SMCHD1

Summary

SMCHD1 (structural maintenance of chromosomes flexible hinge domain containing 1, HGNC:29090) is a protein-coding gene on chromosome 18p11.32, encoding Structural maintenance of chromosomes flexible hinge domain-containing protein 1 (A6NHR9). Non-canonical member of the structural maintenance of chromosomes (SMC) protein family that plays a key role in epigenetic silencing by regulating chromatin architecture.

This gene encodes a protein which contains a hinge region domain found in members of the SMC (structural maintenance of chromosomes) protein family.

Source: NCBI Gene 23347 — RefSeq curated summary.

At a glance

• Gene–disease (curated): arhinia, choanal atresia, and microphthalmia (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 2
• Clinical variants (ClinVar): 1,790 total — 100 pathogenic, 38 likely-pathogenic
• Phenotypes (HPO): 93
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_015295

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29090
Approved symbol	SMCHD1
Name	structural maintenance of chromosomes flexible hinge domain containing 1
Location	18p11.32
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0650, FSHD2
Ensembl gene	ENSG00000101596
Ensembl biotype	protein_coding
OMIM	614982
Entrez	23347

Gene structure

Transcript identifiers

Ensembl transcripts: 29 — 15 retained_intron, 7 nonsense_mediated_decay, 4 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000320876, ENST00000577300, ENST00000577880, ENST00000581226, ENST00000581383, ENST00000581631, ENST00000581711, ENST00000583344, ENST00000583441, ENST00000583800, ENST00000584897, ENST00000585229, ENST00000609587, ENST00000642953, ENST00000645355, ENST00000684915, ENST00000685656, ENST00000686763, ENST00000686864, ENST00000688342, ENST00000688708, ENST00000688964, ENST00000689034, ENST00000689800, ENST00000690757, ENST00000693213, ENST00000693522, ENST00000939310, ENST00000958515

RefSeq mRNA: 1 — MANE Select: NM_015295 NM_015295

CCDS: CCDS45822

Canonical transcript exons

ENST00000320876 — 48 exons

Exon	Start	End
ENSE00000664904	2778169	2778239
ENSE00001261629	2688394	2688508
ENSE00001261634	2674015	2674145
ENSE00001261643	2673281	2673363
ENSE00001261650	2666870	2667031
ENSE00001261658	2666157	2666232
ENSE00001317367	2688628	2688747
ENSE00001497515	2722519	2722663
ENSE00001497523	2707563	2707645
ENSE00001497524	2706364	2706470
ENSE00001497528	2703692	2703886
ENSE00001543723	2802528	2805017
ENSE00001543772	2700735	2700918
ENSE00001596332	2700539	2700659
ENSE00001667695	2697831	2698041
ENSE00001792652	2697032	2697122
ENSE00002727195	2655726	2656261
ENSE00003464723	2718315	2718434
ENSE00003469704	2763637	2763789
ENSE00003483753	2732265	2732492
ENSE00003488962	2784450	2784621
ENSE00003489090	2769989	2770108
ENSE00003493726	2707807	2707920
ENSE00003500098	2750043	2750122
ENSE00003510475	2775734	2775924
ENSE00003510793	2795949	2796107
ENSE00003524641	2750350	2750507
ENSE00003538096	2729275	2729409
ENSE00003540590	2752488	2752552
ENSE00003549953	2777806	2777915
ENSE00003571277	2743761	2743928
ENSE00003581834	2796407	2796521
ENSE00003582479	2772250	2772372
ENSE00003595608	2694527	2694693
ENSE00003597802	2740703	2740821
ENSE00003614148	2771533	2771618
ENSE00003624960	2726452	2726524
ENSE00003630872	2751278	2751393
ENSE00003643529	2739432	2739520
ENSE00003651209	2705694	2705807
ENSE00003651275	2760652	2760739
ENSE00003657613	2738397	2738545
ENSE00003667392	2718158	2718235
ENSE00003670948	2728457	2728596
ENSE00003672907	2724899	2724995
ENSE00003683576	2747522	2747647
ENSE00003683975	2769694	2769820
ENSE00003694044	2762105	2762236

Expression profiles

Bgee: expression breadth ubiquitous, 290 present calls, max score 98.62.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 55.9551 / max 2466.5819, expressed in 1821 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
169107	30.6950	1771
169108	21.6489	1800
169105	1.9696	1153
169106	1.0785	693
169103	0.4899	106
169104	0.0732	35

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	98.62	gold quality
colonic epithelium	UBERON:0000397	98.21	gold quality
blood	UBERON:0000178	97.11	gold quality
bone marrow cell	CL:0002092	96.67	gold quality
adrenal tissue	UBERON:0018303	96.57	gold quality
monocyte	CL:0000576	96.17	gold quality
leukocyte	CL:0000738	96.16	gold quality
mononuclear cell	CL:0000842	96.15	gold quality
bone marrow	UBERON:0002371	95.40	gold quality
superficial temporal artery	UBERON:0001614	95.25	gold quality
right lung	UBERON:0002167	94.32	gold quality
granulocyte	CL:0000094	94.28	gold quality
jejunal mucosa	UBERON:0000399	94.09	gold quality
spleen	UBERON:0002106	94.03	gold quality
vermiform appendix	UBERON:0001154	94.00	gold quality
lymph node	UBERON:0000029	93.75	gold quality
ventricular zone	UBERON:0003053	93.54	gold quality
body of uterus	UBERON:0009853	93.31	gold quality
body of pancreas	UBERON:0001150	93.26	gold quality
small intestine Peyer’s patch	UBERON:0003454	93.03	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	92.97	gold quality
rectum	UBERON:0001052	92.97	gold quality
tendon	UBERON:0000043	92.93	gold quality
right testis	UBERON:0004534	92.74	gold quality
tonsil	UBERON:0002372	92.58	gold quality
ectocervix	UBERON:0012249	92.54	gold quality
mucosa of stomach	UBERON:0001199	92.53	gold quality
stromal cell of endometrium	CL:0002255	92.40	gold quality
epithelium of nasopharynx	UBERON:0001951	92.35	gold quality
left ovary	UBERON:0002119	92.31	gold quality

Single-cell (SCXA)

Detected in 10 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-CURD-120	yes	1660.74
E-MTAB-8142	yes	81.87
E-GEOD-135922	yes	35.14
E-CURD-122	yes	28.30
E-MTAB-9221	yes	27.57
E-CURD-119	yes	4.81
E-CURD-97	no	4215.76
E-MTAB-11011	no	2046.38
E-CURD-89	no	957.05
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

149 targeting SMCHD1, 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-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502

Literature-anchored findings (GeneRIF, showing 40)

• The study identified SMCHD1 as an epigenetic modifier of the D4Z4 metastable epiallele and as a causal genetic determinant of facioscapulohumeral muscular dystrophy type 2 and possibly other human diseases subject to epigenetic regulation. (PMID:23143600)
• our observations collectively highlight a hitherto uncharacterized role for SMCHD1 as a candidate tumor suppressor gene in hematopoietic cancers. (PMID:23269277)
• Thus, the molecular network involving HBiX1 (previously termed C1orf103) and SMCHD1 links the H3K9me3 and XIST-H3K27me3 domains to organize the compact inactive X chromosome structure. (PMID:23542155)
• Each of these individuals also carries a mutation in the SMCHD1 gene. (PMID:24075187)
• study reports a novel mutation p.Lys275del in SMCHD1 in a family with facioscapulohumeral muscular dystrophy 2; conclude that the SMCHD1 mutation is the likely cause of the disease in this family (PMID:24128691)
• SmcHD1 is an important regulator of imprinted and clustered genes (PMID:24818964)
• SMCHD1 recruitment to DNA damage foci is regulated by 53BP1. (PMID:25294876)
• findings confirm the role of SMCHD1 mutations in FSHD2 and as a modifier of disease severity. (PMID:25370034)
• The synergistic effect has been demonstrated of two SMCHD1 variants on D4Z4 hypomethylation site and disease penetrance in facioscapulohumeral muscular dystrophy-2 patients. (PMID:25782668)
• Two facioscapulohumeral muscular dystrophy type 2 families with a 1.2-Mb deletion encompassing the SMCHD1 gene are described; they have only one copy of SMCHD1. (PMID:25820463)
• In the case of FSHD1, a contraction of the D4Z4 repeat array is disease causing whereas FSHD2 is most often caused by mutations in the structural maintenance of chromosomes hinge domain 1 (SMCHD1) gene. (PMID:26356006)
• An indirect interaction mediated by the LRIF1 and HP1 proteins loads SMCHD1 onto chromatin marked by trimethylation of histone H3 lysine 9 (H3K9me3). (PMID:26391951)
• This approach was successfully employed in the context of the in silico prediction of potential remotely acting regulatory elements for the SMCHD1 gene. Subsequent sequencing of these predicted regions identified three sequence variants in FSHD patients (PMID:26446085)
• This study demonstrated that the the linkage peak revealed a variant (rs574972) within an intron of the gene SMCHD1 is linkaged to major depression in Mexican Americans. (PMID:26485182)
• Study identified novel SMCHD1 mutations in a Japanese cohort of facioscapulohumeral muscular dystrophy 2 patients, confirming the presence of this disease in a wider population than previously known (PMID:27061275)
• Mutations in SMCHD1 thus contribute to distinct phenotypic spectra. (PMID:28067909)
• SMCHD1 as a key player in nasal development. (PMID:28067911)
• SMCHD1 mutations cause Bosma arhinia microphthalmia syndrome. (PMID:28138148)
• We summarise here current understanding of the mechanism of action of SMCHD1, its role in these diseases, and what has been learnt from study of mouse models null for Smchd1 in the decade since the discovery of SMCHD1 (PMID:28222895)
• SMCHD1 acts as a repressor on a limited set of autosomal gene clusters, as an observed reduction in methylation associates with a loss of SMCHD1 binding and increased expression for some of the loci. (PMID:28587678)
• We discuss the involvement of this rearrangement in Facioscapulohumeral dystrophy (FSHD), since all mutations in SMCHD1 are not associated with D4Z4 hypomethylation and do not always segregate with the disease (PMID:28744936)
• 18p deletions leading to haploinsufficiency of SMCHD1, together with a moderately sized FSHD permissive D4Z4 allele, can associate with symptoms and molecular features of FSHD. We propose that patients with 18p deletion should be characterised for their D4Z4 repeat size and haplotype and monitored for clinical features of FSHD. (PMID:29563141)
• SMCHD1 mutation affects the expression of small RNAs in the facioscapulohumeral muscular dystrophy muscle cells. (PMID:29741619)
• A mutation in SMCHD1 gene reported in both an FSHD2 patient and a BAMS patient results in increased ATPase activity and a smaller Xenopus eye size. (PMID:29748383)
• Regions necessary for SMCHD1 protein nuclear localization, dimerization, and cleavage sites were identified. (PMID:30071896)
• We generated FSHD2-derived isogenic control clones with SMCHD1 mutation corrected by clustered regularly interspaced short palindromic repeats (CRISPR)/ CRISPR associated 9 (Cas9) and homologous recombination and found in the myocytes obtained from these clones that DUX4 basal expression and the OS-induced upregulation were markedly suppressed due to an increase in the heterochromatic state at 4q35. (PMID:30107443)
• FSHD2 patients with unusually large 4qA alleles of 21-70 D4Z4 units were identified. Most of these large 4qA alleles represent duplication alleles in which the long D4Z4 repeat arrays are followed by a small FSHD-sized D4Z4 repeat array duplication. These duplication alleles are associated with DUX4 expression. (PMID:30281091)
• we report two Japanese FSHD2 siblings (brother and sister) with a new SMCHD1 nonsense mutation (a heterogeneous c. 1654C>T substitution, leading to a stop codon Arg552 *). (PMID:30327220)
• SMCHD1 is required for the dynamic methylation of the D4Z4 macrosatellite upon reprogramming but seems dispensable for methylation maintenance. We find that Facio-Scapulo-Humeral Dystrophy (FSHD) and Bosma Arhinia Microphtalmia Syndrome patient’s cells carrying SMCHD1 mutations are both permissive for DUX4 expression, a transcription factor whose regulation has been proposed as the main trigger for FSHD. (PMID:30698748)
• analysis of the crystal structure of the human SMCHD1 N-terminal GHKL-ATPase/transducer module (PMID:31312724)
• our study demonstrates preservation of XCI in arhinia and FSHD2, and implicates SMCHD1 in the regulation of the 3D organization of select autosomal gene clusters (PMID:31420322)
• Sequence analysis of SMCHD1 in patients with FSHD (facioscapulohumeral muscular dystrophy) found 82 variants localized in the introns, exons and 3’UTR region. pathogenic/likely pathogenic variants were identified in patients were predicted to disrupt the structure and conformation of SMCHD1, resulting in the loss of GHKL-ATPase and SMC hinge essential domains. These results are consistent with the FSHD symptomatology. (PMID:31600781)
• The estimated intronic mutation frequency of almost 2% in Facioscapulohumeral dystrophy(FSHD2), as exemplified by the two novel intronic SMCHD1 variants identified here, emphasises the importance of screening for intronic variants in SMCHD1. (PMID:31676591)
• SMCHD1 promotes ATM-dependent DNA damage signaling and repair of uncapped telomeres. (PMID:32080884)
• Rare variant of the epigenetic regulator SMCHD1 in a patient with pituitary hormone deficiency. (PMID:32620854)
• Relating SMCHD1 structure to its function in epigenetic silencing. (PMID:32779700)
• A Three Protein-Coding Gene Prognostic Model Predicts Overall Survival in Bladder Cancer Patients. (PMID:33150179)
• SMCHD1’s ubiquitin-like domain is required for N-terminal dimerization and chromatin localization. (PMID:34109974)
• A novel start codon variant in SMCHD1 from a Chinese family causes facioscapulohumeral muscular dystrophy type 2. (PMID:34845997)
• A proteomics study identifying interactors of the FSHD2 gene product SMCHD1 reveals RUVBL1-dependent DUX4 repression. (PMID:34880314)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	smchd1	ENSDARG00000104374
mus_musculus	Smchd1	ENSMUSG00000024054
rattus_norvegicus	Smchd1	ENSRNOG00000014319

Protein

Protein identifiers

Structural maintenance of chromosomes flexible hinge domain-containing protein 1 — A6NHR9 (reviewed: A6NHR9)

All UniProt accessions (9): A6NHR9, A0A2R8YCU7, A0A2R8YE92, A0A8I5KQZ7, A0A8I5KRS9, A0A8I5KW02, J3KRK8, J3KTL8, J3QSH1

UniProt curated annotations — full annotation on UniProt →

Function. Non-canonical member of the structural maintenance of chromosomes (SMC) protein family that plays a key role in epigenetic silencing by regulating chromatin architecture. Promotes heterochromatin formation in both autosomes and chromosome X, probably by mediating the merge of chromatin compartments. Plays a key role in chromosome X inactivation in females by promoting the spreading of heterochromatin. Recruited to inactivated chromosome X by Xist RNA and acts by mediating the merge of chromatin compartments: promotes random chromatin interactions that span the boundaries of existing structures, leading to create a compartment-less architecture typical of inactivated chromosome X. Required to facilitate Xist RNA spreading. Also required for silencing of a subset of clustered autosomal loci in somatic cells, such as the DUX4 locus. Has ATPase activity; may participate in structural manipulation of chromatin in an ATP-dependent manner as part of its role in gene expression regulation. Also plays a role in DNA repair: localizes to sites of DNA double-strand breaks in response to DNA damage to promote the repair of DNA double-strand breaks. Acts by promoting non-homologous end joining (NHEJ) and inhibiting homologous recombination (HR) repair.

Subunit / interactions. Homodimer; homodimerizes via its SMC hinge domain. Interacts with LRIF1.

Subcellular location. Chromosome.

Post-translational modifications. Sumoylated with SUMO1.

Disease relevance. Facioscapulohumeral muscular dystrophy 2, digenic (FSHD2) [MIM:158901] A degenerative muscle disease characterized by slowly progressive weakness of the muscles of the face, upper-arm, and shoulder girdle. The onset of symptoms usually occurs in the first or second decade of life. Affected individuals usually present with impairment of upper extremity elevation. This tends to be followed by facial weakness, primarily involving the orbicularis oris and orbicularis oculi muscles. The disease is caused by variants affecting the gene represented in this entry. SMCHD1 mutations lead to DUX4 expression in somatic tissues, including muscle cells, when an haplotype on chromosome 4 is permissive for DUX4 expression. Ectopic expression of DUX4 in skeletal muscle activates the expression of stem cell and germline genes, and, when overexpressed in somatic cells, DUX4 can ultimately lead to cell death. FSHD2 and FSHD1 share a common pathophysiological pathway in which the FSHD2 gene SMCHD1 can act as a modifier for disease severity in families affected by FSHD1. Bosma arhinia microphthalmia syndrome (BAMS) [MIM:603457] An autosomal dominant syndrome characterized by severe hypoplasia of the nose, palatal abnormalities, hypoplasia of the eyes, sensory abnormalities of taste and smell, hypogonadotropic hypogonadism with cryptorchidism, and normal intelligence. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. Atypical member of the structural maintenance of chromosomes (SMC) protein family. Like other members of the SMC family, has ATPase activity, which is probably necessary for its engagement with chromatin, and a SMC hinge domain. However, the SMC hinge domain adopts an unconventional homodimeric arrangement augmented by an intermolecular coiled coil formed between the two monomers. This suggests that protein may assemble as a head-to-head parallel dimer without adopting a hairpin shape at the hinge domain, unlike the dimeric arrangement conventionally found in other members of the SMC protein family. The SMC hinge domain binds DNA and RNA.

Similarity. Belongs to the SMC family. Highly divergent.

Isoforms (3)

UniProt ID	Names	Canonical?
A6NHR9-1	1	yes
A6NHR9-2	2
A6NHR9-3	3

RefSeq proteins (1): NP_056110* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR010935	SMC_hinge	Domain
IPR036277	SMC_hinge_sf	Homologous_superfamily
IPR036890	HATPase_C_sf	Homologous_superfamily
IPR038892	SMCHD1	Family
IPR055109	SMCHD1_S5	Domain
IPR058611	Ig_SMCHD1_1st	Domain
IPR058612	Ig_SMCHD1_2nd	Domain
IPR058613	Ig_SMCHD1_4th	Domain
IPR058614	Ig_SMCHD1_5th	Domain
IPR058615	Ig_SMCHD1_6th	Domain
IPR058616	Ig_SMCHD1_8th	Domain
IPR058617	Ig_SMCHD1_7th	Domain

Pfam: PF06470, PF13589, PF22899, PF26194, PF26195, PF26196, PF26197, PF26198, PF26199, PF26201

Catalyzed reactions (Rhea), 1 shown:

• ATP + H2O = ADP + phosphate + H(+) (RHEA:13065)

UniProt features (125 total): sequence variant 59, helix 21, strand 21, modified residue 5, splice variant 5, turn 4, cross-link 2, region of interest 2, sequence conflict 2, initiator methionine 1, chain 1, domain 1, compositionally biased region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
6MW7	X-RAY DIFFRACTION	2.19

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A6NHR9-F1	81.17	0.20

Functional residue map

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

Post-translational modifications (7): 1974, 1374, 1496, 2, 1349, 1499, 1802

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 387 (showing top): GOBP_REGULATION_OF_DOUBLE_STRAND_BREAK_REPAIR, GOBP_CHROMOSOME_ORGANIZATION, TURASHVILI_BREAST_LOBULAR_CARCINOMA_VS_DUCTAL_NORMAL_UP, GOBP_REGULATION_OF_DNA_RECOMBINATION, GOBP_NEGATIVE_REGULATION_OF_DNA_REPAIR, GOBP_NEGATIVE_REGULATION_OF_DNA_RECOMBINATION, GOBP_REGULATION_OF_DOUBLE_STRAND_BREAK_REPAIR_VIA_HOMOLOGOUS_RECOMBINATION, GOBP_REGULATION_OF_DNA_REPAIR, GOBP_NEGATIVE_REGULATION_OF_GENE_EXPRESSION_EPIGENETIC, ONKEN_UVEAL_MELANOMA_UP, GOBP_NOSE_DEVELOPMENT, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, MODULE_301, GOBP_REGULATION_OF_RESPONSE_TO_STRESS, DACOSTA_UV_RESPONSE_VIA_ERCC3_COMMON_DN

GO Biological Process (12): double-strand break repair (GO:0006302), dosage compensation by inactivation of X chromosome (GO:0009048), nose development (GO:0043584), positive regulation of DNA repair (GO:0045739), chromosome organization (GO:0051276), random inactivation of X chromosome (GO:0060816), autosome genomic imprinting (GO:0141068), negative regulation of double-strand break repair via homologous recombination (GO:2000042), positive regulation of double-strand break repair via nonhomologous end joining (GO:2001034), DNA repair (GO:0006281), chromatin organization (GO:0006325), DNA damage response (GO:0006974)

GO Molecular Function (6): DNA binding (GO:0003677), ATP binding (GO:0005524), ATP hydrolysis activity (GO:0016887), protein homodimerization activity (GO:0042803), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (7): Barr body (GO:0001740), nucleoplasm (GO:0005654), nuclear body (GO:0016604), site of double-strand break (GO:0035861), chromosome, telomeric region (GO:0000781), chromosome (GO:0005694), nuclear lumen (GO:0031981)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA repair	2
intracellular membraneless organelle	2
sex-chromosome dosage compensation	1
heterochromatin formation	1
sensory organ development	1
respiratory system development	1
regulation of DNA repair	1
positive regulation of response to stimulus	1
positive regulation of DNA metabolic process	1
organelle organization	1
dosage compensation by inactivation of X chromosome	1
genomic imprinting	1
double-strand break repair via homologous recombination	1
regulation of double-strand break repair via homologous recombination	1
negative regulation of DNA recombination	1
negative regulation of double-strand break repair	1
double-strand break repair via nonhomologous end joining	1
positive regulation of double-strand break repair	1
regulation of double-strand break repair via nonhomologous end joining	1
DNA metabolic process	1
DNA damage response	1
cellular component organization	1
cellular response to stress	1
nucleic acid binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
ribonucleoside triphosphate phosphatase activity	1
ATP-dependent activity	1
identical protein binding	1
protein dimerization activity	1
binding	1
catalytic activity	1
nuclear chromosome	1
X chromosome	1
condensed chromatin of inactivated sex chromosome	1
nuclear lumen	1
cellular anatomical structure	1
nucleoplasm	1
site of DNA damage	1
chromosomal region	1

Protein interactions and networks

STRING

1386 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SMCHD1	LRIF1	Q5T3J3	943
SMCHD1	DUX4L2	P0CJ85	872
SMCHD1	CBX3	Q13185	612
SMCHD1	ZSCAN4	Q8NAM6	587
SMCHD1	TRIM43	Q96BQ3	584
SMCHD1	MBD3L2	Q8NHZ7	577
SMCHD1	DNMT3B	Q9UBC3	572
SMCHD1	METTL4	Q8N3J2	560
SMCHD1	CTCF	P49711	536
SMCHD1	SMC1A	Q14683	508
SMCHD1	TYMS	P04818	501
SMCHD1	FRG1	Q14331	492
SMCHD1	MORC1	Q86VD1	482
SMCHD1	MACROH2A2	Q9P0M6	474
SMCHD1	GNL1	P36915	469

IntAct

258 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
LRIF1	SMCHD1	psi-mi:“MI:0914”(association)	0.680
LRIF1	SMCHD1	psi-mi:“MI:0915”(physical association)	0.680
MPDZ	SMCHD1	psi-mi:“MI:0914”(association)	0.590
SMCHD1	MPDZ	psi-mi:“MI:0407”(direct interaction)	0.590
BIN1	SMCHD1	psi-mi:“MI:0914”(association)	0.550
TRPC4AP	SMCHD1	psi-mi:“MI:0914”(association)	0.530
AURKB	SMCHD1	psi-mi:“MI:0914”(association)	0.530
DDX21	MED19	psi-mi:“MI:2364”(proximity)	0.480
MAST2	SMCHD1	psi-mi:“MI:0407”(direct interaction)	0.440
SMCHD1	PATJ	psi-mi:“MI:0407”(direct interaction)	0.440
SMCHD1	PDZD2	psi-mi:“MI:0407”(direct interaction)	0.440
SMCHD1	SYNJ2BP	psi-mi:“MI:0407”(direct interaction)	0.440
SMCHD1	DLG1	psi-mi:“MI:0407”(direct interaction)	0.440
SMCHD1	ARHGEF12	psi-mi:“MI:0407”(direct interaction)	0.440
SMCHD1	MAGI3	psi-mi:“MI:0407”(direct interaction)	0.440
SMCHD1	DLG4	psi-mi:“MI:0407”(direct interaction)	0.440
SMCHD1	PDZD7	psi-mi:“MI:0407”(direct interaction)	0.440
SMCHD1	ARHGEF11	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (244): SMCHD1 (Affinity Capture-MS), SMCHD1 (Affinity Capture-MS), SMCHD1 (Affinity Capture-MS), SMCHD1 (Affinity Capture-MS), SMCHD1 (Affinity Capture-MS), SMCHD1 (Reconstituted Complex), KIAA0368 (Co-fractionation), MVB12A (Co-fractionation), SMCHD1 (Co-fractionation), TRIM25 (Co-fractionation), WARS (Co-fractionation), SMCHD1 (Affinity Capture-MS), SMCHD1 (Affinity Capture-MS), SMCHD1 (Proximity Label-MS), SMCHD1 (Proximity Label-MS)

ESM2 similar proteins: A0A2R8VHF7, A0JM23, A2QRA0, A4IIA7, A4IIV4, A6NFN9, A6NHR9, A7MBF6, F4IG73, F4JSE7, O17482, O95876, P12540, P21784, P34089, P38899, P55895, P56696, Q08AW4, Q0D2D7, Q12789, Q13829, Q28DC9, Q2WGJ8, Q3E7Y5, Q3UUE9, Q4R907, Q4VXA5, Q5BK83, Q5EA90, Q5F476, Q5HZS2, Q5M9F0, Q5RAX4, Q5RBH4, Q5RD21, Q6AYL6, Q6DGA7, Q6PIY5, Q70XZ2

Diamond homologs: A6NHR9, Q6P5D8

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 182 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
Negative regulation of NMDA receptor-mediated neuronal transmission	7	33.1×	3e-07
Ras activation upon Ca2+ influx through NMDA receptor	6	29.8×	5e-06
Unblocking of NMDA receptors, glutamate binding and activation	6	28.4×	6e-06
Long-term potentiation	6	24.8×	1e-05
Assembly and cell surface presentation of NMDA receptors	9	19.9×	3e-07
Neurexins and neuroligins	9	15.4×	1e-06
Protein-protein interactions at synapses	5	11.6×	4e-03
Oncogenic MAPK signaling	5	10.8×	5e-03

GO biological processes:

GO term	Partners	Fold	FDR
protein localization to synapse	6	28.9×	3e-05
establishment or maintenance of epithelial cell apical/basal polarity	7	25.6×	9e-06
receptor clustering	6	23.6×	6e-05
regulation of postsynaptic membrane neurotransmitter receptor levels	5	15.6×	3e-03
chromatin remodeling	11	5.0×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

1790 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	100
Likely pathogenic	38
Uncertain significance	833
Likely benign	531
Benign	148

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1012231	NM_015295.3(SMCHD1):c.3469G>T (p.Gly1157Ter)	Pathogenic
1012232	NM_015295.3(SMCHD1):c.5150_5151del (p.Lys1717fs)	Pathogenic
1012233	NM_015295.3(SMCHD1):c.2129dup (p.Ala711fs)	Pathogenic
1069242	NM_015295.3(SMCHD1):c.1886dup (p.Arg630fs)	Pathogenic
1072742	NM_015295.3(SMCHD1):c.340C>T (p.Arg114Ter)	Pathogenic
1074206	NM_015295.3(SMCHD1):c.3772_3773insA (p.Leu1258fs)	Pathogenic
1180607	NM_015295.3(SMCHD1):c.2377C>T (p.Gln793Ter)	Pathogenic
1180771	NM_015295.3(SMCHD1):c.1786T>G (p.Trp596Gly)	Pathogenic
1236185	NM_015295.3(SMCHD1):c.4346+1G>T	Pathogenic
1323621	NM_015295.3(SMCHD1):c.4007+1G>A	Pathogenic
1323622	NM_015295.3(SMCHD1):c.2071_2075del (p.Asp691fs)	Pathogenic
1323623	NM_015295.3(SMCHD1):c.727_730del (p.Val243fs)	Pathogenic
1323625	NM_015295.3(SMCHD1):c.5383C>T (p.Arg1795Ter)	Pathogenic
1323627	NM_015295.3(SMCHD1):c.3049-2A>G	Pathogenic
1323628	NM_015295.3(SMCHD1):c.1651C>T (p.Gln551Ter)	Pathogenic
1323629	NM_015295.3(SMCHD1):c.2604-1G>T	Pathogenic
1341966	NM_015295.3(SMCHD1):c.261del (p.Phe87fs)	Pathogenic
1380529	NM_015295.3(SMCHD1):c.2078dup (p.Leu693fs)	Pathogenic
1380939	NC_000018.9:g.(?2656075)(2656280_?)del	Pathogenic
1384984	NM_015295.3(SMCHD1):c.1282del (p.Arg428fs)	Pathogenic
1410081	NM_015295.3(SMCHD1):c.1647+3A>G	Pathogenic
1451574	NM_015295.3(SMCHD1):c.3736C>T (p.Arg1246Ter)	Pathogenic
1455581	NM_015295.3(SMCHD1):c.2732T>G (p.Leu911Ter)	Pathogenic
1456495	NC_000018.9:g.(?2666136)(2667050_?)del	Pathogenic
1457865	NM_015295.3(SMCHD1):c.1396A>T (p.Arg466Ter)	Pathogenic
1957074	NM_015295.3(SMCHD1):c.3019C>T (p.Gln1007Ter)	Pathogenic
2052607	NM_015295.3(SMCHD1):c.3786G>A (p.Trp1262Ter)	Pathogenic
2075369	NM_015295.3(SMCHD1):c.3784_3788del (p.Trp1262fs)	Pathogenic
2125982	NM_015295.3(SMCHD1):c.1314_1317del (p.Tyr439fs)	Pathogenic
2426131	NC_000018.9:g.(?2656075)(2688765_?)del	Pathogenic

SpliceAI

7054 predictions. Top by Δscore:

Variant	Effect	Δscore
18:2656258:TCAGG:T	donor_loss	1.0000
18:2656261:GGTAC:G	donor_loss	1.0000
18:2656262:G:GC	donor_loss	1.0000
18:2656263:T:A	donor_loss	1.0000
18:2666150:T:TA	acceptor_gain	1.0000
18:2666155:A:AG	acceptor_gain	1.0000
18:2666156:G:GG	acceptor_gain	1.0000
18:2666861:T:TA	acceptor_gain	1.0000
18:2666866:A:AG	acceptor_gain	1.0000
18:2666867:C:G	acceptor_gain	1.0000
18:2666868:A:AG	acceptor_gain	1.0000
18:2666868:AGA:A	acceptor_loss	1.0000
18:2666868:AGAT:A	acceptor_gain	1.0000
18:2666869:G:GG	acceptor_gain	1.0000
18:2666869:GA:G	acceptor_gain	1.0000
18:2666869:GAT:G	acceptor_gain	1.0000
18:2666869:GATG:G	acceptor_gain	1.0000
18:2666869:GATGA:G	acceptor_gain	1.0000
18:2667027:TTTGC:T	donor_gain	1.0000
18:2667028:TTGC:T	donor_gain	1.0000
18:2667029:TGC:T	donor_gain	1.0000
18:2667029:TGCG:T	donor_loss	1.0000
18:2667030:GC:G	donor_gain	1.0000
18:2667030:GCG:G	donor_gain	1.0000
18:2667031:CGTA:C	donor_loss	1.0000
18:2667032:G:GG	donor_gain	1.0000
18:2667032:GT:G	donor_loss	1.0000
18:2667036:G:GG	donor_gain	1.0000
18:2673275:TTGCA:T	acceptor_loss	1.0000
18:2673276:TGCAG:T	acceptor_loss	1.0000

AlphaMissense

13281 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
18:2666967:C:A	H120Q	1.000
18:2666967:C:G	H120Q	1.000
18:2667001:T:C	Y132H	1.000
18:2673305:A:T	D150V	1.000
18:2674088:T:C	L194P	1.000
18:2674096:T:A	W197R	1.000
18:2674096:T:C	W197R	1.000
18:2674100:C:A	A198D	1.000
18:2674109:G:C	R201T	1.000
18:2674109:G:T	R201M	1.000
18:2674110:G:C	R201S	1.000
18:2674110:G:T	R201S	1.000
18:2674120:T:C	F205L	1.000
18:2674122:C:A	F205L	1.000
18:2674122:C:G	F205L	1.000
18:2688458:T:C	F235L	1.000
18:2688460:T:A	F235L	1.000
18:2688460:T:G	F235L	1.000
18:2688461:G:C	G236R	1.000
18:2688462:G:A	G236D	1.000
18:2700622:T:A	W476R	1.000
18:2700622:T:C	W476R	1.000
18:2700638:T:A	I481K	1.000
18:2700742:T:A	W491R	1.000
18:2700742:T:C	W491R	1.000
18:2700794:G:T	R508M	1.000
18:2700803:G:A	G511D	1.000
18:2700833:T:A	V521D	1.000
18:2700835:A:C	S522R	1.000
18:2700837:C:A	S522R	1.000

dbSNP variants (sampled 300 via entrez): RS1000010077 (18:2702601 A>C), RS1000048465 (18:2744121 T>C), RS1000052058 (18:2752434 A>G), RS1000058410 (18:2717911 C>T), RS1000078086 (18:2704179 G>A), RS1000079030 (18:2744490 T>A,C), RS1000084058 (18:2769421 C>T), RS1000095224 (18:2682046 G>C), RS1000105318 (18:2695986 C>T), RS1000164626 (18:2727760 TA>T,TAA), RS1000165168 (18:2656602 G>A), RS1000172879 (18:2787322 C>T), RS1000200051 (18:2658186 C>A,G), RS1000202757 (18:2665784 A>G,T), RS1000264178 (18:2678479 GC>G)

Disease associations

OMIM: gene MIM:614982 | disease phenotypes: MIM:158901, MIM:603457, MIM:600416, MIM:214500, MIM:219050, MIM:158900

GenCC curated gene-disease

Disease	Classification	Inheritance
arhinia, choanal atresia, and microphthalmia	Definitive	Autosomal dominant
hyposmia-nasal and ocular hypoplasia-hypogonadotropic hypogonadism syndrome	Supportive	Autosomal dominant
facioscapulohumeral muscular dystrophy	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
arhinia, choanal atresia, and microphthalmia	Definitive	AD

Mondo (15): facioscapulohumeral muscular dystrophy 2 (MONDO:0008031), arhinia, choanal atresia, and microphthalmia (MONDO:0011323), muscular dystrophy (MONDO:0020121), muscular dystrophy, scapulohumeral (MONDO:0010884), Chediak-Higashi syndrome (MONDO:0008963), anosmia (MONDO:0010528), cryptorchidism (MONDO:0009047), facioscapulohumeral muscular dystrophy 1 (MONDO:0008030), stereotypic movement disorder (MONDO:0002265), alopecia (MONDO:0004907), alopecia areata (MONDO:0005340), myopathy (MONDO:0005336), muscular atrophy (MONDO:0004323), (MONDO:0016393), facioscapulohumeral muscular dystrophy (MONDO:0001347)

Orphanet (7): Facioscapulohumeral dystrophy (Orphanet:269), Arrhinia-choanal atresia-microphthalmia syndrome (Orphanet:1135), Hyposmia-nasal and ocular hypoplasia-hypogonadotropic hypogonadism syndrome (Orphanet:2250), Muscular dystrophy (Orphanet:98473), Male infertility with azoospermia or oligozoospermia due to single gene mutation (Orphanet:399805), Chédiak-Higashi syndrome (Orphanet:167), Alopecia (Orphanet:79364)

HPO phenotypes

93 total (30 of 93 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000023	Inguinal hernia
HP:0000028	Cryptorchidism
HP:0000044	Hypogonadotropic hypogonadism
HP:0000047	Hypospadias
HP:0000054	Micropenis
HP:0000059	Hypoplastic labia majora
HP:0000135	Hypogonadism
HP:0000175	Cleft palate
HP:0000176	Submucous cleft hard palate
HP:0000193	Bifid uvula
HP:0000218	High palate
HP:0000298	Mask-like facies
HP:0000309	Abnormal midface morphology
HP:0000316	Hypertelorism
HP:0000327	Hypoplasia of the maxilla
HP:0000365	Hearing impairment
HP:0000377	Abnormal pinna morphology
HP:0000405	Conductive hearing impairment
HP:0000407	Sensorineural hearing impairment
HP:0000413	Atresia of the external auditory canal
HP:0000453	Choanal atresia
HP:0000458	Anosmia
HP:0000491	Keratitis
HP:0000509	Conjunctivitis
HP:0000518	Cataract
HP:0000528	Anophthalmia
HP:0000541	Retinal detachment
HP:0000564	Lacrimal duct atresia
HP:0000568	Microphthalmia

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST002438_8	Conotruncal heart defects	4.000000e-06
GCST008154_30	Trunk fat mass	4.000000e-06

MeSH disease descriptors (13)

Descriptor	Name	Tree numbers
D000505	Alopecia	C17.800.329.937.122; C23.300.035
D000506	Alopecia Areata	C17.800.329.937.122.147
D002609	Chediak-Higashi Syndrome	C11.270.040.772; C15.378.553.774.257; C16.320.798.375; C20.673.774.257; C20.673.795.375
D003456	Cryptorchidism	C12.100.500.829.258; C12.200.294.829.258; C12.200.706.258; C12.800.258; C16.131.939.258; C19.391.829.258
D009133	Muscular Atrophy	C10.597.613.612; C23.300.070.500; C23.888.592.608.612
D009136	Muscular Dystrophies	C05.651.534.500; C10.668.491.175.500; C16.320.577
D020391	Muscular Dystrophy, Facioscapulohumeral	C05.651.534.500.400; C10.668.491.175.500.400; C16.320.577.400
D000857	Olfaction Disorders	C10.597.751.600; C23.888.592.763.550
D019956	Stereotypic Movement Disorder	F03.625.984
C537429	Arhinia, choanal atresia, and microphthalmia (supp.)
C563557	Facioscapulohumeral Muscular Dystrophy 1B (supp.)
C536391	Facioscapulohumeral muscular dystrophy 1a (supp.)
C562932	Muscular Dystrophy, Scapulohumeral (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5725097 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.97	IC50	1070	nM	MOLIBRESIB
5.88	Kd	1304	nM	MOLIBRESIB

PubChem BioAssay actives

2 with measured affinity, of 7 total; 1 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
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178845: Inhibition of SMCHD1 (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	1.0700	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance, increases expression	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression, decreases expression	2
Nickel	increases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
TAK-243	decreases sumoylation	1
geldanamycin	increases expression	1
2,4,6-tribromophenol	decreases expression	1
alpha-pinene	increases oxidation, increases abundance, affects cotreatment	1
deoxynivalenol	increases expression	1
decabromobiphenyl ether	decreases expression	1
trichostatin A	affects cotreatment, decreases expression	1
arsenite	decreases reaction, affects binding	1
methylparaben	increases expression	1
cypermethrin	increases expression	1
butyraldehyde	decreases expression	1
tetrabromobisphenol A	decreases expression	1
manganese chloride	decreases expression, increases abundance	1
nivalenol	increases expression	1
methacrylaldehyde	increases abundance, affects cotreatment, increases oxidation	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	increases reaction, affects binding	1
dorsomorphin	affects cotreatment, decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
jinfukang	decreases expression	1
LDN 193189	affects cotreatment, increases expression	1
Irinotecan	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5697575	Binding	Inhibition of SMCHD1 (unknown origin) assessed as fold change at 10 uM incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. — Nature

Cellosaurus cell lines

6 cell lines: 4 induced pluripotent stem cell, 1 telomerase immortalized cell line, 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_F1J2	MB200	Telomerase immortalized cell line	Male
CVCL_XT55	HAP1 SMCHD1 (-)	Cancer cell line	Male
CVCL_ZA41	CIRAi005-A	Induced pluripotent stem cell	Female
CVCL_ZA42	CIRAi005-A-1	Induced pluripotent stem cell	Female
CVCL_ZA43	CIRAi006-A	Induced pluripotent stem cell	Female
CVCL_ZA44	CIRAi006-A-1	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

278 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
NCT04528329	PHASE4	UNKNOWN	Anosmia and / or Ageusia and Early Corticosteroid Use
NCT04797936	PHASE4	COMPLETED	BNO 1030 Extract (Imupret) in the Treatment of Mild Forms of COVID-19
NCT04853836	PHASE4	COMPLETED	Olfactory Disfunction and Co-ultraPEALut
NCT02110745	PHASE4	COMPLETED	The Effect of Induction Technique on Postoperative Pain and Agitation
NCT05397470	PHASE3	TERMINATED	Efficacy and Safety of Losmapimod in Treating Participants With Facioscapulohumeral Muscular Dystrophy (FSHD) (REACH)
NCT07038200	PHASE3	RECRUITING	A Study to Evaluate Del-brax (Also Referred to as AOC 1020) in Participants With FSHD
NCT01254019	PHASE3	COMPLETED	A Clinical Study to Assess the Efficacy and Safety of GSK2402968 in Subjects With Duchenne Muscular Dystrophy
NCT01480245	PHASE3	TERMINATED	Open Label Study of GSK2402968 in Subjects With Duchenne Muscular Dystrophy
NCT01803412	PHASE3	TERMINATED	A Study of the Safety, Tolerability & Efficacy of Long-term Administration of Drisapersen in US & Canadian Subjects
NCT01826487	PHASE3	COMPLETED	Phase 3 Study of Ataluren in Participants With Nonsense Mutation Duchenne Muscular Dystrophy (nmDMD)
NCT01890798	PHASE3	WITHDRAWN	Drisapersen Duchenne Muscular Dystrophy (DMD) Treatment Protocol
NCT02090959	PHASE3	TERMINATED	An Extension Study of Ataluren (PTC124) in Participants With Nonsense Mutation Dystrophinopathy
NCT02432885	PHASE3	COMPLETED	Myocardial Fibrosis Progression in Duchenne and Becker Muscular Dystrophy - ACE Inhibitor Therapy Trial
NCT03179631	PHASE3	COMPLETED	Long-Term Outcomes of Ataluren in Duchenne Muscular Dystrophy
NCT05126758	PHASE3	ACTIVE_NOT_RECRUITING	A Study of Deramiocel (CAP-1002) in Ambulatory and Non-Ambulatory Patients With Duchenne Muscular Dystrophy
NCT07587242	PHASE3	NOT_YET_RECRUITING	A Phase 3 Study to Evaluate the Safety and Efficacy of AOC 1044 (Also Referred to as Delpacibart Zotadirsen) in Participants With DMD With Gene Mutations Amenable to Exon 44 Skipping
NCT07608432	PHASE3	RECRUITING	Efficacy, Safety, and Tolerability of Zeleciment Rostudirsen (DYNE-251) Administered Intravenously Every 4 Weeks in Ambulatory Participants With Duchenne Muscular Dystrophy (FORZETTO)
NCT03680911	PHASE3	TERMINATED	NAC for Head Trauma-induced Anosmia
NCT04361474	PHASE3	COMPLETED	Trial Evaluating the Efficacy of Local Budesonide Therapy in the Management of Hyposmia in COVID-19 Patients Without Signs of Severity
NCT04484493	PHASE3	COMPLETED	Corticosteroid Nasal Spray in COVID-19 Anosmia
NCT05461365	PHASE3	COMPLETED	Intranasal Insulin for COVID-19-related Smell Loss
NCT07151703	PHASE3	NOT_YET_RECRUITING	Topical Versus Injection PRP for Olfactory Dysfunction
NCT04826484	PHASE3	TERMINATED	Opioid Reduction Initiative During Outpatient Pediatric Urologic Procedures Using Exparel
NCT02927080	PHASE2	TERMINATED	Study of ACE-083 in Patients With Facioscapulohumeral Muscular Dystrophy (FSHD)
NCT03943290	PHASE2	TERMINATED	Extension Study to Evaluate the Long-Term Effects of ACE-083 in Patients With Facioscapulohumeral Muscular Dystrophy (FSHD) and Charcot-Marie Tooth (CMT) Disease Types 1 and X (CMT1 and CMTX)
NCT04003974	PHASE2	COMPLETED	Efficacy and Safety of Losmapimod in Subjects With Facioscapulohumeral Muscular Dystrophy (FSHD)
NCT04264442	PHASE2	TERMINATED	Efficacy and Safety of Losmapimod in Treating Subjects With Facioscapulohumeral Muscular Dystrophy (FSHD) With Open-Label Extension (OLE)
NCT05548556	PHASE2	ACTIVE_NOT_RECRUITING	A Study to Evaluate RO7204239 in Participants With Facioscapulohumeral Muscular Dystrophy
NCT06547216	PHASE2	ACTIVE_NOT_RECRUITING	Phase 2 Open-label Extension Study of AOC 1020 in Participants With Facioscapulohumeral Muscular Dystrophy (FSHD)
NCT07435129	PHASE2	NOT_YET_RECRUITING	Phase 2 Study Evaluating Apitegromab for the Treatment of FSHD
NCT01153932	PHASE2	COMPLETED	Phase II Doubleblind Exploratory Study of GSK2402968 in Ambulant Subjects With Duchenne Muscular Dystrophy
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