LYZL6

Summary

LYZL6 (lysozyme like 6, HGNC:29614) is a protein-coding gene on chromosome 17q12, encoding Lysozyme-like protein 6 (O75951). May be involved sperm-egg plasma membrane adhesion and fusion during fertilization.

This gene encodes a member of the C-type lysozyme/alpha-lactalbumin family. C-type lysozymes are bacteriolytic factors that play a role in host defense, whereas alpha-lactalbumins mediate lactose biosynthesis. The encoded protein contains catalytic residues characteristic of C-type lysozymes and may play a role in male reproduction. Alternatively spliced transcript variants have been observed for this gene.

Source: NCBI Gene 57151 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 24 total
• MANE Select transcript: NM_020426

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29614
Approved symbol	LYZL6
Name	lysozyme like 6
Location	17q12
Locus type	gene with protein product
Status	Approved
Aliases	LYC1, PRO1485, TKAL754
Ensembl gene	ENSG00000275722
Ensembl biotype	protein_coding
OMIM	612751
Entrez	57151

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000615905, ENST00000617692, ENST00000618542

RefSeq mRNA: 2 — MANE Select: NM_020426 NM_001199951, NM_020426

CCDS: CCDS11302

Canonical transcript exons

ENST00000615905 — 5 exons

Exon	Start	End
ENSE00003713109	35936755	35936833
ENSE00003719858	35943567	35943713
ENSE00003734437	35934518	35934865
ENSE00003743440	35939218	35939558
ENSE00003748493	35937758	35937916

Expression profiles

Bgee: expression breadth broad, 39 present calls, max score 90.95.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0243 / max 23.0053, expressed in 3 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
165408	0.0153	3
165411	0.0089	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	90.95	gold quality
right testis	UBERON:0004534	90.60	gold quality
testis	UBERON:0000473	90.55	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.29	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	54.79	gold quality
sural nerve	UBERON:0015488	42.59	silver quality
granulocyte	CL:0000094	37.94	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
bone marrow cell	CL:0002092	36.16	gold quality
liver	UBERON:0002107	36.16	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
right lobe of liver	UBERON:0001114	35.14	silver quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
vermiform appendix	UBERON:0001154	33.33	silver quality
blood	UBERON:0000178	33.23	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
bone marrow	UBERON:0002371	31.74	gold quality
urinary bladder	UBERON:0001255	31.37	silver quality
leukocyte	CL:0000738	31.15	gold quality
muscle tissue	UBERON:0002385	31.06	gold quality
monocyte	CL:0000576	30.84	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
tonsil	UBERON:0002372	29.07	gold quality
prefrontal cortex	UBERON:0000451	29.04	gold quality
duodenum	UBERON:0002114	28.14	gold quality
descending thoracic aorta	UBERON:0002345	27.59	gold quality
lymph node	UBERON:0000029	27.57	gold quality
right adrenal gland cortex	UBERON:0035827	27.32	silver quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.32

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

28 targeting LYZL6, 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-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-10393-3P	99.72	66.56	961
HSA-MIR-6801-5P	99.72	66.50	981
HSA-MIR-5004-5P	99.68	66.63	1294
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-671-5P	99.52	67.11	1277
HSA-MIR-3612	99.45	66.02	1333
HSA-MIR-650	99.45	65.77	1309
HSA-MIR-125A-5P	99.36	70.59	1640
HSA-MIR-125B-5P	99.36	70.36	1662
HSA-MIR-3678-3P	99.31	67.10	1432
HSA-MIR-10522-5P	99.26	68.50	2087
HSA-MIR-4795-5P	99.11	66.90	876
HSA-MIR-6871-5P	98.90	66.67	671
HSA-MIR-9500	98.62	66.54	1845
HSA-MIR-4443	98.02	66.25	1928
HSA-MIR-7847-3P	96.63	64.58	952

Literature-anchored findings (GeneRIF, showing 1)

• LYZL6, an acidic, bacteriolytic and human sperm-related protein, is likely important for fertilization but not for the innate immunity of the male reproductive tract. (PMID:28182716)

Cross-species orthologs

14 orthologs

Organism	Symbol	Gene ID
mus_musculus	Lyzl6	ENSMUSG00000020945
rattus_norvegicus	Lyzl6	ENSRNOG00000003501
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), LYZL4 (ENSG00000157093), LALBA (ENSG00000167531), SPACA5B (ENSG00000171478), SPACA5 (ENSG00000171489)

Protein

Protein identifiers

Lysozyme-like protein 6 — O75951 (reviewed: O75951)

All UniProt accessions (3): O75951, A0A080YUZ6, A0A087WXX7

UniProt curated annotations — full annotation on UniProt →

Function. May be involved sperm-egg plasma membrane adhesion and fusion during fertilization. Exhibits bacteriolytic activity in vitro against Micrococcus luteus and Staphylococcus aureus. Shows weak bacteriolytic activity against Gram-positive bacteria at physiological pH. Bacteriolytic activity is pH-dependent, with a maximum at around pH 5.6.

Subunit / interactions. Monomer.

Subcellular location. Secreted. Cell surface. Cell projection. Cilium. Flagellum.

Tissue specificity. Expressed in testis, epididymis and spermatozoa (at protein level). Expressed in late-stage spermatocytes and round spermatids.

Similarity. Belongs to the glycosyl hydrolase 22 family.

RefSeq proteins (2): NP_001186880, NP_065159* (*=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 (10 total): disulfide bond 4, active site 2, signal peptide 1, chain 1, domain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75951-F1	92.84	0.86

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): 54; 71

Disulfide bonds (4): 25–145, 49–133, 83–98, 94–112

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 70 (showing top): GOBP_SINGLE_FERTILIZATION, GOCC_SECRETORY_GRANULE, GOBP_MEMBRANE_FUSION, GOBP_PLASMA_MEMBRANE_ORGANIZATION, GOCC_CELL_SURFACE, GGGTGGRR_PAX4_03, SHEPARD_BMYB_MORPHOLINO_DN, MODULE_205, GOBP_CELLULAR_PROCESS_INVOLVED_IN_REPRODUCTION_IN_MULTICELLULAR_ORGANISM, GOBP_ENDOMEMBRANE_SYSTEM_ORGANIZATION, GOBP_PLASMA_MEMBRANE_FUSION, MORF_PDPK1, GOBP_MEMBRANE_ORGANIZATION, GOBP_FERTILIZATION, GOBP_DEFENSE_RESPONSE_TO_BACTERIUM

GO Biological Process (5): fusion of sperm to egg plasma membrane involved in single fertilization (GO:0007342), fertilization (GO:0009566), killing of cells of another organism (GO:0031640), defense response to bacterium (GO:0042742), single fertilization (GO:0007338)

GO Molecular Function (4): lysozyme activity (GO:0003796), catalytic activity (GO:0003824), hydrolase activity (GO:0016787), hydrolase activity, acting on glycosyl bonds (GO:0016798)

GO Cellular Component (9): acrosomal vesicle (GO:0001669), extracellular region (GO:0005576), cell surface (GO:0009986), sperm flagellum (GO:0036126), sperm midpiece (GO:0097225), sperm plasma membrane (GO:0097524), cilium (GO:0005929), motile cilium (GO:0031514), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
single fertilization	1
cellular process involved in reproduction in multicellular organism	1
sexual reproduction	1
reproductive process	1
cell killing	1
disruption of cell in another organism	1
defense response	1
response to bacterium	1
fertilization	1
hydrolase activity, hydrolyzing O-glycosyl compounds	1
peptidoglycan muralytic activity	1
molecular_function	1
catalytic activity	1
hydrolase activity	1
secretory granule	1
9+2 motile cilium	1
sperm flagellum	1
plasma membrane	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
cilium	1

Protein interactions and networks

STRING

482 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LYZL6	C12orf71	A8MTZ7	531
LYZL6	ASTL	Q6HA08	479
LYZL6	ANKRD27	Q96NW4	472
LYZL6	TEX38	Q6PEX7	459
LYZL6	SCP2D1	Q9UJQ7	447
LYZL6	SPRYD4	Q8WW59	443
LYZL6	SPATA31F1	Q6ZU69	432
LYZL6	PRR30	Q53SZ7	430
LYZL6	CIMIP2A	Q6J272	422
LYZL6	CIMIP4	O43247	418
LYZL6	MEGF8	Q7Z7M0	384
LYZL6	CPM	P14384	380
LYZL6	GARIN1B	Q96KD3	374
LYZL6	YEATS4	O95619	371
LYZL6	MIP	P30301	370

IntAct

6 interactions, top by confidence:

A	B	Type	Score
LYZL6	COL6A1	psi-mi:“MI:0914”(association)	0.530
LYZL6	rep	psi-mi:“MI:0915”(physical association)	0.370
ECE1	LYZL6	psi-mi:“MI:0915”(physical association)	0.370
LYZL6	PLXNA2	psi-mi:“MI:0914”(association)	0.350
LYZL6	CLGN	psi-mi:“MI:0914”(association)	0.350

BioGRID (33): TYW3 (Affinity Capture-MS), TMEM132A (Affinity Capture-MS), POGLUT1 (Affinity Capture-MS), SLC25A30 (Affinity Capture-MS), SLC16A10 (Affinity Capture-MS), PLXNA2 (Affinity Capture-MS), TUBB8 (Affinity Capture-MS), VSIG8 (Affinity Capture-MS), EOGT (Affinity Capture-MS), FKBP14 (Affinity Capture-MS), TMEM2 (Affinity Capture-MS), SEMG1 (Affinity Capture-MS), SEMG2 (Affinity Capture-MS), CTSF (Affinity Capture-MS), ATP12A (Affinity Capture-MS)

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, 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

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	20
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

739 predictions. Top by Δscore:

Variant	Effect	Δscore
17:35936685:A:AC	donor_gain	1.0000
17:35936685:ACTG:A	donor_gain	1.0000
17:35936686:C:CC	donor_gain	1.0000
17:35936686:CTGC:C	donor_gain	1.0000
17:35936706:T:TA	donor_gain	1.0000
17:35936834:C:CC	acceptor_gain	1.0000
17:35937916:CCT:C	acceptor_gain	1.0000
17:35937918:T:C	acceptor_gain	1.0000
17:35936676:T:TA	donor_gain	0.9900
17:35936685:ACTGC:A	donor_gain	0.9900
17:35936686:CTG:C	donor_gain	0.9900
17:35936686:CTGCC:C	donor_gain	0.9900
17:35936688:G:GA	donor_gain	0.9900
17:35936689:C:A	donor_gain	0.9900
17:35936709:T:TA	donor_gain	0.9900
17:35936748:T:TA	donor_gain	0.9900
17:35936831:GAT:G	acceptor_gain	0.9900
17:35936833:TC:T	acceptor_loss	0.9900
17:35936834:C:CG	acceptor_loss	0.9900
17:35937915:CCCT:C	acceptor_gain	0.9900
17:35936829:CAGAT:C	acceptor_gain	0.9800
17:35937792:A:C	donor_gain	0.9800
17:35937912:CAGCC:C	acceptor_gain	0.9800
17:35942571:T:A	donor_gain	0.9800
17:35937918:T:TC	acceptor_gain	0.9700
17:35943562:CTTA:C	donor_loss	0.9700
17:35943566:C:CA	donor_loss	0.9700
17:35934864:CC:C	acceptor_gain	0.9600
17:35934865:CC:C	acceptor_gain	0.9600
17:35936786:T:A	donor_gain	0.9600

AlphaMissense

982 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:35934856:C:A	W129C	0.968
17:35934856:C:G	W129C	0.968
17:35934865:C:A	W126C	0.968
17:35934865:C:G	W126C	0.968
17:35937832:A:C	F75C	0.965
17:35937891:G:C	S55R	0.956
17:35937891:G:T	S55R	0.956
17:35937893:T:G	S55R	0.956
17:35937819:G:C	S79R	0.949
17:35937819:G:T	S79R	0.949
17:35937821:T:G	S79R	0.949
17:35937808:C:G	C83S	0.946
17:35937809:A:T	C83S	0.946
17:35937915:C:A	W47C	0.945
17:35937915:C:G	W47C	0.945
17:35936790:T:A	K114N	0.944
17:35936790:T:G	K114N	0.944
17:35937892:C:A	S55I	0.939
17:35934820:C:A	W141C	0.937
17:35934820:C:G	W141C	0.937
17:35937900:A:C	F52L	0.934
17:35937900:A:T	F52L	0.934
17:35937902:A:G	F52L	0.934
17:35937885:G:C	F57L	0.933
17:35937885:G:T	F57L	0.933
17:35937887:A:G	F57L	0.933
17:35937832:A:G	F75S	0.927
17:35939240:A:C	F39L	0.926
17:35939240:A:T	F39L	0.926
17:35939242:A:G	F39L	0.926

dbSNP variants (sampled 300 via entrez): RS1000050714 (17:35942353 T>C), RS1000403681 (17:35942653 A>G), RS1000406439 (17:35935331 T>A,C), RS1000796156 (17:35934908 C>G,T), RS1000853683 (17:35939955 G>A), RS1000873860 (17:35941448 T>G), RS1001004427 (17:35941047 C>A,G), RS1001013387 (17:35945559 C>T), RS1001305766 (17:35939639 T>C), RS1001920820 (17:35944426 G>A), RS1002015576 (17:35944110 T>C), RS1002407179 (17:35939460 A>C), RS1002531869 (17:35944123 T>G), RS1002858361 (17:35937228 G>A), RS1002932122 (17:35943231 G>A,C,T)

Disease associations

OMIM: gene MIM:612751 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

11 total (human), top 11 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects cotreatment	3
entinostat	increases expression, affects cotreatment	2
belinostat	increases expression, affects cotreatment	2
Panobinostat	affects cotreatment, increases expression	2
trichostatin A	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Vorinostat	increases expression	1
Cyclosporine	increases expression	1
Aflatoxin B1	increases methylation	1
Antirheumatic Agents	decreases expression	1

Clinical trials (associated diseases)

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