DSG3

Chr 18AR

desmoglein 3

Also known as: ABOLM, CDHF6, PVA

Desmoglein 3 is a calcium-binding transmembrane glycoprotein that forms desmosome cell-cell junctions essential for epithelial cell adhesion, particularly in oral and laryngeal mucosa. Mutations cause autosomal recessive blistering and acantholytic lesions of the oral and laryngeal mucosa, presenting as a localized form of pemphigus affecting mucosal surfaces. The gene shows very low constraint against loss-of-function variants (LOEUF 1.09), consistent with the recessive inheritance pattern where both copies must be affected to cause disease.

Summary from RefSeq, OMIM, UniProt
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Primary Disease Associations & Inheritance

Blistering, acantholytic, of oral and laryngeal mucosaMIM #619226
AR
0
Active trials
55
Pubs (1 yr)
41
P/LP submissions
0%
P/LP missense
1.09
LOEUF
Multiple*
Mechanism· predicted
Clinical SummaryDSG3
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
39 unique Pathogenic / Likely Pathogenic· 151 VUS of 249 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.09LOEUF
pLI 0.000
Z-score 1.08
OE 0.82 (0.631.09)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.46Z-score
OE missense 0.94 (0.881.02)
509 obs / 539.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.82 (0.631.09)
00.351.4
Missense OE0.94 (0.881.02)
00.61.4
Synonymous OE1.03
01.21.6
LoF obs/exp: 35 / 42.6Missense obs/exp: 509 / 539.0Syn Z: -0.34
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
moderateDSG3-related blistering, acantholytic, of oral and laryngeal mucosaOTHERAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6646th %ile
GOF
0.73top 25%
LOF
0.4038th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

249 submitted variants in ClinVar

Classification Summary

Pathogenic38
Likely Pathogenic1
VUS151
Likely Benign13
Benign42
38
Pathogenic
1
Likely Pathogenic
151
VUS
13
Likely Benign
42
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
38
0
38
Likely Pathogenic
0
0
1
0
1
VUS
1
143
7
0
151
Likely Benign
0
10
2
1
13
Benign
0
5
32
5
42
Total1158806245

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

DSG3 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗