This gene encodes a member of the peptidase S1 family of serine proteases. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed to generate a chymotrypsin-like protease. This protein is reported to be constitutively expressed in the NK (natural killer) cells of the immune system and may pla... See more...

Aliases for GZMH Gene

Aliases for GZMH Gene

  • Granzyme H 2 3 4 5
  • Cathepsin G-Like 2, Protein H-CCPX 2 3
  • Cytotoxic T-Lymphocyte Proteinase 3 4
  • CTSGL2 3 4
  • CCP-X 3 4
  • CSP-C 3 4
  • Cytotoxic T-Lymphocyte-Associated Serine Esterase 1 3
  • Granzyme H (Cathepsin G-Like 2, Protein H-CCPX) 2
  • Cytotoxin Serine Protease-C 3
  • Cytotoxic Serine Protease C 4
  • Cathepsin G-Like 2 4
  • EC 3.4.21.79 52
  • EC 3.4.21.- 4
  • EC 3.4.21 52
  • CGL-2 3
  • CTLA1 3
  • CGL2 4

External Ids for GZMH Gene

Previous HGNC Symbols for GZMH Gene

  • CTSGL2

Previous GeneCards Identifiers for GZMH Gene

  • GC14U990026
  • GC14M023065
  • GC14M024145
  • GC14M025075
  • GC14M005190

Summaries for GZMH Gene

Entrez Gene Summary for GZMH Gene

  • This gene encodes a member of the peptidase S1 family of serine proteases. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed to generate a chymotrypsin-like protease. This protein is reported to be constitutively expressed in the NK (natural killer) cells of the immune system and may play a role in the cytotoxic arm of the innate immune response by inducing target cell death and by directly cleaving substrates in pathogen-infected cells. This gene is present in a gene cluster with another member of the granzyme subfamily on chromosome 14. [provided by RefSeq, Nov 2015]

GeneCards Summary for GZMH Gene

GZMH (Granzyme H) is a Protein Coding gene. Diseases associated with GZMH include Lipodystrophy, Congenital Generalized, Type 2 and Complete Generalized Lipodystrophy. Among its related pathways are Innate Lymphoid Cell Differentiation Pathways and Granzyme Pathway. Gene Ontology (GO) annotations related to this gene include serine-type endopeptidase activity. An important paralog of this gene is GZMB.

UniProtKB/Swiss-Prot Summary for GZMH Gene

  • Cytotoxic chymotrypsin-like serine protease with preference for bulky and aromatic residues at the P1 position and acidic residues at the P3' and P4' sites. Probably necessary for target cell lysis in cell-mediated immune responses. Participates in the antiviral response via direct cleavage of several proteins essential for viral replication.

Gene Wiki entry for GZMH Gene

Additional gene information for GZMH Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for GZMH Gene

Genomics for GZMH Gene

GeneHancer (GH) Regulatory Elements for GZMH Gene

Promoters and enhancers for GZMH Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH14J024607 Promoter/Enhancer 1.2 EPDnew Ensembl ENCODE dbSUPER 500.7 +0.2 186 3.7 TRIM24 NR2F1 EP400 CEBPG ATF4 NR2F6 ZNF175 JUND NR2C1 HNF4G GZMH GZMB CTSG CMA1 ENSG00000258744 KHNYN piR-61772 ENSG00000258657
GH14J024677 Enhancer 1.3 FANTOM5 ENCODE dbSUPER 40.3 -70.0 -69983 4 CTCF NRF1 USF1 REST MEF2C ZBTB25 RCOR1 RAD21 SKI TRIM22 GZMH GZMB STXBP6 CTSG CIDEB KHNYN CMA1 RIPK3 piR-48209-190 LOC105370413
GH14J024672 Enhancer 1.2 FANTOM5 ENCODE dbSUPER 23 -64.4 -64376 2.9 SP1 REST POLR2A BCL11A RELA TCF12 SRF ARNT SPI1 FOSL1 GZMB GZMH CTSG STXBP6 CMA1 CIDEB LTB4R RIPK3 TINF2 KHNYN
GH14J024541 Enhancer 0.5 Ensembl ENCODE 10.8 +67.4 67370 1.4 NONO FOS GZMH ENSG00000258744 CBLN3 piR-48209-189 piR-47211-170
GH14J024662 Enhancer 0.5 FANTOM5 ENCODE 11.1 -53.2 -53208 0.4 SPI1 GZMB CTSG GZMH LTB4R LOC105370413 piR-48209-190
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around GZMH on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for GZMH

Top Transcription factor binding sites by QIAGEN in the GZMH gene promoter:
  • AML1a
  • Elk-1
  • LCR-F1
  • p300
  • p53
  • SEF-1 (1)
  • TGIF
  • YY1

Genomic Locations for GZMH Gene

Genomic Locations for GZMH Gene
chr14:24,606,480-24,609,774
(GRCh38/hg38)
Size:
3,295 bases
Orientation:
Minus strand
chr14:25,075,686-25,078,905
(GRCh37/hg19)
Size:
3,220 bases
Orientation:
Minus strand

Genomic View for GZMH Gene

Genes around GZMH on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
GZMH Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for GZMH Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for GZMH Gene

Proteins for GZMH Gene

  • Protein details for GZMH Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P20718-GRAH_HUMAN
    Recommended name:
    Granzyme H
    Protein Accession:
    P20718
    Secondary Accessions:
    • G3V2C5
    • Q6XGZ0
    • Q6XGZ1

    Protein attributes for GZMH Gene

    Size:
    246 amino acids
    Molecular mass:
    27315 Da
    Quaternary structure:
    No Data Available

    Three dimensional structures from OCA and Proteopedia for GZMH Gene

    Alternative splice isoforms for GZMH Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for GZMH Gene

Selected DME Specific Peptides for GZMH Gene

P20718:
  • NDIMLLQL
  • VLTAAHC
  • GDSGGPL
  • INVTLGAHNIKEQE
  • SGGPLVC
  • VTLGAHN
  • PHSRPYMA

Post-translational modifications for GZMH Gene

  • Glycosylation at Asn71, Asn104, and Asn179
  • Modification sites at PhosphoSitePlus
  • Glycosylation from GlyConnect

Other Protein References for GZMH Gene

Domains & Families for GZMH Gene

Gene Families for GZMH Gene

Protein Domains for GZMH Gene

Blocks:
  • Serine protease, trypsin family
  • Chymotrypsin serine protease family (S1) signature
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for GZMH Gene

GenScript: Design optimal peptide antigens:
  • Cytotoxic serine protease C (GRAH_HUMAN)

Graphical View of Domain Structure for InterPro Entry

P20718

UniProtKB/Swiss-Prot:

GRAH_HUMAN :
  • Belongs to the peptidase S1 family. Granzyme subfamily.
Family:
  • Belongs to the peptidase S1 family. Granzyme subfamily.
genes like me logo Genes that share domains with GZMH: view

Function for GZMH Gene

Molecular function for GZMH Gene

UniProtKB/Swiss-Prot Function:
Cytotoxic chymotrypsin-like serine protease with preference for bulky and aromatic residues at the P1 position and acidic residues at the P3' and P4' sites. Probably necessary for target cell lysis in cell-mediated immune responses. Participates in the antiviral response via direct cleavage of several proteins essential for viral replication.
UniProtKB/Swiss-Prot EnzymeRegulation:
Inhibited by SERPINB1.
GENATLAS Biochemistry:
cytotoxic T-lymphocyte-associated granule serine protease 2,low expression in LAK and NK cells,(cathepsin G-like 2),(see SPAS@)

Enzyme Numbers (IUBMB) for GZMH Gene

Gene Ontology (GO) - Molecular Function for GZMH Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004252 serine-type endopeptidase activity NAS 2193684
GO:0008233 peptidase activity IEA --
GO:0008236 serine-type peptidase activity IEA --
GO:0016787 hydrolase activity IEA --
genes like me logo Genes that share ontologies with GZMH: view
genes like me logo Genes that share phenotypes with GZMH: view

Animal Model Products

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for GZMH

No data available for Phenotypes From GWAS Catalog , Human Phenotype Ontology , Animal Models , miRNA , Transcription Factor Targets and HOMER Transcription for GZMH Gene

Localization for GZMH Gene

Subcellular locations from UniProtKB/Swiss-Prot for GZMH Gene

Cytoplasmic granule. Note=Cytoplasmic granules of cytolytic T-lymphocytes.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for GZMH gene
Compartment Confidence
extracellular 3
plasma membrane 1
cytoskeleton 1
mitochondrion 1
nucleus 1
endoplasmic reticulum 1
endosome 1
cytosol 1
lysosome 1
golgi apparatus 1

Gene Ontology (GO) - Cellular Components for GZMH Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IBA 21873635
GO:0016020 membrane HDA 19946888
genes like me logo Genes that share ontologies with GZMH: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for GZMH Gene

Pathways & Interactions for GZMH Gene

genes like me logo Genes that share pathways with GZMH: view

Gene Ontology (GO) - Biological Process for GZMH Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006508 proteolysis IEA --
GO:0006915 apoptotic process NAS 2193684
GO:0008626 granzyme-mediated apoptotic signaling pathway IBA 21873635
GO:0019835 cytolysis IEA --
genes like me logo Genes that share ontologies with GZMH: view

No data available for SIGNOR curated interactions for GZMH Gene

Drugs & Compounds for GZMH Gene

(1) Drugs for GZMH Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
genes like me logo Genes that share compounds with GZMH: view

Transcripts for GZMH Gene

mRNA/cDNA for GZMH Gene

3 REFSEQ mRNAs :
7 NCBI additional mRNA sequence :
3 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for GZMH

Alternative Splicing Database (ASD) splice patterns (SP) for GZMH Gene

No ASD Table

Relevant External Links for GZMH Gene

GeneLoc Exon Structure for
GZMH

Expression for GZMH Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for GZMH Gene

mRNA differential expression in normal tissues according to GTEx for GZMH Gene

This gene is overexpressed in Whole Blood (x40.9).

Protein differential expression in normal tissues from HIPED for GZMH Gene

This gene is overexpressed in NK cells (30.8), Tlymphocyte (15.4), and Peripheral blood mononuclear cells (8.4).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for GZMH Gene



Protein tissue co-expression partners for GZMH Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for GZMH

SOURCE GeneReport for Unigene cluster for GZMH Gene:

Hs.348264

mRNA Expression by UniProt/SwissProt for GZMH Gene:

P20718-GRAH_HUMAN
Tissue specificity: Constitutively expressed in NK cells.

Evidence on tissue expression from TISSUES for GZMH Gene

  • Pancreas(4.1)
  • Blood(2.3)
genes like me logo Genes that share expression patterns with GZMH: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery and Phenotype-based relationships between genes and organs from Gene ORGANizer for GZMH Gene

Orthologs for GZMH Gene

This gene was present in the common ancestor of mammals.

Orthologs for GZMH Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia GZMH 31 30
  • 98.1 (n)
OneToOne
cow
(Bos Taurus)
Mammalia -- 31
  • 76 (a)
OneToMany
-- 31
  • 69 (a)
OneToMany
rat
(Rattus norvegicus)
Mammalia Gzmf 30
  • 69.86 (n)
mouse
(Mus musculus)
Mammalia Gzmg 17 31 30
  • 68.84 (n)
Gzme 31
  • 57 (a)
OneToMany
Gzmf 31
  • 57 (a)
OneToMany
Gzmn 31
  • 57 (a)
OneToMany
Gzmd 31
  • 56 (a)
OneToMany
oppossum
(Monodelphis domestica)
Mammalia -- 31
  • 52 (a)
OneToMany
platypus
(Ornithorhynchus anatinus)
Mammalia -- 31
  • 47 (a)
OneToMany
Species where no ortholog for GZMH was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • chicken (Gallus gallus)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • dog (Canis familiaris)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • lizard (Anolis carolinensis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • tropical clawed frog (Silurana tropicalis)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)
  • zebrafish (Danio rerio)

Evolution for GZMH Gene

ENSEMBL:
Gene Tree for GZMH (if available)
TreeFam:
Gene Tree for GZMH (if available)
Aminode:
Evolutionary constrained regions (ECRs) for GZMH: view image

Paralogs for GZMH Gene

Paralogs for GZMH Gene

genes like me logo Genes that share paralogs with GZMH: view

Variants for GZMH Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for GZMH Gene

SNP ID Clinical significance and condition Chr 14 pos Variation AA Info Type
779654 Benign: not provided 24,606,604(-) T/A STOP_LOST
rs20545 - p.Arg84Gln

Additional dbSNP identifiers (rs#s) for GZMH Gene

Structural Variations from Database of Genomic Variants (DGV) for GZMH Gene

Variant ID Type Subtype PubMed ID
esv2748495 CNV deletion 23290073
nsv510631 CNV deletion 20534489

Variation tolerance for GZMH Gene

Residual Variation Intolerance Score: 85.4% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.62; 31.12% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for GZMH Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
GZMH

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for GZMH Gene

Disorders for GZMH Gene

MalaCards: The human disease database

(2) MalaCards diseases for GZMH Gene - From: DISEASES

Disorder Aliases PubMed IDs
lipodystrophy, congenital generalized, type 2
  • lipoatrophic diabetes
complete generalized lipodystrophy
- elite association - COSMIC cancer census association via MalaCards
Search GZMH in MalaCards View complete list of genes associated with diseases

Additional Disease Information for GZMH

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with GZMH: view

No data available for UniProtKB/Swiss-Prot and Genatlas for GZMH Gene

Publications for GZMH Gene

  1. Structure and evolutionary origin of the human granzyme H gene. (PMID: 2049336) Haddad P … Sasportes M (International immunology 1991) 2 3 4 23 54
  2. Characterization of a novel, human cytotoxic lymphocyte-specific serine protease cDNA clone (CSP-C). (PMID: 2402757) Klein JL … Dupont B (Tissue antigens 1990) 3 4 23 54
  3. Identification of SERPINB1 as a physiological inhibitor of human granzyme H. (PMID: 23269243) Wang L … Fan Z (Journal of immunology (Baltimore, Md. : 1950) 2013) 3 4 54
  4. Structural insights into the substrate specificity of human granzyme H: the functional roles of a novel RKR motif. (PMID: 22156497) Wang L … Fan Z (Journal of immunology (Baltimore, Md. : 1950) 2012) 3 4 54
  5. Investigation of genetic susceptibility factors for human longevity - a targeted nonsynonymous SNP study. (PMID: 20800603) Flachsbart F … Nebel A (Mutation research 2010) 3 41 54

Products for GZMH Gene

Sources for GZMH Gene