DSG3

Summary

DSG3 (desmoglein 3, HGNC:3050) is a protein-coding gene on chromosome 18q12.1, encoding Desmoglein-3 (P32926). A component of desmosome cell-cell junctions which are required for positive regulation of cellular adhesion.

This gene encodes a member of the desmoglein family and cadherin cell adhesion molecule superfamily of proteins. Desmogleins are calcium-binding transmembrane glycoprotein components of desmosomes, cell-cell junctions between epithelial, myocardial, and other cell types. The encoded preproprotein is proteolytically processed to generate the mature glycoprotein. This gene is present in a gene cluster with other desmoglein gene family members on chromosome 18. The encoded protein has been identified as the autoantigen of the autoimmune blistering disease pemphigus vulgaris.

Source: NCBI Gene 1830 — RefSeq curated summary.

At a glance

• Gene–disease (curated): blistering, acantholytic, of oral and laryngeal mucosa (Moderate, GenCC)
• GWAS associations: 2
• Clinical variants (ClinVar): 203 total — 1 pathogenic
• Phenotypes (HPO): 3
• MANE Select transcript: NM_001944

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3050
Approved symbol	DSG3
Name	desmoglein 3
Location	18q12.1
Locus type	gene with protein product
Status	Approved
Aliases	CDHF6
Ensembl gene	ENSG00000134757
Ensembl biotype	protein_coding
OMIM	169615
Entrez	1830

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000257189, ENST00000851332

RefSeq mRNA: 1 — MANE Select: NM_001944 NM_001944

CCDS: CCDS11898

Canonical transcript exons

ENST00000257189 — 16 exons

Exon	Start	End
ENSE00000916028	31458445	31458600
ENSE00000916029	31459033	31459177
ENSE00000916031	31460833	31460961
ENSE00000916032	31461227	31461412
ENSE00000916033	31464111	31464382
ENSE00000916034	31465318	31465457
ENSE00000916035	31466530	31466754
ENSE00000916036	31469089	31469349
ENSE00000916037	31472284	31472423
ENSE00000916038	31472725	31472788
ENSE00000916039	31474121	31474404
ENSE00000998593	31459845	31460011
ENSE00001143311	31456993	31457124
ENSE00001143586	31456440	31456475
ENSE00001169606	31475646	31478702
ENSE00001169614	31447741	31447925

Expression profiles

Bgee: expression breadth ubiquitous, 143 present calls, max score 99.62.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 8.5043 / max 844.3272, expressed in 158 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
169817	7.7721	153
169816	0.7321	102

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
gingiva	UBERON:0001828	99.62	gold quality
gingival epithelium	UBERON:0001949	99.59	gold quality
pharyngeal mucosa	UBERON:0000355	99.36	gold quality
oral cavity	UBERON:0000167	99.14	gold quality
body of tongue	UBERON:0011876	98.97	gold quality
lower esophagus mucosa	UBERON:0035834	98.55	gold quality
penis	UBERON:0000989	98.52	gold quality
tongue squamous epithelium	UBERON:0006919	98.51	gold quality
esophagus squamous epithelium	UBERON:0006920	98.45	gold quality
esophagus mucosa	UBERON:0002469	98.12	gold quality
mammalian vulva	UBERON:0000997	97.86	gold quality
epithelium of esophagus	UBERON:0001976	97.67	gold quality
squamous epithelium	UBERON:0006914	97.62	gold quality
cervix epithelium	UBERON:0004801	96.68	gold quality
tongue	UBERON:0001723	95.26	gold quality
upper leg skin	UBERON:0004262	92.76	gold quality
skin of abdomen	UBERON:0001416	91.49	gold quality
cervix squamous epithelium	UBERON:0006922	90.58	gold quality
zone of skin	UBERON:0000014	90.45	gold quality
upper arm skin	UBERON:0004263	90.20	gold quality
skin of hip	UBERON:0001554	89.92	gold quality
superior surface of tongue	UBERON:0007371	89.49	gold quality
skin of leg	UBERON:0001511	89.46	gold quality
vagina	UBERON:0000996	88.03	gold quality
epithelium of nasopharynx	UBERON:0001951	87.79	gold quality
hair follicle	UBERON:0002073	87.18	gold quality
nipple	UBERON:0002030	87.10	gold quality
tonsil	UBERON:0002372	82.96	gold quality
periodontal ligament	UBERON:0008266	79.93	gold quality
amniotic fluid	UBERON:0000173	79.80	gold quality

Single-cell (SCXA)

Detected in 10 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-ANND-2	yes	1312.78
E-MTAB-9467	yes	20.65
E-CURD-88	yes	18.29
E-HCAD-4	yes	18.14
E-MTAB-6701	yes	9.89
E-MTAB-10596	no	751.64
E-MTAB-6108	no	182.52
E-CURD-10	no	4.31
E-GEOD-137537	no	3.62
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

89 targeting DSG3, 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-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4775	99.98	75.00	6394
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-4525	99.94	64.38	675
HSA-MIR-5010-5P	99.94	64.11	705
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-4302	99.89	67.94	1187
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909

Literature-anchored findings (GeneRIF, showing 40)

• Data strongly support the view that desmoglein 3 contributes to the regulation of epidermal differentiation. (PMID:12138195)
• During high-level expression, keratin insertion at cell-cell contact sites was inhibited in desmoglein 1 but not in desmoglein 3, and desmoplakin was stained at cell-cell contact sites in desmoglein 3 but not in desmoglein 1. (PMID:12485422)
• The appearance of DSG3-reactive Th2 cells is constant at different stages of pemphigus vulgaris (PV), while DSG3-reactive Th1 cells are detected at a significantly higher frequency in chronic active PV. (PMID:12496453)
• In trichilemmal keratinization in follicle, and in cysts in these areas, desmoglein 3 expressed throughout outer root sheath and cyst wall. In areas of epidermal-like keratinization, desmoglein 3 expression was limited mainly to the basal layer. (PMID:12787134)
• a novel negative marker for epidermal stem cell-containing population of keratinocytes (PMID:12953062)
• Dsg3(AA145-192)-specific cells preferentially utilize the TCRVbeta13 gene, while Dsg3(AA240-303)- and Dsg3 (AA570-614)-specific cells utilize Vbeta7 and Vbeta17 genes, respectively (PMID:14675184)
• The five genes, and three of the encoded proteins, were shown differentially expressed between a group of keratoconus patients and a reference group using different techniques (PMID:16015083)
• Dsg3 endocytosis, keratin filament retraction, and the loss of keratinocyte cell-cell adhesion are coordinated responses to PV IgG (PMID:16377623)
• autoantibodies against desmoglein 3 (Dsg3) have been detected in sera from patients with fogo selvagem (PMID:16763546)
• analysis of desmoglein 3 ectodomain in pemphigus vulgaris (PMID:16842599)
• Overexpression of DSG3 is associated with head and neck cancer (PMID:16878157)
• Desmoglein 3 status indicated a poor prognosis in lung cancers. (PMID:17084439)
• The T cellular autoimmune response against immunodominant peptides of Dsg3 in patients with pemphigus vulgaris is monitored with highly specific HLA-DRbeta1*0402 tetramers. (PMID:17113829)
• These data indicate that Dsg3(dim) populations from primary human adult keratinocytes and long-term established keratinocyte lines possess certain stem/progenitor cell-like properties. (PMID:17255524)
• Data suggest that although the desmoglein (Dsg)3 depletion is not indicative for adhesive strength, it may indicate pathogenic changes within the cell and it plays a role in skin fragility or susceptibility to blister formation in pemphigus patients. (PMID:17428808)
• Reduction of Dsg3 might be relevant to blister formation in pemphigus vulgaris. (PMID:17431647)
• pemphigus vulgaris-IgG-dependent uPA activation is not related to anti-Dsg3 antibody activity (PMID:17532189)
• Data show that both pemphigus foliaceus-IgG containing Dsg 1- but not Dsg 3-specific antibodies and pemphigus vulgaris-IgG with antibodies to Dsg 1 and Dsg 3 were effective in causing epidermal splitting in human skin and keratinocyte dissociation. (PMID:17640963)
• results suggest an abnormal expression of Dsc3, Dsg3, & beta-catenin induced in the progression of oral carcinomas & that Dsc3 expression level might be related to the regulation of beta-catenin in lymph node metastasis and cell proliferation in OSCCs. (PMID:17846785)
• Autoantibody from pemphigus vulgaris sera react with non-conformational epitopes of desmoglein 3. (PMID:18095943)
• results indicate that the membrane proximal region in the IA region of Dsg3 is necessary for complex formation with P120-catenin and to maintain free Dsg3 at the cell surface before it is integrated into desmosomes (PMID:18343367)
• Pemphigus vulgaris (PV) IgG-induced Dsg3 internalization is mediated through a clathrin- and dynamin-independent pathway and Dsg3 endocytosis is tightly coupled to the pathogenic activity of PV IgG (PMID:18434319)
• proteolytic processing of Dsg3 can lead to depletion of Dsg3 from the cell in pemphigus vulgaris (PMID:18505410)
• Our method for the isolation of Dsg3-specific B cells will allow the systematic analysis of immunoglobulin gene usage in pemphigus vulgaris patients, which may elucidate the mechanism of immunopathogenesis. (PMID:18586466)
• The expression of Dsg3 (highly expressed in proliferating epidermal layers) was conversely regulated by these isoenzymes, and was also inhibited by the differentiation inducer Ca-dependent ‘conventional’ cPKCalpha. (PMID:18637128)
• Abs to Dsg 3 contribute to Pemphigus vulgaris by direct inhibition of Dsg transinteraction (PMID:18641320)
• direct inhibition of Dsg3 binding is important for PV pathogenesis and that peptidomimetics stabilizing Dsg transinteraction may provide a novel approach for PV treatment. (PMID:19164289)
• These results suggest that N-terminal truncated intracellular domain of Dg3 have a role in keratinocyte differentiation, and that may be related with tumorigenesis of epithelial origin. (PMID:19287199)
• Overexpression of DSG3 is associated with squamous cell carcinoma of the lung. (PMID:19342368)
• Both the binding of desmocollin 3 (Dsc3) to plakoglobin and Dsc3 phosphorylation are involved in Dsc3 binding to desmoglein 3 (Dsg3) during Ca2+ -induced desmosome assembly. (PMID:19348003)
• results argue against the hypothesis that DSG3 coding variants play a role in pemphigus vulgaris susceptibility (PMID:19678820)
• p38MAPK is capable of regulating PV IgG-mediated DSG3 internalization (PMID:20093368)
• The genetic background of the local population may explain why pemphigus occurs more commonly than bullous pemphigoid in Northwestern Romania compared with the population of Western Europe (PMID:20618495)
• Study demonstrated a molecular switching in gene expression within the desmoglein subfamily between DSG3 and DSG2 during oral cancer progression. (PMID:20923451)
• Dsg3, as an up-stream regulator of Src activity, helps regulate adherens junction formation through its interaction with E-cadherin (PMID:21151980)
• Silencing desmoglein 3 caused defects in cell-cell adhesion and concomitant reduction in cell proliferation in both HaCaT and MDCK cells. (PMID:21702856)
• These data indicate a contribution of Dsg depletion to pemphigus vulgaris pathogenesis dependent on Ca(2+)-induced differentiation. (PMID:21864491)
• The identification of desmogleins 1 and 3, desmosomal adhesion glycoproteins, as targets in pemphigus, a fatal autoimmune blistering disease of the skin and mucous membranes, provided the first link between desmosomes, desmogleins, and human diseases. (PMID:22189787)
• Report mapping of B cell epitopes on desmoglein 3 in pemphigus vulgaris patients by the use of overlapping peptides. (PMID:22261006)
• These findings suggest a novel function for Dsg3 in the control of E-cadherin-Src signalling and cell-cell adhesion. (PMID:22294297)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Dsg3	ENSMUSG00000056632
rattus_norvegicus	Dsg3	ENSRNOG00000016632

Paralogs (6): DSG2 (ENSG00000046604), DSC2 (ENSG00000134755), DSG1 (ENSG00000134760), DSC3 (ENSG00000134762), DSC1 (ENSG00000134765), DSG4 (ENSG00000175065)

Protein

Protein identifiers

Desmoglein-3 — P32926 (reviewed: P32926)

Alternative names: 130 kDa pemphigus vulgaris antigen, Cadherin family member 6

All UniProt accessions (1): P32926

UniProt curated annotations — full annotation on UniProt →

Function. A component of desmosome cell-cell junctions which are required for positive regulation of cellular adhesion. Required for adherens and desmosome junction assembly in response to mechanical force in keratinocytes. Required for desmosome-mediated cell-cell adhesion of cells surrounding the telogen hair club and the basal layer of the outer root sheath epithelium, consequently is essential for the anchoring of telogen hairs in the hair follicle. Required for the maintenance of the epithelial barrier via promoting desmosome-mediated intercellular attachment of suprabasal epithelium to basal cells. May play a role in the protein stability of the desmosome plaque components DSP, JUP, PKP1, PKP2 and PKP3. Required for YAP1 localization at the plasma membrane in keratinocytes in response to mechanical strain, via the formation of an interaction complex composed of DSG3, PKP1 and YWHAG. May also be involved in the positive regulation of YAP1 target gene transcription and as a result cell proliferation. Positively regulates cellular contractility and cell junction formation via organization of cortical F-actin bundles and anchoring of actin to tight junctions, in conjunction with RAC1. The cytoplasmic pool of DSG3 is required for the localization of CDH1 and CTNNB1 at developing adherens junctions, potentially via modulation of SRC activity. Inhibits keratinocyte migration via suppression of p38MAPK signaling, may therefore play a role in moderating wound healing.

Subunit / interactions. Homodimer. Part of a complex that contains DSG3, PKP1, YAP1 and YWHAG; the complex is required for localization of DSG3 and YAP1 to the cell membrane in keratinocytes. Interacts with PKP2. Interacts with CTNND1; the interaction facilitates DSG3 localization and retention at cell-cell junctions. Interacts with CDH1; the interaction is required for CDH1 localization to developing adherens junctions. Interacts with RAC1; the interaction is required for DSG3 translocation to cell-cell junctions, organization of cortical F-actin bundles and actin anchoring at cell-cell junctions. Interacts with DSC3; the interaction may limit the interaction of DSC3 with p38MAPK family members and therefore repress p38MAPK signaling activation.

Subcellular location. Cell membrane. Cell junction. Desmosome. Cytoplasm. Tight junction.

Tissue specificity. Expressed throughout the basal and spinous layer of the epidermis with weak expression in the granular layer (at protein level). Expressed in skin and mucosa (at protein level). Expressed in the basal layer of the outer root sheath of the telogen hair club, specifically at the cell membrane between the apex of the cells and the surrounding hair club (at protein level). Expression is less abundant between the lateral margins of the outer root sheath basal cells (at protein level). Also expressed in the tongue, tonsil and esophagus.

Disease relevance. Blistering, acantholytic, of oral and laryngeal mucosa (ABOLM) [MIM:619226] An autosomal recessive disorder characterized by recurrent, suprabasal acantholytic blisters in the oral and laryngeal mucosa. Skin, conjunctival and genital mucosa, nail folds, and nails are unaffected. Normal structure is observed in the scalp epidermis and hair follicle. The disease may be caused by variants affecting the gene represented in this entry.

Domain organisation. Three calcium ions are usually bound at the interface of each cadherin domain and rigidify the connections, imparting a strong curvature to the full-length ectodomain.

Induction. Induced in the hours following cyclic mechanical strain in keratinocytes.

Miscellaneous. Pemphigus vulgaris (PV) is a potentially lethal skin disease in which epidermal blisters occur as the result of the loss of cell-cell adhesion caused by the action of autoantibodies against desmoglein 3. Loss of expression at points of cell-cell contact between the basal and suprabasal layers in blisters and immediately adjacent to blisters in PV. In a PV patient acantholysis extends from the epidermis of the scalp down the entire outer root sheath of mostly empty dilated hair follicles that contain only small residual unanchored hair shafts and necrotic detached cells. Although hair loss is not a major phenotype in PV due to the lower number of hair follicles in telogen phase in humans, this would suggest DSG3 disruption results in hair follicle abnormalities.

RefSeq proteins (1): NP_001935* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002126	Cadherin-like_dom	Domain
IPR009122	Desmosomal_cadherin	Family
IPR015919	Cadherin-like_sf	Homologous_superfamily
IPR020894	Cadherin_CS	Conserved_site
IPR027397	Catenin-bd_sf	Homologous_superfamily
IPR050971	Cadherin-domain_protein	Family

Pfam: PF00028

UniProt features (72 total): strand 32, turn 14, glycosylation site 4, helix 4, domain 4, sequence variant 3, repeat 2, sequence conflict 2, topological domain 2, signal peptide 1, propeptide 1, region of interest 1, chain 1, transmembrane region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
5EQX	X-RAY DIFFRACTION	3.05

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P32926-F1	66.37	0.36

Functional residue map

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

Glycosylation sites (4): 110, 180, 459, 545

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-351906	Apoptotic cleavage of cell adhesion proteins
R-HSA-6805567	Keratinization
R-HSA-6809371	Formation of the cornified envelope

MSigDB gene sets: 146 (showing top): JAEGER_METASTASIS_DN, GOBP_APICAL_JUNCTION_ASSEMBLY, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, AREB6_01, GOBP_REGULATION_OF_CELL_JUNCTION_ASSEMBLY, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GGGTGGRR_PAX4_03, GOBP_NEGATIVE_REGULATION_OF_MAPK_CASCADE, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, GOBP_CELL_CELL_ADHESION, RICKMAN_METASTASIS_DN, GOBP_POSITIVE_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_CELL_JUNCTION_ORGANIZATION, chr18q12, INAMURA_LUNG_CANCER_SCC_UP

GO Biological Process (13): desmosome assembly (GO:0002159), actin filament organization (GO:0007015), homophilic cell-cell adhesion (GO:0007156), negative regulation of cell migration (GO:0030336), regulation of protein stability (GO:0031647), adherens junction assembly (GO:0034333), cell-cell adhesion (GO:0098609), tight junction assembly (GO:0120192), positive regulation of bicellular tight junction assembly (GO:1903348), negative regulation of p38MAPK cascade (GO:1903753), positive regulation of protein localization to adherens junction (GO:1904704), positive regulation of protein localization to membrane (GO:1905477), cell adhesion (GO:0007155)

GO Molecular Function (4): calcium ion binding (GO:0005509), protein dimerization activity (GO:0046983), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (12): cornified envelope (GO:0001533), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), cell-cell junction (GO:0005911), bicellular tight junction (GO:0005923), cell junction (GO:0030054), desmosome (GO:0030057), extracellular exosome (GO:0070062), tight junction (GO:0070160), membrane (GO:0016020), anchoring junction (GO:0070161)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Apoptotic cleavage of cellular proteins	1
Developmental Biology	1
Keratinization	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
cell-cell junction assembly	3
cell-cell junction	2
desmosome organization	1
actin cytoskeleton organization	1
supramolecular fiber organization	1
cell-cell adhesion	1
cell migration	1
regulation of cell migration	1
negative regulation of cell motility	1
regulation of biological quality	1
adherens junction organization	1
cell adhesion	1
tight junction organization	1
bicellular tight junction assembly	1
positive regulation of cell junction assembly	1
regulation of bicellular tight junction assembly	1
p38MAPK cascade	1
negative regulation of MAPK cascade	1
regulation of p38MAPK cascade	1
protein localization to adherens junction	1
positive regulation of protein localization to cell-cell junction	1
regulation of protein localization to adherens junction	1
positive regulation of cellular process	1
protein localization to membrane	1
positive regulation of protein localization	1
regulation of protein localization to membrane	1
cellular process	1
metal ion binding	1
protein binding	1
binding	1
cation binding	1
plasma membrane	1
intracellular anatomical structure	1
cytoplasm	1
membrane	1
cell periphery	1
anchoring junction	1
apical junction complex	1
tight junction	1

Protein interactions and networks

STRING

854 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DSG3	PKP3	Q9Y446	893
DSG3	DSP	P15924	867
DSG3	DST	Q03001	863
DSG3	PPL	O60437	835
DSG3	PKP1	Q13835	835
DSG3	EVPL	Q92817	817
DSG3	DSC2	Q02487	814
DSG3	COL17A1	Q9UMD9	773
DSG3	CHRNA9	Q9UGM1	761
DSG3	DSC3	Q14574	741
DSG3	PLEC	Q15149	732
DSG3	PKP2	Q99959	719
DSG3	KRT1	P04264	716
DSG3	KRT14	P02533	688
DSG3	DSG2	Q14126	634

IntAct

33 interactions, top by confidence:

A	B	Type	Score
OAZ3	AZIN1	psi-mi:“MI:0914”(association)	0.800
FRMD1	A2ML1	psi-mi:“MI:0914”(association)	0.530
SRRT	A2ML1	psi-mi:“MI:0914”(association)	0.350
STX17	A2ML1	psi-mi:“MI:0914”(association)	0.350
ST6GALNAC6	A2ML1	psi-mi:“MI:0914”(association)	0.350
GOT1	A2ML1	psi-mi:“MI:0914”(association)	0.350
PPP2R2B	A2ML1	psi-mi:“MI:0914”(association)	0.350
HSF2	A2ML1	psi-mi:“MI:0914”(association)	0.350
PRXL2A	A2ML1	psi-mi:“MI:0914”(association)	0.350
STK11	A2ML1	psi-mi:“MI:0914”(association)	0.350
CCR1	UBA6	psi-mi:“MI:0914”(association)	0.350
NRSN1	IGLC7	psi-mi:“MI:0914”(association)	0.350
SSUH2	IGLC7	psi-mi:“MI:0914”(association)	0.350
RNF115	IGLC7	psi-mi:“MI:0914”(association)	0.350
CERS3	IGLC7	psi-mi:“MI:0914”(association)	0.350
C18orf21	A2ML1	psi-mi:“MI:0914”(association)	0.350
PINK1	A2ML1	psi-mi:“MI:0914”(association)	0.350
FNDC5	A2ML1	psi-mi:“MI:0914”(association)	0.350
AGPAT1	A2ML1	psi-mi:“MI:0914”(association)	0.350
FSTL1	A2ML1	psi-mi:“MI:0914”(association)	0.350
SARAF	A2ML1	psi-mi:“MI:0914”(association)	0.350
MBNL1	A2ML1	psi-mi:“MI:0914”(association)	0.350
SIK1	KLK10	psi-mi:“MI:0914”(association)	0.350
CSGALNACT1	CTSV	psi-mi:“MI:0914”(association)	0.350
CACUL1	AMY1A	psi-mi:“MI:0914”(association)	0.350
BMP4	A2ML1	psi-mi:“MI:0914”(association)	0.350
OLFM4	SPINT1	psi-mi:“MI:0914”(association)	0.350
RSRP1	A2ML1	psi-mi:“MI:0914”(association)	0.350

BioGRID (38): DSG3 (Affinity Capture-MS), DSG3 (Affinity Capture-MS), DSG3 (Two-hybrid), DSG3 (Affinity Capture-Western), JUP (Affinity Capture-Western), DSG3 (Affinity Capture-MS), DSG3 (Affinity Capture-MS), DSG3 (Affinity Capture-MS), DSG3 (Affinity Capture-MS), DSG3 (Affinity Capture-MS), DSG3 (Affinity Capture-MS), DSG3 (Affinity Capture-MS), DSG3 (Affinity Capture-MS), DSG3 (Affinity Capture-MS), DSG3 (Affinity Capture-MS)

ESM2 similar proteins: A0A8M2BIB6, F1QSQ0, F8W3X3, H2EQR6, O35902, O54800, O55111, O93319, P32926, P33545, P55280, P55285, P55286, P55287, P55288, P55289, P55292, P55849, P55850, P70407, P70408, P79995, P97291, P97326, Q01107, Q02413, Q02487, Q08554, Q08DJ5, Q13634, Q14126, Q14574, Q28060, Q3SWX5, Q5DWV1, Q5RJH3, Q61495, Q68SP4, Q6W3B0, Q7TMD7

Diamond homologs: A0A8M2BIB6, B0KW95, B2KI42, B4USZ0, F1PAA9, H2EQR6, O18926, O35902, O55075, O55111, O88277, P08641, P09803, P10287, P10288, P12830, P15116, P19022, P19534, P19535, P20310, P22223, P24503, P30944, P32926, P33145, P33146, P33147, P33148, P33150, P33152, P33545, P39038, P55283, P55290, P55291, P55292, P55849, P55850, P79883

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	145
Likely benign	11
Benign	42

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1013500	NM_001944.3(DSG3):c.859C>T (p.Arg287Ter)	Pathogenic

SpliceAI

1768 predictions. Top by Δscore:

Variant	Effect	Δscore
18:31447923:GTG:G	donor_gain	1.0000
18:31447923:GTGGT:G	donor_loss	1.0000
18:31447924:TGGTA:T	donor_loss	1.0000
18:31447926:G:A	donor_loss	1.0000
18:31447926:G:GG	donor_gain	1.0000
18:31447927:T:G	donor_loss	1.0000
18:31456989:T:G	acceptor_gain	1.0000
18:31456991:A:G	acceptor_gain	1.0000
18:31458431:ATTT:A	acceptor_gain	1.0000
18:31458434:T:TA	acceptor_gain	1.0000
18:31458435:G:A	acceptor_gain	1.0000
18:31458443:A:AG	acceptor_gain	1.0000
18:31458444:G:GA	acceptor_gain	1.0000
18:31458444:GA:G	acceptor_gain	1.0000
18:31458444:GAT:G	acceptor_gain	1.0000
18:31458444:GATT:G	acceptor_gain	1.0000
18:31458444:GATTA:G	acceptor_gain	1.0000
18:31458598:CTG:C	donor_gain	1.0000
18:31458598:CTGG:C	donor_loss	1.0000
18:31458599:TG:T	donor_gain	1.0000
18:31458599:TGGT:T	donor_loss	1.0000
18:31458600:GG:G	donor_gain	1.0000
18:31458600:GGTA:G	donor_loss	1.0000
18:31458601:G:GA	donor_loss	1.0000
18:31458601:G:GG	donor_gain	1.0000
18:31458602:TAAG:T	donor_loss	1.0000
18:31459031:A:AG	acceptor_gain	1.0000
18:31459032:G:GG	acceptor_gain	1.0000
18:31459178:G:GG	donor_gain	1.0000
18:31459976:G:GT	donor_gain	1.0000

AlphaMissense

6499 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
18:31458527:T:C	F100S	0.999
18:31458578:G:C	R117P	0.999
18:31459088:T:C	L143P	0.999
18:31459094:T:A	V145D	0.999
18:31459953:T:C	F209S	0.999
18:31457061:G:C	W51C	0.998
18:31457061:G:T	W51C	0.998
18:31457119:G:C	A71P	0.998
18:31458481:T:G	Y85D	0.998
18:31458548:G:T	G107V	0.998
18:31459039:T:C	C127R	0.998
18:31459041:T:G	C127W	0.998
18:31457059:T:A	W51R	0.997
18:31457059:T:C	W51R	0.997
18:31458548:G:A	G107E	0.997
18:31458554:T:A	I109N	0.997
18:31458554:T:G	I109S	0.997
18:31459953:T:G	F209C	0.997
18:31460852:T:C	L235P	0.997
18:31460931:C:A	N261K	0.997
18:31460931:C:G	N261K	0.997
18:31458526:T:C	F100L	0.996
18:31458527:T:G	F100C	0.996
18:31458528:T:A	F100L	0.996
18:31458528:T:G	F100L	0.996
18:31458572:T:A	V115D	0.996
18:31458596:T:C	F123S	0.996
18:31459106:A:T	D149V	0.996
18:31459869:C:A	A181D	0.996
18:31459952:T:C	F209L	0.996

dbSNP variants (sampled 300 via entrez): RS1000025261 (18:31453405 A>G), RS1000136064 (18:31477705 C>T), RS1000164967 (18:31453506 A>C,G), RS1000374960 (18:31477994 C>T), RS1000401557 (18:31457028 G>A,T), RS1000597602 (18:31458138 G>A), RS1000648862 (18:31470306 C>A,G), RS1000680067 (18:31470721 C>G,T), RS1000733149 (18:31458374 T>C), RS1000758870 (18:31476738 T>A), RS1000853556 (18:31453964 T>G), RS1000855911 (18:31471434 G>A), RS1000874779 (18:31453749 G>A), RS1000907699 (18:31446812 A>G), RS1001169124 (18:31461496 G>A)

Disease associations

OMIM: gene MIM:169615 | disease phenotypes: MIM:619226

GenCC curated gene-disease

Disease	Classification	Inheritance
blistering, acantholytic, of oral and laryngeal mucosa	Moderate	Autosomal recessive

Mondo (1): blistering, acantholytic, of oral and laryngeal mucosa (MONDO:0030986)

Orphanet (0):

HPO phenotypes

3 total (3 of 3 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0031446	Erosion of oral mucosa
HP:0200097	Oral mucosal blisters

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST000490_1	Parkinson’s disease (age of onset)	4.000000e-06
GCST002822_5	Survival in colon cancer	4.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004847	age at onset
EFO:0000638	overall survival

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tobacco Smoke Pollution	increases expression, affects expression, decreases expression	5
sodium arsenite	decreases expression, increases expression	4
Benzo(a)pyrene	decreases expression, decreases methylation	3
Estradiol	affects cotreatment, decreases expression	2
Nickel	increases expression	2
Particulate Matter	decreases expression, increases abundance, affects cotreatment, increases expression	2
fluorene-9-bisphenol	increases expression	1
bisphenol A	decreases expression	1
lead acetate	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, increases expression, affects localization, decreases expression	1
ethyl-p-hydroxybenzoate	increases expression	1
tobacco tar	decreases expression	1
cupric chloride	decreases expression	1
puerarin	decreases expression	1
dibenzo(a,l)pyrene	decreases expression	1
epigallocatechin gallate	decreases expression	1
seocalcitol	increases expression	1
osajin	decreases expression	1
trans-3,4’-dimethyl-3-hydroxyflavanone	increases expression	1
rosavin	decreases expression	1
Aerosols	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Calcitriol	increases expression	1
Chlorogenic Acid	decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	increases expression	1
Furaldehyde	affects cotreatment, increases expression, affects localization, decreases expression	1
Gasoline	affects cotreatment, increases abundance, increases expression	1
Methotrexate	increases expression	1
Methyl Methanesulfonate	increases expression	1

Clinical trials (associated diseases)

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