DYSF

Summary

DYSF (dysferlin, HGNC:3097) is a protein-coding gene on chromosome 2p13.2, encoding Dysferlin (O75923). Key calcium ion sensor involved in the Ca(2+)-triggered synaptic vesicle-plasma membrane fusion.

The protein encoded by this gene belongs to the ferlin family and is a skeletal muscle protein found associated with the sarcolemma. It is involved in muscle contraction and contains C2 domains that play a role in calcium-mediated membrane fusion events, suggesting that it may be involved in membrane regeneration and repair. In addition, the protein encoded by this gene binds caveolin-3, a skeletal muscle membrane protein which is important in the formation of caveolae. Specific mutations in this gene have been shown to cause autosomal recessive limb girdle muscular dystrophy type 2B (LGMD2B) as well as Miyoshi myopathy. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 8291 — RefSeq curated summary.

At a glance

• Gene–disease (curated): autosomal recessive limb-girdle muscular dystrophy (Definitive, ClinGen) — +5 more curated relationships
• GWAS associations: 12
• Clinical variants (ClinVar): 4,643 total — 509 pathogenic, 361 likely-pathogenic
• Phenotypes (HPO): 81
• MANE Select transcript: NM_001130987

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3097
Approved symbol	DYSF
Name	dysferlin
Location	2p13.2
Locus type	gene with protein product
Status	Approved
Aliases	FER1L1
Ensembl gene	ENSG00000135636
Ensembl biotype	protein_coding
OMIM	603009
Entrez	8291

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 18 protein_coding, 6 protein_coding_CDS_not_defined

ENST00000258104, ENST00000394120, ENST00000409366, ENST00000409582, ENST00000409651, ENST00000409744, ENST00000409762, ENST00000410020, ENST00000410041, ENST00000413539, ENST00000429174, ENST00000461565, ENST00000468173, ENST00000472873, ENST00000475076, ENST00000479049, ENST00000487180, ENST00000493767, ENST00000494501, ENST00000698057, ENST00000698058, ENST00000698059, ENST00000873664, ENST00000873665

RefSeq mRNA: 14 — MANE Select: NM_001130987 NM_001130455, NM_001130976, NM_001130977, NM_001130978, NM_001130979, NM_001130980, NM_001130981, NM_001130982, NM_001130983, NM_001130984, NM_001130985, NM_001130986, NM_001130987, NM_003494

CCDS: CCDS1918, CCDS46323, CCDS46324, CCDS46325, CCDS46326, CCDS46327, CCDS46328, CCDS46329, CCDS46330, CCDS46331, CCDS46332

Canonical transcript exons

ENST00000410020 — 56 exons

Exon	Start	End
ENSE00000761306	71551607	71551720
ENSE00000761308	71553807	71553931
ENSE00000761309	71555965	71556071
ENSE00000761310	71561752	71561944
ENSE00000761314	71569820	71569934
ENSE00000761316	71570229	71570334
ENSE00000761318	71570599	71570741
ENSE00000761319	71574198	71574371
ENSE00000846589	71551041	71551156
ENSE00000920763	71564058	71564213
ENSE00000920764	71567951	71568082
ENSE00000920765	71568172	71568338
ENSE00001072833	71526220	71526346
ENSE00001072845	71539157	71539239
ENSE00001072846	71516180	71516242
ENSE00001072849	71535021	71535089
ENSE00001072850	71503214	71503319
ENSE00001072851	71511807	71511921
ENSE00001072854	71528298	71528401
ENSE00001072855	71535268	71535311
ENSE00001072856	71516989	71517039
ENSE00001072857	71515623	71515751
ENSE00001072865	71513716	71513921
ENSE00001122705	71520789	71520904
ENSE00001122715	71520178	71520208
ENSE00001122758	71481879	71481970
ENSE00001122765	71480883	71480938
ENSE00001580450	71513240	71513332
ENSE00002480060	71553011	71553188
ENSE00003463707	71601499	71601528
ENSE00003472400	71679057	71679235
ENSE00003494116	71667376	71667515
ENSE00003495281	71589593	71589686
ENSE00003495395	71602776	71602805
ENSE00003497725	71674197	71674296
ENSE00003500649	71612641	71612806
ENSE00003510739	71643965	71644063
ENSE00003519442	71620547	71620609
ENSE00003533440	71664268	71664438
ENSE00003548775	71681001	71681110
ENSE00003550093	71613334	71613410
ENSE00003552220	71669112	71669207
ENSE00003567354	71660560	71660651
ENSE00003567669	71600702	71600842
ENSE00003600853	71658878	71659033
ENSE00003612101	71665162	71665304
ENSE00003618663	71656162	71656290
ENSE00003620355	71682530	71682677
ENSE00003637790	71668754	71668842
ENSE00003642866	71590211	71590288
ENSE00003649549	71598564	71598745
ENSE00003652872	71611245	71611346
ENSE00003666914	71611465	71611626
ENSE00003683266	71669605	71669746
ENSE00003844323	71466699	71466933
ENSE00003850764	71686454	71686763

Expression profiles

Bgee: expression breadth ubiquitous, 257 present calls, max score 96.59.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 21.6250 / max 2087.2487, expressed in 1297 samples.

FANTOM5 promoters (21 alternative TSS)

Promoter ID	TPM avg	Samples expressed
20900	8.2279	784
20892	4.2235	787
20895	4.2146	488
20897	1.1461	400
20912	0.7835	67
20896	0.5734	305
20917	0.5266	117
20901	0.4833	282
20898	0.3771	192
20899	0.1857	105

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
blood	UBERON:0000178	96.59	gold quality
hindlimb stylopod muscle	UBERON:0004252	96.16	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	95.96	gold quality
triceps brachii	UBERON:0001509	95.69	gold quality
apex of heart	UBERON:0002098	95.60	gold quality
skeletal muscle tissue	UBERON:0001134	95.50	gold quality
vastus lateralis	UBERON:0001379	95.49	gold quality
lateral globus pallidus	UBERON:0002476	95.47	gold quality
gastrocnemius	UBERON:0001388	95.34	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	95.04	gold quality
gluteal muscle	UBERON:0002000	95.02	gold quality
muscle organ	UBERON:0001630	94.60	gold quality
skeletal muscle organ	UBERON:0014892	94.60	gold quality
biceps brachii	UBERON:0001507	94.59	gold quality
quadriceps femoris	UBERON:0001377	94.57	gold quality
deltoid	UBERON:0001476	94.47	gold quality
muscle of leg	UBERON:0001383	94.46	gold quality
spleen	UBERON:0002106	94.11	gold quality
muscle tissue	UBERON:0002385	93.88	gold quality
heart right ventricle	UBERON:0002080	93.50	gold quality
tibialis anterior	UBERON:0001385	92.91	silver quality
cardiac ventricle	UBERON:0002082	92.91	gold quality
heart left ventricle	UBERON:0002084	92.88	gold quality
trabecular bone tissue	UBERON:0002483	92.73	gold quality
monocyte	CL:0000576	92.66	gold quality
substantia nigra pars compacta	UBERON:0001965	92.64	gold quality
saphenous vein	UBERON:0007318	92.56	gold quality
leukocyte	CL:0000738	92.51	gold quality
mononuclear cell	CL:0000842	92.51	gold quality
bone marrow cell	CL:0002092	92.47	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-6678	yes	7.20
E-ANND-3	yes	6.39

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): VDR

miRNA regulators (miRDB)

23 targeting DYSF, 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-3120-5P	100.00	65.56	965
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-10395-5P	99.86	67.35	676
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-5093	99.67	69.26	2291
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-452-5P	99.65	69.63	1762
HSA-MIR-4676-3P	99.65	69.31	1733
HSA-MIR-892C-3P	99.65	69.38	1745
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-6770-5P	98.97	66.76	1853
HSA-MIR-330-5P	98.73	67.63	1788
HSA-MIR-654-3P	98.38	67.61	905
HSA-MIR-326	98.25	66.44	1565
HSA-MIR-4303	98.01	68.13	2304
HSA-MIR-4665-5P	97.91	67.69	1536
HSA-MIR-3151-3P	97.80	66.16	479

Literature-anchored findings (GeneRIF, showing 40)

• The dysferlin gene, a strong candidate gene responsible for two other distal myopathies in the same region, is located centromeric to PAC3-H52 and can thereby formally be excluded as cause for Welander distal myopathy (PMID:12836053)
• Isolated calf atrophy and weakness with onset after age 30, and associated with serum CK levels that are only moderately elevated, represents a distinct myopathy phenotype. (PMID:14506716)
• In muscular dystrophy with dysferlinopathy, the inflammatory response is triggered by altered expression of dysferlin and is involved in muscle degeneration. (PMID:14512171)
• the importance of dysferlin-caveolin 3 relationship for skeletal muscle integrity (PMID:14749532)
• If, in particular, a dysferlinopathy is supposed, the underlying mutation should be identified to confirm the diagnosis and as a basis for current and future therapeutic interventions. (PMID:15221058)
• Dysferlin and its differentially spliced isoforms play different roles in myogenic cell differentiation, hence dysferlin function in peripheral nerve might be accomplished by this novel spliced variant isoform. (PMID:15318348)
• This study identified 11 different mutations, including eight missense and three deletion mutations. Nine of them were novel mutations. (PMID:15469449)
• Miyoshi distal myopathy in these 2 Chinese families demonstrated a homogenous phenotype and compound heterozygous mutations. Among the 4 mutations, 3 were novel mutations that, to our knowledge, have not been reported previously. (PMID:15477515)
• Dysferlin expression when satellite cells are activated confirm the involvement of dysferlin in human muscle regeneration/repair and its possible role in fusion events during muscle development. (PMID:15535137)
• Data show that affixin is a dysferlin binding protein that colocalizes with dysferlin at the sarcolemma of normal skeletal muscle. (PMID:15835269)
• LGMD2B mutational analysis in Miyoshi myopathy, and atypical dysferlinopathies (PMID:16010686)
• The new R1905X dysferlin founder mutation produced the 3 possible dysferlinopathy phenotypes without intrafamilial heterogeneity. (PMID:16087766)
• annexin A1 and A2 may have roles in dysferlin deficiency and in muscular dystrophies (PMID:16100712)
• Two severely affected sisters sith limb-girdle muscular dystrophy were homozygous for a dysferlin null mutation. (PMID:16606933)
• there is a functional link between dysferlin and myogenin in the differentiation of skeletal muscle (PMID:16608842)
• dysferlin is present in glomeruli and may be associated with glomerular permeabi (PMID:16797397)
• membrane attack complex deposits and a pro-inflammatory milieu in the absence of interleukin-10 expression may contribute to progressive muscle damage in dysferlinopathies (PMID:16862423)
• DYSF_v1 retains phylogenic conservancy and shows similar expression pattern as the currently known human dysferlin. (PMID:16896923)
• While the quantity of beta-sarcoglycan was nearly normal in the limb girdle muscular dystrophy (LGMD)2E carrier, the levels of dysferlin protein were reduced to 50% of controls in the carriers of LGMD2B. (PMID:16934466)
• Thus, alteration of structurally important residues in dysferlin could lead to improper folding and degradation of the mutant protein. (PMID:16996541)
• The diagnosis of symptomatic carriers of dysferlin mutations should be considered when a pathologic pattern of dysferlin protein is observed. (PMID:17287450)
• dysferlin is not expressed at the plasmalemma of myotubes but mostly localizes to the T-tubule network. However, dysferlin translocated to the site of injury and toward the plasma membrane in a Ca2+-dependent fashion in response to a wounding assay (PMID:17363620)
• A proteomics screen of human placental microvillous syncytiotrophoblasts (STBs) revealed the expression of dysferlin (DYSF), a plasma membrane repair protein associated with certain muscular dystrophies. (PMID:17554076)
• Phenotypic study in 40 patients with dysferlin gene mutations (PMID:17698709)
• Genomic analysis of the dysferlin coding sequence performed in patients from Caucasus Jews, who lacked muscle dysferlin, revealed a homozygous frameshift mutation predicting a truncated dysferlin and a complete loss of functional protein. (PMID:17825554)
• These data suggest that disturbances in dysferlin as well as Z-line proteins and transcription factors particularly under mechanical stress cause cardiomyopathy. (PMID:17828519)
• study reports a novel pair of heterozygous mutations in the 3’-splicing site of exon 26 and the translation site of exon 28 of the dysferlin gene in two siblings (PMID:17868276)
• Cytoplasmic localization of dysferlin correlates with fiber regeneration in a subset of muscular dystrophy patients. We also identified patients with forms of LGMD and with abnormal dysferlin localization that doesn’t correlate with fiber regeneration. (PMID:17897828)
• Dysferlin deficiency enhances monocyte phagocytosis. (PMID:18276788)
• missense mutation c.4253G>A on the DYSF gene in a Mexican family from an endogamic population (PMID:18294055)
• Mutations located between exons 7 and 16, corresponding to the predicted second and third C2 domain of dysferlin, are amyloidogenic. (PMID:18306167)
• A case represents the eldest age of onset of dysferlinopathy reported so far and widens the clinical spectrum of this disease. (PMID:18396043)
• solution structure of the inner DysF domain of the dysferlin paralogue myoferlin, which has a unique fold held together by stacking of arginine and tryptophans, mutations that lead to clinical disease in dysferlin (PMID:18495154)
• AQP4 expression was analyzed in muscle biopsies from patients affected by Limb Girdle Muscular Dystrophies. (PMID:18641458)
• Rab27A/Slp2a expression in limb girdle muscular dystrophy 2B muscle provides a compensatory vesicular trafficking pathway that is able to repair membrane damage in the absence of dysferlin. (PMID:18832576)
• The mutational spectrum significantly shows a higher proportion of nonsense mutations in DYSf gene, but a lower proportion of deleterious missense changes as compared to previous series . (PMID:18853459)
• We report two patients with a new phenotype of dysferlinopathy presenting as congenital muscular disease. Muscle biopsy showed mild dystrophic features and the absence of dysferlin. (PMID:19084402)
• study identified alternative splicing involving novel dysferlin exons 5a & 40a, in addition to previously reported exon 17; differences in frequencies of dysferlin transcripts in skeletal muscle & blood were characterized (PMID:19221801)
• In trophoblastic cells, there was a positive correlation between cell fusion and increased dysferlin expression. (PMID:19228595)
• Dysferlin’s C2A domain was able to bind to phosphoinositides in a Ca(2+)-dependent fashion. (PMID:19253956)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	dysf	ENSDARG00000007370
mus_musculus	Dysf	ENSMUSG00000033788
rattus_norvegicus	Dysf	ENSRNOG00000032788
drosophila_melanogaster	mfr	FBGN0266757

Paralogs (4): OTOF (ENSG00000115155), MYOF (ENSG00000138119), FER1L6 (ENSG00000214814), FER1L5 (ENSG00000249715)

Protein

Protein identifiers

Dysferlin — O75923 (reviewed: O75923)

Alternative names: Dystrophy-associated fer-1-like protein, Fer-1-like protein 1

All UniProt accessions (6): A0A8V8TLD2, A0A8V8TLV7, A0A8V8TMV5, A0A8V8TN49, B7Z2R1, O75923

UniProt curated annotations — full annotation on UniProt →

Function. Key calcium ion sensor involved in the Ca(2+)-triggered synaptic vesicle-plasma membrane fusion. Plays a role in the sarcolemma repair mechanism of both skeletal muscle and cardiomyocytes that permits rapid resealing of membranes disrupted by mechanical stress.

Subunit / interactions. Interacts with CACNA1S. Interacts with ANXA1; the interaction is Ca(2+)- and injury state-dependent. Interacts with ANXA2; the interaction is Ca(2+)- and injury state-dependent. Interacts with CACNA1S and PARVB. Interacts with TRIM72/MG53; interaction is required for transport to sites of cell injury during repair patch formation. Interacts with RIPOR2; this interaction occurs during early myogenic differentiation. Interacts with CAV3 and PARVB. Interacts with AHNAK; the interaction is direct and Ca(2+)-independent. Interacts with AHNAK2; the interaction is direct and Ca(2+)-independent.

Subcellular location. Cell membrane. Sarcolemma. Cytoplasmic vesicle membrane. Late endosome membrane.

Tissue specificity. Expressed in skeletal muscle, myoblast, myotube and in the syncytiotrophoblast (STB) of the placenta (at protein level). Ubiquitous. Highly expressed in skeletal muscle. Also found in heart, brain, spleen, intestine, placenta and at lower levels in liver, lung, kidney and pancreas.

Disease relevance. Muscular dystrophy, limb-girdle, autosomal recessive 2 (LGMDR2) [MIM:253601] An autosomal recessive degenerative myopathy characterized by weakness and atrophy starting in the proximal pelvifemoral muscles, with onset in the late teens or later, massive elevation of serum creatine kinase levels and slow progression. Scapular muscle involvement is minor and not present at onset. Upper limb girdle involvement follows some years after the onset in lower limbs. The disease is caused by variants affecting the gene represented in this entry. Miyoshi muscular dystrophy 1 (MMD1) [MIM:254130] A late-onset muscular dystrophy involving the distal lower limb musculature. It is characterized by weakness that initially affects the gastrocnemius muscle during early adulthood. The disease is caused by variants affecting the gene represented in this entry. Distal myopathy with anterior tibial onset (DMAT) [MIM:606768] Onset of the disorder is between 14 and 28 years of age and the anterior tibial muscles are the first muscle group to be involved. Inheritance is autosomal recessive. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. All seven C2 domains associate with lipid membranes in a calcium-dependent manner. Domains C2 1 and 3 have the highest affinity for calcium, the C2 domain 1 seems to be largely unstructured in the absence of bound ligands. The C2 domain 1 from isoform 14 does not bind calcium in the absence of bound phospholipid.

Miscellaneous. Produced by alternative promoter usage.

Similarity. Belongs to the ferlin family.

Isoforms (15)

UniProt ID	Names	Canonical?
O75923-1	1	yes
O75923-2	2
O75923-3	3
O75923-4	4
O75923-5	5
O75923-6	6
O75923-7	7
O75923-8	8
O75923-9	9
O75923-10	10
O75923-11	11
O75923-12	12
O75923-13	13
O75923-14	14, Dysferlin_v1, DYSF_v1
O75923-15	15

RefSeq proteins (14): NP_001123927, NP_001124448, NP_001124449, NP_001124450, NP_001124451, NP_001124452, NP_001124453, NP_001124454, NP_001124455, NP_001124456, NP_001124457, NP_001124458, NP_001124459, NP_003485 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000008	C2_dom	Domain
IPR006614	Peroxin/Ferlin	Domain
IPR012560	Ferlin_A-domain	Domain
IPR012561	Ferlin_B-domain	Domain
IPR012968	FerIin_dom	Domain
IPR032362	Ferlin_C	Domain
IPR035892	C2_domain_sf	Homologous_superfamily
IPR037720	C2B_Ferlin	Domain
IPR037721	Ferlin	Family
IPR037722	C2C_Ferlin	Domain
IPR037723	C2D_Ferlin	Domain
IPR037724	C2E_Ferlin	Domain
IPR037725	C2F_Ferlin	Domain
IPR037726	C2A_Ferlin	Domain
IPR055072	Ferlin_DSRM	Domain

Pfam: PF00168, PF08150, PF08151, PF08165, PF16165, PF22901

UniProt features (154 total): sequence variant 78, strand 20, binding site 15, modified residue 13, domain 7, splice variant 6, mutagenesis site 5, topological domain 2, region of interest 2, helix 2, compositionally biased region 2, chain 1, transmembrane region 1

Structure

Experimental structures (PDB)

11 structures.

PDB	Method	Resolution (Å)
4IQH	X-RAY DIFFRACTION	1.76
4CAH	X-RAY DIFFRACTION	1.9
7JOF	X-RAY DIFFRACTION	2
4IHB	X-RAY DIFFRACTION	2.04
9DYQ	X-RAY DIFFRACTION	2.05
4CAI	X-RAY DIFFRACTION	2.2
9B8K	ELECTRON MICROSCOPY	2.96
9QLS	ELECTRON MICROSCOPY	3.54
9B8L	ELECTRON MICROSCOPY	4.65
7K6B	SOLUTION NMR
7KRB	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75923-F1	79.25	0.28

Functional residue map

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

Ligand- & substrate-binding residues (15): 18; 19; 21; 40; 1168; 1174; 1230; 1232; 1594; 1600; 1649; 1651 …

Post-translational modifications (13): 166, 197, 166, 197, 166, 197, 167, 198, 167, 198, 167, 198, 166

Mutagenesis-validated functional residues (5):

Position	Phenotype
16	fails to bind calcium.
21	fails to bind calcium.
71	fails to bind calcium.
79	moderately increased calcium affinity.
80	reduced calcium affinity.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-445355	Smooth Muscle Contraction

MSigDB gene sets: 320 (showing top): GOBP_MACROPHAGE_ACTIVATION_INVOLVED_IN_IMMUNE_RESPONSE, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, GOBP_NEGATIVE_REGULATION_OF_ENDOCYTOSIS, GOBP_NEUROTRANSMITTER_TRANSPORT, GOBP_VESICLE_MEDIATED_TRANSPORT, CAGCTG_AP4_Q5, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOBP_CELL_CELL_SIGNALING, GOBP_REGULATION_OF_VESICLE_MEDIATED_TRANSPORT, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, GOBP_CELL_ACTIVATION_INVOLVED_IN_IMMUNE_RESPONSE, GOBP_NEGATIVE_REGULATION_OF_TRANSPORT, GOBP_MYELOID_LEUKOCYTE_ACTIVATION, BACH2_01

GO Biological Process (4): monocyte activation involved in immune response (GO:0002280), macrophage activation involved in immune response (GO:0002281), regulation of neurotransmitter secretion (GO:0046928), negative regulation of phagocytosis (GO:0050765)

GO Molecular Function (6): calcium ion binding (GO:0005509), phospholipid binding (GO:0005543), calcium-dependent phospholipid binding (GO:0005544), protein binding (GO:0005515), lipid binding (GO:0008289), metal ion binding (GO:0046872)

GO Cellular Component (16): endosome (GO:0005768), early endosome (GO:0005769), late endosome (GO:0005770), plasma membrane (GO:0005886), endocytic vesicle (GO:0030139), T-tubule (GO:0030315), cytoplasmic vesicle membrane (GO:0030659), synaptic vesicle membrane (GO:0030672), late endosome membrane (GO:0031902), centriolar satellite (GO:0034451), sarcolemma (GO:0042383), extracellular exosome (GO:0070062), sperm midpiece (GO:0097225), endomembrane system (GO:0012505), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Muscle contraction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
cytoplasmic vesicle	3
myeloid cell activation involved in immune response	2
immune response	2
binding	2
endosome	2
plasma membrane	2
monocyte activation	1
leukocyte activation involved in immune response	1
macrophage activation	1
neurotransmitter secretion	1
modulation of chemical synaptic transmission	1
regulation of neurotransmitter transport	1
regulation of secretion by cell	1
phagocytosis	1
negative regulation of endocytosis	1
regulation of phagocytosis	1
metal ion binding	1
lipid binding	1
phospholipid binding	1
cation binding	1
endomembrane system	1
membrane	1
cell periphery	1
sarcolemma	1
vesicle membrane	1
synaptic vesicle	1
exocytic vesicle membrane	1
late endosome	1
endosome membrane	1
centrosome	1
extracellular vesicle	1
sperm flagellum	1
vacuole	1
cytoplasm	1
intracellular vesicle	1

Protein interactions and networks

STRING

1578 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DYSF	CAV3	P56539	998
DYSF	CAPN3	P20807	985
DYSF	AHNAK	Q09666	982
DYSF	DMD	P11532	959
DYSF	TRIM72	Q6ZMU5	949
DYSF	ANXA2	P07355	944
DYSF	ANO5	Q75V66	939
DYSF	ANXA1	P04083	915
DYSF	SGCA	Q16586	905
DYSF	LAMA2	P24043	866
DYSF	SGCG	Q13326	864
DYSF	FKRP	Q9H9S5	863
DYSF	MMD2	Q8IY49	854
DYSF	EHD2	Q9NZN4	842
DYSF	SGCB	Q16585	832

IntAct

108 interactions, top by confidence:

A	B	Type	Score
LPAR1	TMEM223	psi-mi:“MI:0914”(association)	0.530
DYSF	ALMS1	psi-mi:“MI:0403”(colocalization)	0.500
DGKD	DYSF	psi-mi:“MI:0403”(colocalization)	0.500
CMYA5	DYSF	psi-mi:“MI:0403”(colocalization)	0.500
DYSF	FLNC	psi-mi:“MI:0403”(colocalization)	0.500
OPTN	DYSF	psi-mi:“MI:0403”(colocalization)	0.500
SNAPIN	DYSF	psi-mi:“MI:0403”(colocalization)	0.500
DYSF	DES	psi-mi:“MI:0403”(colocalization)	0.500
DYSF	DES	psi-mi:“MI:2364”(proximity)	0.500
DYSF	SNAPIN	psi-mi:“MI:2364”(proximity)	0.500
OPTN	DYSF	psi-mi:“MI:2364”(proximity)	0.500
FLNC	DYSF	psi-mi:“MI:2364”(proximity)	0.500
DYSF	CMYA5	psi-mi:“MI:2364”(proximity)	0.500
DGKD	DYSF	psi-mi:“MI:2364”(proximity)	0.500
DYSF	ALMS1	psi-mi:“MI:2364”(proximity)	0.500
DYSF	MYOM1	psi-mi:“MI:2364”(proximity)	0.450
DYSF	ACTN2	psi-mi:“MI:2364”(proximity)	0.450
DYSF	APPL1	psi-mi:“MI:2364”(proximity)	0.450
MYOM2	DYSF	psi-mi:“MI:2364”(proximity)	0.450
DYSF	SAMHD1	psi-mi:“MI:2364”(proximity)	0.450
DYSF	DNAJB6	psi-mi:“MI:2364”(proximity)	0.450
TTN	DYSF	psi-mi:“MI:2364”(proximity)	0.450
DYSF	SGCG	psi-mi:“MI:2364”(proximity)	0.450
DYSF	KIF1B	psi-mi:“MI:0403”(colocalization)	0.440
DYSF	ITSN1	psi-mi:“MI:0407”(direct interaction)	0.440
NEB	DYSF	psi-mi:“MI:0403”(colocalization)	0.380
NEB	DYSF	psi-mi:“MI:2364”(proximity)	0.380
CD177	MYO1G	psi-mi:“MI:0914”(association)	0.350
KLK10	IGLL5	psi-mi:“MI:0914”(association)	0.350
CD226	TMED7-TICAM2	psi-mi:“MI:0914”(association)	0.350

BioGRID (90): DYSF (Affinity Capture-Western), DYSF (Affinity Capture-Western), FAM65B (Affinity Capture-Western), DYSF (Affinity Capture-MS), DYSF (Affinity Capture-MS), DYSF (Affinity Capture-MS), DYSF (Affinity Capture-MS), DYSF (Affinity Capture-MS), DYSF (Affinity Capture-MS), DYSF (Two-hybrid), DYSF (Affinity Capture-Western), APPL1 (Affinity Capture-Western), KIF1B (Affinity Capture-Western), SNAPIN (Affinity Capture-Western), DYSF (Affinity Capture-Western)

ESM2 similar proteins: A0AVI2, A0FGR9, A3KGK3, A6NCM1, A6QQP7, B0DOB4, B3DLH6, B7FF09, B7ZC32, D3ZGS3, F1S5L4, O00329, O35904, O70145, O75923, P0DM40, P32019, P58069, P97564, Q0VA04, Q15283, Q17I16, Q1LXZ7, Q2WGJ9, Q32PH0, Q5DTI8, Q5GJ77, Q5RE88, Q5T0N1, Q5XIZ9, Q61586, Q62240, Q63713, Q69ZN7, Q6DCF6, Q6P5U7, Q6PA97, Q86VS3, Q86YR7, Q8BWR4

Diamond homologs: A0AVI2, A3KGK3, A6QQP7, B3DLH6, O75923, P0DM40, Q69ZN7, Q8LFN9, Q9C6B7, Q9ESD7, Q9NZM1, Q9Z268, A0JJX5, A1CQG2, A1ZBD6, A2QQ28, A4IFJ5, A8KBH6, B1WAZ6, B8N7E5, G0S9J5, O14065, O14795, O43581, O75131, O94812, P04409, P05126, P05128, P05129, P05696, P05771, P05772, P0C869, P0C871, P10102, P10829, P13677, P17252, P20444

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
“MYOD1/SWI/SNF complex”	“up-regulates quantity by expression”	DYSF	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 60 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.

Reactome pathways:

Pathway	Partners	Fold	FDR
Striated Muscle Contraction	7	46.0×	3e-08

GO biological processes:

GO term	Partners	Fold	FDR
sarcomere organization	9	65.0×	4e-12

Disease & clinical

Clinical variants and AI predictions

ClinVar

4643 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	509
Likely pathogenic	361
Uncertain significance	1142
Likely benign	1852
Benign	189

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1068079	NM_001130987.2(DYSF):c.345+2T>C	Pathogenic
1068508	NM_001130987.2(DYSF):c.3018_3019delinsAA (p.Cys1006_Pro1007delinsTer)	Pathogenic
1068645	NM_001130987.2(DYSF):c.4434_4435insTTTTTTTTNNNNNNNNNNTTTAGCCGGGATGGTCTCGATCTCCTGACCTCGTGATCCGCCCGCCTCGGCCTCCCAAAGTGCTGGGATTACAGGCGTGAGCCACCGCGCCCGGCCAACTCATCGACATT (p.Asp1479delinsPhePheXaaXaaXaaXaaPheSerArgAspGlyLeuAspLeuLeuThrSerTer)	Pathogenic
1069223	NM_001130987.2(DYSF):c.5514_5515insA (p.Pro1839fs)	Pathogenic
1069450	NM_001130987.2(DYSF):c.1271del (p.Pro424fs)	Pathogenic
1069589	NM_001130987.2(DYSF):c.1276_1276+7del	Pathogenic
1071301	NM_001130987.2(DYSF):c.179del (p.Leu60fs)	Pathogenic
1071822	NM_001130987.2(DYSF):c.4177del (p.Arg1393fs)	Pathogenic
1073503	NM_001130987.2(DYSF):c.1380+1G>C	Pathogenic
1073586	NM_001130987.2(DYSF):c.1778_1782dup (p.Ala595fs)	Pathogenic
1074366	NM_001130987.2(DYSF):c.1984+2T>C	Pathogenic
1075165	NM_001130987.2(DYSF):c.1501del (p.Arg500_Leu501insTer)	Pathogenic
1076980	NC_000002.11:g.(?71783085)(71913729_?)del	Pathogenic
1180844	NM_001130987.2(DYSF):c.3630dup (p.Asn1211fs)	Pathogenic
1300184	NM_001130987.2(DYSF):c.3427del (p.Glu1143fs)	Pathogenic
1300185	NM_001130987.2(DYSF):c.4989del (p.Glu1663fs)	Pathogenic
1322794	NM_001130987.2(DYSF):c.3134G>A (p.Trp1045Ter)	Pathogenic
1322801	NM_001130987.2(DYSF):c.2523C>G (p.Tyr841Ter)	Pathogenic
1322803	NM_001130987.2(DYSF):c.2149C>T (p.Gln717Ter)	Pathogenic
1322805	NM_001130987.2(DYSF):c.689_690dup (p.Gly231fs)	Pathogenic
1322807	NM_001130987.2(DYSF):c.923del (p.Glu308fs)	Pathogenic
1322808	NM_001130987.2(DYSF):c.1965C>G (p.Tyr655Ter)	Pathogenic
1322809	NM_001130987.2(DYSF):c.1493+1G>C	Pathogenic
1322813	NM_001130987.2(DYSF):c.1494G>A (p.Trp498Ter)	Pathogenic
1326969	NM_001130987.2(DYSF):c.5849G>A (p.Trp1950Ter)	Pathogenic
1350242	NM_001130987.2(DYSF):c.5718C>A (p.Phe1906Leu)	Pathogenic
1350756	NM_001130987.2(DYSF):c.2697+5G>A	Pathogenic
1361687	NM_001130987.2(DYSF):c.5251_5258del (p.Lys1751fs)	Pathogenic
1362444	NM_001130987.2(DYSF):c.5211del (p.Ser1738fs)	Pathogenic
1367528	NM_001130987.2(DYSF):c.5578A>T (p.Arg1860Ter)	Pathogenic

SpliceAI

9855 predictions. Top by Δscore:

Variant	Effect	Δscore
2:71454082:TGCAG:T	donor_loss	1.0000
2:71454084:CAG:C	donor_loss	1.0000
2:71454085:AG:A	donor_loss	1.0000
2:71454086:GG:G	donor_loss	1.0000
2:71454088:T:G	donor_loss	1.0000
2:71480881:AG:A	acceptor_gain	1.0000
2:71480882:GG:G	acceptor_gain	1.0000
2:71480936:GAG:G	donor_gain	1.0000
2:71480939:GTAT:G	donor_gain	1.0000
2:71481873:TTCCA:T	acceptor_loss	1.0000
2:71481874:TCCA:T	acceptor_loss	1.0000
2:71481875:CCA:C	acceptor_loss	1.0000
2:71481876:CA:C	acceptor_loss	1.0000
2:71481877:A:AG	acceptor_gain	1.0000
2:71481877:A:G	acceptor_loss	1.0000
2:71481877:AG:A	acceptor_gain	1.0000
2:71481877:AGG:A	acceptor_gain	1.0000
2:71481878:G:GG	acceptor_gain	1.0000
2:71481878:GG:G	acceptor_gain	1.0000
2:71481878:GGG:G	acceptor_gain	1.0000
2:71481968:CAGG:C	donor_loss	1.0000
2:71481969:AGGTA:A	donor_loss	1.0000
2:71481970:GGT:G	donor_loss	1.0000
2:71481971:G:T	donor_loss	1.0000
2:71503317:GGG:G	donor_gain	1.0000
2:71503318:GGG:G	donor_gain	1.0000
2:71513714:A:AG	acceptor_gain	1.0000
2:71513715:G:GG	acceptor_gain	1.0000
2:71515613:T:TA	acceptor_gain	1.0000
2:71515614:G:A	acceptor_gain	1.0000

AlphaMissense

13969 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:71480930:T:A	W46R	1.000
2:71480930:T:C	W46R	1.000
2:71520809:T:A	W320R	1.000
2:71520809:T:C	W320R	1.000
2:71568298:T:A	W924R	1.000
2:71568298:T:C	W924R	1.000
2:71598638:T:A	W1199R	1.000
2:71598638:T:C	W1199R	1.000
2:71480931:G:C	W46S	0.999
2:71480932:G:C	W46C	0.999
2:71480932:G:T	W46C	0.999
2:71481888:T:A	W52R	0.999
2:71481888:T:C	W52R	0.999
2:71481940:T:A	V69D	0.999
2:71520861:T:C	L337P	0.999
2:71535060:T:A	W442R	0.999
2:71535060:T:C	W442R	0.999
2:71553104:A:C	S616R	0.999
2:71553106:C:A	S616R	0.999
2:71553106:C:G	S616R	0.999
2:71568316:T:A	W930R	0.999
2:71568316:T:C	W930R	0.999
2:71569902:T:A	W965R	0.999
2:71569902:T:C	W965R	0.999
2:71570298:T:A	W999R	0.999
2:71570298:T:C	W999R	0.999
2:71590229:T:C	L1154P	0.999
2:71598579:T:A	V1179D	0.999
2:71679194:T:A	W1969R	0.999
2:71679194:T:C	W1969R	0.999

dbSNP variants (sampled 300 via entrez): RS1000006955 (2:71623706 CTTAAAGT>C), RS1000028590 (2:71585469 A>G,T), RS1000035677 (2:71500517 C>G,T), RS1000067571 (2:71584528 G>A), RS1000071697 (2:71542277 A>G), RS1000074474 (2:71463125 G>A), RS1000084652 (2:71635307 T>C), RS1000103779 (2:71508759 C>G,T), RS1000106253 (2:71547965 T>C), RS1000119632 (2:71474047 C>T), RS1000120257 (2:71579812 C>A,T), RS1000130144 (2:71474530 A>G), RS1000159415 (2:71630290 G>A), RS1000164717 (2:71508949 T>C), RS1000165070 (2:71659952 G>A,T)

Disease associations

OMIM: gene MIM:603009 | disease phenotypes: MIM:253601, MIM:254130, MIM:606768, MIM:253600, MIM:181500

GenCC curated gene-disease

Disease	Classification	Inheritance
neuromuscular disease caused by qualitative or quantitative defects of dysferlin	Definitive	Autosomal recessive
autosomal recessive limb-girdle muscular dystrophy type 2B	Strong	Autosomal recessive
distal myopathy with anterior tibial onset	Strong	Autosomal recessive
autosomal recessive limb-girdle muscular dystrophy	Strong	Autosomal recessive
congenital myopathy, Paradas type	Supportive	Autosomal recessive
Miyoshi myopathy	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

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

Mondo (14): autosomal recessive limb-girdle muscular dystrophy type 2B (MONDO:0009676), neuromuscular disease caused by qualitative or quantitative defects of dysferlin (MONDO:0016145), Miyoshi muscular dystrophy 1 (MONDO:0024545), distal myopathy with anterior tibial onset (MONDO:0011721), autosomal recessive limb-girdle muscular dystrophy (MONDO:0015152), muscular dystrophy (MONDO:0020121), schizophrenia (MONDO:0005090), dilated cardiomyopathy (MONDO:0005021), restrictive cardiomyopathy (MONDO:0005201), Miyoshi myopathy (MONDO:0009685), peripheral neuropathy (MONDO:0005244), limb-girdle muscular dystrophy (MONDO:0016971), myopathy (MONDO:0005336), congenital myopathy, Paradas type (MONDO:0016049)

Orphanet (10): Qualitative or quantitative defects of dysferlin (Orphanet:207073), Dysferlin-related limb-girdle muscular dystrophy R2 (Orphanet:268), Miyoshi myopathy (Orphanet:45448), Distal myopathy with anterior tibial onset (Orphanet:178400), Autosomal recessive limb-girdle muscular dystrophy (Orphanet:102015), Muscular dystrophy (Orphanet:98473), Dilated cardiomyopathy (Orphanet:217604), Restrictive cardiomyopathy (Orphanet:217632), Limb-girdle muscular dystrophy (Orphanet:263), NON RARE IN EUROPE: Schizophrenia (Orphanet:3140)

HPO phenotypes

81 total (30 of 81 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000467	Neck muscle weakness
HP:0001288	Gait disturbance
HP:0001315	Reduced tendon reflexes
HP:0001626	Abnormality of the cardiovascular system
HP:0001640	Cardiomegaly
HP:0001667	Right ventricular hypertrophy
HP:0001761	Pes cavus
HP:0002015	Dysphagia
HP:0002072	Chorea
HP:0002460	Distal muscle weakness
HP:0002505	Loss of ambulation
HP:0002540	Inability to walk
HP:0002747	Respiratory insufficiency due to muscle weakness
HP:0002996	Limited elbow movement
HP:0003115	Abnormal EKG
HP:0003198	Myopathy
HP:0003202	Skeletal muscle atrophy
HP:0003236	Elevated circulating creatine kinase concentration
HP:0003306	Spinal rigidity
HP:0003307	Hyperlordosis
HP:0003325	Limb-girdle muscle weakness
HP:0003326	Myalgia
HP:0003438	Absent Achilles reflex
HP:0003458	EMG: myopathic abnormalities
HP:0003474	Somatic sensory dysfunction
HP:0003547	Shoulder girdle muscle weakness
HP:0003551	Difficulty climbing stairs
HP:0003552	Muscle stiffness
HP:0003555	Muscle fiber splitting

GWAS associations

12 associations (top):

Study	Trait	p-value
GCST000189_8	Protein quantitative trait loci	1.000000e-06
GCST002279_79	PR interval in Tripanosoma cruzi seropositivity	1.000000e-07
GCST002829_14	Urate levels in overweight individuals	5.000000e-06
GCST005309_2	Nonalcoholic steatohepatitis-derived hepatocellular carcinoma	5.000000e-07
GCST006269_760	General cognitive ability	5.000000e-09
GCST007044_5	Extremely high intelligence	6.000000e-09
GCST008156_123	Hip circumference adjusted for BMI	7.000000e-06
GCST010042_111	Asthma	4.000000e-08
GCST010043_97	Asthma	3.000000e-10
GCST012227_1200	Hip circumference adjusted for BMI	4.000000e-08
GCST012227_1201	Hip circumference adjusted for BMI	4.000000e-08
GCST90000025_753	Appendicular lean mass	6.000000e-34

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004462	PR interval
EFO:0004531	urate measurement
EFO:0004337	intelligence
EFO:0008039	BMI-adjusted hip circumference
EFO:0004980	appendicular lean mass

MeSH disease descriptors (9)

Descriptor	Name	Tree numbers
D002311	Cardiomyopathy, Dilated	C14.280.195.160; C14.280.238.070; C16.320.488.750
D002313	Cardiomyopathy, Restrictive	C14.280.238.160
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
C537995	Dysferlinopathy (supp.)
C538640	Limb-girdle muscular dystrophy autosomal recessive (supp.)
C535899	Limb-girdle muscular dystrophy, type 2B (supp.)
C537480	Miyoshi myopathy (supp.)
C564664	Myopathy, Distal, with Anterior Tibial Onset (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases methylation, affects cotreatment, increases abundance, increases expression, decreases expression	5
Estradiol	affects cotreatment, increases expression, affects binding, increases reaction	4
Acetaminophen	decreases expression	3
Benzo(a)pyrene	decreases expression, affects methylation	3
Tretinoin	increases expression	3
Aflatoxin B1	decreases expression, increases methylation	3
Particulate Matter	affects methylation, increases abundance, increases expression	3
Air Pollutants	affects expression, increases abundance, affects methylation	2
Calcitriol	increases expression, affects cotreatment	2
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
FR900359	increases phosphorylation	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, decreases methylation	1
2-methyl-4-isothiazolin-3-one	decreases expression	1
ethyl-p-hydroxybenzoate	increases expression	1
arsenite	affects binding, decreases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
cobaltous chloride	decreases expression	1
benzo(e)pyrene	increases methylation	1
potassium chromate(VI)	decreases expression	1
aflatoxin B2	increases methylation	1
nickel sulfate	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
abrine	increases expression	1
jinfukang	increases expression	1
incobotulinumtoxinA	decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Norethindrone Acetate	affects cotreatment, increases expression	1
Amiloride	decreases expression	1

Cellosaurus cell lines

34 cell lines: 23 induced pluripotent stem cell, 9 telomerase immortalized cell line, 1 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_6B28	LGMD2Cl11	Telomerase immortalized cell line	Sex unspecified
CVCL_AS33	JFHZ1	Induced pluripotent stem cell	Male
CVCL_AS34	JFHZ2	Induced pluripotent stem cell	Male
CVCL_AS35	JFHZ3	Induced pluripotent stem cell	Male
CVCL_AS36	JFMD1	Induced pluripotent stem cell	Male
CVCL_AS37	JFMD2	Induced pluripotent stem cell	Male
CVCL_AS38	JFMD3	Induced pluripotent stem cell	Male
CVCL_AS39	JFMD4	Induced pluripotent stem cell	Male
CVCL_AS40	JFMD5	Induced pluripotent stem cell	Male
CVCL_AS41	JFNY1	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01882400	PHASE4	COMPLETED	Assessment of Response to Treatment of Osteoporosis With Oral Bisphosphonates in Patients With Muscular Dystrophy
NCT00000374	PHASE4	COMPLETED	Treatment for First-Episode Schizophrenia
NCT00001656	PHASE4	COMPLETED	Comparison of Clozapine vs Olanzapine in Childhood-Onset Psychotic Disorders
NCT00007774	PHASE4	COMPLETED	To Determine if Olanzapine is More Cost Effective Than Haloperidol for the Treatment of Schizophrenia
NCT00014001	PHASE4	COMPLETED	CATIE- Schizophrenia Trial
NCT00018668	PHASE4	COMPLETED	Antipsychotic Response in Schizophrenia
NCT00034801	PHASE4	COMPLETED	Olanzapine Versus Active Comparator in the Treatment of Depression in Patients With Schizophrenia
NCT00034905	PHASE4	COMPLETED	A Comparison of Seroquel vs. Risperidone in Schizophrenia
NCT00036088	PHASE4	COMPLETED	Olanzapine Versus An Active Comparator in the Treatment of Schizophrenia
NCT00044187	PHASE4	COMPLETED	The Assessment of a Weight-Gain Agent for the Treatment of Olanzapine-Associated Anti-Obesity Agent in Patients With Schizophrenia, Schizophreniform Disorder, Schizoaffective Disorder, and Bipolar I Disorder
NCT00044655	PHASE4	COMPLETED	Switching Medication to Treat Schizophrenia
NCT00048828	PHASE4	COMPLETED	Treating Drug-Resistant Childhood Schizophrenia
NCT00053703	PHASE4	COMPLETED	Treatment of Early Onset Schizophrenia Spectrum Disorders (TEOSS)
NCT00056498	PHASE4	COMPLETED	Risperidone Treatment in Schizophrenia Patients Who Are Currently Taking Clozapine
NCT00061802	PHASE4	COMPLETED	Efficacy and Safety of Two Atypical Antipsychotics vs. Placebo in Patients With an Acute Exacerbation of Either Schizophrenia or Schizoaffective Disorder
NCT00080327	PHASE4	COMPLETED	Study of Three Doses of Aripiprazole in Patients With Acute Schizophrenia
NCT00088049	PHASE4	COMPLETED	Study of Olanzapine vs. Aripiprazole in the Treatment of Schizophrenia
NCT00090012	PHASE4	COMPLETED	Comparison of Continuing Olanzapine to Switching to Quetiapine in Overweight or Obese Patients With Schizophrenia and Schizoaffective Disorder
NCT00100776	PHASE4	COMPLETED	Efficacy of High Dose Olanzapine for the Treatment of Schizophrenia and Schizoaffective Disorder
NCT00103571	PHASE4	COMPLETED	Olanzapine Versus Aripiprazole in the Treatment of Acutely Ill Patients With Schizophrenia
NCT00108368	PHASE4	COMPLETED	The Effects of Risperidone and Olanzapine on Thinking
NCT00114595	PHASE4	COMPLETED	Ethyl-Eicosapentaenoic Acid and Tardive Dyskinesia
NCT00130923	PHASE4	COMPLETED	Risperidone Long-acting Versus Oral Risperidone in Patients With Schizophrenia and Alcohol Use Disorder
NCT00137020	PHASE4	COMPLETED	Clinical Effect Of Cross Titration Of Antipsychotics With Ziprasidone In Schizophrenia Or Schizoaffective Disorder
NCT00140166	PHASE4	COMPLETED	Treatment of Acute Schizophrenia With Vitamin Therapy
NCT00145847	PHASE4	COMPLETED	Naltrexone Treatment of Alcohol Abuse in Schizophrenia
NCT00148564	PHASE4	COMPLETED	Energy Homeostasis Under Treatment With Atypical Antipsychotics
NCT00156715	PHASE4	COMPLETED	Efficacy of Quetiapine in the Treatment of Patients With Schizophrenia and a Comorbid Substance Use Disorder
NCT00158223	PHASE4	COMPLETED	Effectiveness of Pimozide in Augmenting the Effects of Clozapine in the Treatment of Schizophrenia
NCT00159081	PHASE4	COMPLETED	One Year Drug Treatment in First-Episode Schizophrenia
NCT00159120	PHASE4	COMPLETED	Maintenance Treatment vs. Stepwise Drug Discontinuation in First-Episode Schizophrenia
NCT00159133	PHASE4	COMPLETED	Prodrome-Based Early Intervention With Antipsychotics vs. Benzodiazepines in First-Episode Schizophrenia
NCT00159757	PHASE4	TERMINATED	12 Week Open, Non-Comparative Switch Study Of Oral Ziprazidone In Previously Treated Schizophrenic Patients
NCT00167817	PHASE4	COMPLETED	Effect of Switch to Aripiprazole on Health and Smoking Parameters in Patients With Schizophrenia: A Pilot Study
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NCT00169039	PHASE4	TERMINATED	Clozapine Versus Chlorpromazine for Treatment-Unresponsive Schizophrenia
NCT00169065	PHASE4	COMPLETED	Effectiveness of Clozapine Versus Olanzapine for Treatment-resistant Schizophrenia
NCT00169091	PHASE4	TERMINATED	Clozapine Versus Haloperidol for Treating the First Episode of Schizophrenia
NCT00176423	PHASE4	COMPLETED	Efficacy Study of Galantamine for Cognitive Impairments in Schizophrenia
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