GSDMB

Summary

GSDMB (gasdermin B, HGNC:23690) is a protein-coding gene on chromosome 17q21.1, encoding Gasdermin-B (Q8TAX9). Precursor of a pore-forming protein that acts as a downstream mediator of granzyme-mediated cell death.

This gene encodes a member of the gasdermin-domain containing protein family. Other gasdermin-family genes are implicated in the regulation of apoptosis in epithelial cells, and are linked to cancer. Alternative splicing and the use of alternative promoters results in multiple transcript variants. Additional variants have been described, but they are candidates for nonsense-mediated mRNA decay (NMD) and are unlikely to be protein-coding.

Source: NCBI Gene 55876 — RefSeq curated summary.

At a glance

• GWAS associations: 71
• Clinical variants (ClinVar): 71 total
• MANE Select transcript: NM_001165958

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23690
Approved symbol	GSDMB
Name	gasdermin B
Location	17q21.1
Locus type	gene with protein product
Status	Approved
Aliases	PRO2521
Ensembl gene	ENSG00000073605
Ensembl biotype	protein_coding
OMIM	611221
Entrez	55876

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 14 protein_coding, 5 retained_intron, 4 nonsense_mediated_decay

ENST00000309481, ENST00000360317, ENST00000394175, ENST00000394179, ENST00000418519, ENST00000464556, ENST00000468820, ENST00000477054, ENST00000479136, ENST00000486560, ENST00000519429, ENST00000520542, ENST00000522564, ENST00000523371, ENST00000524039, ENST00000901434, ENST00000901435, ENST00000901436, ENST00000901437, ENST00000959627, ENST00000959628, ENST00000959629, ENST00000959630

RefSeq mRNA: 10 — MANE Select: NM_001165958 NM_001042471, NM_001165958, NM_001165959, NM_001369402, NM_001388420, NM_001388421, NM_001388422, NM_001388423, NM_001388424, NM_018530

CCDS: CCDS11354, CCDS42313, CCDS54119, CCDS54120

Canonical transcript exons

ENST00000418519 — 11 exons

Exon	Start	End
ENSE00001432962	39917082	39917330
ENSE00001801908	39908176	39908214
ENSE00002106772	39918534	39918635
ENSE00003490852	39909756	39909924
ENSE00003509921	39905847	39905985
ENSE00003545000	39908958	39909042
ENSE00003548828	39905426	39905496
ENSE00003585262	39912326	39912497
ENSE00003589159	39906961	39906987
ENSE00003597408	39904595	39904964
ENSE00003688141	39906111	39906271

Expression profiles

Bgee: expression breadth ubiquitous, 206 present calls, max score 96.67.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2374 / max 61.3937, expressed in 56 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
165649	0.2045	51
165648	0.0329	16

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
rectum	UBERON:0001052	96.67	gold quality
right lobe of liver	UBERON:0001114	96.14	gold quality
mucosa of transverse colon	UBERON:0004991	95.80	gold quality
granulocyte	CL:0000094	95.30	gold quality
small intestine Peyer’s patch	UBERON:0003454	95.07	gold quality
ileal mucosa	UBERON:0000331	94.53	gold quality
small intestine	UBERON:0002108	93.91	gold quality
duodenum	UBERON:0002114	93.74	gold quality
transverse colon	UBERON:0001157	93.72	gold quality
cerebellar hemisphere	UBERON:0002245	93.09	gold quality
right hemisphere of cerebellum	UBERON:0014890	93.08	gold quality
cerebellar cortex	UBERON:0002129	92.91	gold quality
jejunal mucosa	UBERON:0000399	92.72	gold quality
cerebellum	UBERON:0002037	90.93	gold quality
intestine	UBERON:0000160	90.58	gold quality
lower esophagus mucosa	UBERON:0035834	89.90	gold quality
body of stomach	UBERON:0001161	89.78	gold quality
large intestine	UBERON:0000059	89.64	gold quality
colon	UBERON:0001155	89.56	gold quality
right uterine tube	UBERON:0001302	89.49	gold quality
omental fat pad	UBERON:0010414	88.95	gold quality
peritoneum	UBERON:0002358	88.88	gold quality
colonic epithelium	UBERON:0000397	88.79	gold quality
gall bladder	UBERON:0002110	88.59	gold quality
adipose tissue of abdominal region	UBERON:0007808	88.56	gold quality
spleen	UBERON:0002106	87.85	gold quality
stomach	UBERON:0000945	87.70	gold quality
body of pancreas	UBERON:0001150	87.60	gold quality
liver	UBERON:0002107	87.56	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	87.56	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.25
E-CURD-10	no	197.88

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

14 targeting GSDMB, 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-1193	100.00	65.93	529
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-6762-3P	99.66	66.94	1188
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-491-5P	99.13	65.98	1468
HSA-MIR-4463	98.56	66.05	1071
HSA-MIR-4490	98.51	68.47	943
HSA-MIR-4299	98.28	66.96	850
HSA-MIR-647	97.73	67.79	927
HSA-MIR-6796-5P	95.37	66.08	1120
HSA-MIR-6717-5P	91.67	66.93	68

Literature-anchored findings (GeneRIF, showing 40)

• Evolutionary recombination hotspot around the GSDML-GSDM locus is closely linked to oncogenomic recombination hotspot around the PPP1R1B-STARD3-TCAP-PNMT-PERLD1-ERBB2-C17orf37-GRB7 amplicon at human chromosome 17q12. (PMID:15010812)
• GSDML may be a secretory or metabolic product involved in a secretory pathway, and changes in the regulation of GSDML splicing variant transcription and translation may be seen in the development and/or progression of gastrointestinal and hepatic cancers. (PMID:18038310)
• Study investigated the expression pattern of the GSDM family genes in the upper gastrointestinal epithelium and cancers (PMID:19051310)
• polymorphisms in ORMDL3 and the adjacent GSDML may contribute to childhood asthma. (PMID:19133921)
• The disease-linked haplotype and putative causal DNA variants of ZPBP2/GSDMB/ORMDL3 locus via a combination of genetic and functional analyses, were identified. (PMID:19732864)
• The GSDMA (rs7212938) and GSDMB (rs7216389) polymorphisms are associated with asthma susceptibility and intermediate asthma phenotypes. (PMID:21337730)
• Five markers on chromosome 17q12-21 showed statistically significant association with bronchial asthma .SNP rs7216389 with the strongest evidence for association is located within the first intron of the GSDMB gene. (PMID:22295569)
• Significant associations between two SNPs, rs2305480 and rs8067378 in the GSDML gene, and asthma were found in this study. (PMID:22370936)
• GSDMB/ORMDL3 variants contribute to asthma susceptibility and eosinophil-mediated bronchial hyperresponsiveness. (PMID:22732088)
• rs11078928 is associated with the production of a novel GSDMB transcript lacking an internal segment (PMID:24044605)
• GSDMB SNP rs2305480 (Ser311Pro) was associated with asthma diagnosis (p = 8.9x10-4), bronchial hyperresponsiveness to methacholine (p = 8.2x10-4) and severity (p = 1.5x10-4) with supporting evidence from a second GSDMB SNP rs11078927 (intronic). (PMID:24066901)
• 3 SNPs associated with the fraction of exhaled nitric oxide in childhood asthma are rs3751972 in LYRM9; rs944722 in NOS2; and rs8069176 near GSDMB; all at 17q12-q21. (PMID:24315451)
• Gasdermin-B promotes invasion and metastasis in breast cancer cells (PMID:24675552)
• No association between GSDMB polymorphisms and rheumatoid arthritis was observed. (PMID:24848122)
• Results confirmed the genetic association between GSDMB/ ORMDL3 and childhood asthma and show significant differences in the DNA methylation levels of ORMDL3 promoter of asthmatic children. (PMID:25256354)
• The GSDMB-driven HSVtk expression vector had a therapeutic effect on the occult peritoneal dissemination model mice. (PMID:26016667)
• GSDMB variants have been shown to be associated with Asthma in children with Rhinovirus infections -induced wheezing illnesses. (PMID:26270739)
• Based on our results and published findings on GSDMA, GSDMB, LRRC3C, and related proteins, we propose that this locus in part affects IBD susceptibility via effects on apoptosis and cell proliferation (PMID:26484354)
• childhood asthma is associated with gene polymorphism; meta-analysis (PMID:26534891)
• we investigated the association between GSDMA and GSDMB variants and the incidence of adult and childhood asthma among Jordanians.An association between the GSDMB T/C single nucleotide polymorphism (SNP) genotype and the incidence of childhood asthma was found (PMID:26886240)
• Data identifies the ERBB2 co-amplified and co-expressed gene GSDMB as a critical determinant of poor prognosis and therapeutic response in HER2-positive breast cancer. (PMID:27462779)
• These studies demonstrate that GSDMB, a gene highly linked to asthma but whose function in asthma is previously unknown, regulates AHR and airway remodeling without airway inflammation through a previously unrecognized pathway in which GSDMB induces 5-LO to induce TGF-beta1 in bronchial epithelium. (PMID:27799535)
• We found strong associations among GSDMB polymorphisms and the presence of AERD and FEV1 in Korean patients with asthma. Our findings indicated that genetic variations of GSDMB may be associated with the development of AERD and aspirin-induced bronchospasm. (PMID:28052796)
• The rs8067378 SNP variants may increase the expression of GSDMB and the risk of the development and progression of cervical SCC. (PMID:28120299)
• Full-length GSDMB and its N-terminal domain bind to phosphoinositides or sulfatide, but not cardiolipin. The GSDMB N-terminal domain binds liposomes containing sulfatide, suggesting a role in sulfatide transport. A loop with SNP AAs from controls (Gly299:Pro306) shows high conformational flexibility, but one with AAs (Arg299:Ser306) from people at risk for IBD and asthma is less so and has higher positive surface charge. (PMID:28154144)
• GSDMB levels are significantly modulated by NMD. Importantly, both AS isoforms and the identified ecircRNA were significantly dysregulated in peripheral blood mononuclear cells of relapsing-remitting MS patients compared to controls. (PMID:28272342)
• These results showed that the PBC susceptibility allele of rs12946510 disrupted the enhancer region for ORMDL3 and GSDMB gene expression (Fig. 6). Chromatin interaction between the sequence that contains rs12946510 and the upstream sequence of ORMDL3 and GSDMB also supported this enhancer model (PMID:28588209)
• Chromosome 17q21 genes ORMDL3 and GSDMB are linked to asthma and other immune diseases. (Review) (PMID:28826527)
• Our study identified a functional asthma variant in the GSDMB gene of the 17q21 locus and implicates GSDMB-mediated epithelial cell pyroptosis in pathogenesis. (PMID:29330013)
• we show that local CpG methylation mediates a proportion, but not all, of the functional effects of cis-acting asthma-susceptibility regulatory variants on GSDMB and ORMDL3 gene expression (PMID:29374573)
• GSDMB promotes caspase-4 activity, which is required for the cleavage of GSDMD in non-canonical pyroptosis, by directly binding to the CARD domain of caspase-4. (PMID:30321352)
• this study demonstrated that GZMA from cytotoxic lymphocytes cleaves and activates GSDMB to induce target cell pyroptosis. (PMID:32299851)
• Association between Gasdermin A, Gasdermin B Polymorphisms and Allergic Rhinitis Amongst Jordanians. (PMID:32496997)
• Genetic analyses identify GSDMB associated with asthma severity, exacerbations, and antiviral pathways. (PMID:32795586)
• Household mold exposure interacts with inflammation-related genetic variants on childhood asthma: a case-control study. (PMID:33810791)
• ORMDL3/GSDMB genotype is associated with distinct phenotypes of adult asthma. (PMID:33941434)
• Association of Gasdermin B Gene GSDMB Polymorphisms with Risk of Allergic Diseases. (PMID:33963941)
• Pathogenic ubiquitination of GSDMB inhibits NK cell bactericidal functions. (PMID:34022140)
• The GSDMB rs7216389 SNP is associated with chronic rhinosinusitis in a multi-institutional cohort. (PMID:34076350)
• USP24-GSDMB complex promotes bladder cancer proliferation via activation of the STAT3 pathway. (PMID:34326684)

Cross-species orthologs

1 orthologs

Organism	Symbol	Gene ID
danio_rerio	pjvk	ENSDARG00000079945

Paralogs (4): GSDMD (ENSG00000104518), GSDMC (ENSG00000147697), GSDMA (ENSG00000167914), PJVK (ENSG00000204311)

Protein

Protein identifiers

Gasdermin-B — Q8TAX9 (reviewed: Q8TAX9)

Alternative names: Gasdermin-like protein

All UniProt accessions (5): Q8TAX9, B2CM71, B2CM72, B2CM73, J3QLF0

UniProt curated annotations — full annotation on UniProt →

Function. Precursor of a pore-forming protein that acts as a downstream mediator of granzyme-mediated cell death. This form constitutes the precursor of the pore-forming protein: upon cleavage, the released N-terminal moiety (Gasdermin-B, N-terminal) binds to membranes and forms pores, triggering pyroptosis. Also acts as a regulator of epithelial cell repair independently of programmed cell death: translocates to the plasma membrane and promotes epithelial maintenance and repair by regulating PTK2/FAK-mediated phosphorylation of PDGFA. Pore-forming protein produced by cleavage by granzyme A (GZMA), which causes membrane permeabilization and pyroptosis in target cells of cytotoxic T and natural killer (NK) cells. Key downstream mediator of granzyme-mediated cell death: (1) granzyme A (GZMA), delivered to target cells from cytotoxic T- and NK-cells, (2) specifically cleaves Gasdermin-B to generate this form. After cleavage, moves to the plasma membrane, homooligomerizes within the membrane and forms pores of 10-15 nanometers (nm) of inner diameter, triggering pyroptosis. The different isoforms recognize and bind different phospholipids on membranes, promoting cell death of different target cells. Precursor of a pore-forming protein that acts as a downstream mediator of granzyme-mediated cell death and mediates pyroptosis. Following cleavage and activation by granzyme A (GZMA), the N-terminal part binds to membrane inner leaflet lipids, homooligomerizes within the human plasma membrane and forms pores of 10-15 nanometers (nm) of inner diameter, triggering pyroptosis. Recognizes and binds membrane inner leaflet lipids of human cells, such as phosphatidylinositol 4-phosphate, phosphatidylinositol 5-phosphate, bisphosphorylated phosphatidylinositols, such as phosphatidylinositol (4,5)-bisphosphate, and more weakly to phosphatidic acid. Also binds sufatide, a component of the apical membrane of epithelial cells. Precursor of a pore-forming protein that acts as a downstream mediator of granzyme-mediated cell death and mediates pyroptosis of human cells. Following cleavage and activation by granzyme A (GZMA), the N-terminal part binds to membrane inner leaflet lipids, homooligomerizes within the human plasma membrane and forms pores of 10-15 nanometers (nm) of inner diameter, triggering pyroptosis. Precursor of a pore-forming protein that acts as a downstream mediator of granzyme-mediated cell death and specifically mediates cell death of Gram-negative bacteria in response to infection. Following cleavage and activation by granzyme A (GZMA), the N-terminal part recognizes and binds phospholipids found on Gram-negative bacterial membranes, such as lipid A and cariolipin, homooligomerizes within the bacterial membranes and forms pores, triggering pyroptosis followed by cell death. In contrast to isoform 4, does not bind to membrane inner leaflet lipids of host human cell, such as phosphatidylinositol 4-phosphate, phosphatidylinositol 5-phosphate, bisphosphorylated phosphatidylinositols, such as phosphatidylinositol (4,5)-bisphosphate. Not able to trigger pyroptosis. Not able to trigger pyroptosis.

Subunit / interactions. Homooligomer; homooligomeric ring-shaped pore complex containing 24-26 subunits when inserted in the membrane.

Subcellular location. Cytoplasm Cell membrane.

Tissue specificity. In the gastrointestinal tract, expressed in proliferating cells, including in the basal cell layer of esophagus and in isthmus/neck of stomach.

Post-translational modifications. Cleavage by granzyme A (GZMA) relieves autoinhibition by releasing the N-terminal moiety (Gasdermin-B, N-terminal) that initiates pyroptosis. Not cleaved by other granzymes. Major cleavage site takes places after Lys-244; a minor cleavage site takes place after Lys-229. Cleavage by neutrophil elastase ELANE, inhibits its ability to trigger pyroptosis. Palmitoylated. (Microbial infection) Ubiquitinated by S.flexneri IpaH7.8, leading to its degradation by the proteasome, thereby preventing its ability to form pores in bacterial-derived membranes.

Activity regulation. The full-length protein before cleavage is inactive: intramolecular interactions between N- and C-terminal domains mediate autoinhibition in the absence of activation signal. The intrinsic pyroptosis-inducing activity is carried by the released N-terminal moiety (Gasdermin-B, N-terminal) following cleavage by granzyme A (GZMA).

Domain organisation. Intramolecular interactions between N- and C-terminal domains are important for autoinhibition in the absence of activation signal. The intrinsic pyroptosis-inducing activity is carried by the N-terminal domain.

Induction. Expression is induced by interferon-gamma (IFNG). Overexpressed in inflammatory bowel disease (IBD).

Miscellaneous. Long terminal repeat (LTR) of endogenous retrovirus HERV-H with reverse orientation may serve as alternative promoters of GSDMB gene. Non canonical splice junctions. GSDMB may be used as predictive markers of cervical lymph node metastasis and may help, with a panel of other genes, to discriminate between primary tumors of oral squamous cell carcinoma that metastasize to cervical lymph node and those that do not metastasize.

Similarity. Belongs to the gasdermin family.

Isoforms (6)

UniProt ID	Names	Canonical?
Q8TAX9-4	4, GSDMB3, Isoform 4	yes
Q8TAX9-1	1
Q8TAX9-2	2, GSDMB2
Q8TAX9-3	3, GSDMB1, Isoform 1
Q8TAX9-5	5
Q8TAX9-6	6, GSDMB4, Isoform 4

RefSeq proteins (10): NP_001035936, NP_001159430, NP_001159431, NP_001356331, NP_001375349, NP_001375350, NP_001375351, NP_001375352, NP_001375353, NP_061000 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007677	Gasdermin	Family
IPR040460	Gasdermin_pore	Domain
IPR041263	Gasdermin_PUB	Domain

Pfam: PF04598, PF17708

UniProt features (100 total): mutagenesis site 34, helix 20, strand 12, sequence variant 6, cross-link 5, splice variant 5, site 4, transmembrane region 4, chain 3, turn 3, region of interest 2, sequence conflict 1, coiled-coil region 1

Structure

Experimental structures (PDB)

11 structures.

PDB	Method	Resolution (Å)
5TIB	X-RAY DIFFRACTION	2.6
9K1S	X-RAY DIFFRACTION	2.69
7WJQ	X-RAY DIFFRACTION	2.7
8GTJ	X-RAY DIFFRACTION	2.7
5TJ2	X-RAY DIFFRACTION	2.8
8GTK	X-RAY DIFFRACTION	3.1
8GTN	ELECTRON MICROSCOPY	3.17
5TJ4	X-RAY DIFFRACTION	3.5
8EFP	ELECTRON MICROSCOPY	3.8
8ET1	ELECTRON MICROSCOPY	4.48
8ET2	ELECTRON MICROSCOPY	4.96

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TAX9-F1	71.86	0.19

Functional residue map

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

Catalytic / active sites (4): 91–92 (cleavage; by caps3, caps6 and caps9); 220–221 (cleavage; by elane); 229–230 (cleavage; by granzyme a); 244–245 (cleavage; by granzyme a)

Post-translational modifications (5): 177, 190, 192, 166, 308

Mutagenesis-validated functional residues (34):

Position	Phenotype
10–14	slightly decreased formation of pore.
15	decreased ability to trigger pyroptosis. abolished ubiquitination by s.flexneri ipah7.8.
17–21	abolished ubiquitination by s.flexneri ipah7.8.
17	decreased interaction with s.flexneri ipah7.8. does not affect ability to trigger pyroptosis.
21	decreased interaction with s.flexneri ipah7.8.
26	reduced ability to trigger pyroptosis; when associated with a-51.
43	decreased ability to trigger pyroptosis.
44	decreased ability to trigger pyroptosis.
50	decreased ability to trigger pyroptosis.
51	reduced ability to trigger pyroptosis; when associated with a-26.
51	abolished ability to mediate pyroptosis.
96	decreased interaction with s.flexneri ipah7.8.
97	decreased interaction with s.flexneri ipah7.8. does not affect ability to trigger pyroptosis.
124	decreased interaction with s.flexneri ipah7.8. abolished ubiquitination by s.flexneri ipah7.8; when associated with a-20
171	decreased ability to trigger pyroptosis.
174	decreased ability to trigger pyroptosis.
208	decreased interaction with s.flexneri ipah7.8. abolished ubiquitination by s.flexneri ipah7.8; when associated with a-12
212	abolished ability to mediate pyroptosis.
225	reduced ability to trigger pyroptosis.
227	reduced ability to trigger pyroptosis.
229	does not prevent cleavage by granzyme a (gzma). reduced ability to trigger pyroptosis.
233	reduced ability to trigger pyroptosis.
244	abolished cleavage by granzyme a (gzma), preventing release of the n-terminal moiety (gasdermin-b, n-terminal) and abili
254	does not relieve autoinhibition. relieves autoinhibition; when associated with d-399.
339–343	does not relieve autoinhibition.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 84 (showing top): GOBP_INFLAMMATORY_RESPONSE, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, ACEVEDO_LIVER_TUMOR_VS_NORMAL_ADJACENT_TISSUE_DN, ODONNELL_TARGETS_OF_MYC_AND_TFRC_UP, GOBP_DEFENSE_RESPONSE_TO_GRAM_NEGATIVE_BACTERIUM, GOBP_BIOLOGICAL_PROCESS_INVOLVED_IN_INTERACTION_WITH_SYMBIONT, GOBP_DEFENSE_RESPONSE_TO_BACTERIUM, GOBP_CELL_KILLING, GOBP_TRANSMEMBRANE_TRANSPORT, MULLIGHAN_MLL_SIGNATURE_2_DN, SMID_BREAST_CANCER_LUMINAL_B_DN, GOMF_PHOSPHATIDYLINOSITOL_4_5_BISPHOSPHATE_BINDING, NIKOLSKY_MUTATED_AND_AMPLIFIED_IN_BREAST_CANCER, GOMF_PHOSPHATIDYLINOSITOL_PHOSPHATE_BINDING, GOMF_PASSIVE_TRANSMEMBRANE_TRANSPORTER_ACTIVITY

GO Biological Process (8): programmed cell death (GO:0012501), killing of cells of another organism (GO:0031640), defense response to bacterium (GO:0042742), defense response to Gram-negative bacterium (GO:0050829), obsolete killing by host of symbiont cells (GO:0051873), pyroptotic inflammatory response (GO:0070269), cytotoxic T cell pyroptotic cell death (GO:1902483), transmembrane transport (GO:0055085)

GO Molecular Function (6): phosphatidylserine binding (GO:0001786), phospholipid binding (GO:0005543), phosphatidylinositol-4,5-bisphosphate binding (GO:0005546), wide pore channel activity (GO:0022829), phosphatidylinositol-4-phosphate binding (GO:0070273), cardiolipin binding (GO:1901612)

GO Cellular Component (4): cytoplasm (GO:0005737), plasma membrane (GO:0005886), endomembrane system (GO:0012505), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
anion binding	2
phosphatidylinositol phosphate binding	2
signal transduction	1
cell death	1
cell killing	1
disruption of cell in another organism	1
defense response	1
response to bacterium	1
defense response to bacterium	1
inflammatory response	1
pyroptotic cell death	1
transport	1
cellular process	1
phospholipid binding	1
modified amino acid binding	1
lipid binding	1
phosphatidylinositol bisphosphate binding	1
channel activity	1
phosphatidylglycerol binding	1
intracellular anatomical structure	1
membrane	1
cell periphery	1
vacuole	1
plasma membrane	1

Protein interactions and networks

STRING

682 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GSDMB	GSDMC	Q9BYG8	977
GSDMB	ORMDL3	Q8N138	961
GSDMB	ZPBP2	Q6X784	954
GSDMB	GSDME	O60443	888
GSDMB	IKZF3	Q9UKT9	849
GSDMB	PJVK	Q0ZLH3	827
GSDMB	SCAF11	Q99590	659
GSDMB	PGAP3	Q96FM1	651
GSDMB	CDHR3	Q6ZTQ4	626
GSDMB	IL1RL1	Q01638	621
GSDMB	LRRC3C	A6NJW4	617
GSDMB	CTCF	P49711	614
GSDMB	CASP5	P51878	602
GSDMB	CASP1	P29466	598
GSDMB	SMAD3	P84022	589

IntAct

7 interactions, top by confidence:

A	B	Type	Score
GSDMB	AGT	psi-mi:“MI:0915”(physical association)	0.370
GSDMB	HIVEP1	psi-mi:“MI:0915”(physical association)	0.370
GSDMB	IGFBP2	psi-mi:“MI:0915”(physical association)	0.370
GSDMB	ORM1	psi-mi:“MI:0915”(physical association)	0.370
GSDMB	PEBP1	psi-mi:“MI:0915”(physical association)	0.370
SERPINA1	GSDMB	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (14): GSDMB (Biochemical Activity), GSDMB (Affinity Capture-RNA), STAT3 (Affinity Capture-Western), USP24 (Affinity Capture-Western), GSDMB (Affinity Capture-Western), GSDMB (Affinity Capture-Western), GSDMB (Affinity Capture-RNA), APP (Reconstituted Complex), HIVEP1 (Two-hybrid), ORM1 (Two-hybrid), SERPINA1 (Two-hybrid), IGFBP2 (Two-hybrid), PEBP1 (Two-hybrid), GSDMB (Two-hybrid)

ESM2 similar proteins: A1L3T7, A2CJ06, C9JE40, O15287, O15482, P33076, P57764, P70434, P79621, P85967, Q00978, Q14653, Q15572, Q2KHK6, Q32M21, Q3TR54, Q3UPH7, Q499Z3, Q4JF28, Q4R3B7, Q571B6, Q5JYT7, Q5PNP6, Q5XIS1, Q5Y4Y6, Q6AXX1, Q6P773, Q6PDZ2, Q7TSI1, Q80VA5, Q8BHW9, Q8BMG1, Q8BTN6, Q8CB12, Q8CE13, Q8CFK6, Q8CIE4, Q8K330, Q8TAX9, Q8TE77

Diamond homologs: Q8TAX9, Q96QA5, Q9EST1, P57764, Q2KHK6, Q32M21, Q3TR54, Q5Y4Y6, Q8CB12, Q99NB5, Q9BYG8, Q9D8T2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	44
Likely benign	9
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1585 predictions. Top by Δscore:

Variant	Effect	Δscore
17:39905420:TCTCA:T	donor_loss	1.0000
17:39905421:CTCA:C	donor_loss	1.0000
17:39905422:TCA:T	donor_loss	1.0000
17:39905423:CACCT:C	donor_loss	1.0000
17:39905425:C:CT	donor_loss	1.0000
17:39905492:CAGCT:C	acceptor_gain	1.0000
17:39905493:AGCT:A	acceptor_gain	1.0000
17:39905494:GCTCT:G	acceptor_loss	1.0000
17:39905495:CT:C	acceptor_gain	1.0000
17:39905496:TC:T	acceptor_loss	1.0000
17:39905497:C:CA	acceptor_loss	1.0000
17:39905497:C:CC	acceptor_gain	1.0000
17:39905504:C:CT	acceptor_gain	1.0000
17:39905505:A:T	acceptor_gain	1.0000
17:39905840:T:TA	donor_gain	1.0000
17:39905842:CTCA:C	donor_loss	1.0000
17:39905843:TCA:T	donor_loss	1.0000
17:39905844:CA:C	donor_loss	1.0000
17:39905846:C:A	donor_loss	1.0000
17:39905846:CCTAG:C	donor_gain	1.0000
17:39905850:G:C	donor_gain	1.0000
17:39906099:AGGGT:A	donor_gain	1.0000
17:39906109:A:AC	donor_gain	1.0000
17:39906109:ACT:A	donor_gain	1.0000
17:39906110:C:CC	donor_gain	1.0000
17:39906110:CT:C	donor_gain	1.0000
17:39906110:CTC:C	donor_gain	1.0000
17:39906110:CTCT:C	donor_gain	1.0000
17:39906139:T:TA	donor_gain	1.0000
17:39906157:G:C	donor_gain	1.0000

AlphaMissense

2738 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000014002 (17:39920026 T>C), RS1000029296 (17:39906610 G>A), RS1000056489 (17:39907658 G>A), RS1000066259 (17:39919781 G>A), RS1000156607 (17:39912277 C>G,T), RS1000715347 (17:39909235 C>A,G,T), RS1000882808 (17:39919415 C>G,T), RS1000934722 (17:39919730 A>T), RS1001588086 (17:39915718 C>T), RS1001809325 (17:39915530 T>C), RS1001972156 (17:39911043 T>C), RS1002156941 (17:39915195 C>T), RS1002273950 (17:39904161 G>C), RS1002320497 (17:39916873 G>A), RS1002388783 (17:39910789 T>A,G)

Disease associations

OMIM: gene MIM:611221 | disease phenotypes: MIM:607487, MIM:192600

GenCC curated gene-disease

Mondo (2): hypertrophic cardiomyopathy 25 (MONDO:0011843), familial hypertrophic cardiomyopathy (MONDO:0024573)

Orphanet (2): Rare familial disorder with hypertrophic cardiomyopathy (Orphanet:99739), NON RARE IN EUROPE: Familial isolated hypertrophic cardiomyopathy (Orphanet:155)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

71 associations (top):

Study	Trait	p-value
GCST000624_15	Ulcerative colitis	3.000000e-08
GCST000733_2	Primary biliary cholangitis	2.000000e-09
GCST000804_8	Asthma	1.000000e-07
GCST000964_1	Ulcerative colitis	5.000000e-11
GCST001137_10	White blood cell count	9.000000e-35
GCST001137_8	White blood cell count	2.000000e-31
GCST001182_4	Asthma	2.000000e-16
GCST001685_2	Primary biliary cholangitis	4.000000e-09
GCST001725_54	Inflammatory bowel disease	4.000000e-38
GCST002082_3	Cervical cancer	9.000000e-10
GCST002083_32	Self-reported allergy	9.000000e-09
GCST002275_2	Asthma (childhood onset)	6.000000e-23
GCST002304_15	Fractional exhaled nitric oxide (childhood)	5.000000e-06
GCST002304_21	Fractional exhaled nitric oxide (childhood)	2.000000e-08
GCST003155_23	Systemic lupus erythematosus	8.000000e-09
GCST003589_1	Bronchial hyperresponsiveness in asthma	3.000000e-20
GCST003832_16	Asthma (childhood onset)	5.000000e-06
GCST003832_6	Asthma (childhood onset)	3.000000e-06
GCST003990_5	Allergy	3.000000e-15
GCST004131_33	Inflammatory bowel disease	2.000000e-26
GCST004132_116	Crohn’s disease	1.000000e-16
GCST004133_16	Ulcerative colitis	2.000000e-16
GCST004202_2	Systemic sclerosis	1.000000e-10
GCST004390_1	Asthma	4.000000e-12
GCST004390_2	Asthma	1.000000e-12
GCST004609_80	Monocyte percentage of white cells	2.000000e-31
GCST005038_96	Allergic disease (asthma, hay fever or eczema)	6.000000e-30
GCST005213_4	Asthma (childhood onset)	4.000000e-26
GCST005536_38	Type 1 diabetes	1.000000e-08
GCST005568_3	Rheumatoid arthritis (ACPA-positive)	3.000000e-09

EFO canonical traits (10, from GWAS)

EFO ID	Trait name
EFO:0004267	biliary liver cirrhosis
EFO:0004833	neutrophil count
EFO:0005536	nitric oxide exhalation measurement
EFO:0007989	monocyte percentage of leukocytes
EFO:0009598	feeling miserable measurement
EFO:0004847	age at onset
EFO:0009941	Inhalant adrenergic use measurement
EFO:0009942	Glucocorticoid use measurement
EFO:0004533	alkaline phosphatase measurement
EFO:0007614	asthma exacerbation measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D024741	Cardiomyopathy, Hypertrophic, Familial	C14.280.238.100.500; C14.280.484.048.750.070.160.500; C16.320.160
C564388	Cardiomyopathy, Dilated, 1N (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, increases abundance, decreases expression	3
Rotenone	increases expression	2
1-Methyl-4-phenylpyridinium	increases expression	2
aristolochic acid I	increases expression	1
FR900359	increases phosphorylation	1
trichostatin A	affects expression	1
phenanthrene	increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
deguelin	decreases expression	1
entinostat	increases expression	1
monomethylarsonous acid	decreases expression	1
ICG 001	increases expression	1
abrine	decreases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Leflunomide	increases expression	1
Acetaminophen	decreases expression	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Cadmium	increases abundance, increases expression	1
Carbamazepine	affects expression	1
Cisplatin	decreases expression	1
Estradiol	decreases expression	1
Quercetin	increases expression	1
Silicon Dioxide	increases expression	1
Smoke	increases expression	1
Tetrachlorodibenzodioxin	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	decreases expression	1

Cellosaurus cell lines

2 cell lines: 1 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D7R2	Ubigene A-549 GSDMB KO	Cancer cell line	Male
CVCL_D9WV	Ubigene HTR-8/SVneo GSDMB KO	Transformed cell line	Sex unspecified

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01792960	Not specified	COMPLETED	Registry and Prevalence of Gene Mutation in Korean Patients With Familial Hypertrophic Cardiomyopathy
NCT05100420	Not specified	ENROLLING_BY_INVITATION	Hypertrophic Cardiomyopathy Registry, Biobank and Imaging Data Repository