GZMM

protein-coding

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

Gene summary

Human natural killer (NK) cells and activated lymphocytes express and store a distinct subset of neutral serine proteases together with proteoglycans and other immune effector molecules in large cytoplasmic granules. These serine proteases are collectively termed granzymes and include 4 distinct gene products: granzyme A, granzyme B, granzyme H, and the protein encoded by this gene, granzyme M. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]

MANE transcript

NM_005317.4

Inheritance

—

ClinVar variants

U:47B:5

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.52

Max pathogenic AF

—

Genomic locus

chr19:544,034-549,924

External References & Databases

Ensembl (ENSG00000197540)

Transcript & Mutation Effects

hg38 • Region Span ~5.9 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 GZMM variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 45

not providedTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005317.4. 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			2 clinvar	1 clinvar	1 clinvar	4
missense			45 clinvar	1 clinvar	2 clinvar	48
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	47	2	3	52

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 7 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005317.4	RefSeq	NP_005308.2	5	MANE Select
ENST00000264553.6	Ensembl	ENSP00000264553.1	5	MANE Select
NM_001258351.2	RefSeq	NP_001245280.2	4	Standard
ENST00000592501.5	Ensembl	ENSP00000476255.2	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Innate Immune System
Immune System
Initial triggering of complement
Complement cascade
Alternative complement activation

Biological Process

T cell mediated cytotoxicity
proteolysis
apoptotic process
cell death
cytolysis

Molecular Function

serine-type endopeptidase activity
protein binding
serine-type peptidase activity

Cellular Component

extracellular region
membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000264553
Coding exons: 5
Length: 5886
Individuals with no LoFs: 125594
Homozygous LoFs: 2
Heterozygous LoFs: 21
Defined: 125617
p: 0.0000916

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.0733	166	163	1.02	0.0000108	1596
Missense (PolyPhen)		61	55.157	1.1059		577
Synonymous	-1.00	86	74.9	1.15	0.00000511	568
Loss of Function	1.22	4	7.62	0.525	3.25e-7	89

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00012	0.00011	rare
Finnish	0.00032	0.00028	rare
European (Non-Finnish)	0.000032	0.000026	rare
South Asian	0.00044	0.00033	rare
Other	0.00020	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Cleaves peptide substrates after methionine, leucine, and norleucine. Physiological substrates include EZR, alpha- tubulins and the apoptosis inhibitor BIRC5/Survivin. Promotes caspase activation and subsequent apoptosis of target cells. {ECO:0000269|PubMed:18523284, ECO:0000269|PubMed:20406824}.;

Intolerance Scores

RVIS EVS: 0.98
RVIS percentile EVS: 90.38

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.189

Gene Damage Prediction

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