GZMH

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

Basic information

Region (hg38): 14:24606480-24609699

Previous symbols: [ "CTSGL2" ]

Links

ENSG00000100450 ∙ NCBI:2999 ∙ OMIM:116831 ∙ HGNC:4710 ∙ Uniprot:P20718 ∙ 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 GZMH gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GZMH 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			20	3		23
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	20	3	0

Variants in GZMH

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

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

Position	Type	Phenotype	Significance	ClinVar
14-24606604-T-A			Benign (Aug 20, 2018)
14-24606610-C-T		not specified	Uncertain significance (Dec 08, 2023)
14-24606611-G-A		not specified	Likely benign (May 08, 2024)
14-24606614-T-C		not specified	Uncertain significance (Sep 17, 2021)
14-24606698-G-T		not specified	Uncertain significance (Dec 11, 2024)
14-24606703-C-T		not specified	Uncertain significance (Feb 11, 2025)
14-24606737-C-T		not specified	Uncertain significance (Feb 20, 2025)
14-24607157-C-T		not specified	Likely benign (Feb 07, 2025)
14-24607168-T-G		not specified	Likely benign (May 15, 2024)
14-24607191-C-A		not specified	Uncertain significance (Sep 03, 2024)
14-24607196-T-G		not specified	Uncertain significance (Jan 26, 2022)
14-24607198-G-A		not specified	Uncertain significance (Feb 05, 2025)
14-24607225-C-T		not specified	Uncertain significance (Jan 10, 2025)
14-24607226-G-A		not specified	Uncertain significance (Jan 31, 2025)
14-24607271-G-C		not specified	Uncertain significance (Aug 23, 2021)
14-24607334-G-A		not specified	Uncertain significance (Mar 11, 2025)
14-24607351-C-T		not specified	Uncertain significance (Jun 10, 2024)
14-24607355-T-C		not specified	Uncertain significance (Dec 21, 2022)
14-24607373-G-A		not specified	Uncertain significance (Feb 26, 2024)
14-24607375-A-G		not specified	Uncertain significance (Oct 20, 2024)
14-24607402-T-C		not specified	Uncertain significance (Oct 20, 2023)
14-24607629-C-T		not specified	Uncertain significance (Jun 23, 2021)
14-24607632-T-C		not specified	Uncertain significance (Nov 28, 2024)
14-24607715-A-G		not specified	Uncertain significance (Jan 29, 2024)
14-24607725-C-A		not specified	Uncertain significance (May 06, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GZMH	protein_coding	protein_coding	ENST00000216338	5	3220

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.28e-7	0.115	125703	0	45	125748	0.000179

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.596	157	137	1.14	0.00000728	1590
Missense in Polyphen		57	45.35	1.2569		545
Synonymous	-1.50	67	53.1	1.26	0.00000267	490
Loss of Function	-0.309	10	9.00	1.11	3.81e-7	110

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00139	0.00138
Ashkenazi Jewish	0.00	0.00
East Asian	0.000218	0.000217
Finnish	0.00	0.00
European (Non-Finnish)	0.0000894	0.0000879
Middle Eastern	0.000218	0.000217
South Asian	0.000231	0.000229
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: 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. {ECO:0000269|PubMed:22156497, ECO:0000269|PubMed:23269243}.
• Pathway: Peptide hormone metabolism;Metabolism of proteins;Metabolism of Angiotensinogen to Angiotensins;Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) (Consensus)

Recessive Scores

• pRec: 0.135

Intolerance Scores

• loftool: 0.358
• rvis_EVS: 0.31
• rvis_percentile_EVS: 72.23

Haploinsufficiency Scores

• pHI: 0.289
• hipred: N
• hipred_score: 0.112
• ghis: 0.391

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.00000215

Gene Damage Prediction

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

Gene ontology

• Biological process: proteolysis;apoptotic process;granzyme-mediated apoptotic signaling pathway;cytolysis
• Cellular component: cytoplasm;membrane
• Molecular function: serine-type endopeptidase activity