LCE3C

Summary

LCE3C (late cornified envelope 3C, HGNC:16612) is a protein-coding gene on chromosome 1q21.3, encoding Late cornified envelope protein 3C (Q5T5A8). A structural component of the cornified envelope of the stratum corneum involved in innate cutaneous host defense.

Involved in defense response to Gram-negative bacterium; defense response to Gram-positive bacterium; and killing of cells of another organism.

Source: NCBI Gene 353144 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 13 total
• MANE Select transcript: NM_178434

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16612
Approved symbol	LCE3C
Name	late cornified envelope 3C
Location	1q21.3
Locus type	gene with protein product
Status	Approved
Aliases	LEP15
Ensembl gene	ENSG00000244057
Ensembl biotype	protein_coding
OMIM	612615
Entrez	353144

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000333881, ENST00000684028

RefSeq mRNA: 1 — MANE Select: NM_178434 NM_178434

CCDS: CCDS1015

Canonical transcript exons

ENST00000684028 — 2 exons

Exon	Start	End
ENSE00003920490	152600707	152601086
ENSE00003921335	152600234	152600284

Expression profiles

Bgee: expression breadth broad, 22 present calls, max score 95.22.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0339 / max 19.1837, expressed in 6 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
5306	0.0339	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	95.22	gold quality
tonsil	UBERON:0002372	41.11	gold quality
sural nerve	UBERON:0015488	38.38	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
skin of leg	UBERON:0001511	36.75	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
zone of skin	UBERON:0000014	35.86	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
skin of abdomen	UBERON:0001416	34.17	gold quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
esophagus mucosa	UBERON:0002469	31.87	gold quality
bone marrow	UBERON:0002371	31.74	gold quality
muscle tissue	UBERON:0002385	31.06	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
urinary bladder	UBERON:0001255	29.49	silver quality
ectocervix	UBERON:0012249	29.11	gold quality
prefrontal cortex	UBERON:0000451	29.04	gold quality
uterine cervix	UBERON:0000002	29.01	gold quality
duodenum	UBERON:0002114	28.14	gold quality
liver	UBERON:0002107	28.04	gold quality
lymph node	UBERON:0000029	27.57	gold quality
islet of Langerhans	UBERON:0000006	26.55	gold quality
vermiform appendix	UBERON:0001154	26.42	gold quality
esophagus	UBERON:0001043	26.22	gold quality
gall bladder	UBERON:0002110	25.98	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	25.89	gold quality
placenta	UBERON:0001987	25.81	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.99

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 24)

• paper describing nomenclature changes and expression in range of tissues and in response to UV (PMID:15854049)
• LCE3C_LCE3B-del shows epistatic effects with the HLA-Cw6 allele on the development of psoriasis. (PMID:19169253)
• study confirms the recently published finding that the deletion of the two LCE genes is a susceptibility factor for psoriasis vulgaris with dosage effect (PMID:20016497)
• we have verified a pleiotropic effect of a common genetic risk factor (LCE3C_LCE3B-del) for autoimmune diseases that is involved in both psoriasis and rheumatoid arthritis (PMID:20213803)
• work suggested that homozygosity for a common LCE3C_LCE3B deletion contributes to the risk of developing chronic plaque type Ps without psoriatic arthritis (PMID:20331852)
• no genetic association betwwen LCE3B and LCE3c deletions and atopic dermatitis (PMID:20376060)
• the deletion of LCE3C and LCE3B is a common genetic factor for susceptibility to psoriasis in the European, Chinese and Mongolian populations. (PMID:21107349)
• LCE3C_LCE3B deletion is a susceptibility factor for Psoriatic arthritis, confirming the existence of a shared risk factor involving the epidermal skin barrier in autoimmune disorders. (PMID:21400479)
• LCE3B/C deletion may have a role in psoriasis (PMID:21435436)
• Our study confirms an association between the deletion of LCE3C and LCE3B and psoriasis in a Chinese population. (PMID:21509048)
• This study provides evidence for an association between LCE3C_LCE3B-del and RA in non-Caucasian populations, and SNPs rs4112788 and rs4085613 tagging LCE3C_LCE3B-del were novel susceptibility factors for SLE. (PMID:21628307)
• The findings indicate that the LCE3C_LCE3B-del is an important risk factor in the pathogenesis of psoriasis and that the LCE3C_LCE3B-del does not show an epistatic effect with the HLA-Cw6 allele on susceptibility to psoriasis in the northern Chinese. (PMID:21711330)
• A deletion of LCE3B and LCE3C genes may promote the development of allergic contact dermatitis (PMID:21995181)
• results suggest that the Koebner phenomenon in psoriasis is unlikely to be dependent on the LCE3B/C genotype (PMID:22048733)
• LCE3C_LCE3B-del is a common risk factor for (auto)immune diseases (PMID:22384135)
• Paediatric-onset psoriasis is associated with ………. LCE3C_LCE3B deletion (PMID:22512642)
• The LCE3C_LCE3B-del might play a role in familial psoriasis in the Tunisian population. (PMID:22926764)
• Our meta-analysis demonstrates a significant association between psoriasis and the LCE3C_LCE3B-del polymorphism in Europeans and Asians, but no association with psoriatic arthritis. (PMID:23631431)
• No evidence of association was seen between the LCE3C_LCE3B-del and psoriasis in 34 patients from 7 multiplex Tunisian families. No epistasic effect was found between the deletion and PSORS1 locus. (PMID:24485035)
• Our data suggest that The LCE deletion, previously identified in patients with psoriasis, is not of a major importance in the development of PsA in Tunisian patients (PMID:24566688)
• analysis of disease variants at the LCE3 cluster among the psoriasis patients in India (PMID:27048876)
• Investigation of the clinical characteristics and copy number variations (CNVs) of DEFB4, IL22, and LCE3C in the three subclassifications revealed no significant differences in gender ratio and in Ps area and severity index (PASI) score. The CNVs of DEFB4 and LCE3C showed no significant differences but the CNV of IL22 significantly differed among the three subclassifications. (PMID:29623515)
• Copy Number Variation Analysis of IL22 and LCE3C in Different Subtypes of Psoriasis in a Chinese Han Population. (PMID:34853291)
• Antimicrobial Late Cornified Envelope Proteins: The Psoriasis Risk Factor Deletion of LCE3B/C Genes Affects Microbiota Composition. (PMID:34942199)

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), LCE3E (ENSG00000185966), LCE5A (ENSG00000186207), LCE1E (ENSG00000186226), LCE2A (ENSG00000187173), LCE2C (ENSG00000187180), LCE2D (ENSG00000187223), LCE3B (ENSG00000187238), KPLCE (ENSG00000198854), PRR9 (ENSG00000203783), LELP1 (ENSG00000203784), LCE1F (ENSG00000240386)

Protein

Protein identifiers

Late cornified envelope protein 3C — Q5T5A8 (reviewed: Q5T5A8)

Alternative names: Late envelope protein 15, Small proline-rich-like epidermal differentiation complex protein 3A

All UniProt accessions (1): Q5T5A8

UniProt curated annotations — full annotation on UniProt →

Function. A structural component of the cornified envelope of the stratum corneum involved in innate cutaneous host defense. Possesses defensin-like antimicrobial activity against a broad spectrum of Gram-positive and Gram-negative bacteria, both aerobic and anaerobic species. Upon inflammation, may regulate skin barrier repair by shaping cutaneous microbiota composition and immune response to bacterial antigens.

Subunit / interactions. Interacts with CYSRT1; the interaction is direct.

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.

Similarity. Belongs to the LCE family.

RefSeq proteins (1): NP_848521* (*=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-Q5T5A8-F1	56.98	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: 21 (showing top): GSE45365_NK_CELL_VS_BCELL_DN, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_EPIDERMAL_CELL_DIFFERENTIATION, GOBP_DEFENSE_RESPONSE_TO_GRAM_NEGATIVE_BACTERIUM, GOBP_EPIDERMIS_DEVELOPMENT, GOBP_DEFENSE_RESPONSE_TO_GRAM_POSITIVE_BACTERIUM, GOBP_KERATINIZATION, GOBP_DEFENSE_RESPONSE_TO_BACTERIUM, GOBP_CELL_KILLING, GOBP_SKIN_DEVELOPMENT, chr1q21, GOBP_RESPONSE_TO_BACTERIUM, BRUINS_UVC_RESPONSE_VIA_TP53_GROUP_A, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY, REACTOME_KERATINIZATION

GO Biological Process (5): keratinization (GO:0031424), killing of cells of another organism (GO:0031640), defense response to Gram-negative bacterium (GO:0050829), defense response to Gram-positive bacterium (GO:0050830), 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
defense response to bacterium	2
keratinocyte differentiation	1
multicellular organismal process	1
cell killing	1
disruption of cell in another organism	1
tissue development	1
binding	1

Protein interactions and networks

STRING

438 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LCE3C	LCE1A	Q5T7P2	887
LCE3C	HLA-C	P04222	796
LCE3C	PGLYRP3	Q96LB9	725
LCE3C	PGLYRP4	Q96LB8	723
LCE3C	LORICRIN	P23490	692
LCE3C	IVL	P07476	665
LCE3C	RPTN	Q6XPR3	658
LCE3C	TNIP1	Q15025	649
LCE3C	FLG	P20930	606
LCE3C	LCE1C	Q5T751	601
LCE3C	LCE6A	A0A183	584
LCE3C	TRAF3IP2	O43734	580
LCE3C	LCE2C	Q5TA81	576
LCE3C	LCE2A	Q5TA79	571
LCE3C	LCE2D	Q5TA82	571

IntAct

239 interactions, top by confidence:

A	B	Type	Score
KRTAP5-9	LCE3C	psi-mi:“MI:0915”(physical association)	0.740
LCE3C	KRTAP10-5	psi-mi:“MI:0915”(physical association)	0.740
LCE3C	KRTAP5-9	psi-mi:“MI:0915”(physical association)	0.740
KRTAP10-5	LCE3C	psi-mi:“MI:0915”(physical association)	0.740
LCE3C	KRTAP10-8	psi-mi:“MI:0915”(physical association)	0.720
KRTAP10-9	LCE3C	psi-mi:“MI:0915”(physical association)	0.720
LCE3C	ADAMTSL4	psi-mi:“MI:0915”(physical association)	0.720
KRTAP4-2	LCE3C	psi-mi:“MI:0915”(physical association)	0.720
LCE3C	KRTAP3-2	psi-mi:“MI:0915”(physical association)	0.720
KRTAP10-8	LCE3C	psi-mi:“MI:0915”(physical association)	0.720
LCE3C	KRTAP10-9	psi-mi:“MI:0915”(physical association)	0.720
ADAMTSL4	LCE3C	psi-mi:“MI:0915”(physical association)	0.720
LCE3C	KRTAP4-2	psi-mi:“MI:0915”(physical association)	0.720

BioGRID (75): LCE3C (Two-hybrid), LCE3C (Two-hybrid), LCE3C (Two-hybrid), LCE3C (Two-hybrid), LCE3C (Two-hybrid), LCE3C (Two-hybrid), LCE3C (Two-hybrid), LCE3C (Two-hybrid), LCE3C (Two-hybrid), LCE3C (Two-hybrid), LCE3C (Two-hybrid), KRTAP10-9 (Two-hybrid), KRTAP10-5 (Two-hybrid), KRTAP10-8 (Two-hybrid), KRTAP10-3 (Two-hybrid)

ESM2 similar proteins: A0A286YEV6, A0A286YEY9, A0A286YF60, A0A286YF77, A0A286YFG1, A2A591, A2A5X5, A8MUX0, A8MX34, O14633, O70562, P02438, P02439, P02440, P08131, P0C5Y4, P0DSO2, P0DV60, P22532, P35325, P35326, P60329, Q07627, Q3V2C1, Q4KL71, Q5T5A8, Q5T5B0, Q5T750, Q5T751, Q5T752, Q5T753, Q5T754, Q5T7P2, Q5T7P3, Q5TA76, Q5TA77, Q5TA78, Q5TA79, Q5TA81, Q5TA82

Diamond homologs: O14633, Q5T5A8, Q5T5B0, Q5TA76, Q5TA77, Q5TA78, Q5TA79, Q5TA81, Q5TA82, Q5TCM9, Q9BYE3, Q5T751, Q5T752, Q5T753, Q5T754, Q5T7P2, Q5T7P3

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 52 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	29	36.7×	2e-39

GO biological processes:

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

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	9
Likely benign	0
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

120 predictions. Top by Δscore:

Variant	Effect	Δscore
1:152600755:GCA:G	donor_gain	0.7200
1:152600758:G:GG	donor_gain	0.6900
1:152600757:A:AG	donor_gain	0.6800
1:152600906:C:T	donor_gain	0.6800
1:152600776:T:TA	donor_gain	0.6600
1:152601078:A:T	donor_gain	0.6400
1:152601077:G:GT	donor_gain	0.6300
1:152600966:C:A	donor_gain	0.6200
1:152600915:TCCC:T	donor_gain	0.6100
1:152600664:TCTG:T	donor_gain	0.5800
1:152600760:GCC:G	donor_gain	0.5600
1:152600663:GTC:G	donor_gain	0.5400
1:152600704:AAG:A	donor_loss	0.5300
1:152600705:AGGT:A	donor_loss	0.5300
1:152600708:T:G	donor_loss	0.5300
1:152600815:GT:G	donor_gain	0.5200
1:152600846:C:CG	donor_gain	0.5200
1:152601050:G:C	acceptor_gain	0.5000
1:152600670:GGT:G	donor_gain	0.4900
1:152600905:GCACT:G	donor_gain	0.4900
1:152600895:G:T	acceptor_gain	0.4800
1:152600665:C:A	donor_gain	0.4700
1:152600777:T:TA	donor_gain	0.4700
1:152600916:C:A	donor_gain	0.4700
1:152600707:G:GG	donor_gain	0.4600
1:152600709:A:C	donor_loss	0.4600
1:152600774:A:AG	donor_gain	0.4400
1:152600775:G:GG	donor_gain	0.4400
1:152600843:GCTC:G	donor_gain	0.4400
1:152600946:C:CT	acceptor_gain	0.4400

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1005150828 (1:152599629 T>C), RS1005744645 (1:152600246 C>A), RS1013117222 (1:152599561 A>G), RS1013564984 (1:152598939 T>C), RS1022094910 (1:152600975 G>A), RS1023210167 (1:152598970 A>T), RS1024012614 (1:152601419 C>T), RS1029448904 (1:152599828 G>T), RS1029788145 (1:152600412 A>G), RS1030775664 (1:152601475 A>G), RS1037221187 (1:152601152 G>A), RS1037284718 (1:152600323 G>C), RS1040974749 (1:152601196 T>C), RS1041277774 (1:152598605 C>T), RS1043100377 (1:152599367 C>T)

Disease associations

OMIM: gene MIM:612615 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST007563_33	Allergic disease (asthma, hay fever or eczema)	3.000000e-11
GCST007564_24	Asthma or allergic disease (pleiotropy)	5.000000e-12
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

9 total (human), top 9 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenate	decreases expression, increases abundance	1
sodium arsenite	increases expression	1
perfluorooctanoic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
perfluoro-n-nonanoic acid	increases expression	1
Arsenic	decreases expression, increases abundance	1
Aflatoxin B1	increases methylation	1
Cadmium Chloride	decreases expression	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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