DSG3

Chr 18AR

desmoglein 3

Also known as: ABOLM, CDHF6, PVA

NCBI Gene: 1830 ENSG00000134757 UniProt: P32926 OMIM: 169615

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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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. [provided by RefSeq, Jan 2016]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

?Blistering, acantholytic, of oral and laryngeal mucosaMIM #619226

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.09

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.09LOEUF

pLI 0.000

Z-score 1.08

OE 0.82 (0.63–1.09)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.46Z-score

OE missense 0.94 (0.88–1.02)

509 obs / 539.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.82 (0.63–1.09)

0≤0.351.4

Missense OE?0.94 (0.88–1.02)

0≤0.61.4

Synonymous OE?1.03

0≤1.21.6

LoF obs/exp: 35 / 42.6Missense obs/exp: 509 / 539.0Syn Z: -0.34

Background carrier burden — how many people carry a rare variant somewhere in DSG3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 51

1,317 rare PASS variants

Rare truncating (LoF)

1 in 590

183 rare PASS variants

Rare synonymous (reference)

1 in 85

480 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for DSG3. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 59	1 in 1,000
South Asian	~43k	1 in 48	1 in 480
Remaining (unassigned)	~30k	1 in 43	1 in 440
European (Finnish)	~27k	1 in 290	≈ 1 in 13,000
Admixed American	~22k	1 in 50	1 in 240
African / African American	~21k	1 in 44	1 in 1,000
East Asian	~20k	1 in 47	1 in 320
Ashkenazi Jewish	~13k	1 in 210	1 in 670
Middle Eastern	~2,884	1 in 37	≈ 1 in 1,400

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 14 of 16 coding exons well covered in gnomAD exomes; exons 2, 10 marginal. Genomes: all 16.? see exons ↓