GZMA

granzyme A, the group of Granule associated serine proteases of immune defence

Basic information

Region (hg38): 5:55102646-55110252

Previous symbols: [ "HFSP", "CTLA3" ]

Links

ENSG00000145649 ∙ NCBI:3001 ∙ OMIM:140050 ∙ HGNC:4708 ∙ Uniprot:P12544 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GZMA gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GZMA gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous						0
missense			19	2	1	22
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	19	2	1

Variants in GZMA

This is a list of pathogenic ClinVar variants found in the GZMA region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
5-55102728-G-A		not specified	Likely benign (Oct 16, 2024)
5-55102728-G-T		not specified	Uncertain significance (Jun 30, 2023)
5-55105474-A-T		not specified	Uncertain significance (Oct 03, 2022)
5-55105519-C-T		not specified	Uncertain significance (May 24, 2024)
5-55105593-G-A		not specified	Uncertain significance (Aug 13, 2021)
5-55107916-G-A		not specified	Uncertain significance (Mar 26, 2024)
5-55108142-A-C		not specified	Uncertain significance (Apr 29, 2024)
5-55108180-A-T		not specified	Uncertain significance (Nov 20, 2024)
5-55108185-G-C		not specified	Uncertain significance (Mar 10, 2025)
5-55108219-C-T		not specified	Uncertain significance (Jun 30, 2024)
5-55108244-T-G		not specified	Uncertain significance (May 26, 2024)
5-55108285-T-C		not specified	Uncertain significance (Aug 01, 2022)
5-55108300-T-C		not specified	Uncertain significance (Nov 01, 2022)
5-55108312-G-A		not specified	Uncertain significance (Jul 09, 2021)
5-55108345-T-C		not specified	Uncertain significance (Apr 07, 2023)
5-55108350-A-G			Benign (Jun 05, 2018)
5-55108372-G-A		not specified	Uncertain significance (Jun 11, 2024)
5-55108383-G-C		not specified	Uncertain significance (Jun 26, 2024)
5-55110034-G-A		not specified	Uncertain significance (May 25, 2022)
5-55110106-G-A		not specified	Likely benign (Jan 16, 2025)
5-55110118-T-C		not specified	Uncertain significance (Nov 27, 2023)
5-55110148-A-G		not specified	Likely benign (Jun 07, 2024)
5-55110172-G-T		not specified	Uncertain significance (Aug 04, 2021)
5-55110177-G-A		not specified	Uncertain significance (May 28, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GZMA	protein_coding	protein_coding	ENST00000274306	5	7605

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000205	0.280	125625	0	22	125647	0.0000876

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.169	136	142	0.960	0.00000687	1705
Missense in Polyphen		59	54.164	1.0893		664
Synonymous	0.795	43	50.2	0.857	0.00000263	520
Loss of Function	0.183	9	9.61	0.936	4.69e-7	122

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000182	0.000181
Ashkenazi Jewish	0.00	0.00
East Asian	0.000219	0.000218
Finnish	0.00	0.00
European (Non-Finnish)	0.000106	0.000106
Middle Eastern	0.000219	0.000218
South Asian	0.0000980	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Abundant protease in the cytosolic granules of cytotoxic T-cells and NK-cells which activates caspase-independent cell death with morphological features of apoptosis when delivered into the target cell through the immunological synapse. It cleaves after Lys or Arg. Cleaves APEX1 after 'Lys-31' and destroys its oxidative repair activity. Cleaves the nucleosome assembly protein SET after 'Lys-189', which disrupts its nucleosome assembly activity and allows the SET complex to translocate into the nucleus to nick and degrade the DNA. {ECO:0000269|PubMed:11555662, ECO:0000269|PubMed:12524539, ECO:0000269|PubMed:12628186, ECO:0000269|PubMed:16818237}.
• Pathway: Neuroactive ligand-receptor interaction - Homo sapiens (human);granzyme a mediated apoptosis pathway;tsp-1 induced apoptosis in microvascular endothelial cell;IL12-mediated signaling events (Consensus)

Recessive Scores

• pRec: 0.0673

Intolerance Scores

• loftool: 0.494
• rvis_EVS: -0.23
• rvis_percentile_EVS: 37.32

Haploinsufficiency Scores

• pHI: 0.105
• hipred: N
• hipred_score: 0.147
• ghis: 0.429

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.192

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Gzma
• Phenotype: mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype; neoplasm; immune system phenotype

Gene ontology

• Biological process: apoptotic process;immune response;response to bacterium;cytolysis;negative regulation of endodeoxyribonuclease activity;positive regulation of apoptotic process;negative regulation of DNA binding;negative regulation of oxidoreductase activity;proteolysis involved in cellular protein catabolic process
• Cellular component: immunological synapse;extracellular region;nucleus
• Molecular function: serine-type endopeptidase activity;protein binding;protein homodimerization activity