LYZL4

Summary

LYZL4 (lysozyme like 4, HGNC:28387) is a protein-coding gene on chromosome 3p22.1, encoding Lysozyme-like protein 4 (Q96KX0). May be involved in fertilization.

Lysozymes (see LYZ; MIM 153450), especially C-type lysozymes, are well-recognized bacteriolytic factors widely distributed in the animal kingdom and play a mainly protective role in host defense. LYZL4 is a member of a family of lysozyme-like genes (Zhang et al., 2005 [PubMed 16014814]).

Source: NCBI Gene 131375 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 32 total
• MANE Select transcript: NM_144634

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28387
Approved symbol	LYZL4
Name	lysozyme like 4
Location	3p22.1
Locus type	gene with protein product
Status	Approved
Aliases	MGC26768, LYC4
Ensembl gene	ENSG00000157093
Ensembl biotype	protein_coding
OMIM	612750
Entrez	131375

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000287748, ENST00000441172, ENST00000470991

RefSeq mRNA: 2 — MANE Select: NM_144634 NM_001304386, NM_144634

CCDS: CCDS2697

Canonical transcript exons

ENST00000287748 — 5 exons

Exon	Start	End
ENSE00001030268	42407113	42407343
ENSE00001078159	42410417	42410610
ENSE00001686444	42397083	42397334
ENSE00003506119	42404046	42404124
ENSE00003675539	42406846	42406998

Expression profiles

Bgee: expression breadth broad, 58 present calls, max score 93.17.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0103 / max 10.8260, expressed in 4 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
41783	0.0103	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	93.17	gold quality
left testis	UBERON:0004533	91.94	gold quality
right testis	UBERON:0004534	91.70	gold quality
testis	UBERON:0000473	88.71	gold quality
pancreatic ductal cell	CL:0002079	86.95	silver quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.04	gold quality
adult organism	UBERON:0007023	80.82	gold quality
buccal mucosa cell	CL:0002336	62.99	gold quality
ileal mucosa	UBERON:0000331	60.77	silver quality
parotid gland	UBERON:0001831	60.29	gold quality
pigmented layer of retina	UBERON:0001782	60.24	gold quality
tibialis anterior	UBERON:0001385	59.38	silver quality
endothelial cell	CL:0000115	58.76	silver quality
Brodmann (1909) area 23	UBERON:0013554	58.75	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	58.73	gold quality
middle temporal gyrus	UBERON:0002771	58.26	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	58.24	gold quality
myocardium	UBERON:0002349	58.01	gold quality
esophagus squamous epithelium	UBERON:0006920	57.76	gold quality
prefrontal cortex	UBERON:0000451	57.38	gold quality
cartilage tissue	UBERON:0002418	57.34	gold quality
tendon of biceps brachii	UBERON:0008188	56.88	gold quality
decidua	UBERON:0002450	56.59	gold quality
deltoid	UBERON:0001476	55.28	gold quality
skin of hip	UBERON:0001554	54.56	gold quality
cardiac muscle of right atrium	UBERON:0003379	54.34	gold quality
anterior cingulate cortex	UBERON:0009835	54.25	gold quality
left ventricle myocardium	UBERON:0006566	54.23	gold quality
Brodmann (1909) area 9	UBERON:0013540	53.98	gold quality
kidney epithelium	UBERON:0004819	53.93	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.28

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

19 targeting LYZL4, 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-513B-5P	99.99	69.96	2150
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-498-3P	99.91	71.27	1114
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-4796-3P	99.08	68.38	1681
HSA-MIR-511-5P	98.97	70.94	2268
HSA-MIR-3136-5P	98.53	67.68	793
HSA-MIR-4439	98.53	67.53	793
HSA-MIR-7855-5P	97.39	67.18	925
HSA-MIR-6729-3P	96.91	66.79	703
HSA-MIR-4680-5P	96.43	67.15	893
HSA-MIR-6763-3P	90.80	64.32	80

Cross-species orthologs

14 orthologs

Organism	Symbol	Gene ID
mus_musculus	Lyzl4	ENSMUSG00000032530
rattus_norvegicus	Lyzl4	ENSRNOG00000019350
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	CG8492	FBGN0035813
drosophila_melanogaster	CG30062	FBGN0050062

Paralogs (8): LYZ (ENSG00000090382), LYZL1 (ENSG00000120563), SPACA3 (ENSG00000141316), LYZL2 (ENSG00000151033), LALBA (ENSG00000167531), SPACA5B (ENSG00000171478), SPACA5 (ENSG00000171489), LYZL6 (ENSG00000275722)

Protein

Protein identifiers

Lysozyme-like protein 4 — Q96KX0 (reviewed: Q96KX0)

All UniProt accessions (2): Q96KX0, A0A080YUZ5

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in fertilization. Has no detectable bacteriolytic and lysozyme activities in vitro.

Subunit / interactions. Monomer.

Subcellular location. Secreted. Cytoplasmic vesicle. Secretory vesicle. Acrosome. Cell projection. Cilium. Flagellum.

Tissue specificity. Expressed in testis and epididymis.

Similarity. Belongs to the glycosyl hydrolase 22 family.

RefSeq proteins (2): NP_001291315, NP_653235* (*=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

UniProt features (8 total): disulfide bond 4, signal peptide 1, chain 1, domain 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96KX0-F1	92.97	0.85

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 (1): 54

Disulfide bonds (4): 25–144, 49–131, 84–96, 92–110

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 68 (showing top): GOBP_SINGLE_FERTILIZATION, GOCC_SECRETORY_GRANULE, GOBP_MEMBRANE_FUSION, GOBP_PLASMA_MEMBRANE_ORGANIZATION, chr3p22, GOBP_CELLULAR_PROCESS_INVOLVED_IN_REPRODUCTION_IN_MULTICELLULAR_ORGANISM, GOBP_ENDOMEMBRANE_SYSTEM_ORGANIZATION, NAKAMURA_TUMOR_ZONE_PERIPHERAL_VS_CENTRAL_DN, GOBP_PLASMA_MEMBRANE_FUSION, GOBP_MEMBRANE_ORGANIZATION, GOBP_FERTILIZATION, GOBP_DEFENSE_RESPONSE_TO_BACTERIUM, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, TGGAAA_NFAT_Q4_01, GOCC_SECRETORY_VESICLE

GO Biological Process (3): fusion of sperm to egg plasma membrane involved in single fertilization (GO:0007342), fertilization (GO:0009566), single fertilization (GO:0007338)

GO Molecular Function (1): lysozyme activity (GO:0003796)

GO Cellular Component (9): acrosomal vesicle (GO:0001669), obsolete extracellular space (GO:0005615), nucleus (GO:0005634), sperm flagellum (GO:0036126), extracellular region (GO:0005576), cilium (GO:0005929), cytoplasmic vesicle (GO:0031410), motile cilium (GO:0031514), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
single fertilization	1
cellular process involved in reproduction in multicellular organism	1
sexual reproduction	1
reproductive process	1
fertilization	1
hydrolase activity, hydrolyzing O-glycosyl compounds	1
peptidoglycan muralytic activity	1
secretory granule	1
intracellular membrane-bounded organelle	1
9+2 motile cilium	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
cytoplasm	1
intracellular vesicle	1
cilium	1

Protein interactions and networks

STRING

322 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LYZL4	C12orf71	A8MTZ7	519
LYZL4	TMEM244	Q5VVB8	512
LYZL4	C1orf115	Q9H7X2	481
LYZL4	RASGEF1C	Q8N431	477
LYZL4	YEATS4	O95619	460
LYZL4	ASTL	Q6HA08	445
LYZL4	SPRYD4	Q8WW59	433
LYZL4	OR51D1	Q8NGF3	432
LYZL4	DUSP13B	Q9UII6	405
LYZL4	TEX38	Q6PEX7	404
LYZL4	DEFB108B	Q8NET1	390
LYZL4	KIF16B	Q96L93	384
LYZL4	CPM	P14384	375
LYZL4	MIP	P30301	366
LYZL4	NUP107	P57740	364

IntAct

2 interactions, top by confidence:

A	B	Type	Score
BMP2K	LYZL4	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (1): LYZL4 (Affinity Capture-Luminescence)

ESM2 similar proteins: A2AE20, C0HLB7, C1IIX1, D4ABW7, D9J142, D9J143, G3XDT7, O75951, P00702, P00709, P00710, P00711, P00712, P00713, P00714, P00716, P05105, P07458, P08334, P08896, P09462, P11375, P11376, P12065, P18137, P28546, P29752, P30805, P37161, P48816, P50717, P50718, P51782, P61944, P81646, P81708, P85045, Q06655, Q29145, Q29RT1

Diamond homologs: A0JNM6, A2AE20, A6QQ77, B6VH75, B6VH76, B6VH77, B6VH79, D4ABW7, G3XDT7, O75951, P00697, P00698, P00699, P00700, P00701, P00702, P00703, P00704, P00705, P00706, P00707, P00708, P08905, P11375, P11376, P11941, P12066, P12067, P12068, P12069, P16973, P17607, P17897, P19849, P22910, P24364, P24533, P30201, P37712, P37714

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	27
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1111 predictions. Top by Δscore:

Variant	Effect	Δscore
3:42404125:C:CC	acceptor_gain	1.0000
3:42406839:GACTT:G	donor_loss	1.0000
3:42406840:ACTT:A	donor_loss	1.0000
3:42406841:CTTA:C	donor_loss	1.0000
3:42406842:TTA:T	donor_loss	1.0000
3:42406843:TACCG:T	donor_loss	1.0000
3:42406844:A:AC	donor_gain	1.0000
3:42406844:A:T	donor_loss	1.0000
3:42406844:AC:A	donor_gain	1.0000
3:42406845:C:CA	donor_gain	1.0000
3:42406845:CC:C	donor_gain	1.0000
3:42406845:CCGGA:C	donor_gain	1.0000
3:42406994:CACCC:C	acceptor_gain	1.0000
3:42406996:CCC:C	acceptor_gain	1.0000
3:42406997:CC:C	acceptor_gain	1.0000
3:42406997:CCC:C	acceptor_gain	1.0000
3:42406998:CC:C	acceptor_gain	1.0000
3:42406998:CCT:C	acceptor_loss	1.0000
3:42406999:C:CC	acceptor_gain	1.0000
3:42406999:C:CG	acceptor_loss	1.0000
3:42407000:T:A	acceptor_loss	1.0000
3:42407004:A:AC	acceptor_gain	1.0000
3:42407109:TCACA:T	donor_loss	1.0000
3:42407110:CACA:C	donor_loss	1.0000
3:42407111:A:AC	donor_gain	1.0000
3:42407111:ACA:A	donor_loss	1.0000
3:42407112:C:CC	donor_gain	1.0000
3:42407112:CA:C	donor_gain	1.0000
3:42407112:CAGTT:C	donor_gain	1.0000
3:42410457:T:A	donor_gain	1.0000

AlphaMissense

951 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:42397334:C:A	W124C	0.981
3:42397334:C:G	W124C	0.981
3:42406911:A:C	F76C	0.979
3:42406967:G:C	F57L	0.976
3:42406967:G:T	F57L	0.976
3:42406969:A:G	F57L	0.976
3:42397286:C:A	W140C	0.973
3:42397286:C:G	W140C	0.973
3:42397325:C:A	W127C	0.969
3:42397325:C:G	W127C	0.969
3:42406997:C:A	W47C	0.968
3:42406997:C:G	W47C	0.968
3:42397275:C:G	C144S	0.966
3:42397276:A:T	C144S	0.966
3:42397314:C:G	C131S	0.964
3:42397315:A:T	C131S	0.964
3:42406979:G:C	F53L	0.963
3:42406979:G:T	F53L	0.963
3:42406981:A:G	F53L	0.963
3:42406992:C:G	C49S	0.959
3:42406993:A:T	C49S	0.959
3:42406910:A:C	F76L	0.958
3:42406910:A:T	F76L	0.958
3:42406912:A:G	F76L	0.958
3:42406911:A:G	F76S	0.956
3:42404047:A:G	W124R	0.952
3:42404047:A:T	W124R	0.952
3:42406919:A:C	F73L	0.952
3:42406919:A:T	F73L	0.952
3:42406921:A:G	F73L	0.952

dbSNP variants (sampled 300 via entrez): RS1000070559 (3:42379776 C>G), RS1000077853 (3:42385500 G>A,C), RS1000175253 (3:42364803 A>G), RS1000193070 (3:42385249 T>A), RS1000334027 (3:42397055 T>C), RS1000400637 (3:42370814 G>A), RS1000422007 (3:42379484 A>G,T), RS1000460069 (3:42365092 T>G), RS1000481794 (3:42405943 T>A), RS1000525772 (3:42383795 A>G), RS1000574324 (3:42393365 A>C), RS1000589932 (3:42399542 T>C), RS1000593879 (3:42390120 G>A,T), RS1000620859 (3:42395983 A>C,G), RS1000631101 (3:42391660 C>T)

Disease associations

OMIM: gene MIM:612750 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST000885_2	Response to antipsychotic treatment in schizophrenia (reasoning)	1.000000e-06
GCST003542_74	Night sleep phenotypes	2.000000e-06
GCST004865_69	Itch intensity from mosquito bite adjusted by bite size	1.000000e-06
GCST004904_156	Body mass index	3.000000e-11
GCST008103_63	Bipolar disorder	6.000000e-07
GCST012299_4	Schizophrenia, bipolar disorder or major depressive disorder x sex interaction (3df)	4.000000e-06

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004350	reasoning
EFO:0007827	nighttime rest measurement
EFO:0008377	mosquito bite reaction itch intensity measurement
EFO:0008378	mosquito bite reaction size measurement
EFO:0004340	body mass index
EFO:0008343	sex interaction measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

8 total (human), top 8 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
CGP 52608	affects binding, increases reaction	1
Acetaminophen	increases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	increases expression	1
Methyl Methanesulfonate	increases expression	1
Valproic Acid	decreases methylation	1
Aflatoxin B1	increases expression	1

Clinical trials (associated diseases)

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