GZMK

protein-coding

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

Gene summary

This gene product is a member of a group of related serine proteases from the cytoplasmic granules of cytotoxic lymphocytes. Cytolytic T lymphocytes (CTL) and natural killer (NK) cells share the remarkable ability to recognize, bind, and lyse specific target cells. They are thought to protect their host by lysing cells bearing on their surface 'nonself' antigens, usually peptides or proteins resulting from infection by intracellular pathogens. The protein described here lacks consensus sequences for N-glycosylation present in other granzymes. [provided by RefSeq, Jul 2008]

MANE transcript

NM_002104.3

Inheritance

—

ClinVar variants

U:35B:7

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.46

Max pathogenic AF

—

Genomic locus

chr5:55,024,256-55,034,570

External References & Databases

Ensembl (ENSG00000113088)

Transcript & Mutation Effects

hg38 • Region Span ~10.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to GZMK variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 38

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002104.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous						0
missense			35 clinvar	7 clinvar		42
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	35	7	0	42

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 3 of 3 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002104.3	RefSeq	NP_002095.1	5	MANE Select
ENST00000231009.3	Ensembl	ENSP00000231009.2	5	MANE Select
ENST00001090631.1	Ensembl	ENSP00000760437.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

proteolysis

Molecular Function

serine-type endopeptidase activity
serine-type peptidase activity

Cellular Component

extracellular region

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000231009
Coding exons: 5
Length: 10318
Individuals with no LoFs: 125673
Homozygous LoFs: 0
Heterozygous LoFs: 72
Defined: 125745
p: 0.000286

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.318	132	143	0.925	0.00000706	1701
Missense (PolyPhen)		58	58.34	0.99416		682
Synonymous	-0.321	57	54.0	1.06	0.00000293	528
Loss of Function	1.66	5	10.9	0.458	6.09e-7	129

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0021	0.0021	notable
Latino/Admixed American	0.00085	0.00084	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000035	0.000035	rare
South Asian	0.000066	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Intolerance Scores

LoFtool: 0.303
RVIS EVS: -0.27
RVIS percentile EVS: 34.6

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0788

Gene Damage Prediction

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