LCE3B

Summary

LCE3B (late cornified envelope 3B, HGNC:29462) is a protein-coding gene on chromosome 1q21.3, encoding Late cornified envelope protein 3B (Q5TA77). 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 353143 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 7 total
• MANE Select transcript: NM_178433

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29462
Approved symbol	LCE3B
Name	late cornified envelope 3B
Location	1q21.3
Locus type	gene with protein product
Status	Approved
Aliases	LEP14
Ensembl gene	ENSG00000187238
Ensembl biotype	protein_coding
OMIM	612614
Entrez	353143

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000335633

RefSeq mRNA: 1 — MANE Select: NM_178433 NM_178433

CCDS: CCDS1016

Canonical transcript exons

ENST00000335633 — 1 exons

Exon	Start	End
ENSE00001338458	152613811	152614098

Expression profiles

Bgee: expression breadth tissue_specific, 8 present calls, max score 49.39.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	49.39	silver quality
tonsil	UBERON:0002372	37.65	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
ganglionic eminence	UBERON:0004023	35.49	gold quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
bone marrow	UBERON:0002371	31.74	gold quality
muscle tissue	UBERON:0002385	31.06	gold quality
sural nerve	UBERON:0015488	30.93	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
prefrontal cortex	UBERON:0000451	29.04	gold quality
duodenum	UBERON:0002114	28.14	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
gall bladder	UBERON:0002110	25.98	gold quality
blood	UBERON:0000178	25.93	silver quality
olfactory segment of nasal mucosa	UBERON:0005386	25.89	gold quality
placenta	UBERON:0001987	25.81	gold quality
urinary bladder	UBERON:0001255	25.72	gold quality
muscle of leg	UBERON:0001383	24.74	gold quality
primary visual cortex	UBERON:0002436	24.61	gold quality
monocyte	CL:0000576	24.52	gold quality
superior frontal gyrus	UBERON:0002661	24.08	gold quality
right lobe of liver	UBERON:0001114	23.85	silver quality
frontal cortex	UBERON:0001870	23.71	gold quality
gastrocnemius	UBERON:0001388	23.49	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.29

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 22)

• 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 Psoriasis without psoriatic arthritis (PMID:20331852)
• no genetic association between 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)
• 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), KPLCE (ENSG00000198854), PRR9 (ENSG00000203783), LELP1 (ENSG00000203784), LCE1F (ENSG00000240386), LCE3C (ENSG00000244057)

Protein

Protein identifiers

Late cornified envelope protein 3B — Q5TA77 (reviewed: Q5TA77)

Alternative names: Late envelope protein 14

All UniProt accessions (1): Q5TA77

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.

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_848520* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR028205	LCE	Family

Pfam: PF14672

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

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5TA77-F1	58.17	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: 45 (showing top): GOBP_EPITHELIUM_DEVELOPMENT, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, DARWICHE_SKIN_TUMOR_PROMOTER_UP, DARWICHE_PAPILLOMA_RISK_LOW_UP, DARWICHE_PAPILLOMA_RISK_HIGH_UP, DARWICHE_SQUAMOUS_CELL_CARCINOMA_UP, 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

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

350 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LCE3B	LCE1A	Q5T7P2	874
LCE3B	PGLYRP4	Q96LB8	800
LCE3B	PGLYRP3	Q96LB9	767
LCE3B	HLA-C	P04222	743
LCE3B	IVL	P07476	700
LCE3B	LORICRIN	P23490	693
LCE3B	TRAF3IP2	O43734	599
LCE3B	RPTN	Q6XPR3	590
LCE3B	ERAP1	Q9NZ08	571
LCE3B	FBXL19	Q6PCT2	571
LCE3B	IL23R	Q5VWK5	544
LCE3B	TNIP1	Q15025	541
LCE3B	CARD14	Q9BXL6	528
LCE3B	FLG	P20930	527
LCE3B	RNF114	Q9Y508	507

IntAct

130 interactions, top by confidence:

A	B	Type	Score
KRTAP5-9	LCE3B	psi-mi:“MI:0915”(physical association)	0.600
LCE3B	KRTAP5-9	psi-mi:“MI:0915”(physical association)	0.600
LCE3B	ZMYM5	psi-mi:“MI:0915”(physical association)	0.560
LCE3B	UBE2I	psi-mi:“MI:0915”(physical association)	0.560
TGFB1	LCE3B	psi-mi:“MI:0915”(physical association)	0.560
LCE3B	LCE2C	psi-mi:“MI:0915”(physical association)	0.560
CYP21A2	LCE3B	psi-mi:“MI:0915”(physical association)	0.560
LCE3B	KRTAP4-5	psi-mi:“MI:0915”(physical association)	0.560
LCE3B	KRTAP9-2	psi-mi:“MI:0915”(physical association)	0.560
ALPP	LCE3B	psi-mi:“MI:0915”(physical association)	0.560
LCE3B	RGS17	psi-mi:“MI:0915”(physical association)	0.560
LCE3B	KRTAP5-2	psi-mi:“MI:0915”(physical association)	0.560
KRTAP1-1	LCE3B	psi-mi:“MI:0915”(physical association)	0.560
LCE3B	KRTAP4-12	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-5	LCE3B	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-6	LCE3B	psi-mi:“MI:0915”(physical association)	0.560
LCE3B	KRTAP4-2	psi-mi:“MI:0915”(physical association)	0.560
LCE3B	KRTAP9-3	psi-mi:“MI:0915”(physical association)	0.560
LCE3B	KRTAP4-11	psi-mi:“MI:0915”(physical association)	0.560
LCE3B	KRTAP4-4	psi-mi:“MI:0915”(physical association)	0.560
CYSRT1	LCE3B	psi-mi:“MI:0915”(physical association)	0.560
LCE3B	KRTAP5-4	psi-mi:“MI:0915”(physical association)	0.560
LCE1B	LCE3B	psi-mi:“MI:0915”(physical association)	0.560
KRTAP1-3	LCE3B	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-7	LCE3B	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-11	LCE3B	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-10	LCE3B	psi-mi:“MI:0915”(physical association)	0.560
LCE1E	LCE3B	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (45): LCE3B (Two-hybrid), LCE3B (Two-hybrid), LCE3B (Two-hybrid), LCE3B (Two-hybrid), LCE3B (Two-hybrid), LCE3B (Two-hybrid), LCE3B (Two-hybrid), LCE3B (Two-hybrid), LCE3B (Two-hybrid), LCE3B (Two-hybrid), LCE3B (Two-hybrid), LCE3B (Two-hybrid), KRTAP9-8 (Two-hybrid), KRTAP10-8 (Two-hybrid), KRTAP10-6 (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 39 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	45.9×	2e-42
Formation of the cornified envelope	7	18.1×	3e-06

GO biological processes:

GO term	Partners	Fold	FDR
hair cycle	5	222.9×	2e-09
keratinization	7	78.0×	5e-10

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	7
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

61 predictions. Top by Δscore:

Variant	Effect	Δscore
1:152613834:GCA:G	donor_gain	0.7000
1:152614048:C:A	donor_gain	0.7000
1:152613997:TCCC:T	donor_gain	0.6900
1:152614040:G:GT	donor_gain	0.6700
1:152613836:A:AG	donor_gain	0.6600
1:152613837:G:GG	donor_gain	0.6600
1:152614047:TCAGC:T	donor_gain	0.6300
1:152614043:GTG:G	donor_gain	0.6200
1:152613885:C:G	donor_gain	0.5900
1:152614042:AGT:A	donor_gain	0.5700
1:152614085:G:GT	donor_gain	0.5500
1:152613855:G:GG	donor_gain	0.5200
1:152613939:CTGTG:C	donor_gain	0.5200
1:152613998:C:A	donor_gain	0.5200
1:152613854:A:AG	donor_gain	0.5100
1:152614041:C:T	donor_gain	0.5000
1:152613989:GCTGC:G	donor_gain	0.4900
1:152614044:T:A	donor_gain	0.4700
1:152613990:C:CG	donor_gain	0.4600
1:152613986:G:T	acceptor_gain	0.4400
1:152614088:GCTGC:G	donor_gain	0.4400
1:152613961:G:GT	donor_gain	0.4100
1:152614042:A:AA	donor_gain	0.3900
1:152613946:G:GA	donor_gain	0.3800
1:152613974:TGAG:T	acceptor_gain	0.3800
1:152614051:C:T	donor_gain	0.3800
1:152613839:GCC:G	donor_gain	0.3700
1:152613894:GT:G	donor_gain	0.3700
1:152613938:GCTGT:G	donor_gain	0.3700
1:152614073:GC:G	donor_gain	0.3700

AlphaMissense

613 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000235638 (1:152614467 T>A,C,G), RS1006211884 (1:152612744 C>T), RS1014213738 (1:152614458 G>A), RS1017599399 (1:152612499 A>C), RS1021907556 (1:152613784 C>G), RS1022639847 (1:152613265 G>A,T), RS1025903488 (1:152614598 C>T), RS1029382741 (1:152613307 T>C), RS1031689850 (1:152613403 G>A), RS1042201243 (1:152612959 C>A,T), RS1043624941 (1:152613939 C>T), RS1043938855 (1:152614365 A>C), RS1044056725 (1:152612293 C>T), RS1045082518 (1:152612791 C>T), RS1047079179 (1:152612330 T>C)

Disease associations

OMIM: gene MIM:612614 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST005527_3	Psoriasis	2.000000e-33
GCST005537_137	Chronic inflammatory diseases (ankylosing spondylitis, Crohn’s disease, psoriasis, primary sclerosing cholangitis, ulcerative colitis) (pleiotropy)	4.000000e-24
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

4 total (human), top 4 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
CGP 52608	affects binding, increases reaction	1
Acetaminophen	decreases expression	1
Atrazine	increases expression	1
Tretinoin	decreases expression	1

Clinical trials (associated diseases)

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