Table 1.
GSDM family members, structures, functions, and disease relevance.
| GSDMA | GSDMB | GSDMC | GSDMD | GSDME | PJVK | Refs | |
|---|---|---|---|---|---|---|---|
| Aliases | GSDM1/FKSG9 | GSDML | MLZE | GSDMDC1/DFNA5L/FKSG10 | DFNA5/ICERE-1 | DFNB59/GSDMF | |
| Gene and chromosomal location | Human: GSDMA: chr17q21
Mouse: Gadma1 Gadma2 Gadma3 :chr11D |
Human: GSDMB:
chr17q21 Not identified in mouse |
Human: GSDMC: chr8q24.2
Mouse: Gsdmc1 Gsdmc2 Gsdmc3 Gsdmc4 :chr15D1 |
Human: GSDMD: chr8q24.3 Mouse: Gsdmd :chr15D3 |
Human: GSDME: chr7p15.3
Mouse: Gsdme/Dfna5:chr6B2.3 |
Human:PJVK: chr2q31.2 Mouse: Pjvk/Dfnb59:chr2.3 |
(1, 2) |
| Domains | GSDM-NT and GSDM-CT | GSDM-NT and GSDM-CT | GSDM-NT and GSDM-CT | GSDM-NT and GSDM-CT | GSDM-NT and GSDM-CT | GSDM-NT and zinc-finger | (3) |
| Activating enzyme | not known | Human: caspase 1 granzyme A |
caspase-8 | Mouse: caspase 1/11 Human: caspase 1/4/5 caspase 8 cathepsin G neutrophil elastase 3C protease of Enterovirus 71 (EV71) |
caspase 3 caspase-8, caspase-7 granzyme B |
not known | (1, 4–9) |
| Lipid binding site | GSDM-NT | full-length and GSDM-NT | GSDM-NT | GSDM-NT | GSDM-NT | GSDM-NT | |
| Type of lipid | phosphoinositides, cardiolipin, phosphatidic acid, phospatidylserine |
phosphoinositides, phosphatidic acid, phosphatidylglycerol sulfatid |
not known | phosphoinositides, cardiolipin, phosphatidic acid |
phosphoinositides, cardiolipin, phosphatidylserin |
not known | (4, 10–12) |
|
Tissue/cell-specific
expression in human |
skin, tongue, esophagus, stomach, mammary glands, bladder, umbilical cord and T lymphocytes |
airway epithelium, gastrointestinal tract, brain, endocrine tissue, bone marrow tissue, lung, liver, kidney, testis and lymphocytes | cerebral cortex, endocrine tissues, skin, trachea, spleen, esophagus, stomach, intestines, vagina and bladder | almost all human organs and tissue, including different subsets of leukocytes | brain, endocrine tissue, muscle tissue, gastrointestinal tract, endometrium and placenta | inner ear , neurons of the auditory system and testis | (1, 13–21) |
| Biological function | mitochondrial homeostasis | pyroptosis, anti-tumor immunity | not known | inflammation, pyroptosis, cytokine release, NETosis, bacteria killing |
pyroptosis, anti-tumor immunity | not known | (17, 22–24) |
| Associated disease | alopecia, asthma, limited cutaneous system sclerosis,and inflammatory bowel disease |
breast cancer and asthma | melanoma | atherosclerosis, type 2 diabetes mellitus, bullous pemphigoid, and cryopyrin-associated periodic syndromes sepsis and septic shock |
deafness, cancer | deafness | (17, 22, 25–41) |
GSDM family genes currently consist of GSDMA, GSDMB, GSDMC, GSDMD, GSDME (DNFA5) and PVJK (GSDMF). Every GSDM member has a distinct and restricted pattern of expression in different tissues leading to diverse diseases.