LCE3E

Summary

LCE3E (late cornified envelope 3E, HGNC:29463) is a protein-coding gene on chromosome 1q21.3, encoding Late cornified envelope protein 3E (Q5T5B0). Precursors of the cornified envelope of the stratum corneum.

Predicted to be involved in keratinization.

Source: NCBI Gene 353145 — RefSeq curated summary.

At a glance

• GWAS associations: 11
• Clinical variants (ClinVar): 25 total
• MANE Select transcript: NM_178435

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29463
Approved symbol	LCE3E
Name	late cornified envelope 3E
Location	1q21.3
Locus type	gene with protein product
Status	Approved
Aliases	LEP17
Ensembl gene	ENSG00000185966
Ensembl biotype	protein_coding
OMIM	612617
Entrez	353145

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000368789

RefSeq mRNA: 1 — MANE Select: NM_178435 NM_178435

CCDS: CCDS1013

Canonical transcript exons

ENST00000368789 — 2 exons

Exon	Start	End
ENSE00001447963	152565654	152566229
ENSE00001447964	152566738	152566780

Expression profiles

Bgee: expression breadth broad, 35 present calls, max score 78.39.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1828 / max 36.6043, expressed in 34 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
14565	0.1828	34

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
skin of leg	UBERON:0001511	78.39	gold quality
zone of skin	UBERON:0000014	75.37	gold quality
skin of abdomen	UBERON:0001416	71.59	gold quality
lower esophagus mucosa	UBERON:0035834	67.21	gold quality
esophagus mucosa	UBERON:0002469	67.19	gold quality
vagina	UBERON:0000996	58.36	gold quality
ectocervix	UBERON:0012249	55.67	gold quality
tonsil	UBERON:0002372	51.58	gold quality
esophagus	UBERON:0001043	47.04	gold quality
uterine cervix	UBERON:0000002	45.67	gold quality
granulocyte	CL:0000094	40.14	gold quality
sural nerve	UBERON:0015488	37.56	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
smooth muscle tissue	UBERON:0001135	36.31	silver quality
bone marrow cell	CL:0002092	36.16	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
minor salivary gland	UBERON:0001830	34.91	gold quality
saliva-secreting gland	UBERON:0001044	34.40	gold quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
right uterine tube	UBERON:0001302	32.34	gold quality
right coronary artery	UBERON:0001625	32.21	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
bone marrow	UBERON:0002371	31.74	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
islet of Langerhans	UBERON:0000006	29.30	gold quality
prefrontal cortex	UBERON:0000451	29.04	gold quality
multicellular organism	UBERON:0000468	28.99	gold quality
duodenum	UBERON:0002114	28.14	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.98

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

15 targeting LCE3E, 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-4267	99.96	66.53	2368
HSA-MIR-7150	99.62	66.80	1322
HSA-MIR-486-5P	99.51	70.39	707
HSA-MIR-6878-3P	99.24	64.23	920
HSA-MIR-6744-3P	99.22	64.41	972
HSA-MIR-4757-5P	99.12	64.51	981
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-4736	97.96	65.89	1287
HSA-MIR-212-5P	96.83	67.43	950
HSA-MIR-6854-5P	96.77	65.96	848

Literature-anchored findings (GeneRIF, showing 1)

• paper describing nomenclature changes and expression in range of tissues and in response to UV (PMID:15854049)

Cross-species orthologs

0 orthologs

Paralogs (20): LCE2B (ENSG00000159455), SPRR2G (ENSG00000159516), LCE3D (ENSG00000163202), SPRR3 (ENSG00000163209), SPRR1B (ENSG00000169469), SPRR1A (ENSG00000169474), LCE1D (ENSG00000172155), SPRR4 (ENSG00000184148), LCE3A (ENSG00000185962), 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 3E — Q5T5B0 (reviewed: Q5T5B0)

Alternative names: Late envelope protein 17

All UniProt accessions (1): Q5T5B0

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.

Induction. By UVB.

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

Similarity. Belongs to the LCE family.

RefSeq proteins (1): NP_848522* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR028205	LCE	Family

Pfam: PF14672

UniProt features (6 total): compositionally biased region 3, region of interest 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5T5B0-F1	59.34	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: 13 (showing top): GOBP_EPITHELIUM_DEVELOPMENT, GOBP_EPIDERMAL_CELL_DIFFERENTIATION, GOBP_EPIDERMIS_DEVELOPMENT, GOBP_KERATINIZATION, GOBP_SKIN_DEVELOPMENT, chr1q21, CAMPS_COLON_CANCER_COPY_NUMBER_DN, REACTOME_KERATINIZATION, REACTOME_FORMATION_OF_THE_CORNIFIED_ENVELOPE, GOBP_KERATINOCYTE_DIFFERENTIATION, GOBP_EPITHELIAL_CELL_DIFFERENTIATION, MIR486_5P, MIR6878_3P

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

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

GO Cellular Component (0):

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

Protein interactions and networks

STRING

332 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LCE3E	LCE2C	Q5TA81	785
LCE3E	LCE2D	Q5TA82	761
LCE3E	LCE1C	Q5T751	757
LCE3E	SPRR2A	P35326	745
LCE3E	SPRR2D	P22532	719
LCE3E	SPRR2G	Q9BYE4	638
LCE3E	LCE1E	Q5T753	627
LCE3E	SPRR2E	P22531	620
LCE3E	LCE2A	Q5TA79	620
LCE3E	LCE1F	Q5T754	596
LCE3E	LCE2B	O14633	595
LCE3E	CDSN	Q15517	579
LCE3E	LCE1B	Q5T7P3	578
LCE3E	LCE1A	Q5T7P2	577
LCE3E	LCE6A	A0A183	571

IntAct

224 interactions, top by confidence:

A	B	Type	Score
KRTAP10-9	LCE3E	psi-mi:“MI:0915”(physical association)	0.740
LCE3E	KRTAP10-9	psi-mi:“MI:0915”(physical association)	0.740
LCE3E	RGS20	psi-mi:“MI:0915”(physical association)	0.720
LCE3E	KRTAP5-9	psi-mi:“MI:0915”(physical association)	0.720
LCE3E	KRTAP10-5	psi-mi:“MI:0915”(physical association)	0.720
KRTAP10-7	LCE3E	psi-mi:“MI:0915”(physical association)	0.720
KRTAP10-8	LCE3E	psi-mi:“MI:0915”(physical association)	0.720
ADAMTSL4	LCE3E	psi-mi:“MI:0915”(physical association)	0.720
LCE3E	MDFI	psi-mi:“MI:0915”(physical association)	0.720
LCE3E	KRTAP4-12	psi-mi:“MI:0915”(physical association)	0.720
LCE3E	KRTAP9-2	psi-mi:“MI:0915”(physical association)	0.720
LCE3E	KRTAP4-2	psi-mi:“MI:0915”(physical association)	0.720
KRTAP5-9	LCE3E	psi-mi:“MI:0915”(physical association)	0.720
LCE3E	KRTAP10-7	psi-mi:“MI:0915”(physical association)	0.720
LCE3E	KRTAP10-8	psi-mi:“MI:0915”(physical association)	0.720
MDFI	LCE3E	psi-mi:“MI:0915”(physical association)	0.720
KRTAP9-2	LCE3E	psi-mi:“MI:0915”(physical association)	0.720

BioGRID (72): LCE3E (Two-hybrid), LCE3E (Two-hybrid), LCE3E (Two-hybrid), LCE3E (Two-hybrid), LCE3E (Two-hybrid), LCE3E (Two-hybrid), LCE3E (Two-hybrid), LCE3E (Two-hybrid), LCE3E (Two-hybrid), LCE3E (Two-hybrid), LCE3E (Two-hybrid), LCE3E (Two-hybrid), KRTAP10-7 (Two-hybrid), KRTAP10-9 (Two-hybrid), KRTAP10-1 (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 49 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	28	38.0×	1e-38

GO biological processes:

GO term	Partners	Fold	FDR
hair cycle	5	167.2×	1e-08

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	23
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

144 predictions. Top by Δscore:

Variant	Effect	Δscore
1:152566734:TTAC:T	donor_loss	0.9900
1:152566735:TAC:T	donor_loss	0.9900
1:152566736:ACC:A	donor_loss	0.9900
1:152566736:A:AC	donor_gain	0.9800
1:152566737:C:CG	donor_gain	0.9800
1:152566737:CCA:C	donor_gain	0.9800
1:152566737:CCAG:C	donor_gain	0.9800
1:152566736:AC:A	donor_gain	0.9700
1:152566737:CC:C	donor_gain	0.9700
1:152566737:CCAGG:C	donor_gain	0.9600
1:152566230:C:CC	acceptor_gain	0.9500
1:152566226:TGTC:T	acceptor_gain	0.9400
1:152566227:GTCC:G	acceptor_loss	0.9400
1:152566228:TCCT:T	acceptor_loss	0.9400
1:152566229:CCTG:C	acceptor_loss	0.9400
1:152566230:CT:C	acceptor_loss	0.9400
1:152566231:T:C	acceptor_loss	0.9400
1:152566732:ACTT:A	donor_loss	0.8600
1:152566232:G:C	acceptor_loss	0.8500
1:152566241:G:T	acceptor_loss	0.8200
1:152566240:C:CT	acceptor_loss	0.8000
1:152566227:GTC:G	acceptor_gain	0.7900
1:152566228:TC:T	acceptor_gain	0.7800
1:152566229:CC:C	acceptor_gain	0.7800
1:152566309:C:CC	acceptor_gain	0.7800
1:152566235:GAAAA:G	acceptor_loss	0.7700
1:152566308:GCTGC:G	acceptor_gain	0.7500
1:152566305:AGAG:A	acceptor_gain	0.6800
1:152566306:GAG:G	acceptor_gain	0.6700
1:152566307:AGCTG:A	acceptor_gain	0.6500

AlphaMissense

598 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:152566163:A:G	C16R	0.625
1:152566055:A:G	C52R	0.581
1:152566161:G:C	C16W	0.576

dbSNP variants (sampled 300 via entrez): RS1000760942 (1:152567527 T>G), RS1000815293 (1:152567248 G>C), RS1001269955 (1:152565226 T>C), RS1001369010 (1:152567404 C>CT), RS1002310908 (1:152567068 T>A,C), RS1002871762 (1:152568126 G>A), RS1002925752 (1:152567660 G>A), RS1003317486 (1:152565796 A>G), RS1004833546 (1:152568564 A>G,T), RS1006174832 (1:152567832 T>C), RS1006836833 (1:152565207 C>A,T), RS1007180366 (1:152566439 C>A,T), RS1008054850 (1:152567209 G>A), RS1009514040 (1:152568031 G>A), RS1010408438 (1:152568424 G>A,C)

Disease associations

OMIM: gene MIM:612617 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST000706_14	Common traits (Other)	1.000000e-10
GCST002740_3	Inflammatory skin disease	5.000000e-25
GCST003184_30	Atopic dermatitis	6.000000e-29
GCST005005_6	Plantar warts	5.000000e-09
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

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0005038	hair morphology
EFO:0008406	susceptibility to plantar warts measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

12 total (human), top 12 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tetrachlorodibenzodioxin	increases expression	3
sodium arsenite	increases expression	2
Benzo(a)pyrene	affects expression, increases methylation	2
bisphenol A	decreases methylation	1
sodium arsenate	decreases expression, increases abundance	1
pentanal	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Arsenic	decreases expression, increases abundance	1
Plant Extracts	affects cotreatment, decreases expression	1
Cadmium Chloride	decreases expression	1
Nanotubes, Carbon	increases expression	1
Particulate Matter	increases expression	1

Clinical trials (associated diseases)

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