LYZ

Summary

LYZ (lysozyme, HGNC:6740) is a protein-coding gene on chromosome 12q15, encoding Lysozyme C (P61626). 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.

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.

Source: NCBI Gene 4069 — RefSeq curated summary.

At a glance

• Gene–disease (curated): familial visceral amyloidosis (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 11
• Clinical variants (ClinVar): 105 total — 5 pathogenic
• Phenotypes (HPO): 16
• MANE Select transcript: NM_000239

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6740
Approved symbol	LYZ
Name	lysozyme
Location	12q15
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000090382
Ensembl biotype	protein_coding
OMIM	153450
Entrez	4069

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000261267, ENST00000548839, ENST00000549690

RefSeq mRNA: 1 — MANE Select: NM_000239 NM_000239

CCDS: CCDS8989

Canonical transcript exons

ENST00000261267 — 4 exons

Exon	Start	End
ENSE00000920752	69352220	69352298
ENSE00000920753	69350108	69350272
ENSE00000920754	69348381	69348544
ENSE00001263888	69353153	69354234

Expression profiles

Bgee: expression breadth ubiquitous, 270 present calls, max score 99.99.

FANTOM5 (CAGE): breadth broad, TPM avg 834.4079 / max 67232.6454, expressed in 609 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
126680	823.7360	609
126691	3.2997	266
126692	2.4619	253
126687	1.5952	227
126690	1.4262	210
126693	1.1432	198
126688	0.3590	142
126686	0.1723	102
126694	0.1186	53
126689	0.0959	64

Top tissues by expression

296 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	99.99	gold quality
leukocyte	CL:0000738	99.98	gold quality
mononuclear cell	CL:0000842	99.98	gold quality
pylorus	UBERON:0001166	99.97	gold quality
granulocyte	CL:0000094	99.95	gold quality
trachea	UBERON:0003126	99.95	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	99.92	gold quality
parotid gland	UBERON:0001831	99.89	gold quality
trabecular bone tissue	UBERON:0002483	99.87	gold quality
bone marrow	UBERON:0002371	99.83	gold quality
nasopharynx	UBERON:0001728	99.82	gold quality
epithelium of nasopharynx	UBERON:0001951	99.82	gold quality
blood	UBERON:0000178	99.79	gold quality
gall bladder	UBERON:0002110	99.79	gold quality
pancreatic ductal cell	CL:0002079	99.77	gold quality
bone marrow cell	CL:0002092	99.72	gold quality
jejunal mucosa	UBERON:0000399	99.71	gold quality
vermiform appendix	UBERON:0001154	99.65	gold quality
superior surface of tongue	UBERON:0007371	99.63	gold quality
visceral pleura	UBERON:0002401	99.61	gold quality
duodenum	UBERON:0002114	99.60	gold quality
cardia of stomach	UBERON:0001162	99.59	gold quality
nasal cavity mucosa	UBERON:0001826	99.57	gold quality
lower lobe of lung	UBERON:0008949	99.46	gold quality
mucosa of sigmoid colon	UBERON:0004993	99.43	gold quality
tonsil	UBERON:0002372	99.40	gold quality
palpebral conjunctiva	UBERON:0001812	99.30	gold quality
adult organism	UBERON:0007023	99.29	gold quality
right lung	UBERON:0002167	99.26	gold quality
rectum	UBERON:0001052	99.10	gold quality

Single-cell (SCXA)

Detected in 67 experiment(s), a significant marker in 66.

Experiment	Marker?	Max mean expression
E-GEOD-89232	yes	138850.68
E-MTAB-10855	yes	31096.56
E-MTAB-9801	yes	26387.77
E-CURD-46	yes	23396.87
E-HCAD-4	yes	21561.64
E-CURD-112	yes	20799.89
E-MTAB-6678	yes	20389.38
E-MTAB-10432	yes	17183.63
E-HCAD-10	yes	16089.58
E-CURD-55	yes	15937.52
E-MTAB-8495	yes	15408.26
E-MTAB-6308	yes	15029.29
E-GEOD-150728	yes	14158.63
E-HCAD-1	yes	13704.35
E-GEOD-139324	yes	13244.21

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTCF, CTNNB1, EHF, ELF1, ELF3, ELF4, ELF5, ETS1, IRF1, MYB, NR3C1, PGR, REL, RELA, RUNX1, SP1, SPI1, SSRP1, YY1

miRNA regulators (miRDB)

61 targeting LYZ, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-2681-5P	99.75	67.64	1655
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-518A-5P	99.70	69.01	2209
HSA-MIR-527	99.70	69.01	2209
HSA-MIR-452-5P	99.65	69.63	1762
HSA-MIR-4676-3P	99.65	69.31	1733
HSA-MIR-892C-3P	99.65	69.38	1745
HSA-MIR-6126	99.62	68.09	996
HSA-MIR-514B-5P	99.50	68.19	1766
HSA-MIR-5571-5P	99.49	66.99	1764
HSA-MIR-12131	99.48	68.72	1673
HSA-MIR-140-5P	99.44	67.20	792
HSA-MIR-183-3P	99.41	69.41	1598
HSA-MIR-3182	99.40	68.15	2454
HSA-MIR-7515	99.31	68.22	1795
HSA-MIR-3606-5P	99.31	69.67	1168

Literature-anchored findings (GeneRIF, showing 40)

• a residue at the N-terminal of lysozyme is required for hydrogen bond networks with ordered water molecules and stabilization of the protein. (PMID:10561612)
• Local cooperativity in the unfolding of an amyloidogenic variant of human lysozyme (PMID:11887182)
• Positive contribution of hydration structure on the surface of human lysozyme to the conformational stability. (PMID:11927576)
• up-regulated by the AML1-MTG8 fusion protein, suggesting a role in the granulocytic maturation characteristic of the t(8;21) acute myelogenous leukemia (PMID:11986950)
• Streptococcal inhibitor of complement inhibits two additional components of the mucosal innate immune system: secretory leukocyte proteinase inhibitor and lysozyme. (PMID:12183536)
• Detailed comparison between the 35 degree C and 4 degree C structures of lysozyme revealed for the first time that an active site lobe has a structural ability to obstruct the polysaccharide-binding cleft only by temperature lowering without a substrate. (PMID:12564923)
• Structural and folding dynamic properties of human lysozyme T70N variant (PMID:12709420)
• promyelocytic leukemia protein, but not Sp100, induced the accumulation of MEF in PML nuclear bodies and MEF and PML physically interacted, stimulating MEF transcriptional activity, resulting in the up-regulation of endogenous lysozyme expression. (PMID:14976184)
• Hydrostatic pressure (3.5 kbar at 57 degrees C, pH 7.4) was used to make amyloidogenic states of WT & variant(Ile56Thr & Asp67His) lysozymes by inducing a conformational state of lysozyme that aggregates readily upon decompression. (PMID:15155566)
• amyloidogenic variants, I56T and D67H, show a specific, partly unfolded intermediate state under physiologically relevant conditions (PMID:15713462)
• the ensemble of reduced denatured conformers initially collapses into a large number of unstructured intermediates with one or two disulphide bonds, the majority of which then fold to form the native-like three-disulphide intermediate, des-[77-95] (PMID:16023673)
• Data suggest that partial unfolding is an intrinsic property of the human lysozyme structure, and suggest that the readiness with which it occurs is a critical feature determining whether or not amyloid deposition occurs in vivo. (PMID:16126226)
• A novel form of systemic ALys amyloidosis, caused by compound heterozygosity in exon 2 (p.T70N) and exon 4 (p.W112R) of the lysozyme gene (LYZ), with both mutations being present on the same allele. (PMID:16329101)
• Lysozyme functions as an antimicrobial peptide, with antibacterial activity. (PMID:16416029)
• findings indicate that a complex interplay between reduced native-state stability, lower secretion levels, and protein aggregation propensity influences the types of mutation that give rise to familial forms of amyloid disease (PMID:16441658)
• report a case of hepatic rupture secondary to hereditary lysozyme amyloidosis that was successfully treated by liver transplantation (PMID:16799949)
• The distortion of the hydrophobic core at the alpha- and beta-interface putatively results in the formation of the initial “seed” for amyloid fibril. (PMID:17054380)
• The structure of the synthetic human lysozyme was confirmed by high-resolution x-ray diffraction, giving the highest-resolution structure (1.04 A) observed to date for this enzyme. (PMID:17360367)
• Clusterin, and perhaps other extracellular chaperones, could have a key role in curtailing the potentially pathogenic effects of the misfolding and aggregation of proteins that, like lysozyme, are secreted into the extracellular environment. (PMID:17407782)
• Thus, we provide a novel strategy for engineering the active site of enzymes. (PMID:17524359)
• The influence of mutant signal peptides on enzymatic activity of lysozyme at high pH or ionic strength were studied. (PMID:18029788)
• short-duration, high-intensity exercise increases the secretion rate of salivary Lysozyme despite no change in the saliva flow rate. (PMID:18344136)
• High salivary lysozyme levels are associated with the odds of hypertension. (PMID:18434581)
• Lysozyme activity in crevicular fluid and in unstimulated saliva correlated with periodontal pocket depth in donors and in patients with gingivitis or periodontitis. (PMID:19179970)
• Results show that the cationic nature is not a major determinant in the anti-HSV action of mucosal innate cationic polypeptides, since whereas human Lactoferrin inhibited HSV-1 infection efficiently, human lysozyme had no HSV-1 inhibiting activity. (PMID:19435495)
• There was no difference in the concentration of lysozyme in children with dental caries than that in controls. (PMID:19563039)
• Raised plasma lysozyme levels may be a useful biomarker of atherosclerotic cardiovascular disease and response to therapy. (PMID:20167661)
• increased production of the antibacterial enzyme lysozyme was found in collagenous colitis and lymphocytic colitis (PMID:21460390)
• Lysozyme is up-regulated in Barrett’s mucosa (PMID:21486364)
• The degree of residual structure of lysozyme correlates with the ability of the protein to form amyloid fibrils. (PMID:21574221)
• We observed that expressing the destabilized F57I and D67H lysozymes triggers unfolded protein response activation, resulting in degradation of these variants. (PMID:21965601)
• When Lzm-S was located in close proximity to vascular smooth muscle cells, it could generate H(2)O(2) to produce lengthening in a human cell culture preparation. (PMID:22096116)
• Lysozyme is up-regulated in Barrett’s mucosa (PMID:23155290)
• The purpose of this study was to evaluate the effect of chronic alcohol intoxication and smoking on the concentration and output of salivary lysozyme. (PMID:23264227)
• Both mRNA and protein levels of lysozyme were significantly higher in patients with biofilm associated chronic rhinosinusitis (CRS) than those with CRS and no biofilm and controls. (PMID:24121782)
• Lzm-S can deposit in the systemic vasculature and kidneys in SS, where this deposition could lead to acute organ dysfunction. (PMID:24296430)
• Data suggest that the invariant loop of PliC (periplasmic inhibitor of c-type lysozyme) from Brucella abortus plays crucial role in inhibition of human c-type lysozyme via its insertion into the active site cleft of lysozyme. (PMID:24308818)
• The dynamics of changes in lysozyme activity and content of lactoferrin content of patients with chronic osteomyelitis (PMID:24340941)
• the protective action of lysozyme on the nephrotoxic effects of advanced glycation end products depend on ability to prevent the production and release of inflammatory mediators, such as IL-6 and to reduce macrophage recruitment in the inflammatory sites. (PMID:24495950)
• Hereditary amyloidosis associated with the p.Trp82Arg lysozyme variant in this new family is predominantly associated with mild upper gastrointestinal tract involvement and in some cases with inflammatory bowel disease. (PMID:25217048)

Cross-species orthologs

13 orthologs

Organism	Symbol	Gene ID
mus_musculus	Lyz3	ENSMUSG00000020177
rattus_norvegicus	RGD1306474	ENSRNOG00000005790
drosophila_melanogaster	LysB	FBGN0004425
drosophila_melanogaster	LysD	FBGN0004427
drosophila_melanogaster	LysE	FBGN0004428
drosophila_melanogaster	LysP	FBGN0004429
drosophila_melanogaster	LysS	FBGN0004430
drosophila_melanogaster	LysX	FBGN0004431
drosophila_melanogaster	CG16756	FBGN0029765
drosophila_melanogaster	CG7798	FBGN0034092
drosophila_melanogaster	CG16799	FBGN0034538
drosophila_melanogaster	CG11159	FBGN0034539
drosophila_melanogaster	CG30062	FBGN0050062

Paralogs (8): LYZL1 (ENSG00000120563), SPACA3 (ENSG00000141316), LYZL2 (ENSG00000151033), LYZL4 (ENSG00000157093), LALBA (ENSG00000167531), SPACA5B (ENSG00000171478), SPACA5 (ENSG00000171489), LYZL6 (ENSG00000275722)

Protein

Protein identifiers

Lysozyme C — P61626 (reviewed: P61626)

Alternative names: 1,4-beta-N-acetylmuramidase C

All UniProt accessions (4): P61626, A0A0B4J259, B2R4C5, F8VV32

UniProt curated annotations — full annotation on UniProt →

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.

Subunit / interactions. Monomer.

Subcellular location. Secreted.

Disease relevance. Amyloidosis, hereditary systemic 5 (AMYLD5) [MIM:620658] A form of hereditary systemic amyloidosis, a disorder characterized by amyloid deposition in multiple tissues resulting in a wide clinical spectrum. AMYLD5 primarily affects the viscera, and the predominant clinical features are renal dysfunction of varying severity, and intra-abdominal bleeding. Inheritance is autosomal dominant. The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous. Lysozyme C is capable of both hydrolysis and transglycosylation; it also shows a slight esterase activity. It acts rapidly on both peptide-substituted and unsubstituted peptidoglycan, and slowly on chitin oligosaccharides.

Similarity. Belongs to the glycosyl hydrolase 22 family.

RefSeq proteins (1): NP_000230* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000974	Glyco_hydro_22_lys	Family
IPR001916	Glyco_hydro_22	Family
IPR019799	Glyco_hydro_22_CS	Domain
IPR023346	Lysozyme-like_dom_sf	Homologous_superfamily

Pfam: PF00062

Enzyme classification (BRENDA):

• EC 3.2.1.17 — lysozyme (BRENDA: 110 organisms, 187 substrates, 100 inhibitors, 8 Km, 2 kcat entries)

Substrate kinetics (BRENDA)

3 substrates with measured Km, best-characterized 3. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
4-METHYLUMBELLIFERYL-BETA-D-N,N’,N’’-TRIACETYLCH	0.0008–0.001	2
P-NITROPHENYL-N,N’,N’’,N’’’,N’’’’-PENTAACETYLCHI	8.33	1
P-NITROPHENYL-GLCNACBETA(1-4)GLCNACBETA(1-4)GLCN	—	0

UniProt features (40 total): strand 9, helix 8, sequence conflict 6, turn 5, disulfide bond 4, sequence variant 3, active site 2, signal peptide 1, chain 1, domain 1

Structure

Experimental structures (PDB)

215 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
2NWD	X-RAY DIFFRACTION	1.04
5LSH	X-RAY DIFFRACTION	1.06
1JSF	X-RAY DIFFRACTION	1.15
7AP7	X-RAY DIFFRACTION	1.15
7XF6	X-RAY DIFFRACTION	1.3
1IWT	X-RAY DIFFRACTION	1.4
1IWU	X-RAY DIFFRACTION	1.4
1IWV	X-RAY DIFFRACTION	1.4
1IWW	X-RAY DIFFRACTION	1.4
1IWX	X-RAY DIFFRACTION	1.4
1IWY	X-RAY DIFFRACTION	1.4
1JWR	X-RAY DIFFRACTION	1.4
6LFH	X-RAY DIFFRACTION	1.46
1IWZ	X-RAY DIFFRACTION	1.48
1LZ1	X-RAY DIFFRACTION	1.5
1LZR	X-RAY DIFFRACTION	1.5
1REX	X-RAY DIFFRACTION	1.5
3FE0	X-RAY DIFFRACTION	1.5
4R0P	X-RAY DIFFRACTION	1.52
7XF7	X-RAY DIFFRACTION	1.55
1JKC	X-RAY DIFFRACTION	1.6
1LMT	X-RAY DIFFRACTION	1.6
1LZS	X-RAY DIFFRACTION	1.6
7XF8	X-RAY DIFFRACTION	1.6
1JKA	X-RAY DIFFRACTION	1.66
1JKB	X-RAY DIFFRACTION	1.66
1GE1	X-RAY DIFFRACTION	1.7
1REY	X-RAY DIFFRACTION	1.7
1REZ	X-RAY DIFFRACTION	1.7
1TAY	X-RAY DIFFRACTION	1.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P61626-F1	94.43	0.89

Antibody-complex structures (SAbDab): 3 — 1OP9, 3EBA, 4I0C

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (2): 53; 71

Disulfide bonds (4): 24–146, 48–134, 83–99, 95–113

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-6798695	Neutrophil degranulation
R-HSA-6803157	Antimicrobial peptides
R-HSA-977225	Amyloid fiber formation
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-392499	Metabolism of proteins

MSigDB gene sets: 334 (showing top): MODULE_172, TURASHVILI_BREAST_LOBULAR_CARCINOMA_VS_DUCTAL_NORMAL_UP, WALLACE_PROSTATE_CANCER_RACE_UP, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_ANTIMICROBIAL_HUMORAL_RESPONSE, MCLACHLAN_DENTAL_CARIES_UP, MODULE_255, GOBP_INFLAMMATORY_RESPONSE, BROWNE_HCMV_INFECTION_8HR_UP, GOCC_SECRETORY_GRANULE, MODULE_151, STEARMAN_LUNG_CANCER_EARLY_VS_LATE_DN, CHIANG_LIVER_CANCER_SUBCLASS_UNANNOTATED_DN, HOEGERKORP_CD44_TARGETS_TEMPORAL_DN, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_DN

GO Biological Process (6): inflammatory response (GO:0006954), antimicrobial humoral response (GO:0019730), killing of cells of another organism (GO:0031640), defense response to bacterium (GO:0042742), defense response to Gram-negative bacterium (GO:0050829), defense response to Gram-positive bacterium (GO:0050830)

GO Molecular Function (5): lysozyme activity (GO:0003796), identical protein binding (GO:0042802), catalytic activity (GO:0003824), hydrolase activity (GO:0016787), hydrolase activity, acting on glycosyl bonds (GO:0016798)

GO Cellular Component (6): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), azurophil granule lumen (GO:0035578), specific granule lumen (GO:0035580), extracellular exosome (GO:0070062), tertiary granule lumen (GO:1904724)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Innate Immune System	2
Metabolism of proteins	1
Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
defense response	2
defense response to bacterium	2
secretory granule lumen	2
humoral immune response	1
defense response to symbiont	1
cell killing	1
disruption of cell in another organism	1
response to bacterium	1
hydrolase activity, hydrolyzing O-glycosyl compounds	1
peptidoglycan muralytic activity	1
protein binding	1
molecular_function	1
catalytic activity	1
hydrolase activity	1
cellular anatomical structure	1
vacuolar lumen	1
azurophil granule	1
specific granule	1
extracellular vesicle	1
intracellular organelle lumen	1
tertiary granule	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

119 interactions, top by confidence:

A	B	Type	Score
SMARCE1	ARID1A	psi-mi:“MI:0914”(association)	0.840
COMMD1	VPS26C	psi-mi:“MI:0914”(association)	0.730
E6	TAX1BP3	psi-mi:“MI:0914”(association)	0.650
ESR1	TRIM24	psi-mi:“MI:0914”(association)	0.640
LYZ	LYZ	psi-mi:“MI:0407”(direct interaction)	0.600
FRMD1	A2ML1	psi-mi:“MI:0914”(association)	0.530
DDX31	IGLL5	psi-mi:“MI:0914”(association)	0.530
HBM	SCGB2A1	psi-mi:“MI:0914”(association)	0.530
RIBC1	CNOT1	psi-mi:“MI:0914”(association)	0.530
EGFL8	MPO	psi-mi:“MI:0914”(association)	0.530
POLR2D	POLR2M	psi-mi:“MI:0914”(association)	0.530
NOS2	GAPDH	psi-mi:“MI:0914”(association)	0.500
CFTR	CNOT1	psi-mi:“MI:0914”(association)	0.480
LYZ	CFP	psi-mi:“MI:0407”(direct interaction)	0.440
	CD5L	psi-mi:“MI:0915”(physical association)	0.400
	LECT2	psi-mi:“MI:0915”(physical association)	0.400
	GNAT3	psi-mi:“MI:0915”(physical association)	0.400
GPC1	GANAB	psi-mi:“MI:0915”(physical association)	0.400
JUN		psi-mi:“MI:0914”(association)	0.350
CDK1	RBMXL2	psi-mi:“MI:0914”(association)	0.350
METTL3	TUBAL3	psi-mi:“MI:0914”(association)	0.350
PRNP	SYNJ1	psi-mi:“MI:0914”(association)	0.350
PRNP	MBP	psi-mi:“MI:0914”(association)	0.350
IFI44L	LDHA	psi-mi:“MI:0914”(association)	0.350
CUL4B	APBB1	psi-mi:“MI:0914”(association)	0.350

BioGRID (139): LYZ (Affinity Capture-MS), LYZ (Affinity Capture-MS), LYZ (Affinity Capture-MS), LYZ (Affinity Capture-MS), LYZ (Affinity Capture-MS), LYZ (Co-crystal Structure), LYZ (Affinity Capture-MS), LYZ (Affinity Capture-MS), LYZ (Affinity Capture-MS), LYZ (Affinity Capture-MS), LYZ (Affinity Capture-MS), LYZ (Affinity Capture-MS), LYZ (Affinity Capture-MS), LYZ (Affinity Capture-MS), LYZ (Affinity Capture-MS)

ESM2 similar proteins: A0JNM6, C5H5C4, O70309, P04421, P12068, P12069, P16973, P17607, P18084, P26012, P26013, P30201, P61626, P61627, P61628, P61629, P61630, P61631, P61632, P61633, P61634, P67977, P67978, P67979, P67980, P79158, P79179, P79180, P79239, P79268, P79294, P79687, P79806, P79811, P79847, P80189, P80190, P80747, Q06283, Q06284

Diamond homologs: A0JNM6, A2AE20, A6QQ77, B6VH75, B6VH76, G3XDT7, O75951, P00697, P00698, P00699, P00700, P00701, P00702, P00703, P00704, P00705, P00706, P00707, P00708, P04421, P08905, P11375, P11376, P11941, P12066, P12067, P12068, P12069, P16973, P17607, P17897, P19849, P22910, P24364, P24533, P30201, P37712, P37713, P49663, P61626

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
ELF4	“up-regulates quantity by expression”	LYZ	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

105 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	0
Uncertain significance	61
Likely benign	12
Benign	15

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
14374	NM_000239.3(LYZ):c.221T>C (p.Ile74Thr)	Pathogenic
14376	NM_000239.3(LYZ):c.244T>C (p.Trp82Arg)	Pathogenic
14377	NM_000239.3(LYZ):c.223T>A (p.Phe75Ile)	Pathogenic
14378	NM_000239.3(LYZ):c.244T>A (p.Trp82Arg)	Pathogenic
1879249	GRCh37/hg19 12q14.2-15(chr12:64609458-70352103)x1	Pathogenic

SpliceAI

462 predictions. Top by Δscore:

Variant	Effect	Δscore
12:69350270:GTG:G	donor_gain	1.0000
12:69352214:TTTCA:T	acceptor_loss	1.0000
12:69352215:TTCA:T	acceptor_loss	1.0000
12:69352216:TCA:T	acceptor_loss	1.0000
12:69352217:CAGC:C	acceptor_loss	1.0000
12:69352218:A:AG	acceptor_gain	1.0000
12:69352218:A:G	acceptor_loss	1.0000
12:69352219:G:GA	acceptor_gain	1.0000
12:69352219:GCT:G	acceptor_gain	1.0000
12:69352219:GCTT:G	acceptor_gain	1.0000
12:69352219:GCTTT:G	acceptor_gain	1.0000
12:69352294:GCATG:G	donor_gain	1.0000
12:69353149:ACAG:A	acceptor_gain	1.0000
12:69350107:GGGAT:G	acceptor_gain	0.9900
12:69350246:T:G	donor_gain	0.9900
12:69350270:GTGGT:G	donor_loss	0.9900
12:69350273:G:GG	donor_gain	0.9900
12:69350273:GTAAG:G	donor_loss	0.9900
12:69350274:T:A	donor_loss	0.9900
12:69350275:AA:A	donor_loss	0.9900
12:69350283:C:G	donor_gain	0.9900
12:69352219:GC:G	acceptor_gain	0.9900
12:69352299:GTATG:G	donor_loss	0.9900
12:69352300:TATGT:T	donor_loss	0.9900
12:69353147:CTACA:C	acceptor_loss	0.9900
12:69353148:TACAG:T	acceptor_loss	0.9900
12:69353150:CAGG:C	acceptor_loss	0.9900
12:69353151:AG:A	acceptor_gain	0.9900
12:69353151:AGGGT:A	acceptor_gain	0.9900
12:69353152:G:T	acceptor_loss	0.9900

AlphaMissense

966 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:69353153:G:C	W127C	0.994
12:69353153:G:T	W127C	0.994
12:69353162:G:C	W130C	0.993
12:69353162:G:T	W130C	0.993
12:69350218:T:A	C83S	0.991
12:69350219:G:C	C83S	0.991
12:69350206:A:C	S79R	0.989
12:69350208:C:A	S79R	0.989
12:69350208:C:G	S79R	0.989
12:69350217:G:C	W82C	0.989
12:69350217:G:T	W82C	0.989
12:69350189:G:A	G73E	0.988
12:69350192:T:A	I74K	0.988
12:69350195:T:G	F75C	0.987
12:69350205:T:A	N78K	0.987
12:69350205:T:G	N78K	0.987
12:69353172:T:A	C134S	0.987
12:69353173:G:C	C134S	0.987
12:69350109:G:C	W46C	0.986
12:69350109:G:T	W46C	0.986
12:69350207:G:T	S79I	0.986
12:69350254:T:A	C95S	0.986
12:69350255:G:C	C95S	0.986
12:69350113:T:A	C48S	0.985
12:69350114:G:C	C48S	0.985
12:69350255:G:A	C95Y	0.985
12:69352297:T:A	W127R	0.985
12:69352297:T:C	W127R	0.985
12:69350195:T:C	F75S	0.984
12:69353160:T:A	W130R	0.984

dbSNP variants (sampled 300 via entrez): RS1000093167 (12:69351621 C>T), RS1000238227 (12:69349129 G>A), RS1000306388 (12:69347649 G>T), RS1001122729 (12:69350829 C>T), RS1001979618 (12:69346444 C>A), RS1002030576 (12:69346616 A>G), RS1002144348 (12:69354334 C>T), RS1002495380 (12:69353834 A>G), RS1002804071 (12:69350937 C>G), RS1003152783 (12:69354580 C>T), RS1003336678 (12:69346619 A>T), RS1004268125 (12:69352807 G>A), RS1004884308 (12:69348901 T>C), RS10049 (12:69353970 C>T), RS1005316423 (12:69354468 T>C)

Disease associations

OMIM: gene MIM:153450 | disease phenotypes: MIM:105200, MIM:620658

GenCC curated gene-disease

Disease	Classification	Inheritance
familial visceral amyloidosis	Strong	Autosomal dominant
ALys amyloidosis	Supportive	Autosomal dominant

Mondo (3): familial visceral amyloidosis (MONDO:0007099), amyloidosis, hereditary systemic 5 (MONDO:0971009), ALys amyloidosis (MONDO:0019732)

Orphanet (1): Hereditary amyloidosis with primary renal involvement (Orphanet:85450)

HPO phenotypes

16 total (16 of 16 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000083	Renal insufficiency
HP:0000093	Proteinuria
HP:0000822	Hypertension
HP:0000967	Petechiae
HP:0001097	Keratoconjunctivitis sicca
HP:0001635	Congestive heart failure
HP:0001903	Anemia
HP:0001917	Renal amyloidosis
HP:0003596	Middle age onset
HP:0003774	Stage 5 chronic kidney disease
HP:0009830	Peripheral neuropathy
HP:0010637	Conjunctival amyloidosis
HP:0011034	Amyloid deposition
HP:0011462	Young adult onset
HP:0012280	Hepatic amyloidosis

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST000175_26	Height	3.000000e-06
GCST000208_1	Response to diuretic therapy	3.000000e-07
GCST004608_179	Granulocyte percentage of myeloid white cells	1.000000e-31
GCST004609_195	Monocyte percentage of white cells	4.000000e-46
GCST004625_123	Monocyte count	1.000000e-53
GCST006585_1484	Blood protein levels	3.000000e-104
GCST007929_72	Medication use (calcium channel blockers)	1.000000e-10
GCST010244_303	Triglyceride levels	4.000000e-12
GCST90002393_420	Monocyte count	9.000000e-169
GCST90002394_372	Monocyte percentage of white cells	7.000000e-139
GCST90002407_289	White blood cell count	6.000000e-15

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0007997	granulocyte percentage of myeloid white cells
EFO:0007989	monocyte percentage of leukocytes
EFO:0005091	monocyte count
EFO:0009930	Calcium channel blocker use measurement
EFO:0004530	triglyceride measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C538249	Amyloidosis, familial visceral (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

56 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Decitabine	increases expression, decreases methylation	2
Calcitriol	increases expression	2
Colforsin	decreases reaction, increases secretion, decreases secretion, affects cotreatment	2
Glyburide	decreases secretion, increases secretion	2
Quercetin	affects cotreatment, decreases reaction, increases secretion, decreases expression	2
Tobacco Smoke Pollution	decreases expression, increases expression	2
Cyclosporine	decreases expression	2
Cadmium Chloride	decreases expression, increases abundance	2
Particulate Matter	affects expression, increases abundance, increases secretion	2
parthenolide	affects cotreatment, decreases reaction, increases secretion	1
tungsten carbide	affects cotreatment, decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects expression	1
potassium persulfate	increases expression	1
trichostatin A	increases expression	1
sodium arsenite	increases expression	1
15-hydroxy-5,8,11,13-eicosatetraenoic acid	affects reaction, affects cotreatment, increases secretion, decreases reaction	1
lead chloride	decreases expression	1
artemisinin	decreases reaction, increases secretion, affects cotreatment	1
SB 203580	decreases reaction, increases secretion	1
1-ethyl-2-benzimidazolinone	affects secretion	1
K 7174	decreases expression	1
3-((3-trifluoromethyl)phenyl)-5-((3-carboxyphenyl)methylene)-2-thioxo-4-thiazolidinone	increases secretion, decreases reaction	1
NSC 689534	increases expression	1
Acetaminophen	increases expression	1
Gemcitabine	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Air Pollutants, Occupational	affects expression	1
Amiodarone	increases expression	1
Arsenicals	decreases expression, decreases secretion	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B1AH	Abcam THP-1 LYZ KO	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.