LCE3D

Summary

LCE3D (late cornified envelope 3D, HGNC:16615) is a protein-coding gene on chromosome 1q21.3, encoding Late cornified envelope protein 3D (Q9BYE3). Precursors of the cornified envelope of the stratum corneum.

Predicted to be involved in keratinization. Predicted to be located in cytosol.

Source: NCBI Gene 84648 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 27 total
• MANE Select transcript: NM_032563

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16615
Approved symbol	LCE3D
Name	late cornified envelope 3D
Location	1q21.3
Locus type	gene with protein product
Status	Approved
Aliases	LEP16
Ensembl gene	ENSG00000163202
Ensembl biotype	protein_coding
OMIM	612616
Entrez	84648

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000368787

RefSeq mRNA: 1 — MANE Select: NM_032563 NM_032563

CCDS: CCDS1014

Canonical transcript exons

ENST00000368787 — 2 exons

Exon	Start	End
ENSE00001072467	152580469	152580516
ENSE00001447961	152579381	152579957

Expression profiles

Bgee: expression breadth ubiquitous, 105 present calls, max score 97.52.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.1428 / max 304.1642, expressed in 59 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
14566	1.1428	59

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
penis	UBERON:0000989	97.52	gold quality
amniotic fluid	UBERON:0000173	96.71	gold quality
buccal mucosa cell	CL:0002336	96.61	gold quality
mammalian vulva	UBERON:0000997	94.22	gold quality
upper arm skin	UBERON:0004263	93.50	gold quality
gingiva	UBERON:0001828	90.59	gold quality
skin of leg	UBERON:0001511	89.55	gold quality
pancreatic ductal cell	CL:0002079	89.30	silver quality
gingival epithelium	UBERON:0001949	87.96	gold quality
zone of skin	UBERON:0000014	86.31	gold quality
skin of abdomen	UBERON:0001416	83.65	gold quality
oral cavity	UBERON:0000167	81.03	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.25	silver quality
tibialis anterior	UBERON:0001385	78.89	silver quality
esophagus squamous epithelium	UBERON:0006920	78.42	gold quality
ileal mucosa	UBERON:0000331	76.05	gold quality
tongue	UBERON:0001723	75.56	gold quality
upper leg skin	UBERON:0004262	75.30	gold quality
kidney epithelium	UBERON:0004819	74.81	gold quality
body of tongue	UBERON:0011876	71.66	gold quality
superior surface of tongue	UBERON:0007371	71.50	gold quality
esophagus mucosa	UBERON:0002469	69.41	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	68.90	gold quality
sperm	CL:0000019	68.81	silver quality
skin of hip	UBERON:0001554	67.48	gold quality
cardiac muscle of right atrium	UBERON:0003379	66.76	gold quality
left ventricle myocardium	UBERON:0006566	66.15	gold quality
deltoid	UBERON:0001476	66.06	gold quality
vagina	UBERON:0000996	65.60	gold quality
nasal cavity epithelium	UBERON:0005384	64.81	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.46

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

23 targeting LCE3D, 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-513A-5P	100.00	69.77	2465
HSA-MIR-489-3P	99.80	66.46	839
HSA-MIR-5004-5P	99.68	66.63	1294
HSA-MIR-6715B-5P	99.64	69.63	1420
HSA-MIR-4269	99.55	69.89	1373
HSA-MIR-1224-5P	99.48	65.59	803
HSA-MIR-1324	99.46	66.57	1302
HSA-MIR-542-3P	99.34	67.58	1270
HSA-MIR-4504	99.10	69.14	1328
HSA-MIR-4501	98.72	67.19	921
HSA-MIR-6811-3P	98.62	66.54	944
HSA-MIR-5089-5P	98.45	66.06	1388
HSA-MIR-4691-5P	98.41	66.77	1343
HSA-MIR-6792-3P	98.41	66.86	1359
HSA-MIR-193B-5P	97.91	65.88	837
HSA-MIR-6855-5P	97.51	66.03	830
HSA-MIR-4314	97.50	67.30	1369
HSA-MIR-6854-5P	96.77	65.96	848
HSA-MIR-3690	96.44	65.18	737
HSA-MIR-3170	95.84	64.32	721
HSA-MIR-4471	95.11	66.84	755
HSA-MIR-6750-5P	93.94	66.68	797
HSA-MIR-6822-5P	93.94	66.34	812

Literature-anchored findings (GeneRIF, showing 4)

• LEP16 is one of a cluster of 16-20 related genes at 1q21 which includes XP5. Proteins incorporate into the cornified envelope of stratified, terminally differentiating epithelia. LEP16 transcripts detected in heart, skin and esophagus. (PMID:11698679)
• paper describing nomenclature changes and expression in range of tissues and in response to UV (PMID:15854049)
• We identified significant combined effects between MHC and LCE, MHC and IL12B on the risk of psoriasis in Chinese population. (PMID:21208785)
• genetic polymorphism is associated with psoriasis vulgaris among Mongolians from Inner Mongolia (PMID:29397434)

Cross-species orthologs

0 orthologs

Paralogs (20): LCE2B (ENSG00000159455), SPRR2G (ENSG00000159516), SPRR3 (ENSG00000163209), SPRR1B (ENSG00000169469), SPRR1A (ENSG00000169474), LCE1D (ENSG00000172155), SPRR4 (ENSG00000184148), LCE3A (ENSG00000185962), LCE3E (ENSG00000185966), LCE5A (ENSG00000186207), LCE1E (ENSG00000186226), LCE2A (ENSG00000187173), LCE2C (ENSG00000187180), LCE2D (ENSG00000187223), LCE3B (ENSG00000187238), KPLCE (ENSG00000198854), PRR9 (ENSG00000203783), LELP1 (ENSG00000203784), LCE1F (ENSG00000240386), LCE3C (ENSG00000244057)

Protein

Protein identifiers

Late cornified envelope protein 3D — Q9BYE3 (reviewed: Q9BYE3)

Alternative names: Late envelope protein 16, Small proline-rich-like epidermal differentiation complex protein 6A, Small proline-rich-like epidermal differentiation complex protein 6B

All UniProt accessions (1): Q9BYE3

UniProt curated annotations — full annotation on UniProt →

Function. Precursors of the cornified envelope of the stratum corneum.

Subunit / interactions. Interacts with CYSRT1.

Tissue specificity. Skin-specific. Expression was readily detected in adult trunk skin, adult arm skin, fetal skin, penal skin, vulva, esophagus and tongue. Not expressed in the cervix, rectum, lung, colon, or placenta.

Miscellaneous. Belongs to the LCE cluster present on 1q21.

Similarity. Belongs to the LCE family.

RefSeq proteins (1): NP_115952* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR028205	LCE	Family

Pfam: PF14672

UniProt features (9 total): compositionally biased region 4, region of interest 2, sequence variant 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BYE3-F1	60.29	0.00

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-6809371	Formation of the cornified envelope
R-HSA-1266738	Developmental Biology
R-HSA-6805567	Keratinization

MSigDB gene sets: 20 (showing top): GOBP_EPITHELIUM_DEVELOPMENT, GOBP_EPIDERMAL_CELL_DIFFERENTIATION, RICKMAN_TUMOR_DIFFERENTIATED_WELL_VS_POORLY_DN, GOBP_EPIDERMIS_DEVELOPMENT, GOBP_KERATINIZATION, GOBP_SKIN_DEVELOPMENT, RICKMAN_HEAD_AND_NECK_CANCER_C, chr1q21, SRC_UP.V1_UP, REACTOME_KERATINIZATION, REACTOME_FORMATION_OF_THE_CORNIFIED_ENVELOPE, GOBP_KERATINOCYTE_DIFFERENTIATION, HES2_TARGET_GENES, GOBP_EPITHELIAL_CELL_DIFFERENTIATION, ZIM3_TARGET_GENES

GO Biological Process (2): keratinization (GO:0031424), epidermis development (GO:0008544)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (1): cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Keratinization	1
Developmental Biology	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
keratinocyte differentiation	1
multicellular organismal process	1
tissue development	1
binding	1
cytoplasm	1
cellular anatomical structure	1

Protein interactions and networks

STRING

536 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LCE3D	SPRR2A	P35326	780
LCE3D	SPRR2D	P22532	747
LCE3D	LCE2D	Q5TA82	729
LCE3D	LCE2C	Q5TA81	726
LCE3D	SPRR2G	Q9BYE4	697
LCE3D	LCE3A	Q5TA76	667
LCE3D	LCE1C	Q5T751	664
LCE3D	LCE1E	Q5T753	642
LCE3D	SPRR2E	P22531	609
LCE3D	ZNF816	Q0VGE8	595
LCE3D	SPRR1A	P35321	595
LCE3D	TNIP1	Q15025	591
LCE3D	ERAP1	Q9NZ08	589
LCE3D	CNFN	Q9BYD5	583
LCE3D	SPRR3	Q9UBC9	582
LCE3D	LCE2B	O14633	582

IntAct

190 interactions, top by confidence:

A	B	Type	Score
MDFI	LCE3D	psi-mi:“MI:0915”(physical association)	0.600
SPRY1	LCE3D	psi-mi:“MI:0915”(physical association)	0.600
LCE3D	MDFI	psi-mi:“MI:0915”(physical association)	0.600
LCE3D	SPRY1	psi-mi:“MI:0915”(physical association)	0.600
KRTAP5-7	LCE3D	psi-mi:“MI:0915”(physical association)	0.560
KRTAP5-9	LCE3D	psi-mi:“MI:0915”(physical association)	0.560
KRTAP12-3	LCE3D	psi-mi:“MI:0915”(physical association)	0.560
FBLN2	LCE3D	psi-mi:“MI:0915”(physical association)	0.560
LCE3D	KRTAP9-3	psi-mi:“MI:0915”(physical association)	0.560
CYSRT1	LCE3D	psi-mi:“MI:0915”(physical association)	0.560
LCE3D	KRTAP9-8	psi-mi:“MI:0915”(physical association)	0.560
RGS20	LCE3D	psi-mi:“MI:0915”(physical association)	0.560
KRTAP1-3	LCE3D	psi-mi:“MI:0915”(physical association)	0.560
KRTAP4-12	LCE3D	psi-mi:“MI:0915”(physical association)	0.560
KRT31	LCE3D	psi-mi:“MI:0915”(physical association)	0.560
LCE3D	RGS17	psi-mi:“MI:0915”(physical association)	0.560
ADAMTSL4	LCE3D	psi-mi:“MI:0915”(physical association)	0.560
KRTAP6-3	LCE3D	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-7	LCE3D	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-8	LCE3D	psi-mi:“MI:0915”(physical association)	0.560
LCE2C	LCE3D	psi-mi:“MI:0915”(physical association)	0.560
LCE3D	KRTAP9-2	psi-mi:“MI:0915”(physical association)	0.560
KRTAP4-1	LCE3D	psi-mi:“MI:0915”(physical association)	0.560
NOTCH2NLC	LCE3D	psi-mi:“MI:0915”(physical association)	0.560
PCSK5	LCE3D	psi-mi:“MI:0915”(physical association)	0.560
KRTAP1-1	LCE3D	psi-mi:“MI:0915”(physical association)	0.560
CCN3	LCE3D	psi-mi:“MI:0915”(physical association)	0.560
LCE3D	KRTAP4-5	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-5	LCE3D	psi-mi:“MI:0915”(physical association)	0.560
VWC2	LCE3D	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (73): LCE3D (Two-hybrid), LCE3D (Two-hybrid), LCE3D (Two-hybrid), LCE3D (Two-hybrid), LCE3D (Two-hybrid), LCE3D (Two-hybrid), LCE3D (Two-hybrid), LCE3D (Two-hybrid), LCE3D (Two-hybrid), LCE3D (Two-hybrid), LCE3D (Two-hybrid), LCE3D (Two-hybrid), LCE3D (Two-hybrid), LCE3D (Two-hybrid), ALPP (Two-hybrid)

ESM2 similar proteins: A0A1B0GTR4, A6QNZ4, O14633, O70554, O70555, O70556, O70557, O70558, O70559, O70560, O70562, P15265, P22528, P22531, P22532, P35321, P35322, P35323, P35324, P35325, P35326, P49901, Q28658, Q32L04, Q4KL71, Q4R956, Q5T5B0, Q5T750, Q5T752, Q5T754, Q5T870, Q5T871, Q5TA76, Q5TA77, Q5TA78, Q5TA79, Q5TA81, Q5TA82, Q5TCM9, Q62266

Diamond homologs: O14633, Q5T5A8, Q5T5B0, Q5TA76, Q5TA77, Q5TA78, Q5TA79, Q5TA81, Q5TA82, Q5TCM9, Q9BYE3

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 54 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Keratinization	27	35.0×	3e-35

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	24
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

96 predictions. Top by Δscore:

Variant	Effect	Δscore
1:152580464:CTCA:C	donor_loss	0.9700
1:152580465:TCACC:T	donor_loss	0.9700
1:152580466:CACCA:C	donor_loss	0.9700
1:152580468:C:CT	donor_loss	0.9700
1:152579958:C:CC	acceptor_gain	0.9600
1:152579955:GTCCT:G	acceptor_loss	0.9500
1:152579956:TCC:T	acceptor_loss	0.9500
1:152579957:CCTG:C	acceptor_loss	0.9500
1:152579958:CTGG:C	acceptor_loss	0.9500
1:152579959:T:G	acceptor_loss	0.9500
1:152580467:A:AC	donor_gain	0.9300
1:152580468:C:CC	donor_gain	0.9300
1:152580468:CCAG:C	donor_gain	0.9200
1:152580462:CACT:C	donor_loss	0.9100
1:152580461:ACACT:A	donor_loss	0.8900
1:152580463:ACTC:A	donor_loss	0.8900
1:152580468:CCA:C	donor_gain	0.8900
1:152579953:TTGTC:T	acceptor_gain	0.8800
1:152579954:TGTC:T	acceptor_gain	0.8800
1:152579963:C:CT	acceptor_gain	0.8600
1:152580467:AC:A	donor_gain	0.8600
1:152580468:CC:C	donor_gain	0.8600
1:152579969:A:T	acceptor_loss	0.8500
1:152579955:GTC:G	acceptor_gain	0.8200
1:152579956:TC:T	acceptor_gain	0.8100
1:152579957:CC:C	acceptor_gain	0.8100
1:152580094:A:AC	donor_gain	0.7900
1:152580095:C:CC	donor_gain	0.7900
1:152580468:CCAGG:C	donor_gain	0.7800
1:152579963:CAAAA:C	acceptor_loss	0.7400

AlphaMissense

596 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:152579891:A:G	C16R	0.677
1:152579889:A:C	C16W	0.617
1:152579661:G:C	C92W	0.615
1:152579925:C:A	Q4H	0.614
1:152579925:C:G	Q4H	0.614
1:152579663:A:G	C92R	0.596
1:152579865:C:A	K24N	0.576
1:152579865:C:G	K24N	0.576
1:152579916:C:A	Q7H	0.565
1:152579916:C:G	Q7H	0.565

dbSNP variants (sampled 300 via entrez): RS1002195034 (1:152579112 T>A,C), RS1002341419 (1:152580132 A>C), RS1002508911 (1:152581985 T>C), RS1004417889 (1:152582315 G>A), RS1005364579 (1:152581887 C>A,T), RS1005907958 (1:152580500 C>A,T), RS1008955747 (1:152581182 A>G), RS1009555883 (1:152582390 A>G), RS1009871209 (1:152581252 G>A,T), RS1014462891 (1:152581520 C>G,T), RS1015200235 (1:152581360 T>A), RS1015918287 (1:152580504 G>T), RS1016201729 (1:152580209 G>A), RS1018269516 (1:152579296 G>A,C), RS1019074953 (1:152580871 A>G)

Disease associations

OMIM: gene MIM:612616 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST000321_2	Psoriasis	7.000000e-30
GCST000833_11	Psoriasis	3.000000e-10
GCST005527_3	Psoriasis	2.000000e-33
GCST007563_33	Allergic disease (asthma, hay fever or eczema)	3.000000e-11
GCST007564_24	Asthma or allergic disease (pleiotropy)	5.000000e-12
GCST008479_3	Psoriasis	6.000000e-11
GCST008479_32	Psoriasis	6.000000e-13
GCST008479_4	Psoriasis	2.000000e-08
GCST008916_82	Asthma	5.000000e-27
GCST008916_88	Asthma	1.000000e-25

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
hydroquinone	increases expression	2
Nickel	increases expression	2
Sodium Dodecyl Sulfate	increases expression	2
Tetrachlorodibenzodioxin	increases expression	2
Tobacco Smoke Pollution	increases expression	2
Particulate Matter	increases expression	2
bisphenol A	affects cotreatment, decreases methylation	1
2-methyl-4-isothiazolin-3-one	increases expression	1
sodium arsenite	increases expression	1
butyraldehyde	increases expression	1
cupric chloride	increases expression	1
pentanal	increases expression	1
CGP 52608	affects binding, increases reaction	1
abrine	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Benzo(a)pyrene	decreases methylation	1
Estradiol	affects cotreatment, increases expression	1
Mustard Gas	increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Silicon Dioxide	increases expression	1
Toluene	decreases methylation, increases expression	1
Tretinoin	decreases expression	1
Valproic Acid	decreases methylation	1
Aflatoxin B1	decreases methylation	1
Cadmium Chloride	decreases expression	1

Clinical trials (associated diseases)

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