LYZ

protein-coding

lysozyme, the group of Lysozymes, c-type

Gene summary

This gene encodes human lysozyme, whose natural substrate is the bacterial cell wall peptidoglycan (cleaving the beta[1-4]glycosidic linkages between N-acetylmuramic acid and N-acetylglucosamine). Lysozyme is one of the antimicrobial agents found in human milk, and is also present in spleen, lung, kidney, white blood cells, plasma, saliva, and tears. The protein has antibacterial activity against a number of bacterial species. Missense mutations in this gene have been identified in heritable renal amyloidosis. [provided by RefSeq, Oct 2014]

MANE transcript

NM_000239.3

Inheritance

ClinVar variants

P:5U:36B:21

Top phenotype

Amyloidosis, systemic nonneuropathic

gnomAD constraint

pLI —, LoF o/e 1.08

Max pathogenic AF

—

Genomic locus

chr12:69,348,381-69,354,234

External References & Databases

Ensembl (ENSG00000090382)

Transcript & Mutation Effects

hg38 • Region Span ~5.9 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

familial visceral amyloidosisSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0007099

Submitter: PanelApp Australia

familial visceral amyloidosisMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0007099

Submitter: Ambry Genetics

familial visceral amyloidosisSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0007099

Submitter: Labcorp Genetics (formerly Invitae)

ALys amyloidosisSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0019732

Submitter: Orphanet

Clinical Genomic Database (CGD)

Amyloidosis, systemic nonneuropathicAD

Manifestation: Dermatologic; Gastrointestinal; Renal

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Comments: The treatment of amyloidosis differs depending on the genetic cause (and genetic diagnosis may additionally help avoid relatively high-risk treatment regimens), and in lysozyme amyloidosis, liver and renal transplantation may be beneficial, but it is not clear that early (genetic) diagnosis would be beneficial

Refs: 8464497; 15745733; 21988333

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to LYZ variants in ClinVar

6 Conditions Cataloged

not providedTotal: 28

Amyloidosis, hereditary systemic 5Total: 26

Inborn genetic diseasesTotal: 19

Familial visceral amyloidosis, Ostertag typeTotal: 11

not specifiedTotal: 9

LYZ-related disordersTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000239.3. 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			1 clinvar	6 clinvar		7
missense	5 clinvar		28 clinvar	12 clinvar	1 clinvar	46
nonsense			4 clinvar	2 clinvar		6
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	5	0	36	20	1	62

Highest pathogenic variant AF is 6.8408065e-7

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_000239.3	RefSeq	NP_000230.1	4	MANE Select
ENST00000261267.7	Ensembl	ENSP00000261267.2	4	MANE Select
ENST00000548839.1	Ensembl	ENSP00000449969.1	2	Standard
ENST00000548839.2	Ensembl	ENSP00000449969.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Salivary secretion - Homo sapiens (human)
Macrophage markers
Macrophage markers
Neutrophil degranulation
Antimicrobial peptides

Biological Process

retina homeostasis
inflammatory response
antimicrobial humoral response
cytolysis
killing of cells of other organism

Molecular Function

lysozyme activity
identical protein binding

Cellular Component

extracellular region
extracellular space
azurophil granule lumen
specific granule lumen
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000261267
Coding exons: 4
Length: 5894
Individuals with no LoFs: 125672
Homozygous LoFs: 0
Heterozygous LoFs: 74
Defined: 125746
p: 0.000294

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.732	65	83.9	0.775	0.00000459	963
Missense (PolyPhen)		10	20.936	0.47764		272
Synonymous	0.0192	28	28.1	0.995	0.00000138	284
Loss of Function	-0.201	8	7.41	1.08	4.13e-7	82

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.00040	0.00040	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.0021	0.0021	notable
Finnish	0	0.0	absent
European (Non-Finnish)	0.00015	0.00014	rare
South Asian	0.000065	0.000065	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Lysozymes have primarily a bacteriolytic function; those in tissues and body fluids are associated with the monocyte- macrophage system and enhance the activity of immunoagents.;
Disease: DISEASE: Amyloidosis 8 (AMYL8) [MIM:105200]: A form of hereditary generalized amyloidosis. Clinical features include extensive visceral amyloid deposits, renal amyloidosis resulting in nephrotic syndrome, arterial hypertension, hepatosplenomegaly, cholestasis, petechial skin rash. There is no involvement of the nervous system. {ECO:0000269|PubMed:8464497}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.101

Intolerance Scores

LoFtool: 0.660
RVIS EVS: 0.3
RVIS percentile EVS: 72.01

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.988

Gene Damage Prediction

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