LCE1A

Summary

LCE1A (late cornified envelope 1A, HGNC:29459) is a protein-coding gene on chromosome 1q21.3, encoding Late cornified envelope protein 1A (Q5T7P2). Precursors of the cornified envelope of the stratum corneum.

LCE1A belongs to the late cornified envelope (LCE) gene cluster within the epidermal differentiation complex (EDC) on chromosome 1. The LCE cluster contains multiple conserved genes that encode stratum corneum proteins, and these genes are expressed relatively late during fetal assembly of the skin cornified envelope (Jackson et al., 2005 [PubMed 15854049]). For further information on the LCE gene cluster, see GENE FAMILY below.

Source: NCBI Gene 353131 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 26 total
• MANE Select transcript: NM_178348

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29459
Approved symbol	LCE1A
Name	late cornified envelope 1A
Location	1q21.3
Locus type	gene with protein product
Status	Approved
Aliases	LEP1
Ensembl gene	ENSG00000186844
Ensembl biotype	protein_coding
OMIM	612603
Entrez	353131

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000335123

RefSeq mRNA: 1 — MANE Select: NM_178348 NM_178348

CCDS: CCDS1028

Canonical transcript exons

ENST00000335123 — 1 exons

Exon	Start	End
ENSE00001333081	152827473	152828097

Expression profiles

Bgee: expression breadth broad, 89 present calls, max score 96.84.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
skin of leg	UBERON:0001511	96.84	gold quality
zone of skin	UBERON:0000014	95.36	gold quality
skin of abdomen	UBERON:0001416	93.22	gold quality
sural nerve	UBERON:0015488	60.23	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	55.63	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	49.80	gold quality
lower esophagus mucosa	UBERON:0035834	45.62	silver quality
gastrocnemius	UBERON:0001388	44.68	gold quality
right adrenal gland cortex	UBERON:0035827	44.20	gold quality
heart left ventricle	UBERON:0002084	43.28	gold quality
apex of heart	UBERON:0002098	42.88	silver quality
muscle of leg	UBERON:0001383	42.37	gold quality
duodenum	UBERON:0002114	41.73	gold quality
popliteal artery	UBERON:0002250	41.41	gold quality
tibial artery	UBERON:0007610	41.27	gold quality
mucosa of stomach	UBERON:0001199	40.63	silver quality
fundus of stomach	UBERON:0001160	40.37	gold quality
muscle layer of sigmoid colon	UBERON:0035805	39.82	gold quality
small intestine Peyer’s patch	UBERON:0003454	39.19	gold quality
small intestine	UBERON:0002108	38.92	gold quality
subcutaneous adipose tissue	UBERON:0002190	38.89	gold quality
right lobe of liver	UBERON:0001114	38.55	gold quality
multicellular organism	UBERON:0000468	38.34	gold quality
heart	UBERON:0000948	38.18	gold quality
blood	UBERON:0000178	38.09	gold quality
skeletal muscle tissue	UBERON:0001134	37.74	gold quality
adipose tissue	UBERON:0001013	37.63	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	37.28	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
body of pancreas	UBERON:0001150	37.10	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.82

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

23 targeting LCE1A, 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-4713-3P	100.00	65.92	505
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-5093	99.67	69.26	2291
HSA-MIR-10394-5P	99.65	66.83	1852
HSA-MIR-1205	99.65	66.76	1826
HSA-MIR-766-5P	99.47	67.91	2225
HSA-MIR-4784	99.15	67.41	1733
HSA-MIR-485-5P	99.10	64.78	1889
HSA-MIR-6884-5P	99.10	64.50	1987
HSA-MIR-4464	98.95	67.73	820
HSA-MIR-4748	98.95	67.53	810
HSA-MIR-3150B-3P	98.81	67.21	1728
HSA-MIR-3135B	98.61	65.33	1470
HSA-MIR-1233-5P	98.19	66.71	1201
HSA-MIR-6778-5P	98.19	66.59	1239
HSA-MIR-450B-3P	97.56	66.12	512
HSA-MIR-769-3P	97.06	64.83	464
HSA-MIR-4474-3P	96.97	65.87	870
HSA-MIR-3174	94.63	63.64	577

Literature-anchored findings (GeneRIF, showing 1)

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

Cross-species orthologs

0 orthologs

Protein

Protein identifiers

Late cornified envelope protein 1A — Q5T7P2 (reviewed: Q5T7P2)

Alternative names: Late envelope protein 1

All UniProt accessions (1): Q5T7P2

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_848125* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR028205	LCE	Family

Pfam: PF14672

UniProt features (7 total): compositionally biased region 4, region of interest 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5T7P2-F1	54.31	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: 31 (showing top): GOBP_EPITHELIUM_DEVELOPMENT, GOBP_EPIDERMAL_CELL_DIFFERENTIATION, MARTINEZ_RB1_TARGETS_DN, GOBP_EPIDERMIS_DEVELOPMENT, GOBP_KERATINIZATION, GOBP_SKIN_DEVELOPMENT, chr1q21, MARTENS_TRETINOIN_RESPONSE_UP, BRUINS_UVC_RESPONSE_VIA_TP53_GROUP_B, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY, REACTOME_KERATINIZATION, REACTOME_FORMATION_OF_THE_CORNIFIED_ENVELOPE, GOBP_KERATINOCYTE_DIFFERENTIATION, GOBP_EPITHELIAL_CELL_DIFFERENTIATION, MIR766_5P

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

286 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LCE1A	LCE1B	Q5T7P3	913
LCE1A	LCE5A	Q5TCM9	910
LCE1A	LCE3C	Q5T5A8	887
LCE1A	LCE3B	Q5TA77	874
LCE1A	LCE4A	Q5TA78	852
LCE1A	LCE1D	Q5T752	785
LCE1A	LCE1C	Q5T751	761
LCE1A	PGLYRP3	Q96LB9	719
LCE1A	PGLYRP4	Q96LB8	719
LCE1A	IVL	P07476	707
LCE1A	LORICRIN	P23490	700
LCE1A	LCE6A	A0A183	691
LCE1A	LCE1F	Q5T754	669
LCE1A	LCE1E	Q5T753	666
LCE1A	LCE2C	Q5TA81	621

IntAct

235 interactions, top by confidence:

A	B	Type	Score
LCE1A	KRTAP4-12	psi-mi:“MI:0915”(physical association)	0.600
LCE1A	KRTAP9-8	psi-mi:“MI:0915”(physical association)	0.600
NOTCH2NLC	LCE1A	psi-mi:“MI:0915”(physical association)	0.560
LCE1E	LCE1A	psi-mi:“MI:0915”(physical association)	0.560
LCE1A	KRTAP4-4	psi-mi:“MI:0915”(physical association)	0.560
PLSCR2	LCE1A	psi-mi:“MI:0915”(physical association)	0.560
LCE1A	RGS17	psi-mi:“MI:0915”(physical association)	0.560
LCE1A	KRTAP9-3	psi-mi:“MI:0915”(physical association)	0.560
LCE1A	KRTAP9-2	psi-mi:“MI:0915”(physical association)	0.560
KRTAP12-3	LCE1A	psi-mi:“MI:0915”(physical association)	0.560
KRTAP12-2	LCE1A	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-8	LCE1A	psi-mi:“MI:0915”(physical association)	0.560
LCE1A	KRTAP3-2	psi-mi:“MI:0915”(physical association)	0.560
CYSRT1	LCE1A	psi-mi:“MI:0915”(physical association)	0.560
HOXA1	LCE1A	psi-mi:“MI:0915”(physical association)	0.560
KRTAP1-1	LCE1A	psi-mi:“MI:0915”(physical association)	0.560
RGS20	LCE1A	psi-mi:“MI:0915”(physical association)	0.560
KRTAP1-3	LCE1A	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-7	LCE1A	psi-mi:“MI:0915”(physical association)	0.560
LCE1A	MDFI	psi-mi:“MI:0915”(physical association)	0.560
LCE1A	KRTAP5-7	psi-mi:“MI:0915”(physical association)	0.560
LCE1A	LCE2C	psi-mi:“MI:0915”(physical association)	0.560
LCE1A	KRTAP5-11	psi-mi:“MI:0915”(physical association)	0.560
LCE1A	KRTAP4-2	psi-mi:“MI:0915”(physical association)	0.560
TGFB1	LCE1A	psi-mi:“MI:0915”(physical association)	0.560
LCE1A	NID2	psi-mi:“MI:0915”(physical association)	0.560
LCE1A	KRTAP4-5	psi-mi:“MI:0915”(physical association)	0.560
LCE1F	LCE1A	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (84): LCE1A (Two-hybrid), LCE1A (Two-hybrid), LCE1A (Two-hybrid), LCE1A (Two-hybrid), LCE1A (Two-hybrid), LCE1A (Two-hybrid), LCE1A (Two-hybrid), LCE1A (Two-hybrid), LCE1A (Two-hybrid), LCE1A (Two-hybrid), LCE1A (Two-hybrid), LCE1A (Two-hybrid), LCE1A (Two-hybrid), LCE1A (Two-hybrid), LCE1A (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: Q5T751, Q5T752, Q5T753, Q5T754, Q5T7P2, Q5T7P3, Q5T5A8, Q5TA79

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 65 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	35	38.2×	2e-48
Formation of the cornified envelope	10	17.2×	7e-09

GO biological processes:

GO term	Partners	Fold	FDR
hair cycle	5	106.4×	2e-07
keratinization	10	53.2×	1e-12

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	22
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

122 predictions. Top by Δscore:

Variant	Effect	Δscore
1:152827552:C:CG	donor_gain	0.8700
1:152827552:C:G	donor_gain	0.8500
1:152827496:GCA:G	donor_gain	0.7900
1:152827517:G:GG	donor_gain	0.7900
1:152827516:A:AG	donor_gain	0.7500
1:152827499:G:GG	donor_gain	0.7300
1:152827498:A:AG	donor_gain	0.7100
1:152827881:T:TA	acceptor_gain	0.7000
1:152827792:G:GT	donor_gain	0.6200
1:152827843:A:AG	donor_gain	0.6200
1:152827882:G:A	acceptor_gain	0.6100
1:152827576:C:G	donor_gain	0.6000
1:152827528:A:AG	donor_gain	0.5900
1:152827529:G:GG	donor_gain	0.5900
1:152827663:G:T	donor_gain	0.5800
1:152827850:A:AG	donor_gain	0.5800
1:152827576:C:CG	donor_gain	0.5400
1:152827605:A:AG	acceptor_gain	0.5000
1:152827606:G:GG	acceptor_gain	0.5000
1:152827606:GT:G	acceptor_gain	0.5000
1:152827501:GCC:G	donor_gain	0.4900
1:152827869:C:G	acceptor_gain	0.4900
1:152827750:G:GT	donor_gain	0.4800
1:152827750:G:T	donor_gain	0.4800
1:152827663:G:GT	donor_gain	0.4700
1:152827841:A:AG	donor_gain	0.4700
1:152827668:G:GA	donor_gain	0.4600
1:152827701:TCCC:T	donor_gain	0.4600
1:152827868:A:AG	acceptor_gain	0.4600
1:152827842:A:G	donor_gain	0.4500

AlphaMissense

719 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:152827488:A:C	S6R	0.813
1:152827490:C:A	S6R	0.813
1:152827490:C:G	S6R	0.813
1:152827484:G:C	Q4H	0.773
1:152827484:G:T	Q4H	0.773
1:152827500:T:C	C10R	0.749
1:152827502:C:G	C10W	0.749
1:152827479:T:C	C3R	0.717
1:152827493:G:C	Q7H	0.715
1:152827493:G:T	Q7H	0.715
1:152827680:A:C	S70R	0.694
1:152827682:C:A	S70R	0.694
1:152827682:C:G	S70R	0.694
1:152827487:G:C	Q5H	0.692
1:152827487:G:T	Q5H	0.692
1:152827529:G:C	K19N	0.689
1:152827529:G:T	K19N	0.689
1:152827517:G:C	K15N	0.683
1:152827517:G:T	K15N	0.683
1:152827530:T:C	C20R	0.682
1:152827557:T:C	C29R	0.681
1:152827518:T:C	C16R	0.672
1:152827541:G:C	K23N	0.669
1:152827541:G:T	K23N	0.669
1:152827532:C:G	C20W	0.659
1:152827559:C:G	C29W	0.650
1:152827671:T:C	C67R	0.641
1:152827800:T:C	C110R	0.641
1:152827802:C:G	C110W	0.639
1:152827520:C:G	C16W	0.638

dbSNP variants (sampled 300 via entrez): RS1000474125 (1:152828366 C>G,T), RS1000978418 (1:152825739 T>C), RS1001480405 (1:152828495 A>C), RS1004651357 (1:152826337 A>C), RS1004935658 (1:152825797 G>C), RS1005094352 (1:152825488 G>A), RS1005423123 (1:152826749 C>T), RS1008564092 (1:152826973 G>A), RS1008792499 (1:152828592 T>A), RS1011463697 (1:152827027 AT>A,ATT), RS1011803184 (1:152826124 C>G), RS1012070213 (1:152828448 C>T), RS1012494498 (1:152826065 G>C,T), RS1012638102 (1:152826459 G>A), RS1012976899 (1:152826707 A>C,T)

Disease associations

OMIM: gene MIM:612603 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST007564_25	Asthma or allergic disease (pleiotropy)	5.000000e-09
GCST008916_87	Asthma	2.000000e-13
GCST008916_92	Asthma	6.000000e-16

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
sodium arsenate	decreases expression, increases abundance	1
CGP 52608	affects binding, increases reaction	1
bisphenol S	decreases methylation	1
Resveratrol	affects cotreatment, decreases expression	1
Arsenic	decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Mustard Gas	increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Silicon Dioxide	increases expression	1
Tetrachlorodibenzodioxin	increases expression	1
Valproic Acid	decreases methylation	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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