15:42399540:C:G	C414W	0.999
15:42399583:T:A	W429R	0.999
15:42399583:T:C	W429R	0.999

dbSNP variants (sampled 300 via entrez): RS1000017273 (15:42409680 C>A,T), RS1000125333 (15:42370209 A>C), RS1000227619 (15:42404782 A>C), RS1000302062 (15:42404485 T>C), RS1000404097 (15:42398758 A>T), RS1000410616 (15:42399330 G>A), RS1000566330 (15:42406016 T>C), RS1000602794 (15:42364912 G>A), RS1000633868 (15:42365295 T>A), RS1000660846 (15:42398457 A>T), RS1000675940 (15:42361837 C>T), RS1000734984 (15:42400153 A>G), RS1000815894 (15:42358860 C>T), RS1000922984 (15:42374938 G>T), RS1000992904 (15:42394503 G>A)

Disease associations

OMIM: gene MIM:114240 | disease phenotypes: MIM:253600, MIM:618129, MIM:160750, MIM:255200, MIM:253601

GenCC curated gene-disease

Disease	Classification	Inheritance
autosomal recessive limb-girdle muscular dystrophy type 2A	Definitive	Autosomal recessive
muscular dystrophy, limb-girdle, autosomal dominant 4	Strong	Autosomal dominant

ClinGen Gene-Disease Validity (2)

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

Disease	Classification	Inheritance
muscular dystrophy, limb-girdle, autosomal dominant	Definitive	AD
autosomal recessive limb-girdle muscular dystrophy	Definitive	AR

Mondo (14): autosomal recessive limb-girdle muscular dystrophy type 2A (MONDO:0009675), limb-girdle muscular dystrophy (MONDO:0016971), muscular dystrophy, limb-girdle, autosomal dominant 4 (MONDO:0029133), autosomal recessive limb-girdle muscular dystrophy (MONDO:0015152), familial idiopathic inflammatory myopathy (MONDO:0600024), migraine disorder (MONDO:0005277), myopathy (MONDO:0005336), cardiac rhythm disease (MONDO:0007263), progressive muscular atrophy (MONDO:0018687), congenital muscular dystrophy (MONDO:0019950), muscular dystrophy (MONDO:0020121), autosomal recessive disease (MONDO:0006025), myopathy, centronuclear, 2 (MONDO:0009709), autosomal recessive limb-girdle muscular dystrophy type 2B (MONDO:0009676)

Orphanet (10): Limb-girdle muscular dystrophy (Orphanet:263), Calpain-3-related limb-girdle muscular dystrophy R1 (Orphanet:267), Calpain-3-related limb-girdle muscular dystrophy D4 (Orphanet:565909), Autosomal recessive limb-girdle muscular dystrophy (Orphanet:102015), Progressive muscular atrophy (Orphanet:454706), Congenital muscular dystrophy (Orphanet:97242), Muscular dystrophy (Orphanet:98473), Qualitative or quantitative defects of calpain (Orphanet:207104), Autosomal recessive centronuclear myopathy (Orphanet:169186), Dysferlin-related limb-girdle muscular dystrophy R2 (Orphanet:268)

HPO phenotypes

42 total (30 of 42 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0001239	Wrist flexion contracture
HP:0001288	Gait disturbance
HP:0001371	Flexion contracture
HP:0001880	Increased total eosinophil count
HP:0002312	Clumsiness
HP:0002987	Elbow flexion contracture
HP:0003089	Hamstring contractures
HP:0003198	Myopathy
HP:0003236	Elevated circulating creatine kinase concentration
HP:0003306	Spinal rigidity
HP:0003307	Hyperlordosis
HP:0003324	Generalized muscle weakness
HP:0003326	Myalgia
HP:0003418	Back pain
HP:0003551	Difficulty climbing stairs
HP:0003555	Muscle fiber splitting
HP:0003557	Increased variability in muscle fiber diameter
HP:0003560	Muscular dystrophy
HP:0003584	Late onset
HP:0003596	Middle age onset
HP:0003621	Juvenile onset
HP:0003687	Centrally nucleated skeletal muscle fibers
HP:0003691	Scapular winging
HP:0003701	Proximal muscle weakness
HP:0005879	Congenital finger flexion contractures
HP:0006466	Ankle flexion contracture
HP:0007126	Proximal amyotrophy
HP:0007340	Lower limb muscle weakness

GWAS associations

28 associations (top):

Study	Trait	p-value
GCST000758_13	Triglycerides	2.000000e-08
GCST002216_11	Triglycerides	2.000000e-11
GCST002897_4	Triglycerides	4.000000e-10
GCST003194_22	Fibrinogen levels	2.000000e-09
GCST004121_6	Fibrinogen levels	6.000000e-10
GCST004608_196	Granulocyte percentage of myeloid white cells	2.000000e-10
GCST004609_212	Monocyte percentage of white cells	8.000000e-13
GCST004625_150	Monocyte count	7.000000e-10
GCST008070_10	HDL cholesterol levels	6.000000e-06
GCST008074_120	Triglyceride levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	5.000000e-12
GCST008074_144	Triglyceride levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	2.000000e-12
GCST008075_177	HDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	7.000000e-11
GCST008075_70	HDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	2.000000e-09
GCST008076_41	Triglyceride levels	1.000000e-07
GCST008076_65	Triglyceride levels	3.000000e-08
GCST008083_120	Triglyceride levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	9.000000e-11
GCST008083_7	Triglyceride levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	2.000000e-11
GCST008084_203	HDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	3.000000e-11
GCST008084_95	HDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	1.000000e-08
GCST008085_101	HDL cholesterol levels in current drinkers	4.000000e-07
GCST008085_167	HDL cholesterol levels in current drinkers	2.000000e-08
GCST008087_123	Triglyceride levels in current drinkers	3.000000e-12
GCST008087_14	Triglyceride levels in current drinkers	2.000000e-12
GCST009363_35	Triglyceride levels x short total sleep time interaction (2df test)	7.000000e-15
GCST009391_661	Metabolite levels	6.000000e-06
GCST010244_65	Triglyceride levels	2.000000e-31
GCST90002393_604	Monocyte count	7.000000e-36
GCST90002394_489	Monocyte percentage of white cells	1.000000e-38

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0004530	triglyceride measurement
EFO:0007997	granulocyte percentage of myeloid white cells
EFO:0007989	monocyte percentage of leukocytes
EFO:0005091	monocyte count
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004329	alcohol drinking
EFO:0010507	lactose measurement

MeSH disease descriptors (8)

Descriptor	Name	Tree numbers
D008881	Migraine Disorders	C10.228.140.546.399.750
D009136	Muscular Dystrophies	C05.651.534.500; C10.668.491.175.500; C16.320.577
D049288	Muscular Dystrophies, Limb-Girdle	C05.651.534.500.280; C10.668.491.175.500.149; C16.320.577.280
C000598744	Idiopathic inflammatory myopathy, familial (supp.)
C538640	Limb-girdle muscular dystrophy autosomal recessive (supp.)
C535895	Limb-girdle muscular dystrophy type 2A (supp.)
C535899	Limb-girdle muscular dystrophy, type 2B (supp.)
C562934	Myopathy, Centronuclear, Autosomal Recessive (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Aflatoxin B1	affects expression, increases methylation	3
Benzo(a)pyrene	decreases expression, increases methylation	2
Valproic Acid	affects cotreatment, increases expression	2
propionaldehyde	increases expression	1
aflatoxin B2	decreases methylation	1
CGP 52608	affects binding, increases reaction	1
pinostrobin	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	decreases expression, affects cotreatment	1
Resveratrol	affects cotreatment, increases expression	1
Decitabine	decreases expression	1
Sunitinib	decreases expression	1
Leflunomide	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Amiodarone	increases expression	1
Cannabidiol	decreases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Succimer	affects cotreatment, decreases expression	1
Doxorubicin	decreases expression	1
Indomethacin	affects cotreatment, decreases expression	1
Pesticides	increases methylation	1
Plant Extracts	affects cotreatment, increases expression	1
Smoke	decreases expression	1
Testosterone	decreases expression	1
Tetrachlorodibenzodioxin	affects expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	increases expression	1
Triclosan	decreases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, decreases expression	1

Cellosaurus cell lines

7 cell lines: 5 induced pluripotent stem cell, 2 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_9S72	iPSC 08-26	Induced pluripotent stem cell	Female
CVCL_9S73	iPSC 09-24	Induced pluripotent stem cell	Female
CVCL_A7HI	iPSC 08-46	Induced pluripotent stem cell	Male
CVCL_A7HJ	iPSC 09-25	Induced pluripotent stem cell	Male
CVCL_BT39	GM17726	Transformed cell line	Female
CVCL_BV68	GM23426	Transformed cell line	Male
CVCL_UM91	iPSC 09-89	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00174395	PHASE4	COMPLETED	A Trial to Study of the Effects of Eletriptan 40mg on Mild vs Moderate to Severe Pain Intensity of Migraine
NCT00208065	PHASE4	COMPLETED	Evaluation of Histamine, CGRP and VIP as Markers for Activation of Trigeminal and Parasympathetic Nerve Fibers
NCT00210496	PHASE4	COMPLETED	Potential Impact (Benefit) of Preventative Treatment With Topamax on the Effectiveness of Axert in the Acute Treatment of Migraine
NCT00210509	PHASE4	COMPLETED	A Study of the Effectiveness and Safety of Almotriptan Versus Placebo in the Treatment of Migraine Headache
NCT00212810	PHASE4	COMPLETED	Evaluation of the Effectiveness of Topiramate in Preventing the Transformation From Episodic Migraine to Chronic Daily Headache.
NCT00212823	PHASE4	COMPLETED	The Effectiveness of Almotriptan Malate (AXERT®) 12.5 Milligrams When Taken at the Onset of Migraine Pain
NCT00216736	PHASE4	COMPLETED	Oral Dexamethasone for Treatment of Migraine
NCT00259636	PHASE4	WITHDRAWN	Zonisamide for Fibromyalgia & Migraine
NCT00259649	PHASE4	COMPLETED	Prospective Survey of Menstrual Migraine & Prevention With Eletriptan
NCT00297375	PHASE4	COMPLETED	A Study Comparing the Effectiveness and Safety of ULTRACET® (Tramadol HCl/Acetaminophen) Versus Placebo for the Treatment of Acute Pain From a Migraine Headache
NCT00335777	PHASE4	COMPLETED	A Research Study Examining Migranal and Skin Sensitivity in Subjects With Migraine
NCT00363506	PHASE4	UNKNOWN	American Migraine Prevention Study
NCT00364806	PHASE4	COMPLETED	Prochlorperazine vs Metoclopramide
NCT00391755	PHASE4	TERMINATED	A Double-Blind Placebo-Controlled Trial of Rozerem in Migraine Headaches
NCT00397254	PHASE4	COMPLETED	Two Rizatriptan Prescribing Portions for Treatment of Migraine
NCT00443352	PHASE4	COMPLETED	A Research Study Examining The Use Of Duloxetine In The Prevention Of Migraine Headache
NCT00449787	PHASE4	COMPLETED	Comparing Naproxen to Sumatriptan for Emergency Headache Patients
NCT00632385	PHASE4	COMPLETED	Efficacy and Safety of Eletriptan for the Treatment of Migraine in Patients Not Satisfied With Rizatriptan Therapy
NCT00634985	PHASE4	COMPLETED	Safety and Efficacy of Eletriptan for the Treatment of Migraine in Subjects Unsuccessfully Treated With Nonsteroidal Anti-inflammatory Drugs
NCT00637286	PHASE4	COMPLETED	ZAP, US. Zomig for Appropriate for Primary Care
NCT00753311	PHASE4	COMPLETED	Rizatriptan in Acute Treatment of Migraine in Patients With Unilateral Trigeminal-autonomic Symptoms.
NCT00792636	PHASE4	COMPLETED	A Study to Determine the Effect of Sumatriptan and Naproxen Sodium Combination Tablet, Sumatriptan Tablet, and Naproxen Sodium Tablet on Blood Pressure When Treating Migraine Headaches That Occur During a 6-month Period
NCT00799045	PHASE4	COMPLETED	Clopidogrel For the Prevention of New Onset Migraine Headache Following Transcatheter Closure of Atrial Septal Defects
NCT00812214	PHASE4	COMPLETED	Treatment of Insomnia in Migraineurs
NCT00846495	PHASE4	COMPLETED	Pilot Study to Compare Frovatriptan vs. Topiramate for Prevention of Migraine
NCT00893737	PHASE4	COMPLETED	Completeness of Response Following Treatment With Treximet™ for Migraine
NCT00910689	PHASE4	COMPLETED	Drug and Non-Drug Treatment Of Severe Migraine
NCT00915473	PHASE4	COMPLETED	Greater Occipital Nerve Block for Migraine Prophylaxis
NCT01016834	PHASE4	COMPLETED	Evaluation of Treatment Satisfaction and Preference for Sumavel DosePro in the Treatment of Migraine
NCT01057160	PHASE4	COMPLETED	Rizatriptan 10 MG RPD in the Treatment of Acute Migraine
NCT01060111	PHASE4	COMPLETED	An Efficacy and Tolerability Study of Topiramate in Participants With Migraine
NCT01071096	PHASE4	COMPLETED	Calcitonin Gene-related Peptide Levels in Chronic Migraine
NCT01071317	PHASE4	COMPLETED	Trial of Comprehensive Migraine Intervention
NCT01090050	PHASE4	COMPLETED	Treximet in the Treatment of Chronic Migraine
NCT01138150	PHASE4	COMPLETED	Ictal and Interictal Inflammatory Markers in Migraine
NCT01211145	PHASE4	COMPLETED	Zomig - Treatment of Acute Migraine Headache in Adolescents
NCT01267864	PHASE4	COMPLETED	Valproate Versus Ketorolac Versus Metoclopramide
NCT01300546	PHASE4	COMPLETED	Treximet Trademark (TM) in the Prevention and Modification of Disease Progression in Migraine
NCT01319825	PHASE4	UNKNOWN	Preventive Treatment of Episodic and Chronic Migraine
NCT01332864	PHASE4	COMPLETED	Effect of Osteopathic Manipulative Treatment for Patients With Chronic Headache