EMD

Summary

EMD (emerin, HGNC:3331) is a protein-coding gene on chromosome Xq28, encoding Emerin (P50402). Stabilizes and promotes the formation of a nuclear actin cortical network.

Emerin is a serine-rich nuclear membrane protein and a member of the nuclear lamina-associated protein family. It mediates membrane anchorage to the cytoskeleton. Dreifuss-Emery muscular dystrophy is an X-linked inherited degenerative myopathy resulting from mutation in the emerin gene.

Source: NCBI Gene 2010 — RefSeq curated summary.

At a glance

• Gene–disease (curated): X-linked Emery-Dreifuss muscular dystrophy (Definitive, GenCC) — +2 more curated relationships
• GWAS associations: 1
• Clinical variants (ClinVar): 703 total — 93 pathogenic, 13 likely-pathogenic
• Phenotypes (HPO): 56
• Druggable target: yes
• MANE Select transcript: NM_000117

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3331
Approved symbol	EMD
Name	emerin
Location	Xq28
Locus type	gene with protein product
Status	Approved
Aliases	STA, LEMD5
Ensembl gene	ENSG00000102119
Ensembl biotype	protein_coding
OMIM	300384
Entrez	2010

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 8 retained_intron, 7 protein_coding, 3 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000369835, ENST00000369842, ENST00000428228, ENST00000468294, ENST00000471965, ENST00000485261, ENST00000486738, ENST00000492448, ENST00000494443, ENST00000682114, ENST00000682478, ENST00000683576, ENST00000683627, ENST00000684082, ENST00000684633, ENST00000684678, ENST00000897866, ENST00000933532, ENST00000933533

RefSeq mRNA: 1 — MANE Select: NM_000117 NM_000117

CCDS: CCDS14745

Canonical transcript exons

ENST00000369842 — 6 exons

Exon	Start	End
ENSE00000868367	154380882	154381523
ENSE00001925261	154379295	154379566
ENSE00003526785	154379690	154379794
ENSE00003542844	154380753	154380802
ENSE00003608886	154379942	154380019
ENSE00003635510	154380234	154380367

Expression profiles

Bgee: expression breadth ubiquitous, 284 present calls, max score 98.61.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 127.1032 / max 704.9435, expressed in 1821 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
198143	76.9769	1819
198142	47.9397	1813
198145	1.0989	636
198144	1.0877	657

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left ovary	UBERON:0002119	98.61	gold quality
left uterine tube	UBERON:0001303	98.51	gold quality
popliteal artery	UBERON:0002250	98.46	gold quality
tibial artery	UBERON:0007610	98.46	gold quality
right ovary	UBERON:0002118	98.44	gold quality
adenohypophysis	UBERON:0002196	98.30	gold quality
mucosa of stomach	UBERON:0001199	98.29	gold quality
body of uterus	UBERON:0009853	98.18	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	98.14	gold quality
aorta	UBERON:0000947	98.10	gold quality
lower esophagus muscularis layer	UBERON:0035833	98.00	gold quality
lower esophagus	UBERON:0013473	97.99	gold quality
right coronary artery	UBERON:0001625	97.92	gold quality
descending thoracic aorta	UBERON:0002345	97.85	gold quality
ectocervix	UBERON:0012249	97.81	gold quality
endocervix	UBERON:0000458	97.77	gold quality
ascending aorta	UBERON:0001496	97.76	gold quality
thoracic aorta	UBERON:0001515	97.75	gold quality
muscle layer of sigmoid colon	UBERON:0035805	97.65	gold quality
left lobe of thyroid gland	UBERON:0001120	97.58	gold quality
right lobe of thyroid gland	UBERON:0001119	97.45	gold quality
left coronary artery	UBERON:0001626	97.44	gold quality
tibial nerve	UBERON:0001323	97.32	gold quality
coronary artery	UBERON:0001621	97.23	gold quality
skin of abdomen	UBERON:0001416	97.21	gold quality
skin of leg	UBERON:0001511	97.20	gold quality
body of pancreas	UBERON:0001150	97.04	gold quality
gastrocnemius	UBERON:0001388	97.01	gold quality
right atrium auricular region	UBERON:0006631	97.00	gold quality
pituitary gland	UBERON:0000007	96.93	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-CURD-95	yes	1126.44
E-MTAB-9388	yes	11.02
E-ANND-3	yes	10.82

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NR4A3, NRG1

miRNA regulators (miRDB)

16 targeting EMD, 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-12118	100.00	65.88	1270
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-4666B	99.64	68.69	1282
HSA-MIR-5700	99.64	69.88	2280
HSA-MIR-7159-5P	99.53	72.12	2472
HSA-MIR-505-3P	99.19	69.71	896
HSA-MIR-4751	98.80	64.95	525
HSA-MIR-6882-3P	98.23	67.01	1119
HSA-MIR-4508	90.37	59.62	240

Literature-anchored findings (GeneRIF, showing 40)

• Disease-linked emerin proteins all remain active for binding directly to barrier-to-autointegration factor (BAF) both in vitro and in vivo, suggesting that disease results from loss of interactions between emerin and lamin A or putative novel partner(s). (PMID:11792821)
• genes known to be responsible for Emery-Dreifuss muscular dystrophy (PMID:11973618)
• emerin binds directly to a transcriptional repressor, GCL, and the emerin-repressor complexes might be regulated by barrier to autointegration factor (PMID:12493765)
• emerin has a regulatory role, as well as a structural role in the cell nucleus (PMID:12755701)
• the lamin a-emerin complex might have a role in muscular dystrophy and cardiomyopathy (PMID:12783988)
• These results suggest that Btf localization is regulated by apoptotic signals, and that loss of emerin binding to Btf may be relevant to muscle wasting in Emery-Dreifuss muscular dystrophy. (PMID:15009215)
• Data describe the mobility of barrier-to-autointegration factor to its partners emerin, LAP2 beta, and MAN1 in the nuclear membrane of living HeLa cells. (PMID:15109603)
• emerin may disrupt transcription factors and nuclear envelope architecture by weakening a nuclear actin network (PMID:15328537)
• Data describe the direct binding of the nuclear membrane protein MAN1 to emerin in vitro. (PMID:15681850)
• phosphorylation at Ser175 regulates the dissociation of emerin from BAF (PMID:16204256)
• Data show that chromosome positioning is largely unaffected in lymphoblastoid cell lines containing emerin or A-type lamin mutations. (PMID:16246140)
• We show that epitope masking in the nucleus is often responsible for failure to detect emerin in human and rat tissues. Pig spleen had fewer emerin-positive nuclei than lung (5% vs. 32%), although their emerin content was similar by Western blotting. (PMID:16283426)
• Ser-4 phosphorylation inhibits BAF binding to emerin and lamin A, and thereby weakens emerin-lamin interactions during both mitosis and interphase. (PMID:16371512)
• Lamin A/C and emerin are critical for skeletal muscle satellite cell differentiation, with deficient cells displaying delayed differentiation kinetics that may underlie dystrophic phenotypes. (PMID:16481476)
• emerin, an integral inner-nuclear-envelope protein, is necessary for HIV-1 infection (PMID:16680152)
• Review summarizes growing evidence that emerin has both architectural and gene-regulatory roles in the nucleus which may contribute to the pathology and mechanism of Emery-Dreifuss muscular dystrophy. (PMID:16761279)
• We found that in inclusion-body myositis (IBM) muscle vacuoles were immunoreactive for the inner nuclear membrane proteins emerin and lamin A/C. (PMID:16823856)
• Emerin regulates the flux of beta-catenin, an important transcription coactivator, into the nucleus. (PMID:16858403)
• Altered nuclear envelope elasticity caused by loss of emerin could contribute to increased nuclear fragility in Emery-Dreifuss muscular dystrophy patients with mutations in the emerin gene. (PMID:16997877)
• Lmo7 positively regulates many EDMD-relevant genes (including emerin), and is feedback-regulated by binding to emerin. (PMID:17067998)
• Mislocalization of emerin to the endoplasmic reticulum in human cells lacking A-type lamins leads to its degradation and provides the first evidence that its degradation is mediated by the proteasome. (PMID:17097067)
• Neither emerin nor LMNA mutations in a subset of families with EDMD-like phenotypes that may imply an existence of other genes causing similar disorders. (PMID:17117676)
• The characterisation of the residues both in emerin and in nesprin-1alpha and -2beta which are involved in their interaction is reported. (PMID:17462627)
• findings highlight the crucial role of lamin A/C-emerin interactions, with evidence for synergistic effects of these mutations that lead to Emery-Dreifuss muscular dystrophy as the worsened result of digenic mechanism in this family (PMID:17536044)
• Mutations in EMD may indicate a limb-girdle muscular dystrophy phenotype. Identification of emerin deficiency among patients with limb-girdle muscular dystrophy is essential to prevent cardiac catastrophe. (PMID:17620497)
• The results suggest a model in which pUS3 and PKCdelta that has been recruited by pUL34 hyperphosphorylate emerin, leading to disruption of its connections with lamin proteins and contributing to the disruption of the nuclear lamina. (PMID:17652388)
• significant fraction of emerin is located at the outer nuclear membrane and peripheral ER, where it interacts directly with the centrosome. (PMID:17785515)
• mutation of EMD can underlie X-linked familial atrial fibrillation; Lys37del is associated with epithelial cell emerin deficiency, as in Emery-Dreifuss muscular dystrophy, yet it causes electrical atriomyopathy in the absence of skeletal muscle disease (PMID:18266676)
• emerin is dispensable for HIV-1 infections. (PMID:18400857)
• Mutations in the genes for nuclear envelope proteins of emerin (EMD) and lamin A/C (LMNA) are known to cause Emery-Dreifuss muscular dystrophy (EDMD) and limb girdle muscular dystrophy (LGMD). (PMID:18646565)
• Knockdown of A-type lamins and emerin in HeLa and C2C12 stimulated phosphorylation and nuclear translocation of ERK as well as activation of genes encoding downstream transcription factors. (PMID:19022376)
• process of adipogenesis is affected by a dynamic link between complexes of emerin and lamins A/C at the nuclear envelope and nucleocytoplasmic distribution of beta-catenin, to influence cellular plasticity and differentiation. (PMID:19126678)
• Decoration of the NM by emerin represents an original approach to identify papillary thyroid carcinomas nuclear shape (PMID:19302538)
• Non-farnesylated and farnesylated carboxymethylated lamin A precursors in human fibroblasts modifies emerin localization. (PMID:19323649)
• An association of Mel18 with emerin was observed in Hutchinson-Gilford progeria syndrome, but not in WT cells. (PMID:19727227)
• BAF and emerin have dynamic roles in genome integrity and might help couple DNA damage responses to the nuclear lamina network (PMID:19759913)
• These findings suggest roles for emerin as a downstream effector and signal integrator for tyrosine kinase signaling pathway(s) at the nuclear envelope. (PMID:19789182)
• Certain patients presenting a typical EDMD phenotype in which no mutations in the EMD or LMNA genes can be confirmed. This may indicate that an Emery-Dreifuss-like dystrophy could also be associated with mutations in other genes. (PMID:20054742)
• Data provide evidence that 4.1R has functional interactions with emerin and A-type lamin that impact upon nuclear architecture, centrosome-nuclear envelope association and the regulation of beta-catenin transcriptional co-activator activity. (PMID:21486941)
• Data augment the number of EMD mutations by 13.8%, equating to an increase of 5.2% in the total known EMD mutations and to an increase of 6.0% in the number of different mutations. (PMID:21697856)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Emd	ENSMUSG00000001964
rattus_norvegicus	Emd	ENSRNOG00000058882

Protein

Protein identifiers

Emerin — P50402 (reviewed: P50402)

All UniProt accessions (6): P50402, A0A804HIG7, A0A804HIV7, A0A804HLA2, F8WEQ1, Q5HY57

UniProt curated annotations — full annotation on UniProt →

Function. Stabilizes and promotes the formation of a nuclear actin cortical network. Stimulates actin polymerization in vitro by binding and stabilizing the pointed end of growing filaments. Inhibits beta-catenin activity by preventing its accumulation in the nucleus. Acts by influencing the nuclear accumulation of beta-catenin through a CRM1-dependent export pathway. Links centrosomes to the nuclear envelope via a microtubule association. Required for proper localization of non-farnesylated prelamin-A/C. Together with NEMP1, contributes to nuclear envelope stiffness in germ cells. EMD and BAF are cooperative cofactors of HIV-1 infection. Association of EMD with the viral DNA requires the presence of BAF and viral integrase. The association of viral DNA with chromatin requires the presence of BAF and EMD.

Subunit / interactions. Interacts with lamins A and C, BANF1, GMCL, BCLAF1 and YTHDC1/YT521. Interacts with TMEM43; the interaction retains emerin in the nuclear inner membrane. Interacts with SUN1 and SUN2. Interacts with ACTB, SPTAN1, F-actin, CTNNB1 and beta-tubulin. Interacts with TMEM201. Interacts with NEMP1.

Subcellular location. Nucleus inner membrane. Nucleus outer membrane.

Tissue specificity. Skeletal muscle, heart, colon, testis, ovary and pancreas.

Post-translational modifications. Found in four different phosphorylated forms, three of which appear to be associated with the cell cycle.

Disease relevance. Emery-Dreifuss muscular dystrophy 1, X-linked (EDMD1) [MIM:310300] A form of Emery-Dreifuss muscular dystrophy, a degenerative myopathy characterized by weakness and atrophy of muscle without involvement of the nervous system, early contractures of the elbows, Achilles tendons and spine, and cardiomyopathy associated with cardiac conduction defects. The disease is caused by variants affecting the gene represented in this entry.

RefSeq proteins (1): NP_000108* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003887	LEM_dom	Domain
IPR011015	LEM/LEM-like_dom_sf	Homologous_superfamily
IPR034989	LEM_emerin	Domain
IPR035004	Emerin	Family

Pfam: PF03020

UniProt features (33 total): modified residue 15, sequence variant 5, mutagenesis site 4, helix 3, region of interest 2, chain 1, transmembrane region 1, domain 1, turn 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
7NDY	X-RAY DIFFRACTION	1.44
6GHD	X-RAY DIFFRACTION	2.1
6RPR	X-RAY DIFFRACTION	2.26
1JEI	SOLUTION NMR
2ODC	SOLUTION NMR
2ODG	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P50402-F1	61.26	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 (15): 60, 87, 98, 141, 142, 143, 161, 171, 173, 175, 1, 8, 29, 49, 54

Mutagenesis-validated functional residues (4):

Position	Phenotype
49	abolishes phosphorylation. no effect on targeting to nuclear envelope nor on interaction with lmna.
49	mimics phosphorylation. no effect on targeting to nuclear envelope nor on interaction with lmna.
196	no loss of binding to f-actin; when associated with a-197.
197	no loss of binding to f-actin; when associated with a-196.

Function

Pathways and Gene Ontology

Reactome pathways

9 pathways

ID	Pathway
R-HSA-2980766	Nuclear Envelope Breakdown
R-HSA-2995383	Initiation of Nuclear Envelope (NE) Reformation
R-HSA-4419969	Depolymerization of the Nuclear Lamina
R-HSA-9013149	RAC1 GTPase cycle
R-HSA-9013404	RAC2 GTPase cycle
R-HSA-9013405	RHOD GTPase cycle
R-HSA-9013408	RHOG GTPase cycle
R-HSA-9013423	RAC3 GTPase cycle
R-HSA-9609523	Insertion of tail-anchored proteins into the endoplasmic reticulum membrane

MSigDB gene sets: 0 (showing top):

GO Biological Process (10): muscle contraction (GO:0006936), muscle organ development (GO:0007517), skeletal muscle cell differentiation (GO:0035914), positive regulation of protein export from nucleus (GO:0046827), negative regulation of fibroblast proliferation (GO:0048147), regulation of canonical Wnt signaling pathway (GO:0060828), cellular response to growth factor stimulus (GO:0071363), nuclear membrane organization (GO:0071763), negative regulation of canonical Wnt signaling pathway (GO:0090090), amyloid fibril formation (GO:1990000)

GO Molecular Function (4): actin binding (GO:0003779), cadherin binding (GO:0045296), beta-tubulin binding (GO:0048487), protein binding (GO:0005515)

GO Cellular Component (15): nuclear envelope (GO:0005635), nuclear inner membrane (GO:0005637), nuclear outer membrane (GO:0005640), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783), spindle (GO:0005819), cytosol (GO:0005829), microtubule (GO:0005874), membrane (GO:0016020), nuclear membrane (GO:0031965), TMEM240-body (GO:0160045), nucleus (GO:0005634), spindle pole centrosome (GO:0031616), cortical endoplasmic reticulum (GO:0032541)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
RHO GTPase cycle	5
Mitotic Prophase	1
Nuclear Envelope (NE) Reassembly	1
Nuclear Envelope Breakdown	1
Protein localization	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
intracellular membrane-bounded organelle	3
canonical Wnt signaling pathway	2
nucleus	2
endomembrane system	2
nuclear membrane	2
cytoplasm	2
microtubule cytoskeleton	2
muscle system process	1
animal organ development	1
muscle structure development	1
skeletal muscle tissue development	1
cell differentiation	1
protein export from nucleus	1
positive regulation of nucleocytoplasmic transport	1
regulation of protein export from nucleus	1
positive regulation of intracellular protein transport	1
negative regulation of cell population proliferation	1
fibroblast proliferation	1
regulation of fibroblast proliferation	1
regulation of Wnt signaling pathway	1
response to growth factor	1
cellular response to endogenous stimulus	1
nuclear envelope organization	1
membrane organization	1
negative regulation of Wnt signaling pathway	1
regulation of canonical Wnt signaling pathway	1
protein metabolic process	1
supramolecular fiber organization	1
cytoskeletal protein binding	1
cell adhesion molecule binding	1
tubulin binding	1
binding	1
organelle envelope	1
organelle inner membrane	1
organelle outer membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
nuclear lumen	1
intracellular anatomical structure	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

1786 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EMD	BANF1	O75531	998
EMD	LMNA	P02545	997
EMD	SUN1	O94901	997
EMD	BANF2	Q9H503	996
EMD	SYNE1	Q8NF91	995
EMD	SYNE2	Q8WXH0	994
EMD	LMO7	Q8WWI1	990
EMD	SUN2	Q9UH99	990
EMD	GUCY2C	P25092	989
EMD	LMNB1	P20700	984
EMD	LEMD3	Q9Y2U8	981
EMD	GUCA2B	Q16661	968
EMD	GUCA2A	Q02747	967
EMD	BCLAF1	Q9NYF8	961
EMD	CTNNB1	P35222	959

IntAct

658 interactions, top by confidence:

A	B	Type	Score
BANF1	EMD	psi-mi:“MI:0915”(physical association)	0.940
EMD	BANF1	psi-mi:“MI:0915”(physical association)	0.940
EMD	FATE1	psi-mi:“MI:0915”(physical association)	0.850
GDI1	RAB4A	psi-mi:“MI:0914”(association)	0.820
BEND7	EMD	psi-mi:“MI:0915”(physical association)	0.810
EMD	CATSPER1	psi-mi:“MI:0915”(physical association)	0.810
LUZP4	EMD	psi-mi:“MI:0915”(physical association)	0.810
EMD	TRAF3IP3	psi-mi:“MI:0915”(physical association)	0.810
CATSPER1	EMD	psi-mi:“MI:0915”(physical association)	0.810
EMD	LUZP4	psi-mi:“MI:0915”(physical association)	0.810
EMD	BEND7	psi-mi:“MI:0915”(physical association)	0.810

BioGRID (1059): EMD (Two-hybrid), EMD (Two-hybrid), ZNF165 (Two-hybrid), ZNF232 (Two-hybrid), ABT1 (Two-hybrid), LUZP4 (Two-hybrid), PAK7 (Two-hybrid), AEN (Two-hybrid), CCDC33 (Two-hybrid), EFHC2 (Two-hybrid), CEP70 (Two-hybrid), TRAF3IP3 (Two-hybrid), FATE1 (Two-hybrid), CATSPER1 (Two-hybrid), MAB21L3 (Two-hybrid)

ESM2 similar proteins: A0A1L8ER70, A2AHC3, A2RUV4, A5WUN7, A5WV69, B1AZP2, D4AEC2, E1BLT8, O01971, O08579, P50402, P97839, Q08AD1, Q148W8, Q2KJD6, Q2MJV9, Q2THW7, Q2THW9, Q2THX1, Q4KM62, Q5R838, Q5RD34, Q5U2Y9, Q5VUB5, Q5VZP5, Q63190, Q640U0, Q66HP6, Q68G75, Q6GLU8, Q709R6, Q71H61, Q75N33, Q75NY9, Q7ZX27, Q80Y56, Q86SQ0, Q8C1B1, Q8K004, Q8K1N2

Diamond homologs: O08579, P50402, Q63190, Q61029, Q61033, Q62733

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
SRC	down-regulates	EMD	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 120 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
RHOF GTPase cycle	5	18.0×	6e-04
Oncogenic MAPK signaling	5	17.2×	6e-04
RHOD GTPase cycle	6	17.0×	3e-04
Translocation of SLC2A4 (GLUT4) to the plasma membrane	7	15.0×	2e-04
Signaling by BRAF and RAF1 fusions	6	14.2×	5e-04
RHOQ GTPase cycle	5	12.6×	2e-03
Anchoring of the basal body to the plasma membrane	6	9.4×	2e-03
ER to Golgi Anterograde Transport	5	9.2×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	93
Likely pathogenic	13
Uncertain significance	227
Likely benign	241
Benign	12

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1013586	GRCh37/hg19 Xq28(chrX:153194251-153623000)x2	Pathogenic
1048786	NM_000117.3(EMD):c.631del (p.Arg211fs)	Pathogenic
1048787	NM_000117.3(EMD):c.449+1G>A	Pathogenic
1070850	NC_000023.10:g.(?153607835)(153609567_?)del	Pathogenic
1071626	NM_000117.3(EMD):c.483C>G (p.Tyr161Ter)	Pathogenic
1072810	NM_000117.3(EMD):c.570dup (p.Met191fs)	Pathogenic
1074346	NM_000117.3(EMD):c.643_653dup (p.Gln219fs)	Pathogenic
1074958	NM_000117.3(EMD):c.2T>G (p.Met1Arg)	Pathogenic
1074959	NM_000117.3(EMD):c.102C>G (p.Tyr34Ter)	Pathogenic
1074960	NM_000117.3(EMD):c.153del (p.Ser52fs)	Pathogenic
1075797	NM_000117.3(EMD):c.650_654del (p.Leu217fs)	Pathogenic
11171	NM_000117.3(EMD):c.506_507del (p.Pro169fs)	Pathogenic
11172	NM_000117.3(EMD):c.1A>G (p.Met1Val)	Pathogenic
11173	NM_000117.3:c.55_83del	Pathogenic
11174	NM_000117.3(EMD):c.139_140dup (p.Leu48fs)	Pathogenic
11176	NM_000117.3(EMD):c.130C>T (p.Gln44Ter)	Pathogenic
11177	NM_000117.3(EMD):c.615del (p.Ile206fs)	Pathogenic
11178	NM_000117.3(EMD):c.548C>A (p.Pro183His)	Pathogenic
11179	NM_000117.3(EMD):c.547C>A (p.Pro183Thr)	Pathogenic
1184471	NM_000117.3(EMD):c.125del (p.Glu42fs)	Pathogenic
1275775	NM_000117.3(EMD):c.282C>A (p.Tyr94Ter)	Pathogenic
1330855	NM_000117.3(EMD):c.187+1G>A	Pathogenic
1374482	NM_000117.3(EMD):c.266-3A>G	Pathogenic
1451449	NM_000117.3(EMD):c.561_567dup (p.Phe190fs)	Pathogenic
1453367	NM_000117.3(EMD):c.399+1G>T	Pathogenic
1455467	NC_000023.10:g.(?153599231)(153609567_?)del	Pathogenic
1456997	NM_000117.3(EMD):c.570del (p.Phe190fs)	Pathogenic
152708	GRCh38/hg38 Xq28(chrX:154017291-154394658)x3	Pathogenic
163403	NM_000117.3(EMD):c.266-2A>G	Pathogenic
1787242	NM_000117.3(EMD):c.217dup (p.Met73fs)	Pathogenic

SpliceAI

537 predictions. Top by Δscore:

Variant	Effect	Δscore
X:154379563:G:GG	donor_gain	1.0000
X:154379791:TCTGG:T	donor_loss	1.0000
X:154379793:TGGTG:T	donor_loss	1.0000
X:154379795:G:GA	donor_loss	1.0000
X:154379795:G:GG	donor_gain	1.0000
X:154379935:A:AG	acceptor_gain	1.0000
X:154379939:CAGAC:C	acceptor_loss	1.0000
X:154379940:A:AG	acceptor_gain	1.0000
X:154379940:A:AT	acceptor_loss	1.0000
X:154379941:G:GG	acceptor_gain	1.0000
X:154379941:GA:G	acceptor_gain	1.0000
X:154379941:GAC:G	acceptor_gain	1.0000
X:154379941:GACT:G	acceptor_gain	1.0000
X:154379941:GACTT:G	acceptor_gain	1.0000
X:154380018:GG:G	donor_gain	1.0000
X:154380019:GG:G	donor_gain	1.0000
X:154380230:CAAG:C	acceptor_loss	1.0000
X:154380232:A:AG	acceptor_gain	1.0000
X:154380233:G:GG	acceptor_gain	1.0000
X:154380365:CAG:C	donor_loss	1.0000
X:154380366:AGGT:A	donor_loss	1.0000
X:154380368:GT:G	donor_loss	1.0000
X:154380798:GA:G	donor_gain	1.0000
X:154379560:GTA:G	donor_gain	0.9900
X:154379562:AGTAG:A	donor_loss	0.9900
X:154379563:GTAGG:G	donor_loss	0.9900
X:154379564:TAG:T	donor_loss	0.9900
X:154379565:AGGTA:A	donor_loss	0.9900
X:154379566:GGT:G	donor_loss	0.9900
X:154379568:T:A	donor_loss	0.9900

AlphaMissense

1643 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:154379546:T:C	I21T	0.991
X:154379519:T:C	L12P	0.988
X:154379712:G:C	E35D	0.988
X:154379712:G:T	E35D	0.988
X:154379720:T:C	I38T	0.987
X:154379698:C:A	R31S	0.983
X:154379699:G:C	R31P	0.982
X:154379531:T:C	L16P	0.981
X:154379546:T:G	I21S	0.980
X:154379720:T:G	I38S	0.980
X:154379707:T:G	Y34D	0.975
X:154379554:G:A	G24R	0.973
X:154379554:G:C	G24R	0.973
X:154379555:G:A	G24E	0.973
X:154381108:T:A	W226R	0.973
X:154381108:T:C	W226R	0.973
X:154379531:T:A	L16Q	0.972
X:154381192:T:C	F254L	0.972
X:154381194:C:A	F254L	0.972
X:154381194:C:G	F254L	0.972
X:154379707:T:C	Y34H	0.971
X:154379720:T:A	I38N	0.968
X:154379554:G:T	G24W	0.967
X:154379546:T:A	I21N	0.965
X:154379696:C:T	T30I	0.963
X:154379728:T:G	Y41D	0.962
X:154379539:T:G	Y19D	0.961
X:154379718:G:C	K37N	0.958
X:154379718:G:T	K37N	0.958
X:154379519:T:A	L12Q	0.956

dbSNP variants (sampled 300 via entrez): RS1000874911 (X:154378408 C>A,T), RS1001556394 (X:154377956 G>A), RS1001950130 (X:154381733 A>G), RS1003076131 (X:154378475 C>T), RS1003796875 (X:154380685 A>G), RS1004200102 (X:154380728 C>T), RS1005870434 (X:154378797 G>T), RS1006011639 (X:154379349 C>T), RS1007682557 (X:154377514 C>T), RS1008233808 (X:154381695 C>T), RS1010675678 (X:154380265 C>T), RS1011683409 (X:154381716 C>T), RS1012345799 (X:154378460 G>A), RS1012376819 (X:154378075 T>A,C), RS1015907558 (X:154381792 T>A)

Disease associations

OMIM: gene MIM:300384 | disease phenotypes: MIM:310300, MIM:301163, MIM:300049, MIM:304120, MIM:309350, MIM:305620, MIM:192600, MIM:300815, MIM:300696, MIM:115200

GenCC curated gene-disease

Disease	Classification	Inheritance
X-linked Emery-Dreifuss muscular dystrophy	Definitive	X-linked
heart conduction disease	Strong	X-linked
Emery-Dreifuss muscular dystrophy 1, X-linked	Strong	X-linked

Mondo (21): X-linked Emery-Dreifuss muscular dystrophy (MONDO:0010680), Emery-Dreifuss muscular dystrophy (MONDO:0016830), intellectual disability (MONDO:0001071), Emery-Dreifuss muscular dystrophy 1, X-linked (MONDO:0100531), cardiomyopathy, dilated, 3C (MONDO:0981022), cardiomyopathy (MONDO:0004994), heterotopia, periventricular, X-linked dominant (MONDO:0010233), otopalatodigital syndrome type 2 (MONDO:0010571), Melnick-Needles syndrome (MONDO:0010650), frontometaphyseal dysplasia (MONDO:0015942), neuromuscular disease (MONDO:0019056), dilated cardiomyopathy (MONDO:0005021), familial hypertrophic cardiomyopathy (MONDO:0024573), chromosome Xq28 duplication syndrome (MONDO:0010436), hypertrophic cardiomyopathy (MONDO:0005045)

Orphanet (19): Emery-Dreifuss muscular dystrophy (Orphanet:261), X-linked Emery-Dreifuss muscular dystrophy (Orphanet:98863), Rare cardiomyopathy (Orphanet:167848), Frontometaphyseal dysplasia (Orphanet:1826), Nodular neuronal heterotopia (Orphanet:2149), Melnick-Needles syndrome (Orphanet:2484), OBSOLETE: Otopalatodigital syndrome (Orphanet:669), Ehlers-Danlos syndrome with periventricular heterotopia (Orphanet:82004), Otopalatodigital syndrome type 2 (Orphanet:90652), Neuromuscular disease (Orphanet:68381), Dilated cardiomyopathy (Orphanet:217604), Rare familial disorder with hypertrophic cardiomyopathy (Orphanet:99739), Proximal Xq28 duplication syndrome (Orphanet:1762), Rare hypertrophic cardiomyopathy (Orphanet:217569), X-linked myopathy with postural muscle atrophy (Orphanet:178461)

HPO phenotypes

56 total (30 of 56 shown, HPO-id order):

HPO	Term
HP:0000464	Abnormality of the neck
HP:0000470	Short neck
HP:0000508	Ptosis
HP:0000767	Pectus excavatum
HP:0000912	Sprengel anomaly
HP:0001249	Intellectual disability
HP:0001252	Hypotonia
HP:0001288	Gait disturbance
HP:0001315	Reduced tendon reflexes
HP:0001387	Joint stiffness
HP:0001419	X-linked recessive inheritance
HP:0001513	Obesity
HP:0001605	Vocal cord paralysis
HP:0001639	Hypertrophic cardiomyopathy
HP:0001645	Sudden cardiac death
HP:0001678	Atrioventricular block
HP:0001692	Atrial arrhythmia
HP:0001771	Achilles tendon contracture
HP:0001962	Palpitations
HP:0002155	Hypertriglyceridemia
HP:0002486	Myotonia
HP:0002505	Loss of ambulation
HP:0002515	Waddling gait
HP:0002650	Scoliosis
HP:0002747	Respiratory insufficiency due to muscle weakness
HP:0002808	Kyphosis
HP:0002987	Elbow flexion contracture
HP:0003141	Increased LDL cholesterol concentration
HP:0003198	Myopathy
HP:0003202	Skeletal muscle atrophy

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST90002397_163	Mean spheric corpuscular volume	2.000000e-12

MeSH disease descriptors (12)

Descriptor	Name	Tree numbers
D009202	Cardiomyopathies	C14.280.238
D002311	Cardiomyopathy, Dilated	C14.280.195.160; C14.280.238.070; C16.320.488.750
D002312	Cardiomyopathy, Hypertrophic	C14.280.238.100; C14.280.484.048.750.070.160
D024741	Cardiomyopathy, Hypertrophic, Familial	C14.280.238.100.500; C14.280.484.048.750.070.160.500; C16.320.160
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D020389	Muscular Dystrophy, Emery-Dreifuss	C05.651.534.500.350; C10.668.491.175.500.350; C16.320.322.625; C16.320.577.350
D009468	Neuromuscular Diseases	C10.668
D000083143	X-Linked Emery-Dreifuss Muscular Dystrophy	C05.651.534.500.350.500; C10.668.491.175.500.350.500; C16.320.322.625.500; C16.320.577.350.500
C567580	Chromosome Xq28 Duplication Syndrome (supp.)
C538064	Frontometaphyseal dysplasia (supp.)
C538089	Oto-palato-digital syndrome, type 2 (supp.)
C536231	familial dilated cardiomyopathy (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066880 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 4 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.30	Kd	501.1	nM	CHEMBL5653589
6.30	ED50	501.1	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 4 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
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148319: Binding affinity to human EMD incubated for 45 mins by Kinobead based pull down assay	kd	0.5011	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression	4
sodium arsenite	decreases expression, increases expression	2
potassium chromate(VI)	affects cotreatment, increases expression, decreases expression	2
Cyclosporine	increases expression	2
FR900359	affects phosphorylation	1
testosterone enanthate	affects expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
sodium arsenate	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression	1
beta-lapachone	increases expression	1
arsenite	affects binding, increases reaction	1
butyraldehyde	increases expression	1
coumarin	affects phosphorylation	1
methyl salicylate	affects expression	1
epigallocatechin gallate	affects cotreatment, increases expression	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
ICG 001	increases expression	1
bisphenol B	increases expression	1
abrine	increases expression	1
LDN 193189	affects cotreatment, decreases expression	1
bisphenol AF	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Temozolomide	increases expression	1
Arsenic Trioxide	increases expression	1
Acrolein	affects expression	1
Air Pollutants	increases abundance, affects expression	1
Ethanol	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651361	Binding	Binding affinity to human EMD incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

17 cell lines: 7 cancer cell line, 6 induced pluripotent stem cell, 3 transformed cell line, 1 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_6B21	GM23707	Transformed cell line	Male
CVCL_6B22	GM16864	Transformed cell line	Male
CVCL_A0ZF	UWRBTi003-A	Induced pluripotent stem cell	Male
CVCL_A0ZG	UWRBTi003-B	Induced pluripotent stem cell	Male
CVCL_A0ZH	UWRBTi003-C	Induced pluripotent stem cell	Male
CVCL_A0ZI	UWRBTi004-A	Induced pluripotent stem cell	Male
CVCL_A0ZJ	UWRBTi004-B	Induced pluripotent stem cell	Male
CVCL_A0ZK	UWRBTi004-C	Induced pluripotent stem cell	Male
CVCL_B2WJ	Abcam HEK293T EMD KO	Transformed cell line	Female
CVCL_E5FZ	SW480 EGFP-emerin clone 1	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT00348530	PHASE4	UNKNOWN	Carvedilol Versus Verapamil in Chronic Heart Failure Secondary to Non-Ischemic Cardiomyopathy
NCT00371891	PHASE4	COMPLETED	Ontario Multidetector Computed Tomographic (MDCT) Coronary Angiography Study (OMCAS)
NCT00401856	PHASE4	COMPLETED	CMR to Assess Fibrosis in Cardiomyopathy Using Eplerenone
NCT00559338	PHASE4	COMPLETED	Impact of Nesiritide Infusion for Decompensated Heart Failure in the Emergency Department
NCT00606775	PHASE4	UNKNOWN	The Preventive Efficacy of Carvedilol on Cardiac Dysfunction in Duchenne Muscular Dystrophy
NCT00658203	PHASE4	COMPLETED	Clinical Evaluation on Advanced Resynchronization
NCT00701220	PHASE4	COMPLETED	Statin Therapy for Ischemic and Nonischemic Cardiomyopathy
NCT00800761	PHASE4	COMPLETED	Intensive Combined Chelation Therapy for Iron-Induced Cardiac Disease in Patients With Thalassemia Major
NCT00806390	PHASE4	TERMINATED	Prevention of Anthracycline or Trastuzumab Induced Cardiomyopathy by Metoprolol
NCT01006473	PHASE4	COMPLETED	Exercise Training in Chagas Cardiomyopathy
NCT01261065	PHASE4	COMPLETED	Mechanisms of Improvement With Beta-Blocker Treatment in Heart Failure
NCT01345188	PHASE4	COMPLETED	Ranolazine in Ischemic Cardiomyopathy
NCT01868841	PHASE4	COMPLETED	123-I mIBG (AdreView) Heart-to-Mediastinal (H/M) Ratio and SPECT Imaging on a Small Field of View-High Efficiency Cardiac SPECT System
NCT02640846	PHASE4	UNKNOWN	Effects of Levosimendan, Milrinone and Norepinephrine on Left and Right Ventricular Function in Septic Shock
NCT03228823	PHASE4	UNKNOWN	Prospective Assessment of Premature Ventricular Contractions Suppression in Cardiomyopathy(PAPS)
NCT04323852	PHASE4	COMPLETED	Can Vitamin D Reduce Heart Muscle Damage After Bypass Surgery?
NCT05034432	PHASE4	RECRUITING	The PIVATAL Study -Study of Ventricular Arrhythmia (VTA) Ablation in Left Ventricular Assist Device (LVAD) Patients
NCT05718128	PHASE4	RECRUITING	Clinical Study of Endocardial Myocardial Biopsy
NCT06964464	PHASE4	RECRUITING	Comparative Effectiveness of Carvedilol Versus Metoprolol Succinate in Heart Failure Patients With an Implantable Cardioverter Defibrillator
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT00170183	PHASE3	COMPLETED	Brain Natriuretic Peptide (BNP) to Preserve Renal Function in Hospitalized Patients With Heart Failure
NCT00270387	PHASE3	COMPLETED	A Study of Short-Term Outcomes and Economic Impact For Patients With Worsening Congestive Heart Failure When Natrecor (Nesiritide) is Added to Standard-Care Therapy, Compared to Administration of Placebo With Standard-Care Therapy
NCT00321295	PHASE3	COMPLETED	Biventricular Pacing In Patients With Left Ventricular Dysfunction After Cardiovascular Surgery
NCT00483197	PHASE3	UNKNOWN	VentrAssistTM LVAD as a Bridge to Cardiac Transplantation - Pivotal Trial
NCT00490321	PHASE3	UNKNOWN	VentrAssistTM LVAD for the Treatment of Advanced Heart Failure - Destination Therapy
NCT00626028	PHASE3	COMPLETED	Comparison of Inhaled Nitric Oxide and Oxygen in Participants Reactivity During Acute Pulmonary Vasodilator Testing
NCT01013714	PHASE3	UNKNOWN	Cardiac Sympathetic Denervation for Prevention of Ventricular Tachyarrhythmias
NCT01217827	PHASE3	COMPLETED	Implantable Cardioverter-Defibrillator Use in the VA System
NCT01648634	PHASE3	COMPLETED	Nebivolol for the Prevention of Left Ventricular Systolic Dysfunction in Patients With Duchenne Muscular Dystrophy
NCT02924285	PHASE3	COMPLETED	Catheter Ablation Versus Amiodarone for Therapy of Premature Ventricular Contractions in Patients With Structural Heart Disease
NCT03860935	PHASE3	COMPLETED	Efficacy and Safety of AG10 in Subjects With Transthyretin Amyloid Cardiomyopathy
NCT04166331	PHASE3	COMPLETED	Adjunctive DobutAmine in sePtic Cardiomyopathy With Tissue Hypoperfusion
NCT05175066	PHASE3	COMPLETED	Bisoprolol Administration to Prevent Anthracycline-induced Cardiotoxicity
NCT05237323	PHASE3	COMPLETED	Micophenolate Mofetil Versus Azathioprine in Myocarditis
NCT06158698	PHASE3	RECRUITING	CMP-MYTHiC Trial and Registry - CardioMyoPathy With MYocarditis THerapy With Colchicine
NCT06563895	PHASE3	RECRUITING	Acoramidis Transthyretin Amyloidosis Prevention Trial in the Young (ACT-EARLY) Study in Asymptomatic Carriers of a Pathogenic TTR Variant