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GSDMC

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Summary

GSDMC (gasdermin C, HGNC:7151) is a protein-coding gene on chromosome 8q24.21, encoding Gasdermin-C (Q9BYG8). This form constitutes the precursor of the pore-forming protein: upon cleavage, the released N-terminal moiety (Gasdermin-C, N-terminal) binds to membranes and forms pores, triggering pyroptosis.

Enables wide pore channel activity. Involved in pyroptotic inflammatory response. Located in cytoplasm. Is active in plasma membrane.

Source: NCBI Gene 56169 — RefSeq curated summary.

At a glance

  • GWAS associations: 35
  • Clinical variants (ClinVar): 81 total
  • MANE Select transcript: NM_031415

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:7151
Approved symbolGSDMC
Namegasdermin C
Location8q24.21
Locus typegene with protein product
StatusApproved
Ensembl geneENSG00000147697
Ensembl biotypeprotein_coding
OMIM608384
Entrez56169

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 retained_intron, 1 protein_coding

ENST00000276708, ENST00000521365, ENST00000522273

RefSeq mRNA: 1 — MANE Select: NM_031415 NM_031415

CCDS: CCDS6360

Canonical transcript exons

ENST00000276708 — 14 exons

ExonStartEnd
ENSE00000981421129776102129776285
ENSE00000981422129765628129765793
ENSE00000981423129762626129762731
ENSE00000981424129760545129760589
ENSE00000981425129752698129752820
ENSE00001089778129777368129777591
ENSE00001521842129786011129786624
ENSE00003463513129749452129749525
ENSE00003530020129751542129751568
ENSE00003551870129749990129750119
ENSE00003556425129748196129748740
ENSE00003597386129750431129750570
ENSE00003602901129751862129751891
ENSE00003646766129752106129752147

Expression profiles

Bgee: expression breadth ubiquitous, 119 present calls, max score 97.20.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.5211 / max 65.3648, expressed in 123 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter IDTPM avgSamples expressed
949830.283682
949840.190774
949850.022510
949810.01238
949820.01195

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
lower esophagus mucosaUBERON:003583497.20gold quality
esophagus mucosaUBERON:000246995.66gold quality
zone of skinUBERON:000001493.73gold quality
skin of abdomenUBERON:000141693.71gold quality
skin of legUBERON:000151193.70gold quality
spleenUBERON:000210693.49gold quality
vaginaUBERON:000099682.48gold quality
hindlimb stylopod muscleUBERON:000425280.49gold quality
primordial germ cell in gonadCL:0000670 ∩ UBERON:000099178.92gold quality
skeletal muscle tissueUBERON:000113475.92gold quality
olfactory segment of nasal mucosaUBERON:000538675.07gold quality
minor salivary glandUBERON:000183074.06gold quality
skeletal muscle organUBERON:001489273.08gold quality
muscle of legUBERON:000138372.97gold quality
gastrocnemiusUBERON:000138872.46gold quality
saliva-secreting glandUBERON:000104471.55gold quality
esophagusUBERON:000104370.23gold quality
heart left ventricleUBERON:000208468.58gold quality
muscle tissueUBERON:000238567.84gold quality
tonsilUBERON:000237267.16gold quality
urinary bladderUBERON:000125560.06gold quality
heartUBERON:000094859.75gold quality
substantia nigraUBERON:000203859.66gold quality
ectocervixUBERON:001224958.41gold quality
C1 segment of cervical spinal cordUBERON:000646957.85gold quality
apex of heartUBERON:000209857.56gold quality
left uterine tubeUBERON:000130357.34gold quality
gall bladderUBERON:000211056.41gold quality
uterine cervixUBERON:000000256.32gold quality
right lobe of thyroid glandUBERON:000111955.01gold quality

Single-cell (SCXA)

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

ExperimentMarker?Max mean expression
E-ANND-3yes3.26
E-MTAB-7303no2.55

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

19 targeting GSDMC, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-4795-3P100.0074.624024
HSA-MIR-5011-5P100.0083.465820
HSA-MIR-1277-5P100.0073.955056
HSA-MIR-428299.9975.366408
HSA-MIR-302C-5P99.9772.563642
HSA-MIR-3616-5P99.5567.02989
HSA-MIR-57399.5567.44955
HSA-MIR-302B-5P99.5069.491857
HSA-MIR-302D-5P99.5069.341863
HSA-MIR-16-1-3P98.7069.231538
HSA-MIR-548AO-5P98.5569.571362
HSA-MIR-548AX98.5569.581362
HSA-MIR-660-5P98.1668.27680
HSA-MIR-468996.9765.791209
HSA-MIR-570296.6868.21958
HSA-MIR-514A-3P96.4367.771048
HSA-MIR-514B-3P96.4367.771048
HSA-MIR-6858-5P96.0564.591020
HSA-MIR-365586.1161.77117

Literature-anchored findings (GeneRIF, showing 11)

  • Study investigated the expression pattern of the GSDM family genes in the upper gastrointestinal epithelium and cancers. (PMID:19051310)
  • Gasdermin C is upregulated by inactivation of Tgfbr2 in the presence of mutated Apc, promoting colorectal cancer cell proliferation. (PMID:27835699)
  • Expression of GSDMC is increased by UV irradiation in human skin keratinocytes. GSDMC induction contributes to the increase of MMP-1 expression specifically via activation of ERK and JNK pathways. (PMID:29428815)
  • These data suggested that TRPV1 may serve an important role in the induction of GSDMC expression by UV and that UVinduced GSDMC expression may be mediated via a calcium/calcineurin/NFATc1 pathway. (PMID:30226565)
  • Overexpression of GSDMC is a prognostic factor for predicting a poor outcome in lung adenocarcinoma. (PMID:31939622)
  • Association of GSDMC polymorphisms with lumbar disc herniation among Chinese Han population. (PMID:32333499)
  • PD-L1-mediated gasdermin C expression switches apoptosis to pyroptosis in cancer cells and facilitates tumour necrosis. (PMID:32929201)
  • Two GWAS-identified variants are associated with lumbar spinal stenosis and Gasdermin-C expression in Chinese population. (PMID:33273635)
  • High Expression of GSDMC Is Associated with Poor Survival in Kidney Clear Cell Cancer. (PMID:34778452)
  • System analysis based on the pyroptosis-related genes identifies GSDMC as a novel therapy target for pancreatic adenocarcinoma. (PMID:36199146)
  • The Pyroptosis-Related Signature Composed of GSDMC Predicts Prognosis and Contributes to Growth and Metastasis of Hepatocellular Carcinoma. (PMID:37919059)

Cross-species orthologs

6 orthologs

OrganismSymbolGene ID
danio_reriopjvkENSDARG00000079945
mus_musculusGsdmc4ENSMUSG00000055748
mus_musculusGsdmc3ENSMUSG00000055827
mus_musculusGsdmc2ENSMUSG00000056293
mus_musculusGsdmcENSMUSG00000079025
rattus_norvegicusGsdmcENSRNOG00000054576

Paralogs (4): GSDMB (ENSG00000073605), GSDMD (ENSG00000104518), GSDMA (ENSG00000167914), PJVK (ENSG00000204311)

Protein

Protein identifiers

Gasdermin-C — Q9BYG8 (reviewed: Q9BYG8)

Alternative names: Melanoma-derived leucine zipper-containing extranuclear factor

All UniProt accessions (1): Q9BYG8

UniProt curated annotations — full annotation on UniProt →

Function. This form constitutes the precursor of the pore-forming protein: upon cleavage, the released N-terminal moiety (Gasdermin-C, N-terminal) binds to membranes and forms pores, triggering pyroptosis. Pore-forming protein that causes membrane permeabilization and pyroptosis. Produced by the cleavage of gasdermin-C by caspase CASP8 in response to death signals. After cleavage, moves to the plasma membrane where it strongly binds to membrane inner leaflet lipids. Homooligomerizes within the membrane and forms pores of 10-15 nanometers (nm) of inner diameter, triggering pyroptosis.

Subunit / interactions. Homooligomer; homooligomeric ring-shaped pore complex containing 27-28 subunits when inserted in the membrane.

Subcellular location. Cytoplasm. Cytosol Cell membrane.

Tissue specificity. Expressed mainly in trachea and spleen. In the esophagus, expressed in differentiating cells and probably in differentiated cells. Also detected in gastric epithelium.

Post-translational modifications. Cleavage by CASP8 relieves autoinhibition by releasing the N-terminal moiety (Gasdermin-C, N-terminal) that initiates pyroptosis. The cleavage site is unclear. According to a publication, it takes place after Asp-240 in response to alpha-ketoglutarate. Another paper reports cleavage by CASP8 after Asp-365. Palmitoylated.

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-C, N-terminal) following cleavage by caspase CASP8.

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 in induced by STAT3 and CD274/PD-L1 in response to hypoxia.

Similarity. Belongs to the gasdermin family.

RefSeq proteins (1): NP_113603* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR007677GasderminFamily
IPR040460Gasdermin_poreDomain
IPR041263Gasdermin_PUBDomain

Pfam: PF04598, PF17708

UniProt features (17 total): mutagenesis site 8, chain 3, sequence variant 3, site 2, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-Q9BYG8-F174.590.40

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 (2): 240–241 (cleavage; by casp8); 365–366 (cleavage; by casp8)

Mutagenesis-validated functional residues (8):

PositionPhenotype
233does not affect cleavage by casp8 in response to alpha-ketoglutarate.
240impaired cleavage by casp8 in response to alpha-ketoglutarate.
276does not affect cleavage by casp8 in response to alpha-ketoglutarate.
319low spontaneous pyroptosis-inducing activity.
365abolished cleavage by casp8.
398low spontaneous pyroptosis-inducing activity.
402spontaneous pyroptosis-inducing activity.
231–232does not affect cleavage by casp8 in response to alpha-ketoglutarate.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 63 (showing top): GOBP_INFLAMMATORY_RESPONSE, DARWICHE_PAPILLOMA_PROGRESSION_RISK, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_UP, RICKMAN_TUMOR_DIFFERENTIATED_WELL_VS_POORLY_DN, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_UP, GOBP_DEFENSE_RESPONSE_TO_BACTERIUM, GOBP_TRANSMEMBRANE_TRANSPORT, GOMF_PHOSPHATIDYLINOSITOL_4_5_BISPHOSPHATE_BINDING, GOMF_PHOSPHATIDYLINOSITOL_PHOSPHATE_BINDING, GOMF_PASSIVE_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GOMF_PHOSPHATIDYLINOSITOL_BINDING, GOMF_PHOSPHATIDYLSERINE_BINDING, GOMF_PHOSPHATIDYLINOSITOL_BISPHOSPHATE_BINDING, GOMF_MODIFIED_AMINO_ACID_BINDING, GOMF_WIDE_PORE_CHANNEL_ACTIVITY

GO Biological Process (3): programmed cell death (GO:0012501), defense response to bacterium (GO:0042742), pyroptotic inflammatory response (GO:0070269)

GO Molecular Function (3): phosphatidylserine binding (GO:0001786), phosphatidylinositol-4,5-bisphosphate binding (GO:0005546), phosphatidylinositol-4-phosphate binding (GO:0070273)

GO Cellular Component (4): cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
cellular anatomical structure3
anion binding2
phosphatidylinositol phosphate binding2
signal transduction1
cell death1
defense response1
response to bacterium1
inflammatory response1
phospholipid binding1
modified amino acid binding1
phosphatidylinositol bisphosphate binding1
intracellular anatomical structure1
cytoplasm1
membrane1
cell periphery1

Protein interactions and networks

STRING

450 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
GSDMCGSDMBQ8TAX9977
GSDMCGSDMEO60443901
GSDMCPJVKQ0ZLH3840
GSDMCSCAF11Q99590619
GSDMCCASP5P51878608
GSDMCLRATD2Q96KN1595
GSDMCNLRP7Q8WX94583
GSDMCCASP1P29466582
GSDMCNLRP1Q9C000581
GSDMCCASP4P49662573
GSDMCNLRP6P59044544
GSDMCAIM2O14862543
GSDMCNLRC4Q9NPP4542
GSDMCNLRP2Q9NX02540
GSDMCPYCARDQ9ULZ3513

IntAct

4 interactions, top by confidence:

ABTypeScore
STX17A2ML1psi-mi:“MI:0914”(association)0.350
GSDMCMYO9Apsi-mi:“MI:0914”(association)0.350
SSUH2IGLC7psi-mi:“MI:0914”(association)0.350

BioGRID (6): GSDMC (Synthetic Lethality), GSDMC (Affinity Capture-MS), GSDMC (Affinity Capture-MS), C14orf80 (Affinity Capture-MS), MYO9A (Affinity Capture-MS), GSDMC (Affinity Capture-MS)

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: P57764, Q32M21, Q5Y4Y6, Q96QA5, Q9BYG8, Q9D8T2, Q9EST1, P85967, Q2KHK6, Q3TR54, Q8CB12, Q99NB5, Q8TAX9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance60
Likely benign4
Benign4

Top pathogenic / likely-pathogenic (0)

SpliceAI

2745 predictions. Top by Δscore:

VariantEffectΔscore
8:129749451:CCAG:Cdonor_gain1.0000
8:129749521:CAGCA:Cacceptor_gain1.0000
8:129749522:AGCA:Aacceptor_gain1.0000
8:129749524:CA:Cacceptor_gain1.0000
8:129749526:C:CCacceptor_gain1.0000
8:129749532:G:Cacceptor_gain1.0000
8:129749532:G:GCacceptor_gain1.0000
8:129749540:CA:Cacceptor_gain1.0000
8:129749541:A:ACacceptor_gain1.0000
8:129749541:A:Cacceptor_gain1.0000
8:129750116:CCAG:Cacceptor_gain1.0000
8:129750117:CAGC:Cacceptor_gain1.0000
8:129750120:C:CCacceptor_gain1.0000
8:129750592:G:Tacceptor_gain1.0000
8:129750596:A:Tacceptor_gain1.0000
8:129752104:A:ACdonor_gain1.0000
8:129752105:C:CCdonor_gain1.0000
8:129765672:CACTA:Cdonor_gain1.0000
8:129765676:A:ACdonor_gain1.0000
8:129765677:C:CCdonor_gain1.0000
8:129765687:A:ACdonor_gain1.0000
8:129765688:C:CCdonor_gain1.0000
8:129765688:CAGCA:Cdonor_gain1.0000
8:129776096:CCTCA:Cdonor_loss1.0000
8:129776097:CTCA:Cdonor_loss1.0000
8:129776098:TCA:Tdonor_loss1.0000
8:129776099:CA:Cdonor_loss1.0000
8:129776100:A:AGdonor_loss1.0000
8:129776281:AGTTT:Aacceptor_gain1.0000
8:129776282:GTTT:Gacceptor_gain1.0000

AlphaMissense

3352 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
8:129760552:A:CF238L0.991
8:129760552:A:TF238L0.991
8:129760554:A:GF238L0.991
8:129748578:A:GW484R0.980
8:129748578:A:TW484R0.980
8:129762643:A:GL220P0.976
8:129760553:A:GF238S0.975
8:129765752:C:GR149P0.971
8:129760553:A:CF238C0.970
8:129777475:A:TI38K0.967
8:129762643:A:TL220Q0.966
8:129748576:C:AW484C0.964
8:129748576:C:GW484C0.964
8:129750566:G:CF316L0.964
8:129750566:G:TF316L0.964
8:129750568:A:GF316L0.964
8:129762662:C:GA214P0.963
8:129748628:A:GL467P0.961
8:129765713:A:TV162D0.961
8:129748727:A:GL434P0.960
8:129749453:A:GL429P0.960
8:129765734:A:GL155P0.957
8:129748690:G:CF446L0.955
8:129748690:G:TF446L0.955
8:129748692:A:GF446L0.955
8:129750441:A:GL358P0.952
8:129777475:A:CI38R0.949
8:129749461:T:AQ426H0.948
8:129749461:T:GQ426H0.948
8:129748714:G:CF438L0.946

dbSNP variants (sampled 300 via entrez): RS1000061891 (8:129735664 C>G), RS1000120967 (8:129714748 C>T), RS1000125815 (8:129785175 C>T), RS1000155664 (8:129747617 G>A), RS1000169434 (8:129788416 C>G,T), RS1000181603 (8:129708995 G>A,C), RS1000271113 (8:129766424 C>A), RS1000331848 (8:129727415 A>C), RS1000335928 (8:129782169 A>C), RS1000346086 (8:129766457 T>A,C), RS1000364914 (8:129705485 G>A), RS1000427114 (8:129721089 A>G), RS1000432067 (8:129747395 T>C), RS1000517331 (8:129710359 T>A), RS1000556156 (8:129778342 A>G)

Disease associations

OMIM: gene MIM:608384 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

35 associations (top):

StudyTraitp-value
GCST000353_2Orofacial clefts3.000000e-24
GCST000817_101Height2.000000e-28
GCST001134_18White blood cell types2.000000e-10
GCST001137_6White blood cell count3.000000e-20
GCST001854_6Retinopathy in non-diabetics5.000000e-06
GCST002646_14Infant length1.000000e-06
GCST002647_145Height1.000000e-41
GCST002702_61Height1.000000e-13
GCST004067_138Hip circumference adjusted for BMI1.000000e-11
GCST004067_3Hip circumference adjusted for BMI2.000000e-09
GCST004067_95Hip circumference adjusted for BMI8.000000e-18
GCST004098_1Sciatica caused by lumbar disc herniation (treated with microdiscectomy)6.000000e-12
GCST004129_2White blood cell count (monocyte)6.000000e-12
GCST004500_138Waist circumference adjusted for BMI (adjusted for smoking behaviour)3.000000e-12
GCST004501_56Waist circumference adjusted for BMI (joint analysis main effects and smoking interaction)9.000000e-11
GCST004504_54Waist circumference adjusted for BMI in non-smokers9.000000e-10
GCST007152_3Chronic back pain4.000000e-13
GCST007294_100Body fat distribution (trunk fat ratio)5.000000e-14
GCST007294_153Body fat distribution (trunk fat ratio)8.000000e-10
GCST007295_115Body fat distribution (leg fat ratio)3.000000e-09
GCST007295_97Body fat distribution (leg fat ratio)3.000000e-08
GCST008839_481Height7.000000e-26
GCST009391_903Metabolite levels5.000000e-07
GCST011011_59Youthful appearance (self-reported)2.000000e-55
GCST011743_78HDL cholesterol levels in HIV infection6.000000e-06
GCST012227_34Hip circumference adjusted for BMI1.000000e-11
GCST012227_37Hip circumference adjusted for BMI1.000000e-11
GCST012227_38Hip circumference adjusted for BMI2.000000e-08
GCST90011900_203Serum alkaline phosphatase levels1.000000e-08
GCST90014033_89Haemorrhoidal disease2.000000e-09

EFO canonical traits (12, from GWAS)

EFO IDTrait name
EFO:0003959cleft lip
EFO:0005091monocyte count
EFO:0006785infant body height
EFO:0008039BMI-adjusted hip circumference
EFO:0007941LDH-related sciatica symptom severity measurement
EFO:1002005lumbar disc herniation
EFO:0004318smoking behavior
EFO:0007789BMI-adjusted waist circumference
EFO:0004341body fat distribution
EFO:0010442triacylglycerol 58:8 measurement
EFO:0004612high density lipoprotein cholesterol measurement
EFO:0004533alkaline phosphatase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

ChemicalActions (top 5)PubMed papers
sodium arseniteincreases expression2
sotorasibaffects cotreatment, increases expression1
sodium arsenateincreases abundance, decreases expression1
4-aminophenylarsenoxideaffects binding, decreases reaction1
1-nitropyrenedecreases expression1
S-(1,2-dichlorovinyl)cysteineaffects response to substance, increases expression1
CGP 52608affects binding, increases reaction1
monomethylarsonous aciddecreases expression1
abrinedecreases expression1
trametinibaffects cotreatment, increases expression1
NVP-BKM120affects cotreatment, increases expression1
theaflavin-3,3’-digallateaffects expression1
Resveratrolaffects cotreatment, decreases expression1
Arsenic Trioxideaffects binding, decreases reaction1
Air Pollutantsdecreases expression, increases abundance1
Arsenicdecreases expression, increases abundance1
Benzo(a)pyrenedecreases methylation1
Copperaffects cotreatment, decreases expression1
Estradiolaffects cotreatment, decreases expression1
Lipopolysaccharidesaffects response to substance, increases expression1
Methylcholanthreneaffects binding, increases reaction1
Nickelincreases expression1
Silicon Dioxidedecreases expression1
Tobacco Smoke Pollutionaffects expression1
Aflatoxin B1increases methylation1
Lactic Aciddecreases expression1
Particulate Matterdecreases expression, increases abundance1

Clinical trials (associated diseases)

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

  • Disease cohort memberships (association, not causation — diseases whose associated-gene cohort lists this gene; a subset are also under Associated diseases): hemorrhoid

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
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BioBTree
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Sources 74

This page pulls from 74 datasets indexed by BioBTree:

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