LCE3A

Summary

LCE3A (late cornified envelope 3A, HGNC:29461) is a protein-coding gene on chromosome 1q21.3, encoding Late cornified envelope protein 3A (Q5TA76). 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 353142 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 14 total
• MANE Select transcript: NM_178431

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29461
Approved symbol	LCE3A
Name	late cornified envelope 3A
Location	1q21.3
Locus type	gene with protein product
Status	Approved
Aliases	LEP13
Ensembl gene	ENSG00000185962
Ensembl biotype	protein_coding
OMIM	612613
Entrez	353142

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000335674

RefSeq mRNA: 1 — MANE Select: NM_178431 NM_178431

CCDS: CCDS1017

Canonical transcript exons

ENST00000335674 — 1 exons

Exon	Start	End
ENSE00001338480	152622834	152623103

Expression profiles

Bgee: expression breadth broad, 54 present calls, max score 89.19.

Top tissues by expression

110 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	89.19	gold quality
lower esophagus mucosa	UBERON:0035834	59.55	gold quality
tonsil	UBERON:0002372	51.46	gold quality
vagina	UBERON:0000996	46.99	gold quality
esophagus mucosa	UBERON:0002469	45.51	gold quality
right testis	UBERON:0004534	42.34	gold quality
skin of leg	UBERON:0001511	42.08	gold quality
zone of skin	UBERON:0000014	41.23	gold quality
left testis	UBERON:0004533	40.35	gold quality
testis	UBERON:0000473	39.71	gold quality
skin of abdomen	UBERON:0001416	39.32	gold quality
sural nerve	UBERON:0015488	38.42	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
omental fat pad	UBERON:0010414	36.15	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
thoracic mammary gland	UBERON:0005200	35.07	gold quality
esophagus	UBERON:0001043	34.33	gold quality
adipose tissue	UBERON:0001013	33.89	gold quality
smooth muscle tissue	UBERON:0001135	33.82	gold quality
muscle tissue	UBERON:0002385	33.51	gold quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
subcutaneous adipose tissue	UBERON:0002190	32.18	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
bone marrow	UBERON:0002371	31.74	gold quality
ectocervix	UBERON:0012249	30.29	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
uterine cervix	UBERON:0000002	29.18	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.40

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 4)

• paper describing nomenclature changes and expression in range of tissues and in response to UV (PMID:15854049)
• analysis of disease variants at the LCE3 cluster among the psoriasis patients in India (PMID:27048876)
• genetic polymorphism is associated with psoriasis vulgaris among Mongolians from Inner Mongolia (PMID:29397434)
• Functional Mapping of Genetic Interactions between HLA-Cw6 and LCE3A in Psoriasis. (PMID:34029573)

Cross-species orthologs

0 orthologs

Paralogs (20): LCE2B (ENSG00000159455), SPRR2G (ENSG00000159516), LCE3D (ENSG00000163202), SPRR3 (ENSG00000163209), SPRR1B (ENSG00000169469), SPRR1A (ENSG00000169474), LCE1D (ENSG00000172155), SPRR4 (ENSG00000184148), 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 3A — Q5TA76 (reviewed: Q5TA76)

Alternative names: Late envelope protein 13

All UniProt accessions (1): Q5TA76

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.

Induction. Induced upon stimulation with inflammatory cytokines produced by T-helper 1 cells (IL1A, TNF, IFNG) and T-helper 17 cells (IL17A, IL22).

Similarity. Belongs to the LCE family.

RefSeq proteins (1): NP_848518* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR028205	LCE	Family

Pfam: PF14672

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

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5TA76-F1	57.44	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: 22 (showing top): 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, REACTOME_KERATINIZATION, REACTOME_FORMATION_OF_THE_CORNIFIED_ENVELOPE, GOBP_KERATINOCYTE_DIFFERENTIATION, GOBP_EPITHELIAL_CELL_DIFFERENTIATION

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

404 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LCE3A	SPRR2A	P35326	721
LCE3A	LCE3D	Q9BYE3	667
LCE3A	LCE1B	Q5T7P3	601
LCE3A	LCE2A	Q5TA79	583
LCE3A	LCE1A	Q5T7P2	582
LCE3A	LCE1C	Q5T751	571
LCE3A	LCE1F	Q5T754	570
LCE3A	SPRR4	Q96PI1	532
LCE3A	LCE2B	O14633	512
LCE3A	RPTN	Q6XPR3	511
LCE3A	LCE1D	Q5T752	507
LCE3A	SPRR2E	P22531	471
LCE3A	LCE4A	Q5TA78	469
LCE3A	HRNR	Q86YZ3	460
LCE3A	LCE6A	A0A183	454

IntAct

247 interactions, top by confidence:

A	B	Type	Score
LCE3A	KRTAP1-5	psi-mi:“MI:0915”(physical association)	0.600
CYSRT1	LCE3A	psi-mi:“MI:0915”(physical association)	0.600
SPRY1	LCE3A	psi-mi:“MI:0915”(physical association)	0.600
LCE3A	KRTAP4-2	psi-mi:“MI:0915”(physical association)	0.600
LCE3A	LCN2	psi-mi:“MI:0915”(physical association)	0.560
LCE3A	NAPSA	psi-mi:“MI:0915”(physical association)	0.560
LCE3A	LCE2C	psi-mi:“MI:0915”(physical association)	0.560
LCE3A	KRTAP5-6	psi-mi:“MI:0915”(physical association)	0.560
LCN2	LCE3A	psi-mi:“MI:0915”(physical association)	0.560
TGM1	LCE3A	psi-mi:“MI:0915”(physical association)	0.560
KRTAP12-3	LCE3A	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-7	LCE3A	psi-mi:“MI:0915”(physical association)	0.560
LCE3A	ADAMTSL4	psi-mi:“MI:0915”(physical association)	0.560
KRTAP1-3	LCE3A	psi-mi:“MI:0915”(physical association)	0.560
LCE3A	KRTAP2-4	psi-mi:“MI:0915”(physical association)	0.560
LCE3A	KRTAP9-2	psi-mi:“MI:0915”(physical association)	0.560
LCE3A	KRTAP5-7	psi-mi:“MI:0915”(physical association)	0.560
RGS20	LCE3A	psi-mi:“MI:0915”(physical association)	0.560
KRTAP4-1	LCE3A	psi-mi:“MI:0915”(physical association)	0.560
LCE3A	KRTAP4-12	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-8	LCE3A	psi-mi:“MI:0915”(physical association)	0.560
NOTCH2NLC	LCE3A	psi-mi:“MI:0915”(physical association)	0.560
LCE3A	MDFI	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-9	LCE3A	psi-mi:“MI:0915”(physical association)	0.560
KRTAP6-3	LCE3A	psi-mi:“MI:0915”(physical association)	0.560
LCE3A	KRTAP3-2	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (76): LCE3A (Two-hybrid), LCE3A (Two-hybrid), LCE3A (Two-hybrid), LCE3A (Two-hybrid), LCE3A (Two-hybrid), LCE3A (Two-hybrid), LCE3A (Two-hybrid), LCE3A (Two-hybrid), LCE3A (Two-hybrid), LCE3A (Two-hybrid), LCE3A (Two-hybrid), LCE3A (Two-hybrid), LCE3A (Two-hybrid), LCE3A (Two-hybrid), LCE3A (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 60 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	34	40.3×	2e-48
Formation of the cornified envelope	6	11.2×	3e-04

GO biological processes:

GO term	Partners	Fold	FDR
hair cycle	5	133.8×	7e-08
keratinization	6	40.1×	1e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	13
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

63 predictions. Top by Δscore:

Variant	Effect	Δscore
1:152622891:T:TA	donor_gain	0.6900
1:152622892:C:A	donor_gain	0.6700
1:152623033:CA:C	donor_gain	0.6600
1:152622893:C:A	donor_gain	0.6500
1:152622939:G:A	donor_gain	0.6400
1:152623011:G:C	donor_gain	0.6400
1:152622884:G:T	donor_gain	0.6200
1:152622958:A:AC	donor_gain	0.5800
1:152622959:G:C	donor_gain	0.5800
1:152622876:G:A	donor_gain	0.5200
1:152622958:AGG:A	donor_gain	0.5200
1:152622934:G:GT	donor_gain	0.5000
1:152622880:TGCTG:T	donor_gain	0.4800
1:152622931:TGAG:T	donor_gain	0.4600
1:152622928:CGGTG:C	donor_gain	0.4500
1:152623058:A:AC	donor_gain	0.4500
1:152623059:C:CC	donor_gain	0.4500
1:152622886:CCA:C	donor_gain	0.4400
1:152622929:GGTGA:G	donor_gain	0.4400
1:152622930:GTGAG:G	donor_gain	0.4400
1:152622864:G:C	donor_gain	0.4300
1:152623009:CAG:C	donor_gain	0.4300
1:152623034:A:AC	donor_gain	0.4300
1:152623035:C:CC	donor_gain	0.4300
1:152622887:CAC:C	donor_gain	0.4200
1:152622888:A:T	donor_gain	0.4200
1:152623031:G:T	donor_gain	0.4200
1:152623035:CTGTG:C	donor_gain	0.4200
1:152623077:CTG:C	donor_gain	0.4000
1:152623060:T:C	donor_gain	0.3900

AlphaMissense

591 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:152623058:A:G	C16R	0.627
1:152623056:G:C	C16W	0.566

dbSNP variants (sampled 300 via entrez): RS1001818535 (1:152622347 T>C), RS1002086957 (1:152623943 T>G), RS1002162147 (1:152623764 G>A), RS1004109554 (1:152623716 C>T), RS1004233053 (1:152624594 T>C,G), RS1004668544 (1:152624425 G>T), RS1005540927 (1:152623325 G>A), RS1007961121 (1:152624065 G>A), RS1008554281 (1:152622696 G>A), RS1009798708 (1:152623702 G>A), RS1011057346 (1:152625100 A>G), RS1011067882 (1:152623209 C>T), RS1011685970 (1:152624811 C>T), RS1012633364 (1:152623688 G>A), RS1012689029 (1:152623430 C>T)

Disease associations

OMIM: gene MIM:612613 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST000321_2	Psoriasis	7.000000e-30
GCST002740_39	Inflammatory skin disease	2.000000e-12
GCST003268_30	Psoriasis vulgaris	4.000000e-12
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
GCST010090_1	Atopic dermatitis	1.000000e-33

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:1001494	psoriasis vulgaris

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
Acetaminophen	decreases expression	2
Tetrachlorodibenzodioxin	increases expression	2
sodium arsenate	decreases expression, increases abundance	1
CGP 52608	affects binding, increases reaction	1
abrine	increases expression	1
bisphenol S	decreases methylation	1
incobotulinumtoxinA	decreases expression	1
Arsenic	decreases expression, increases abundance	1
Benzo(a)pyrene	increases methylation	1
Valproic Acid	increases methylation	1
Cadmium Chloride	increases expression	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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