DSP

Summary

DSP (desmoplakin, HGNC:3052) is a protein-coding gene on chromosome 6p24.3, encoding Desmoplakin (P15924). A component of desmosome cell-cell junctions which are required for positive regulation of cellular adhesion. It is haploinsufficient (ClinGen: sufficient evidence).

This gene encodes a protein that anchors intermediate filaments to desmosomal plaques and forms an obligate component of functional desmosomes. Mutations in this gene are the cause of several cardiomyopathies and keratodermas, including skin fragility-woolly hair syndrome. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 1832 — RefSeq curated summary.

At a glance

• Gene–disease (curated): arrhythmogenic cardiomyopathy with wooly hair and keratoderma (Definitive, ClinGen) — +11 more curated relationships
• GWAS associations: 33 (top 4% of genes corpus-wide)
• Clinical variants (ClinVar): 6,156 total — 512 pathogenic, 211 likely-pathogenic (top 1% of genes corpus-wide)
• GTEx eGene: eQTL in 23 tissues, sQTL in 0 (q < 0.05)
• Phenotypes (HPO): 110
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 1 cancer types (inferred from mutation patterns)
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.44 (moderately constrained)
• MANE Select transcript: NM_004415

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3052
Approved symbol	DSP
Name	desmoplakin
Location	6p24.3
Locus type	gene with protein product
Status	Approved
Aliases	KPPS2, PPKS2, DPI, DPII, DP
Ensembl gene	ENSG00000096696
Ensembl biotype	protein_coding
OMIM	125647
Entrez	1832

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 9 protein_coding, 6 nonsense_mediated_decay, 4 retained_intron

MANE Select: ENST00000379802

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 3: 1

ENST00000379802, ENST00000418664, ENST00000506617, ENST00000682228, ENST00000683563, ENST00000683682, ENST00000684395, ENST00000710359, ENST00000713869, ENST00000713903, ENST00000713904, ENST00000713909, ENST00000713910, ENST00000713911, ENST00000713912, ENST00000713913, ENST00000713918, ENST00000713924, ENST00001137435

RefSeq mRNA: 4 — MANE Select: NM_004415 NM_001008844, NM_001319034, NM_001406591, NM_004415

CCDS: CCDS4501, CCDS47368

Canonical transcript exons

ENST00000379802 — 24 exons

Exon	Start	End
ENSE00001154944	7578464	7578562
ENSE00001154954	7577779	7577886
ENSE00001154962	7576959	7577042
ENSE00001154968	7576294	7576456
ENSE00001154975	7575295	7575488
ENSE00001154978	7574657	7574795
ENSE00001154981	7574086	7574252
ENSE00001154985	7571842	7572068
ENSE00001154992	7571383	7571584
ENSE00001154996	7570437	7570563
ENSE00001155002	7569186	7569340
ENSE00001155008	7568437	7568589
ENSE00001155013	7567781	7567906
ENSE00001155018	7567354	7567449
ENSE00001155330	7566377	7566481
ENSE00001155338	7565359	7565520
ENSE00001155357	7559226	7559400
ENSE00001155361	7558116	7558264
ENSE00001155370	7555718	7555820
ENSE00003488058	7562652	7562780
ENSE00003691486	7563736	7563786
ENSE00004021647	7579275	7581569
ENSE00004021766	7541671	7542085
ENSE00004021782	7582642	7586714

Expression profiles

Bgee: expression breadth ubiquitous, 253 present calls, max score 99.86.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 67.5201 / max 7657.2682, expressed in 1325 samples.

Highest expression (Bgee): skin of hip, upper leg skin, hair follicle, penis, gingival epithelium.

Genetic regulation across tissues (GTEx eQTL / sQTL)

DSP is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 23 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 23 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Lung	eqtl	9.6e-70	-0.70	6:7562999:T:G
Nerve Tibial	eqtl	6.4e-45	+0.66	6:7402342:C:T
Adipose Subcutaneous	eqtl	9.0e-35	-0.44	6:7387588:T:TCA
Spleen	eqtl	1.6e-17	+0.62	6:7442378:A:G
Whole Blood	eqtl	1.6e-13	+0.32	6:7441489:T:C
Cells EBV-transformed lymphocytes	eqtl	6.7e-08	+0.77	6:7542670:C:G
Esophagus Muscularis	eqtl	1.9e-07	-0.31	6:7411598:T:G
Brain Nucleus accumbens basal ganglia	eqtl	1.0e-06	-0.43	6:7360935:C:T
Brain Cerebellar Hemisphere	eqtl	5.7e-06	+1.00	6:7345640:A:G
Muscle Skeletal	eqtl	7.8e-06	-0.27	6:7334881:C:T
Adipose Visceral Omentum	eqtl	7.7e-05	+0.14	6:7399656:C:T
Uterus	eqtl	2.8e-04	+0.54	6:7486547:C:T
Esophagus Gastroesophageal Junction	eqtl	1.6e-03	-0.24	6:7389844:C:T
Heart Atrial Appendage	eqtl	7.1e-03	-0.08	6:7424822:T:G
Adrenal Gland	eqtl	1.2e-02	-0.21	6:7542278:TC:T
Esophagus Mucosa	eqtl	1.3e-02	+0.07	6:7438728:C:G
Heart Left Ventricle	eqtl	2.1e-02	-0.13	6:7518950:T:C
Brain Caudate basal ganglia	eqtl	2.4e-02	-0.21	6:7543997:C:T
Thyroid	eqtl	2.9e-02	-0.11	6:7548823:C:A
Cells Cultured fibroblasts	eqtl	3.0e-02	-0.12	6:7566153:T:C

FANTOM5 promoters

showing 10 of 19 alternative TSS:

Promoter ID	TPM avg	Samples expressed
65658	33.2920	1053
65657	16.9911	1031
65656	3.3531	607
65653	2.8164	798
65678	2.2549	541
65679	2.0247	512
65703	1.6463	496
65655	1.5381	642
65677	0.8801	341
65681	0.7223	288

Top tissues by expression

showing 100 of 288 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
skin of hip	UBERON:0001554	99.86	gold quality
upper leg skin	UBERON:0004262	99.84	gold quality
hair follicle	UBERON:0002073	99.83	gold quality
penis	UBERON:0000989	99.80	gold quality
gingival epithelium	UBERON:0001949	99.80	gold quality
gingiva	UBERON:0001828	99.79	gold quality
cervix squamous epithelium	UBERON:0006922	99.78	gold quality
mammalian vulva	UBERON:0000997	99.77	gold quality
squamous epithelium	UBERON:0006914	99.76	gold quality
upper arm skin	UBERON:0004263	99.75	gold quality
esophagus squamous epithelium	UBERON:0006920	99.73	gold quality
oral cavity	UBERON:0000167	99.72	gold quality
tongue squamous epithelium	UBERON:0006919	99.70	gold quality
nipple	UBERON:0002030	99.68	gold quality
pharyngeal mucosa	UBERON:0000355	99.63	gold quality
cervix epithelium	UBERON:0004801	99.53	gold quality
skin of abdomen	UBERON:0001416	99.39	gold quality
epithelium of nasopharynx	UBERON:0001951	99.36	gold quality
zone of skin	UBERON:0000014	99.34	gold quality
body of tongue	UBERON:0011876	99.29	gold quality
heart right ventricle	UBERON:0002080	99.19	gold quality
jejunal mucosa	UBERON:0000399	99.18	gold quality
skin of leg	UBERON:0001511	99.16	gold quality
left ventricle myocardium	UBERON:0006566	99.01	gold quality
lower esophagus mucosa	UBERON:0035834	98.93	gold quality
epithelium of esophagus	UBERON:0001976	98.83	gold quality
tongue	UBERON:0001723	98.81	gold quality
myocardium	UBERON:0002349	98.76	gold quality
esophagus mucosa	UBERON:0002469	98.76	gold quality
cardiac muscle of right atrium	UBERON:0003379	98.63	gold quality
mucosa of sigmoid colon	UBERON:0004993	98.60	gold quality
palpebral conjunctiva	UBERON:0001812	98.55	gold quality
colonic mucosa	UBERON:0000317	98.40	gold quality
corpus epididymis	UBERON:0004359	98.22	gold quality
nasal cavity epithelium	UBERON:0005384	98.22	gold quality
parotid gland	UBERON:0001831	98.09	gold quality
superior surface of tongue	UBERON:0007371	97.96	gold quality
epithelium of mammary gland	UBERON:0003244	97.92	gold quality
amniotic fluid	UBERON:0000173	97.88	gold quality
mammary duct	UBERON:0001765	97.86	gold quality
tonsil	UBERON:0002372	97.84	gold quality
bronchial epithelial cell	CL:0002328	97.70	gold quality
ileal mucosa	UBERON:0000331	97.69	gold quality
islet of Langerhans	UBERON:0000006	97.61	gold quality
epithelium of bronchus	UBERON:0002031	97.61	gold quality
bronchus	UBERON:0002185	97.54	gold quality
germinal epithelium of ovary	UBERON:0001304	97.48	gold quality
duodenum	UBERON:0002114	97.06	gold quality
placenta	UBERON:0001987	96.97	gold quality
endometrium epithelium	UBERON:0004811	96.85	gold quality
nasal cavity mucosa	UBERON:0001826	96.75	gold quality
oviduct epithelium	UBERON:0004804	96.69	gold quality
caput epididymis	UBERON:0004358	96.59	gold quality
trachea	UBERON:0003126	96.44	gold quality
pancreas	UBERON:0001264	96.30	gold quality
body of pancreas	UBERON:0001150	95.86	gold quality
urethra	UBERON:0000057	95.57	gold quality
cardiac ventricle	UBERON:0002082	95.47	gold quality
nephron tubule	UBERON:0001231	95.36	gold quality
heart left ventricle	UBERON:0002084	95.36	gold quality
thymus	UBERON:0002370	95.34	gold quality
epithelial cell of pancreas	CL:0000083	95.20	gold quality
mouth mucosa	UBERON:0003729	95.10	gold quality
mucosa of paranasal sinus	UBERON:0005030	94.99	gold quality
saliva-secreting gland	UBERON:0001044	94.89	gold quality
vena cava	UBERON:0004087	94.88	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	94.86	gold quality
minor salivary gland	UBERON:0001830	94.39	gold quality
rectum	UBERON:0001052	94.38	gold quality
cardiac atrium	UBERON:0002081	94.31	gold quality
pigmented layer of retina	UBERON:0001782	94.10	gold quality
choroid plexus epithelium	UBERON:0003911	93.97	gold quality
right atrium auricular region	UBERON:0006631	93.90	gold quality
vagina	UBERON:0000996	93.75	gold quality
seminal vesicle	UBERON:0000998	93.36	gold quality
cauda epididymis	UBERON:0004360	93.21	gold quality
renal medulla	UBERON:0000362	92.98	gold quality
apex of heart	UBERON:0002098	92.76	gold quality
mammary gland	UBERON:0001911	92.70	gold quality
thoracic mammary gland	UBERON:0005200	92.69	gold quality
periodontal ligament	UBERON:0008266	92.65	gold quality
heart	UBERON:0000948	92.42	gold quality
liver	UBERON:0002107	92.14	gold quality
type B pancreatic cell	CL:0000169	92.08	gold quality
kidney epithelium	UBERON:0004819	91.68	gold quality
mucosa of transverse colon	UBERON:0004991	91.66	gold quality
parietal pleura	UBERON:0002400	91.63	gold quality
pylorus	UBERON:0001166	91.53	gold quality
stromal cell of endometrium	CL:0002255	91.46	gold quality
pleura	UBERON:0000977	90.80	gold quality
visceral pleura	UBERON:0002401	90.30	gold quality
fallopian tube	UBERON:0003889	90.28	gold quality
thyroid gland	UBERON:0002046	89.73	gold quality
pancreatic ductal cell	CL:0002079	89.70	gold quality
kidney	UBERON:0002113	89.67	gold quality
endometrium	UBERON:0001295	89.29	gold quality
left lobe of thyroid gland	UBERON:0001120	89.12	gold quality
adult mammalian kidney	UBERON:0000082	88.75	gold quality
right lobe of thyroid gland	UBERON:0001119	88.73	gold quality
right lobe of liver	UBERON:0001114	88.64	gold quality

Single-cell (SCXA)

Detected in 17 experiment(s), a significant marker in 15.

Experiment	Marker?	Max mean expression
E-MTAB-8142	yes	2121.08
E-HCAD-23	yes	1248.30
E-CURD-79	yes	884.17
E-MTAB-10662	yes	425.70
E-HCAD-1	yes	285.73
E-GEOD-124472	yes	217.11
E-MTAB-6701	yes	119.83
E-CURD-114	yes	56.30
E-MTAB-10287	yes	44.82
E-HCAD-31	yes	26.63
E-HCAD-10	yes	25.26
E-MTAB-6678	yes	16.98
E-MTAB-9388	yes	7.82
E-GEOD-130148	yes	5.23
E-MTAB-10596	no	3981.02

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 78 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Skin 1	tissue	807.7	medium
Esophagus	tissue	294.2	medium
Vagina	tissue	274.5	high
Pancreas	tissue	105.4	low
Tonsil	tissue	73.9	medium
Breast	tissue	61.8	not detected
Heart muscle	tissue	61.0	high
Placenta	tissue	59.8	low
Parathyroid gland	tissue	51.7	not detected
Duodenum	tissue	49.3	low
Salivary gland	tissue	48.0	low
Stomach 1	tissue	45.7	low
Colon	tissue	43.2	not detected
Choroid plexus	tissue	42.3
Rectum	tissue	40.7	low
Small intestine	tissue	39.9	not detected
Liver	tissue	39.2	not detected
Thyroid gland	tissue	38.9	not detected
Thymus	tissue	34.6
Prostate	tissue	28.2	not detected
Epididymis	tissue	26.2	not detected
Superior colliculi	tissue	22.1
Kidney	tissue	20.9	not detected
Retina	tissue	19.7
Cervix	tissue	16.4	not detected
Fallopian tube	tissue	15.4	not detected
Spinal cord	tissue	12.7
Urinary bladder	tissue	12.3	low
Seminal vesicle	tissue	11.0	not detected
Pituitary gland	tissue	8.3
Gallbladder	tissue	7.3	low
Appendix	tissue	6.6	not detected
Adrenal gland	tissue	6.2	not detected
Lung	tissue	5.7	not detected
Endometrium 1	tissue	5.1	not detected
Periaqueductal gray	tissue	5.0
Hippocampus	tissue	4.9	not detected
Substantia nigra	tissue	3.9
Medulla oblongata	tissue	3.7
Lymph node	tissue	3.5	not detected
Skeletal muscle	tissue	3.2	not detected
Nucleus accumbens	tissue	3.2
Spleen	tissue	3.0	not detected
Smooth muscle	tissue	2.7	not detected
Hippocampal formation	tissue	2.7
Thalamus	tissue	2.3
Adipose tissue	tissue	2.1	not detected
Pons	tissue	2.0
Locus coeruleus	tissue	1.8
Entorhinal cortex	tissue	1.8
Postcentral gyrus	tissue	1.7
Ovary	tissue	1.6	low
Hypothalamus	tissue	1.5
Testis	tissue	1.4	not detected
Midbrain	tissue	1.1
Septum	tissue	1.0
Olfactory bulb	tissue	0.9
Cerebral cortex	tissue	0.7	not detected
Motor cortex	tissue	0.7
Temporal cortex	tissue	0.7

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Dorsal spinal cord (12.7), Corticomedial amygdala (9.5), Basal amygdala (8.1), Anterior insular cortex, dorsal (8.0), Hippocampus, CA3 (7.9).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTNNB1, LEF1, PKP1, PKP3, SATB1, TCF12

miRNA regulators (miRDB)

Targeting DSP by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 65 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488

Functional genomics

gnomAD constraint: pLI 1, LOEUF 0.443, missense Z 2.65 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000379802 splits into 5 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
6:7,541,916–7,570,467	646 / 684.3	0.94	no
6:7,570,468–7,571,855	81 / 130.5	0.62	no
6:7,571,856–7,583,869	1714 / 1844.5	0.93	no
6:7,583,870–7,584,566	207 / 281.2	0.74	no
6:7,584,567–7,585,875	582 / 555.4	1.05	no
ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• Compound heterozygosity for non-sense and mis-sense mutations in desmoplakin underlies skin fragility/woolly hair syndrome. haploinsufficiency (PMID:11841538)
• non-small cell lung carcinoma subtypes have specific patterns of desmoplakin 1 and 2 and cytokeratin 18 gene expression, protein content and biodistribution (PMID:11955647)
• Mutation (S299R) in exon 7 of desmoplakin causes arrhythmogenic right ventricular cardiomyopathy, unlinked to other causes. (PMID:12373648)
• desmoplakin has a role in capillary formation (PMID:15190119)
• terminal tail is responsible for discerning among binding of factors to the armadillo domain (PMID:15381698)
• Naxos disease is not caused by the desmoplakin gene mutation in an arab family. (PMID:15494820)
• the involvement of desmoplakin (DP), plectin, and periplakin in the destruction of epithelial cell integrity ensures the efficient elimination of cytoskeleton, but also provides specificity for selectively targeting individual adhesion molecules (PMID:15500642)
• dominant mutation in desmoplakin that causes left-sided arrhythmogenic left ventricular cardiomyopathywith arrhythmias of left ventricular origin. (PMID:16061754)
• dramatic phenotype, which we named “lethal acantholytic epidermolysis bullosa,” underscores the paramount role of desmoplakin in epidermal integrity (PMID:16175511)
• Our data are consistent with the idea that DP assembles into nascent junctions from both diffusible and particulate pools in a temporally overlapping series of events triggered by cell-cell contact and regulated by actin and DP-IF interactions. (PMID:16365169)
• This is the first description of a phenotype caused by a mutation affecting only one DSP isoform. (PMID:16467215)
• A novel insertion mutation in desmoplakin is associated with early death from cardiomyopathy in a family with dominant striate palmoplantar keratoderma and wooly hair. (PMID:16628197)
• Mutation analysis of 66 arrhythmogenic right ventricular dysplasia/cardiomyopathy patients identified 4 variants in DSP; V30M, Q90R, W233X, and R2834H. A cause and effect relationship between those DSP missense mutations and ARVD/C was extablished. (PMID:16917092)
• Dp may participate in the regulation of keratinocyte cell proliferation by, in part at least, regulating cell cycle progression (PMID:17475244)
• The Ki67+ proliferation index was inversely correlated with desmoplakin and plakophilin-1 during cervical squamous cell carcinogenesis (PMID:17593084)
• Mutations in the desmosome genes were identified in four of the five patients (three with a DSG2 mutation and one with a DSP mutation). Five gene mutations were noted in four patients and all mutations were novel (one patient had a DSG2 double mutation). (PMID:18632414)
• Loss-of-function mutations in the DSP gene can result in a phenotype similar to ectodermal dysplasia-skin fragility syndrome resulting from PKP1 mutations but only DSP pathology is associated with cardiac disease (PMID:19016709)
• Three proteins were significantly elevated in PTB cases: desmoplakin isoform 1, stratifin, and thrombospondin 1 precursor, providing a foundation for further validation in larger patient cohorts. (PMID:19271751)
• Altered DSP expression at transcriptional and protein levels provides prognostic information in human oropharyngeal cancer. (PMID:19386346)
• we describe a combination of DP mutation phenotypes affecting the skin, heart, hair, and teeth (PMID:19924139)
• Lethal acantholytic epidermolysis bullosa (LAEB) is an autosomal recessive disorder caused by mutations in the gene encoding the desmosomal protein, desmoplakin (DSP) (PMID:19945626)
• A novel minor isoform of desmoplakin that is also produced by alternative splicing of the desmoplakin gene, is described. (PMID:20524011)
• Full sequencing of the DSP showed a novel homozygous c.7097 G>A (p.R2366H) mutation in all skin fragility-woolly hair syndrome affected family members. (PMID:20738328)
• Studies identified two mutations in DSG2, four in DSC2, two in DSP, four in JUP and seven in PKP2. (PMID:20864495)
• autosomal-dominant mutations in the DSP gene are associated with hypo/oligodontia in the setting of Carvajal/Naxos syndrome (PMID:20940358)
• SERCA2-deficient cells exhibited up to a 60% reduction in border translocation of desmoplakin (DP), the desmosomal cytolinker protein necessary for intermediate filament (IF) anchorage to sites of robust cell-cell adhesion (PMID:21156808)
• We detected a novel mutations: DSP T1373A and it may be associated with a risk for tachycardia (PMID:21397041)
• A novel nonsense mutation in the desmoplakin gene and the truncated protein which it produces caused left dominant arrhythmogenic cardiomyopathy (PMID:21458130)
• intimate intramolecular association of the SH3 domain with the preceding SR is also observed in plectin, another plakin protein suggesting that the SH3 domain of plakins contributes to the stability and rigidity of this subfamily of SR-containing proteins (PMID:21536047)
• Mutations in desmoplakin protein is associated with cardiomyopathy. (PMID:21756917)
• Case Report: desmoplakin mutation responsible for juvenile biventricular cardiomyopathy with left ventricular non-compaction and acantholytic palmoplantar keratoderma. (PMID:21789513)
• DP Ser2849Gly promotes hyperadhesion (PMID:21993560)
• Palmitate significantly reduces DSP expression, and treatment with insulin restores the lost expression of DSP. (PMID:22132232)
• desmoplakin is a promising candidate for supportive CSF marker to rule out 14-3-3 false positive cases in sporadic Creutzfeldt-Jakob disease differential diagnosis. (PMID:22213780)
• Desmoplakin disease causes connexin mislocalization in the mouse & man preceding overt histological abnormalities resulting in significant alterations in conduction repolarization kinetics prior to morphological changes detectable on cardiac imaging (PMID:22240500)
• desmoplakin I levels, determined within 1-3 months of the first ischemic stroke, could be a biomarker for statin responsiveness against a new vascular event in post-ischemic stroke patients taking statins (PMID:22304020)
• DSP splice variant is crucial for desmosome-mediated adhesion in HaCaT keratinocytes. (PMID:22454510)
• DSP is inactivated in lung cancer by an epigenetic mechanism, increases the sensitivity to anticancer drug-induced apoptosis and has tumor-suppressive function, possibly through inhibition of the Wnt/beta-catenin signaling pathway in NSCLC cells. (PMID:22791817)
• Desmoplakin and pGSK3beta constitute independent good prognostic factors for progression free survival in Ewing Sarcoma patients. (PMID:22898789)
• In two unrelated patients with Naxos-Carvajal syndrome, a single heterozygous de novo mutation in the desmoplakin gene DSP, p.Leu583Pro and p.Thr564Ile, leading to severe phenotypes was found. (PMID:22949226)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	eppk1	ENSDARG00000096359
mus_musculus	Dsp	ENSMUSG00000054889
rattus_norvegicus	Dsp	ENSRNOG00000013928

Paralogs (36): SYNE2 (ENSG00000054654), SPTB (ENSG00000070182), ACTN1 (ENSG00000072110), ACTN2 (ENSG00000077522), DRP2 (ENSG00000102385), SPTBN1 (ENSG00000115306), MACF1 (ENSG00000127603), FLNC (ENSG00000128591), ACTN4 (ENSG00000130402), SYNE1 (ENSG00000131018), MICAL2 (ENSG00000133816), DTNA (ENSG00000134769), MICAL1 (ENSG00000135596), FLNB (ENSG00000136068), SPTBN5 (ENSG00000137877), DTNB (ENSG00000138101), GAS2L3 (ENSG00000139354), DST (ENSG00000151914), UTRN (ENSG00000152818), SPTBN4 (ENSG00000160460), SPTA1 (ENSG00000163554), CLMN (ENSG00000165959), PKHD1 (ENSG00000170927), SPTBN2 (ENSG00000173898), SYNE3 (ENSG00000176438), PLEC (ENSG00000178209), SMTNL2 (ENSG00000188176), FLNA (ENSG00000196924), SPTAN1 (ENSG00000197694), DMD (ENSG00000198947), PKHD1L1 (ENSG00000205038), DYTN (ENSG00000232125), MICAL3 (ENSG00000243156), ACTN3 (ENSG00000248746), EPPK1 (ENSG00000261150), GAS2L2 (ENSG00000270765)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:109611) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 67 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal heart morphology	2
ruffled hair	2
abnormal epidermal layer morphology	2
cardiac fibrosis	2
prolonged QRS complex duration	2
enlarged heart	1
abnormal myocardial fiber morphology	1
sparse hair	1
enlarged lymph nodes	1
abnormal epidermis stratum basale morphology	1
abnormal epidermis stratum spinosum morphology	1
disheveled coat	1
abnormal ectoderm development	1
abnormal endoderm development	1
decreased embryo size	1
abnormal embryo turning	1
abnormal placenta morphology	1
acanthosis	1
abnormal hair texture	1
premature death	1
abnormal embryonic tissue morphology	1
abnormal neural tube morphology	1
abnormal lymph node morphology	1
impaired ability to fire action potentials	1
abnormal sciatic nerve morphology	1

+42 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Cricetulus griseus	Q9JI55	94.7%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
SNRNP48	protein-coding	154007
DSP-AS1	ncRNA	101928076
BLOC1S5-TXNDC5	ncRNA	100526836
BMP6	protein-coding	654
TXNDC5	protein-coding	81567

Protein

Protein identifiers

Desmoplakin — P15924 (reviewed: P15924)

Alternative names: 250/210 kDa paraneoplastic pemphigus antigen

All UniProt accessions (10): A0A804HL18, A0AAQ5BH17, A0AAQ5BH21, A0AAQ5BH40, A0AAQ5BH43, A0AAQ5BH50, A0AAQ5BH53, A0AAQ5BH65, A0AAQ5BH69, P15924

UniProt curated annotations — full annotation on UniProt →

Function. A component of desmosome cell-cell junctions which are required for positive regulation of cellular adhesion. Critical for cell-cell adhesion in early stage blastocysts and progression through proamniotic cavity formation. Not required for preimplantation morphogenic process in blastocysts. Required for keratin filament anchoring at the desmosome junction and subsequent organization of the keratin intermediate filament network within the cytoplasm. Required for anchoring of desmosomes to the microtubule architecture, via its interaction with NIN. Promotes microtubule-mediated GJA1/CX43 trafficking to cell membranes via its interaction with MAPRE1/EB1, thereby facilitating gap junction intracellular communication. Plays a key role in adhesion and organization of the dermal epithelial barrier. Critical for the maintenance of the neural tube structure following formation and organization of the neuroepithelium. Facilitates outgrowth and repair of motor neuron fibers in regenerating axons following injury, probably by promoting recruitment of a complex containing DSP, CDH2, VIM and JUP to the outgrowth tips. Critical for the normal formation of heart and myocardial tissue during early embryogenesis. Also required for development of vascular capillary structures and intact endothelial cell barriers. Regulates profibrotic gene expression in cardiomyocytes via activation of the MAPK14/p38 MAPK signaling cascade and increase in TGFB1 protein abundance. Maintains cardiac rhythmicity by ensuring correct cell-cell adhesion within the sinoatrial node, via stabilization of protein components of both desmosome and Gap junctions. Involved in maintaining the protein stability and recruitment of GJA1 to functional gap junctions, via inhibition of KRAS-mediated MAPK1/MAPK3 phosphorylation of GJA1. Negative regulator of cell cycle progression and differentiation in keratinocytes, potentially via inhibition of MAPK and phosphoinositide-3-kinase (PI3K) signaling pathways. Mediates the interaction between the desmosome and COP9 signalosome complex (CSN) protein complex. As a result of this interaction, promotes keratinocyte differentiation via deneddylation of EGFR resulting in a reduction in EGFR protein stabilization and translocation away from the cell membrane. Required for the maintenance of protein abundance of desmosome junction components DSG1, DSG2, DSC2, DSC3, PKP1, PKP2 and PKP3. Required for the survival and maintenance of germ cells in the gonads during embryonic development. Binds to telomere DNA (via C-terminus) and acts to prevent telomere damage and maintain telomere length via its interaction with TRF2.

Subunit / interactions. Homodimer. Identified in a complex containing at least DSP, JUP, VIM and CDH2; the complex is more abundant following crush injury in regenerating motor neurons and may promote axon outgrowth and motor fiber repair. Interacts with COL17A1 (via cytoplasmic region). Interacts with DSC2. Interacts with PKP2. Interacts (via head domain) with PKP1. Interacts weakly with TMEM65. Interacts with NIN: the interaction facilitates recruitment of NIN to desmosome cell-cell junctions. Interacts with TRF2 in the nucleus; the interaction is required for DSP telomere binding. Interacts (via N-terminus) with MAPRE1/EB1; the interaction stabilizes microtubules at cell-cell contacts and facilitates GJA1 trafficking to gap junctions. Interacts with JUP. Interacts with intermediate filament proteins. Interacts (via C-terminus) with COPS3; facilitates the interaction between the desmosome and the COP9 signalosome complex (CSN), the interaction acts to mediate EGFR signaling and keratinocyte differentiation.

Subcellular location. Cell projection. Axon. Cell junction. Desmosome. Cell membrane. Cytoplasm. Nucleus.

Tissue specificity. Expressed in oral mucosa (at protein level). Expressed in arrector pili muscle (at protein level). Expressed in the heart (at protein level). Expressed in keratinocytes of the skin (at protein level). Apparently an obligate constituent of all desmosomes. Resides predominantly in tissues and cells of stratified origin.

Post-translational modifications. Methylation by PRMT1 promotes GSK3B-mediated phosphorylation cascade of multiple serine residues at the C-terminus resulting in trafficking to desmosome cell-cell junctions. Phosphorylation by GSK3B occurs sequentially from Ser-2849 along multiple serine residue at the C-terminus. Hyperphosphorylation by GSK3B results in recruitment to desmosome cell-cell junction and promotion of intercellular adhesion. Phosphorylation at Ser-2849 increases association with intermediate filament cytokeratin, potentially facilitating interaction between desmosome junctions and intermediate filament architecture.

Disease relevance. Keratoderma, palmoplantar, striate 2 (SPPK2) [MIM:612908] A dermatological disorder characterized by thickening of the skin on the palms (linear pattern) and the soles (island-like pattern) and flexor aspect of the fingers. Abnormalities of the nails, the teeth and the hair are rarely present. The disease is caused by variants affecting the gene represented in this entry. Cardiomyopathy, dilated, with woolly hair and keratoderma (DCWHK) [MIM:605676] An autosomal recessive cardiocutaneous syndrome characterized by a generalized striate keratoderma particularly affecting the palmoplantar epidermis, woolly hair, and dilated left ventricular cardiomyopathy. The disease is caused by variants affecting the gene represented in this entry. Arrhythmogenic right ventricular dysplasia, familial, 8 (ARVD8) [MIM:607450] A congenital heart disease characterized by infiltration of adipose and fibrous tissue into the right ventricle and loss of myocardial cells, resulting in ventricular and supraventricular arrhythmias. The disease is caused by variants affecting the gene represented in this entry. Epidermolysis bullosa, lethal acantholytic (EBLA) [MIM:609638] A form of epidermolysis bullosa characterized by severe fragility of skin and mucous membranes. The phenotype is lethal in the neonatal period because of immense transcutaneous fluid loss. Typical features include universal alopecia, neonatal teeth, and nail loss. Histopathology of the skin shows suprabasal clefting and acantholysis throughout the spinous layer, mimicking pemphigus. The disease is caused by variants affecting the gene represented in this entry. Erythroderma, congenital, with palmoplantar keratoderma, hypotrichosis, and hyper IgE (EPKHE) [MIM:615508] A syndrome characterized by severe dermatitis, multiple allergies and metabolic wasting. Clinical features include erythroderma, yellowish papules and plaques arranged at the periphery of the palms, along the fingers and over weight-bearing areas of the feet, skin erosions and scaling, and hypotrichosis. Additionally, patients manifest severe food allergies, elevated immunoglobulin E (IgE) levels and recurrent infections with marked metabolic wasting. The disease is caused by variants affecting the gene represented in this entry. Cardiomyopathy, dilated, with woolly hair, keratoderma, and tooth agenesis (DCWHKTA) [MIM:615821] A cardiocutaneous syndrome characterized by biventricular dilated cardiomyopathy, hyperkeratosis, woolly hair, palmoplantar keratoderma, and hypo/oligodontia. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The N-terminal region is required for localization to the desmosomal plaque and interacts with the N-terminal region of PKP1.

Miscellaneous. Minor isoform.

Similarity. Belongs to the plakin or cytolinker family.

Isoforms (3)

UniProt ID	Names	Canonical?
P15924-1	DPI, DP1	yes
P15924-2	DPII, DP2
P15924-3	DSPIa

RefSeq proteins (4): NP_001008844, NP_001305963, NP_001393520, NP_004406* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001101	Plectin_repeat	Repeat
IPR001452	SH3_domain	Domain
IPR018159	Spectrin/alpha-actinin	Repeat
IPR035915	Plakin_repeat_sf	Homologous_superfamily
IPR041573	Desmoplakin_Spectrin-like	Domain
IPR041615	Desmoplakin_SH3	Domain
IPR043197	Plakin	Family

Pfam: PF00681, PF17902, PF18373, PF21019, PF27015

UniProt features (257 total): sequence variant 63, helix 52, strand 34, modified residue 34, repeat 24, turn 20, region of interest 12, mutagenesis site 6, sequence conflict 3, compositionally biased region 3, splice variant 2, chain 1, coiled-coil region 1, short sequence motif 1, domain 1

Structure

Experimental structures (PDB)

4 structures by resolution:

PDB	Title	Method	Resolution (Å)
1LM5	Structures of two intermediate filament-binding fragments of desmoplakin reveal a unique …	X-RAY DIFFRACTION	1.8
5DZZ	Structural characterization of intermediate filaments binding domain of desmoplakin	X-RAY DIFFRACTION	2.6
3R6N	Crystal structure of a rigid four spectrin repeat fragment of the human desmoplakin …	X-RAY DIFFRACTION	2.95
1LM7	Structures of two intermediate filament-binding fragments of desmoplakin reveal a unique …	X-RAY DIFFRACTION	3

Predicted structure (AlphaFold)

No AlphaFold model available for P15924 — AlphaFold DB does not currently provide models for proteins above ~3000 aa.

Human Protein Atlas

Protein class: Transporters, Accessory Factors Involved in Transport, Predicted intracellular proteins, Plasma proteins, Disease related genes, Potential drug targets, Human disease related genes, Congenital malformations, Congenital malformations of the circulatory system, Congenital malformations of skin

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cell junctions

Antibody reliability (HPA): IH enhanced · IF supported

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 (34)

Type	Positions
Phosphoserine	22, 53, 165, 166, 176, 1658, 1708, 2024, 2207, 2209, 2225, 2810, 2815, 2820, 2821, 2825, 2833, 2835, 2837, 2839, 2841, 2843, 2845, 2849, 2868
Phosphotyrosine	56, 2817
Phosphothreonine	61, 2853
Asymmetric dimethylarginine	2826, 2834, 2838, 2846
Omega-n-methylarginine	2847

Mutagenesis-validated functional residues (6)

Position	Phenotype
470	no observable change in the secondary structure folding.
808	reduced thermal stability of protein. no observable change in secondary structure folding.
1122–1126	abolishes localization to the nucleus and binding to telomeres.
2845	abolishes gsk3b phosphorylation of multiple downstream sites within the c-terminus and decreases interaction with gsk3b.
2849	decreases cell-cell adhesion when under mechanical stress.
2853	no effect on gsk3b-mediated phosphorylation of multiple downstream sites within the c-terminus.

Function

Pathways and Gene Ontology

Reactome pathways

6 curated (TAS) of 17; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

17 pathways:

ID	Pathway	Evidence
R-HSA-351906	Apoptotic cleavage of cell adhesion proteins	curated
R-HSA-6809371	Formation of the cornified envelope	curated
R-HSA-6805567	Keratinization	curated
R-HSA-6798695	Neutrophil degranulation	curated
R-HSA-9696273	RND1 GTPase cycle	curated
R-HSA-9696264	RND3 GTPase cycle	curated
R-HSA-109581	Apoptosis	—
R-HSA-111465	Apoptotic cleavage of cellular proteins	—
R-HSA-75153	Apoptotic execution phase	—
R-HSA-1266738	Developmental Biology	—
R-HSA-168256	Immune System	—
R-HSA-168249	Innate Immune System	—
R-HSA-5357801	Programmed Cell Death	—
R-HSA-9012999	RHO GTPase cycle	—
R-HSA-162582	Signal Transduction	—
R-HSA-194315	Signaling by Rho GTPases	—
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3	—

MSigDB gene sets: 541 (showing top): BROWNE_HCMV_INFECTION_30MIN_DN, GOBP_CARDIAC_CHAMBER_DEVELOPMENT, MODULE_52, GOBP_EPITHELIUM_DEVELOPMENT, LEE_NEURAL_CREST_STEM_CELL_DN, GOBP_BUNDLE_OF_HIS_CELL_TO_PURKINJE_MYOCYTE_COMMUNICATION, BROWNE_HCMV_INFECTION_6HR_DN, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_MUSCLE_TISSUE_DEVELOPMENT, GOBP_INTERMEDIATE_FILAMENT_BASED_PROCESS, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_INTERMEDIATE_FILAMENT_ORGANIZATION, GOBP_CARDIAC_CHAMBER_MORPHOGENESIS, MIDORIKAWA_AMPLIFIED_IN_LIVER_CANCER, JAEGER_METASTASIS_DN

GO Biological Process (26): desmosome organization (GO:0002934), ventricular compact myocardium morphogenesis (GO:0003223), epidermis development (GO:0008544), peptide cross-linking (GO:0018149), keratinocyte differentiation (GO:0030216), wound healing (GO:0042060), skin development (GO:0043588), intermediate filament cytoskeleton organization (GO:0045104), intermediate filament organization (GO:0045109), bundle of His cell-Purkinje myocyte adhesion involved in cell communication (GO:0086073), regulation of heart rate by cardiac conduction (GO:0086091), epithelial cell-cell adhesion (GO:0090136), cell-cell adhesion (GO:0098609), regulation of ventricular cardiac muscle cell action potential (GO:0098911), protein localization to cell-cell junction (GO:0150105), telomere maintenance (GO:0000723), desmosome maintenance (GO:0002160), germ cell development (GO:0007281), neural tube patterning (GO:0021532), regulation of protein localization (GO:0032880), negative regulation of cell differentiation (GO:0045596), negative regulation of cell cycle (GO:0045786), protein stabilization (GO:0050821), establishment of endothelial barrier (GO:0061028), positive regulation of protein localization (GO:1903829), positive regulation of vasculogenesis (GO:2001214)

GO Molecular Function (8): DNA binding (GO:0003677), RNA binding (GO:0003723), protein kinase C binding (GO:0005080), structural molecule activity (GO:0005198), structural constituent of cytoskeleton (GO:0005200), cell adhesive protein binding involved in bundle of His cell-Purkinje myocyte communication (GO:0086083), scaffold protein binding (GO:0097110), protein binding (GO:0005515)

GO Cellular Component (16): cornified envelope (GO:0001533), nucleus (GO:0005634), cytoplasm (GO:0005737), intermediate filament (GO:0005882), plasma membrane (GO:0005886), adherens junction (GO:0005912), fascia adherens (GO:0005916), intercalated disc (GO:0014704), basolateral plasma membrane (GO:0016323), cell junction (GO:0030054), desmosome (GO:0030057), axon (GO:0030424), extracellular exosome (GO:0070062), ficolin-1-rich granule membrane (GO:0101003), cytoskeleton (GO:0005856), cell-cell junction (GO:0005911)

Reactome top-level categories

12 top-level categories:

Category	Pathways
RHO GTPase cycle	2
Apoptotic cleavage of cellular proteins	1
Innate Immune System	1
Developmental Biology	1
Keratinization	1
Programmed Cell Death	1
Apoptotic execution phase	1
Immune System	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Apoptosis	1
Signaling by Rho GTPases	1
Signal Transduction	1

GO top-level categories

showing 60 of 66 GO namespaces:

Category	Terms
cell-cell junction	3
cytoskeleton organization	2
nucleic acid binding	2
cellular anatomical structure	2
cell-cell junction organization	1
ventricular cardiac muscle tissue morphogenesis	1
tissue development	1
animal gross anatomical part developmental process	1
protein modification process	1
epidermal cell differentiation	1
skin development	1
response to wounding	1
tissue regeneration	1
animal organ development	1
intermediate filament-based process	1
intermediate filament cytoskeleton organization	1
supramolecular fiber organization	1
heterotypic cell-cell adhesion	1
cardiac muscle cell-cardiac muscle cell adhesion	1
bundle of His cell to Purkinje myocyte communication	1
regulation of heart rate	1
cardiac conduction	1
cell-cell adhesion	1
cell adhesion	1
regulation of cardiac muscle cell contraction	1
ventricular cardiac muscle cell action potential	1
regulation of cardiac muscle cell action potential	1
protein localization to cell junction	1
DNA metabolic process	1
telomere organization	1
desmosome organization	1
cell-cell junction maintenance	1
developmental process involved in reproduction	1
gamete generation	1
cellular process involved in reproduction in multicellular organism	1
cell development	1
regionalization	1
neural tube development	1
intracellular protein localization	1
regulation of localization	1
protein kinase binding	1
molecular_function	1
structural molecule activity	1
cytoskeleton	1
bundle of His cell-Purkinje myocyte adhesion involved in cell communication	1
protein binding involved in heterotypic cell-cell adhesion	1
protein binding	1
binding	1
plasma membrane	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
intermediate filament cytoskeleton	1
polymeric cytoskeletal fiber	1
membrane	1
cell periphery	1
intercalated disc	1
cell-cell contact zone	1
basal plasma membrane	1
plasma membrane region	1
neuron projection	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 16 of 50 annotations. The rest are phylogenetic / computational / electronic (IEA).

16 experimentally-supported GO terms:

GO term	NS	Evidence
bundle of His cell-Purkinje myocyte adhesion involved in cell communication	BP	mutant phenotype
epithelial cell-cell adhesion	BP	mutant phenotype
keratinocyte differentiation	BP	direct assay
peptide cross-linking	BP	direct assay
regulation of heart rate by cardiac conduction	BP	mutant phenotype
regulation of ventricular cardiac muscle cell action potential	BP	mutant phenotype
cell junction	CC	direct assay
cornified envelope	CC	direct assay
desmosome	CC	direct assay
extracellular exosome	CC	high-throughput assay
intercalated disc	CC	direct assay
nucleus	CC	high-throughput assay
plasma membrane	CC	direct assay
RNA binding	MF	high-throughput assay
protein kinase C binding	MF	physical interaction
scaffold protein binding	MF	physical interaction

Protein interactions and networks

STRING

showing 15 of 1,627 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DSP	PKP2	Q99959	970
DSP	PKP1	Q13835	935
DSP	DSG2	Q14126	929
DSP	JUP	P14923	929
DSP	DSC2	Q02487	914
DSP	DSG1	Q02413	897
DSP	DSG3	P32926	824
DSP	PKP4	Q99569	823
DSP	CDH17	Q12864	793
DSP	DSC3	Q14574	745
DSP	KRT8	P05787	743
DSP	TMEM43	Q9BTV4	716
DSP	GJA1	P17302	714
DSP	KRT18	P05783	714
DSP	DSC1	Q08554	684

IntAct

Human interaction partners of DSP in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 38 partners by confidence:

Partner	Interaction type	MIscore	Records
MAPRE1	physical association	0.630	7
JUP	physical association	0.570	3
FES	physical association	0.560	2
DSG1	direct interaction	0.440	2
PECAM1	colocalization	0.430	2
PKP2	proximity	0.430	2
PKP1	physical association	0.400	2
DSC2	physical association	0.400	1
H1-5	physical association	0.400	1
H2BC9	physical association	0.400	1
HMGA1	physical association	0.400	1
HSPA5	physical association	0.400	1
ORF17	physical association	0.400	1
YWHAZ	physical association	0.400	1
BECN1	physical association	0.370	1
CLK4	association	0.350	1
JAK1	association	0.350	1
KRT18	association	0.350	1
MTMR9	association	0.350	1
SEC22A	association	0.350	1
PKP4	colocalization	0.270	1
AKR1B1	physical association	0.000	1
DISC1	physical association	0.000	1
ENO3	physical association	0.000	1
GH1	physical association	0.000	1
IKBKE	physical association	0.000	1
MAP3K8	physical association	0.000	1
MYC	physical association	0.000	1
NFKB2	physical association	0.000	1
NFKBIB	physical association	0.000	1

BioGRID (525 interactions; top human partners by supporting records): JUP (Affinity Capture-MS; 5 records), VIM (Proximity Label-MS; 4 records), YAP1 (Affinity Capture-MS; 4 records), CUL3 (Affinity Capture-MS; 3 records), KRT1 (Co-fractionation; 3 records), KRT18 (Proximity Label-MS; 3 records), MYC (Affinity Capture-MS; 3 records), PCM1 (Affinity Capture-MS; 3 records), PKP1 (Affinity Capture-MS; 3 records), PTPRD (Affinity Capture-MS; 3 records), TRIM47 (Affinity Capture-MS; 3 records), ANLN (Affinity Capture-MS; 2 records), ARAF (Affinity Capture-MS; 2 records), BTRC (Affinity Capture-MS; 2 records), C6orf141 (Affinity Capture-MS; 2 records)

SIGNOR signaling

2 signaling interactions:

A	Effect	B	Mechanism
PRKACA	“down-regulates activity”	DSP	phosphorylation
PKP2	“up-regulates quantity by stabilization”	DSP	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 38 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
Formation of the cornified envelope	7	18.6×	3e-05
Keratinization	7	11.8×	3e-04
Cytokine Signaling in Immune system	7	8.7×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
cell-cell adhesion	7	19.2×	3e-05

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 1 cancer types — NPC.

intOGen’s role is a computational inference from cohort mutation patterns and may diverge from the gene’s curated/literature role; read it alongside the evidence above.

Genetic variants

Variant evidence for DSP: 6,156 ClinVar records (723 pathogenic / likely pathogenic); 33 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

6,156 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	512
Likely pathogenic	211
Uncertain significance	2682
Likely benign	1598
Benign	117

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 723 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
44914	NM_004415.4(DSP):c.4531C>T (p.Gln1511Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	9
199923	NM_004415.4(DSP):c.3735_3741dup (p.Asp1248fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	8
16844	NM_004415.4(DSP):c.6091_6092del (p.Leu2031fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	7
222582	NM_004415.4(DSP):c.5851C>T (p.Arg1951Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	7
1425499	NM_004415.4(DSP):c.448C>T (p.Arg150Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	7
44928	NM_004415.4(DSP):c.5428C>T (p.Gln1810Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	6
199890	NM_004415.4(DSP):c.5212C>T (p.Arg1738Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	6
44852	NM_004415.4(DSP):c.1146del (p.Phe382fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	5
451211	NM_004415.4(DSP):c.250C>T (p.Arg84Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	5
836231	NM_004415.4(DSP):c.1897C>T (p.Gln633Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	5
16837	NM_004415.4(DSP):c.7623del (p.Lys2542fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	4
264512	NM_004415.4(DSP):c.3195C>G (p.Tyr1065Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	4
405223	NM_004415.4(DSP):c.5745dup (p.Lys1916Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	4
464956	NM_004415.4(DSP):c.1060_1061del (p.Leu354fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	4
464964	NM_004415.4(DSP):c.465del (p.Ile156fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	4

Per-variant reference — Sugi Variant

Explore DSP’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 44 predictions of 1,014):

Position(s)	Effect	Δscore	Sites
6:7542086–7542087	donor_loss	1.0000	5
6:7555707	acceptor_gain	1.0000
6:7555716–7555717	acceptor_loss	1.0000	6
6:7555821–7555822	donor_loss	1.0000	3
6:7558114–7558115	acceptor_loss	1.0000	5
6:7558265–7558266	donor_loss	1.0000	4
6:7562650–7562651	acceptor_loss	1.0000	6
6:7562781–7562782	donor_loss	1.0000	5
6:7563734–7563735	acceptor_loss	1.0000	4
6:7563787–7563788	donor_loss	1.0000	5

AlphaMissense

6,100 missense substitutions predicted likely pathogenic (of 19,069 scored), across 1,810 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M316	9	0.982	0.999
M2354	9	0.894	0.993
M2278	9	0.893	0.991
M2477	9	0.874	0.991
M503	9	0.873	0.979
M284	9	0.803	0.942
H371	8	0.994	0.999
N2423	8	0.991	0.998
H2363	8	0.989	0.997
D2417	8	0.987	0.999
N375	8	0.985	0.998
D2379	8	0.984	0.998
F2416	8	0.984	0.999
H341	8	0.982	0.999
F2415	8	0.982	1.000
D2643	8	0.973	0.996
D2411	8	0.970	0.989
D2136	8	0.967	0.994
D556	8	0.962	0.991
D2521	8	0.962	0.993

HPA cancer prognostics

RNA cancer specificity: Cancer enhanced (Head and Neck Squamous Cell Carcinoma)

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	3.33e-05
Kidney Renal Clear Cell Carcinoma (validation)	favorable	0.000983

Disease associations

OMIM: gene MIM:125647 | disease phenotypes: MIM:605676, MIM:607450, MIM:615821, MIM:107970, MIM:607655, MIM:612908, MIM:609638, MIM:620415, MIM:609040, MIM:115200, MIM:604145, MIM:192500, MIM:113900

GenCC curated gene-disease

12 curated gene-disease records:

Disease	Classification	Inheritance	Records
arrhythmogenic cardiomyopathy with wooly hair and keratoderma	Definitive	Autosomal dominant	5
skin fragility-woolly hair-palmoplantar keratoderma syndrome	Definitive	Autosomal recessive	4
keratosis palmoplantaris striata 2	Definitive	Autosomal dominant	3
arrhythmogenic right ventricular dysplasia 8	Definitive	Autosomal dominant	3
lethal acantholytic epidermolysis bullosa	Strong	Autosomal recessive	4
cardiomyopathy, dilated, with wooly hair, keratoderma, and tooth agenesis	Strong	Autosomal dominant	3
neurodevelopmental disorder	Moderate	Autosomal dominant
familial isolated dilated cardiomyopathy	Supportive	Autosomal dominant
severe dermatitis-multiple allergies-metabolic wasting syndrome	Supportive	Autosomal recessive
striate palmoplantar keratoderma	Supportive	Autosomal dominant
hypertrophic cardiomyopathy	Disputed Evidence	Autosomal dominant
familial hypertrophic cardiomyopathy	Disputed Evidence	Autosomal dominant

ClinGen Gene-Disease Validity

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

2 validity classifications:

Disease	Classification	Inheritance
hypertrophic cardiomyopathy	Disputed	AD
arrhythmogenic cardiomyopathy with wooly hair and keratoderma	Definitive	AD

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (14 panels, 14 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

14 panels:

Panel	Rating
Arrhythmogenic right ventricular cardiomyopathy	green
DDG2P	green
Dilated Cardiomyopathy and conduction defects	green
Dilated and arrhythmogenic cardiomyopathy	green
Epidermolysis bullosa	green
Epidermolysis bullosa and congenital skin fragility	green
Fetal anomalies	green
Ichthyosis and erythrokeratoderma	green
Paediatric disorders	green
Paediatric or syndromic cardiomyopathy	green
Palmoplantar keratoderma and erythrokeratodermas	green
Palmoplantar keratodermas	green
Sudden unexplained death or survivors of a cardiac event	green
Unexplained death in infancy and sudden unexplained death in childhood	green

Mondo (27): arrhythmogenic cardiomyopathy with wooly hair and keratoderma (MONDO:0011581), arrhythmogenic right ventricular dysplasia 8 (MONDO:0011831), cardiomyopathy, dilated, with wooly hair, keratoderma, and tooth agenesis (MONDO:0014355), familial isolated arrhythmogenic right ventricular dysplasia (MONDO:0016342), cardiomyopathy (MONDO:0004994), ventricular tachycardia (MONDO:0005477), skin fragility-woolly hair-palmoplantar keratoderma syndrome (MONDO:0011882), arrhythmogenic right ventricular cardiomyopathy (MONDO:0016587), dilated cardiomyopathy (MONDO:0005021), myocarditis (MONDO:0004496), keratosis palmoplantaris striata 2 (MONDO:0013034), lethal acantholytic epidermolysis bullosa (MONDO:0012323), woolly hair-skin fragility syndrome (MONDO:0957307), arrhythmogenic right ventricular dysplasia 9 (MONDO:0012180), dilated cardiomyopathy 1A (MONDO:0007269), cardiac rhythm disease (MONDO:0007263), dilated cardiomyopathy 1G (MONDO:0011400), ventricular fibrillation (MONDO:0000190), long QT syndrome 1 (MONDO:0100316), non-compaction cardiomyopathy (MONDO:0005418), progressive familial heart block (MONDO:0019490), hypertrophic cardiomyopathy (MONDO:0005045), (MONDO:0015470), severe dermatitis-multiple allergies-metabolic wasting syndrome (MONDO:0014218), striate palmoplantar keratoderma (MONDO:0018865), familial hypertrophic cardiomyopathy (MONDO:0024573), neurodevelopmental disorder (MONDO:0700092)

Orphanet (13): Inherited isolated arrhythmogenic cardiomyopathy (Orphanet:217656), Erythrokeratodermia-cardiomyopathy syndrome (Orphanet:476096), Carvajal syndrome (Orphanet:65282), Rare cardiomyopathy (Orphanet:167848), Skin fragility-woolly hair-palmoplantar keratoderma syndrome (Orphanet:293165), Inherited arrhythmogenic cardiomyopathy (Orphanet:247), Dilated cardiomyopathy (Orphanet:217604), Lethal acantholytic erosive disorder (Orphanet:158687), Familial dilated cardiomyopathy with conduction defect due to LMNA mutation (Orphanet:300751), Familial isolated dilated cardiomyopathy (Orphanet:154), Romano-Ward syndrome (Orphanet:101016), Congenital long QT syndrome (Orphanet:768), Hereditary progressive cardiac conduction defect (Orphanet:871)

HPO phenotypes

showing 60 of 110 phenotypes (HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000164	Abnormality of the dentition
HP:0000175	Cleft palate
HP:0000377	Abnormal pinna morphology
HP:0000407	Sensorineural hearing impairment
HP:0000561	Absent eyelashes
HP:0000653	Sparse eyelashes
HP:0000695	Natal tooth
HP:0000924	Abnormality of the skeletal system
HP:0000962	Hyperkeratosis
HP:0000969	Edema
HP:0000972	Palmoplantar hyperkeratosis
HP:0000982	Palmoplantar keratoderma
HP:0000989	Pruritus
HP:0001030	Fragile skin
HP:0001036	Parakeratosis
HP:0001057	Aplasia cutis congenita
HP:0001063	Acrocyanosis
HP:0001159	Syndactyly
HP:0001233	2-3 finger cutaneous syndactyly
HP:0001279	Syncope
HP:0001508	Failure to thrive
HP:0001511	Intrauterine growth retardation
HP:0001562	Oligohydramnios
HP:0001595	Abnormal hair morphology
HP:0001596	Alopecia
HP:0001597	Abnormal nail morphology
HP:0001626	Abnormality of the cardiovascular system
HP:0001635	Congestive heart failure
HP:0001638	Cardiomyopathy
HP:0001640	Cardiomegaly
HP:0001644	Dilated cardiomyopathy
HP:0001645	Sudden cardiac death
HP:0001663	Ventricular fibrillation
HP:0001727	Thromboembolic stroke
HP:0001798	Anonychia
HP:0001802	Absent toenail
HP:0001808	Fragile nails
HP:0001817	Absent fingernail
HP:0001820	Leukonychia
HP:0001836	Camptodactyly of toe
HP:0001852	Sandal gap
HP:0002020	Gastroesophageal reflux
HP:0002110	Bronchiectasis
HP:0002206	Pulmonary fibrosis
HP:0002223	Absent eyebrow
HP:0002224	Woolly hair
HP:0002289	Alopecia universalis
HP:0002298	Absent hair
HP:0002875	Exertional dyspnea
HP:0002878	Respiratory failure
HP:0003198	Myopathy
HP:0003457	EMG abnormality
HP:0003546	Exercise intolerance
HP:0003577	Congenital onset
HP:0003621	Juvenile onset
HP:0003811	Neonatal death
HP:0004057	Mitten deformity
HP:0004209	Clinodactyly of the 5th finger

GWAS associations

showing 30 of 33 associations:

Study	Trait	p-value
GCST009758_16	Idiopathic pulmonary fibrosis	3e-30
GCST004986_3	Idiopathic pulmonary fibrosis	8e-28
GCST007431_84	Lung function (FEV1/FVC)	7e-23
GCST001968_3	Interstitial lung disease	1e-19
GCST010321_182	PR interval	3e-16
GCST010320_37	PR interval	1e-15
GCST010796_4378	Electrocardiogram morphology (amplitude at temporal datapoints)	5e-10
GCST010796_4380	Electrocardiogram morphology (amplitude at temporal datapoints)	5e-10
GCST010796_4382	Electrocardiogram morphology (amplitude at temporal datapoints)	6e-10
GCST010796_4379	Electrocardiogram morphology (amplitude at temporal datapoints)	7e-10
GCST010796_4381	Electrocardiogram morphology (amplitude at temporal datapoints)	7e-10
GCST010796_4385	Electrocardiogram morphology (amplitude at temporal datapoints)	9e-10
GCST010796_4386	Electrocardiogram morphology (amplitude at temporal datapoints)	9e-10
GCST010796_4387	Electrocardiogram morphology (amplitude at temporal datapoints)	9e-10
GCST010796_4383	Electrocardiogram morphology (amplitude at temporal datapoints)	1e-9
GCST010796_4384	Electrocardiogram morphology (amplitude at temporal datapoints)	1e-9
GCST010796_4388	Electrocardiogram morphology (amplitude at temporal datapoints)	1e-9
GCST004147_22	Chronic obstructive pulmonary disease	4e-9
GCST010796_4389	Electrocardiogram morphology (amplitude at temporal datapoints)	9e-9
GCST010796_4397	Electrocardiogram morphology (amplitude at temporal datapoints)	9e-9
GCST010796_4391	Electrocardiogram morphology (amplitude at temporal datapoints)	1e-8
GCST010796_894	Electrocardiogram morphology (amplitude at temporal datapoints)	1e-8
GCST007429_138	Lung function (FVC)	2e-8
GCST010796_4394	Electrocardiogram morphology (amplitude at temporal datapoints)	2e-8
GCST010796_4396	Electrocardiogram morphology (amplitude at temporal datapoints)	2e-8
GCST010796_4398	Electrocardiogram morphology (amplitude at temporal datapoints)	2e-8
GCST010796_4392	Electrocardiogram morphology (amplitude at temporal datapoints)	3e-8
GCST010796_4393	Electrocardiogram morphology (amplitude at temporal datapoints)	3e-8
GCST010796_4395	Electrocardiogram morphology (amplitude at temporal datapoints)	3e-8
GCST003818_17	Resting heart rate	2e-7

EFO canonical traits (from GWAS)

7 canonical traits:

EFO ID	Trait name
EFO:0007681	triglyceride change measurement
EFO:0000768	idiopathic pulmonary fibrosis
EFO:0004312	vital capacity
EFO:0004713	FEV/FVC ratio
EFO:0008354	cognitive function measurement
EFO:0004462	PR interval
EFO:0004327	electrocardiography

MeSH disease descriptors

16 disease descriptors:

Descriptor	Name	Tree numbers
D019571	Arrhythmogenic Right Ventricular Dysplasia	C14.240.400.145; C14.280.238.028; C14.280.400.145; C16.131.240.400.145
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
D009205	Myocarditis	C14.280.238.625
D065886	Neurodevelopmental Disorders	F03.625
D017180	Tachycardia, Ventricular	C14.280.067.845.940; C14.280.123.875.940; C23.550.073.845.940
D014693	Ventricular Fibrillation	C14.280.067.922; C23.550.073.922
C564400	Arrhythmogenic Right Ventricular Dysplasia, Familial, 8 *(supp.)*
C563808	Arrhythmogenic Right Ventricular Dysplasia, Familial, 9 *(supp.)*
C535581	Cardiomyopathy dilated with woolly hair and keratoderma *(supp.)*
C565824	Cardiomyopathy, Dilated, 1g *(supp.)*
C535493	Epidermolysis bullosa, lethal acantholytic *(supp.)*
C565102	Keratosis Palmoplantaris Striata II *(supp.)*
C564359	Skin Fragility-Woolly Hair Syndrome *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL4742273 (PROTEIN-PROTEIN INTERACTION), CHEMBL6066953 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

PharmGKB variant annotations

Per-publication pharmacogenomic findings for this gene (significant associations).

1 published findings:

Variant	Drug(s)	Category	Finding	PMID
rs2076295	nintedanib	Efficacy	Genotype TT is associated with decreased overall survival when treated with nintedanib in people with Pulmonary Fibrosis as compared to genotypes GG + GT.	PMID:34515605

Binding affinities (BindingDB)

1 measured of 1 human assays (2 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL5653589	KD	1440 nM

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
6.54	Kd	287.7	nM	CHEMBL5653589
6.54	ED50	287.7	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 5 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	2148265: Binding affinity to human DSP incubated for 45 mins by Kinobead based pull down assay	kd	0.2877	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, decreases expression	7
trichostatin A	affects cotreatment, increases expression	4
sodium arsenite	decreases reaction, decreases expression, affects methylation, affects binding	4
Benzo(a)pyrene	affects methylation, decreases expression, increases expression, increases methylation	4
bisphenol A	decreases expression, increases expression	3
methylmercuric chloride	decreases expression	2
mercuric bromide	increases expression, affects cotreatment	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	2
Cadmium	affects binding, decreases reaction, increases abundance, increases palmitoylation	2
Doxorubicin	increases expression, affects response to substance	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tetrachlorodibenzodioxin	increases expression	2
Tobacco Smoke Pollution	affects expression, decreases expression	2
Cadmium Chloride	decreases reaction, increases abundance, increases palmitoylation, decreases expression	2
Particulate Matter	decreases expression, increases abundance, affects cotreatment, increases expression	2
GSK-J4	increases expression	1
FR900359	increases phosphorylation	1
dicrotophos	increases expression	1
lead acetate	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects localization, decreases expression, increases expression, affects cotreatment	1
IMOL S-140	increases expression	1
butyraldehyde	decreases expression	1
16 alpha-ethyl-21-hydroxy-19-nor-4-pregnene-3,20-dione	increases expression	1
2-bromopalmitate	decreases reaction, increases abundance, increases palmitoylation	1
potassium chromate(VI)	decreases expression	1
cupric chloride	decreases expression	1
coumarin	decreases phosphorylation	1
triadimefon	decreases expression	1
artenimol	affects binding	1
S-(1,2-dichlorovinyl)cysteine	decreases reaction, increases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4713764	Binding	Protac activity at CRBN/DSP in human BxPC-3 cells assessed as DSP degradation incubated for 16 hrs by proteomic analysis	Discovery of a Napabucasin PROTAC as an Effective Degrader of the E3 Ligase ZFP91. — *J Med Chem*

Cellosaurus cell lines

10 cell lines: 10 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A2EJ	HUBUi001-A	Induced pluripotent stem cell	Female
CVCL_A2EK	HUBUi002-A	Induced pluripotent stem cell	Male
CVCL_A2EL	HUBUi003-A	Induced pluripotent stem cell	Female
CVCL_A8KR	EHTJUi004-A	Induced pluripotent stem cell	Female
CVCL_C6Q1	ISCRMi001-A	Induced pluripotent stem cell	Female
CVCL_D0MM	UGENTi002-A	Induced pluripotent stem cell	Male
CVCL_D0MN	UGENTi002-A-1	Induced pluripotent stem cell	Male
CVCL_WP82	FAMRCi004-A	Induced pluripotent stem cell	Male
CVCL_WP83	FAMRCi004-B	Induced pluripotent stem cell	Male
CVCL_XD52	IBMS-iPSC-045-02	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 591 trials:

NCT	Phase	Status	Title
NCT00879060	Phase 4	COMPLETED	Clinical and Therapeutic Implications of Fibrosis in Hypertrophic Cardiomyopathy
NCT01721967	Phase 4	COMPLETED	Ranolazine for the Treatment of Chest Pain in HCM Patients
NCT02948998	Phase 4	UNKNOWN	Evaluating the Effect of Spironolactone on Hypertrophic Cardiomyopathy
NCT03249272	Phase 4	TERMINATED	Microvascular Dysfunction in Nonischemic Cardiomyopathy: Insights From CMR Assessment of Coronary Flow Reserve
NCT04133532	Phase 4	COMPLETED	Effect of Metoprolol in Post Alcohol Septal Ablation Patients With Hypertrophic Cardiomyopathy
NCT06401343	Phase 4	UNKNOWN	Use of SGLT2i in noHCM With HFpEF
NCT07103655	Phase 4	ENROLLING_BY_INVITATION	The Therapeutic Value of Mavacamten in Hypertrophic Cardiomyopathy With Mid-to-Apical Left Ventricular Obstruction
NCT07600177	Phase 4	RECRUITING	Mavacamten to Aficamten Transition in Patients With Obstructive Hypertrophic Cardiomyopathy
NCT07807384	Phase 4	NOT_YET_RECRUITING	Efficacy and Safety of an LVEF-Guided Mavacamten Dose Up-Titration Strategy in Chinese Patients With Symptomatic Obstructive Hypertrophic Cardiomyopathy
NCT04586348	Phase 4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	Phase 4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT00348530	Phase 4	UNKNOWN	Carvedilol Versus Verapamil in Chronic Heart Failure Secondary to Non-Ischemic Cardiomyopathy
NCT00371891	Phase 4	COMPLETED	Ontario Multidetector Computed Tomographic (MDCT) Coronary Angiography Study (OMCAS)
NCT00401856	Phase 4	COMPLETED	CMR to Assess Fibrosis in Cardiomyopathy Using Eplerenone
NCT00559338	Phase 4	COMPLETED	Impact of Nesiritide Infusion for Decompensated Heart Failure in the Emergency Department
NCT00606775	Phase 4	UNKNOWN	The Preventive Efficacy of Carvedilol on Cardiac Dysfunction in Duchenne Muscular Dystrophy
NCT00658203	Phase 4	COMPLETED	Clinical Evaluation on Advanced Resynchronization
NCT00701220	Phase 4	COMPLETED	Statin Therapy for Ischemic and Nonischemic Cardiomyopathy
NCT00800761	Phase 4	COMPLETED	Intensive Combined Chelation Therapy for Iron-Induced Cardiac Disease in Patients With Thalassemia Major
NCT00806390	Phase 4	TERMINATED	Prevention of Anthracycline or Trastuzumab Induced Cardiomyopathy by Metoprolol
NCT01006473	Phase 4	COMPLETED	Exercise Training in Chagas Cardiomyopathy
NCT01261065	Phase 4	COMPLETED	Mechanisms of Improvement With Beta-Blocker Treatment in Heart Failure
NCT01345188	Phase 4	COMPLETED	Ranolazine in Ischemic Cardiomyopathy
NCT01868841	Phase 4	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	Phase 4	UNKNOWN	Effects of Levosimendan, Milrinone and Norepinephrine on Left and Right Ventricular Function in Septic Shock
NCT03228823	Phase 4	UNKNOWN	Prospective Assessment of Premature Ventricular Contractions Suppression in Cardiomyopathy(PAPS)
NCT04323852	Phase 4	COMPLETED	Can Vitamin D Reduce Heart Muscle Damage After Bypass Surgery?
NCT05034432	Phase 4	RECRUITING	The PIVATAL Study -Study of Ventricular Arrhythmia (VTA) Ablation in Left Ventricular Assist Device (LVAD) Patients
NCT05371496	Phase 4	COMPLETED	Cardiac and Metabolic Effects of Semaglutide in Heart Failure With Preserved Ejection Fraction
NCT05718128	Phase 4	RECRUITING	Clinical Study of Endocardial Myocardial Biopsy
NCT06964464	Phase 4	RECRUITING	Comparative Effectiveness of Carvedilol Versus Metoprolol Succinate in Heart Failure Patients With an Implantable Cardioverter Defibrillator
NCT00317967	Phase 3	COMPLETED	Study to Determine if Atorvastatin Reduces Size and Stiffness of Muscle in the Left Ventricle of the Heart
NCT00698074	Phase 3	UNKNOWN	Diastolic Ventricular Interaction and the Effects of Biventricular Pacing in Hypertrophic Cardiomyopathy
NCT00821353	Phase 3	COMPLETED	Antiarrhythmic Therapy Versus Catheter Ablation for Atrial Fibrillation in Hypertrophic Cardiomyopathy
NCT02431221	Phase 3	WITHDRAWN	Efficacy, Safety, and Tolerability of Perhexiline in Subjects With Hypertrophic Cardiomyopathy and Heart Failure
NCT03470545	Phase 3	COMPLETED	Clinical Study to Evaluate Mavacamten (MYK-461) in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy
NCT05174416	Phase 3	COMPLETED	A Study to Evaluate the Efficacy and Safety of Mavacamten in Chinese Adults With Symptomatic Obstructive HCM
NCT05182658	Phase 3	ACTIVE_NOT_RECRUITING	Empagliflozin in Hypertrophic Cardiomyopathy
NCT05186818	Phase 3	COMPLETED	Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Placebo in Adults With Symptomatic oHCM
NCT05767346	Phase 3	COMPLETED	Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Metoprolol Succinate in Adults With Symptomatic oHCM
NCT06116968	Phase 3	COMPLETED	An Open-Label Study of Aficamten for Chinese Patients With Symptomatic oHCM
NCT06873828	Phase 3	NOT_YET_RECRUITING	Evaluation of the Efficacy and Safety of Wearable ECG (AT-Patch) in Patients With Hypertrophic Cardiomyopathy Requiring 48-Hour Holter MonitoringEvaluation of the Efficacy and Safety of Wearable ECG (AT-Patch) in Patients With Hypertrophic Cardiomyopathy Requiring 48-Hour Holter Monitoring
NCT07021976	Phase 3	ACTIVE_NOT_RECRUITING	A Phase III Trial of HRS-1893 in Patients With Obstructive Hypertrophic Cardiomyopathy
NCT07023341	Phase 3	ACTIVE_NOT_RECRUITING	A Study to Learn More About How Well Aficamten Works in Japanese Participants With Symptomatic Obstructive Hypertrophic Cardiomyopathy
NCT07202897	Phase 3	RECRUITING	LA-HCM Study : Rivaroxaban for Antithrombotic Prevention in Hypertrophic Cardiomyopathy Patients With Abnormal Left Atrial Strain.
NCT02559102	Phase 3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	Phase 3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	Phase 3	RECRUITING	Reducing Missed Appointments
NCT07377032	Phase 3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT00170183	Phase 3	COMPLETED	Brain Natriuretic Peptide (BNP) to Preserve Renal Function in Hospitalized Patients With Heart Failure
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Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for DSP across ~30M SureChEMBL compounds — explore on Sugi Predict.