LCE1C

Summary

LCE1C (late cornified envelope 1C, HGNC:29464) is a protein-coding gene on chromosome 1q21.3, encoding Late cornified envelope protein 1C (Q5T751). Precursors of the cornified envelope of the stratum corneum. It is a selective cancer dependency (DepMap: 60.0% of cell lines).

Predicted to be involved in keratinization.

Source: NCBI Gene 353133 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 19 total
• Cancer dependency (DepMap): dependent in 60.0% of screened cell lines
• MANE Select transcript: NM_178351

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29464
Approved symbol	LCE1C
Name	late cornified envelope 1C
Location	1q21.3
Locus type	gene with protein product
Status	Approved
Aliases	LEP3
Ensembl gene	ENSG00000197084
Ensembl biotype	protein_coding
OMIM	612605
Entrez	353133

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000606576, ENST00000607093

RefSeq mRNA: 2 — MANE Select: NM_178351 NM_001276331, NM_178351

CCDS: CCDS1026

Canonical transcript exons

ENST00000607093 — 2 exons

Exon	Start	End
ENSE00003695306	152804832	152805498
ENSE00003918123	152806601	152806651

Expression profiles

Bgee: expression breadth broad, 99 present calls, max score 97.79.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.7289 / max 637.8096, expressed in 71 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
14570	0.7289	71

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
skin of leg	UBERON:0001511	97.79	gold quality
zone of skin	UBERON:0000014	97.20	gold quality
skin of abdomen	UBERON:0001416	96.30	gold quality
lower esophagus mucosa	UBERON:0035834	59.12	gold quality
apex of heart	UBERON:0002098	55.35	gold quality
esophagus mucosa	UBERON:0002469	52.20	gold quality
gastrocnemius	UBERON:0001388	52.11	gold quality
right adrenal gland cortex	UBERON:0035827	49.53	gold quality
muscle of leg	UBERON:0001383	48.53	gold quality
fundus of stomach	UBERON:0001160	48.28	gold quality
popliteal artery	UBERON:0002250	48.05	gold quality
tibial artery	UBERON:0007610	48.01	gold quality
esophagus	UBERON:0001043	47.00	gold quality
heart left ventricle	UBERON:0002084	46.40	gold quality
sural nerve	UBERON:0015488	46.36	gold quality
subcutaneous adipose tissue	UBERON:0002190	46.23	gold quality
duodenum	UBERON:0002114	46.18	gold quality
right lobe of liver	UBERON:0001114	44.75	gold quality
adipose tissue	UBERON:0001013	44.74	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	44.30	gold quality
right atrium auricular region	UBERON:0006631	44.12	gold quality
descending thoracic aorta	UBERON:0002345	43.77	gold quality
multicellular organism	UBERON:0000468	43.63	gold quality
adult mammalian kidney	UBERON:0000082	43.61	gold quality
omental fat pad	UBERON:0010414	43.28	gold quality
thoracic aorta	UBERON:0001515	43.13	gold quality
right hemisphere of cerebellum	UBERON:0014890	43.00	gold quality
cerebellum	UBERON:0002037	42.90	gold quality
cerebellar hemisphere	UBERON:0002245	42.82	gold quality
heart	UBERON:0000948	42.70	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.08

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

26 targeting LCE1C, 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-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-548AU-3P	99.70	68.22	1373
HSA-MIR-449B-3P	99.20	67.24	1047
HSA-MIR-4291	99.20	68.88	2969
HSA-MIR-422A	99.18	65.83	550
HSA-MIR-378A-3P	98.43	66.10	548
HSA-MIR-378B	98.43	65.36	573
HSA-MIR-378C	98.43	66.10	548
HSA-MIR-378D	98.43	66.10	548
HSA-MIR-378E	98.43	65.99	551
HSA-MIR-378F	98.43	65.66	554
HSA-MIR-378H	98.43	66.16	545
HSA-MIR-378I	98.43	66.10	548
HSA-MIR-7113-5P	97.88	67.33	1735
HSA-MIR-665	97.60	65.64	1781
HSA-MIR-645	97.28	66.30	486
HSA-MIR-4540	96.90	67.46	473
HSA-MIR-212-5P	96.83	67.43	950
HSA-MIR-34A-3P	96.80	67.70	805
HSA-MIR-6085	96.57	64.11	621
HSA-MIR-6828-3P	96.06	67.61	1155
HSA-MIR-6823-3P	95.45	66.14	704
HSA-MIR-2114-3P	95.45	66.11	579
HSA-MIR-4683	95.29	65.98	631
HSA-MIR-6813-5P	94.68	64.20	588

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 60.0% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 3)

• paper describing nomenclature changes and expression in range of tissues and in response to UV (PMID:15854049)
• genetic polymorphism is associated with psoriasis vulgaris among Mongolians from Inner Mongolia (PMID:29397434)
• Luciferase reporter assays using the promoter region of the LCE1C gene confirmed that the phosphorylations of TAp63-T46/T281 contributed to full transcriptional activation of the LCE1C gene. LCE1C interacted with protein arginine methyltransferase 5 (PRMT5) and translocated it from the nucleus to the cytoplasm. (PMID:29559659)

Cross-species orthologs

0 orthologs

Paralogs (1): LCE1B (ENSG00000196734)

Protein

Protein identifiers

Late cornified envelope protein 1C — Q5T751 (reviewed: Q5T751)

Alternative names: Late envelope protein 3

All UniProt accessions (2): Q5T751, U3KQM4

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 (2): NP_001263260, NP_848128* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR028205	LCE	Family

Pfam: PF14672

UniProt features (8 total): compositionally biased region 4, region of interest 2, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5T751-F1	53.24	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): GOBP_EPITHELIUM_DEVELOPMENT, GOBP_EPIDERMAL_CELL_DIFFERENTIATION, GOBP_EPIDERMIS_DEVELOPMENT, GOBP_KERATINIZATION, GOBP_SKIN_DEVELOPMENT, chr1q21, 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, ZNF146_TARGET_GENES, MIR7113_5P, MIR4540

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

288 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LCE1C	LCE1B	Q5T7P3	862
LCE1C	LCE1E	Q5T753	817
LCE1C	LCE2D	Q5TA82	780
LCE1C	LCE2A	Q5TA79	764
LCE1C	LCE1A	Q5T7P2	761
LCE1C	LCE3E	Q5T5B0	757
LCE1C	LCE2C	Q5TA81	756
LCE1C	LCE1D	Q5T752	720
LCE1C	LCE1F	Q5T754	695
LCE1C	LCE3D	Q9BYE3	664
LCE1C	LCE2B	O14633	623
LCE1C	SPRR2A	P35326	621
LCE1C	SPRR2D	P22532	615
LCE1C	LCE3C	Q5T5A8	601
LCE1C	LCE6A	A0A183	597

IntAct

208 interactions, top by confidence:

A	B	Type	Score
KRTAP10-5	LCE1C	psi-mi:“MI:0915”(physical association)	0.560
LCE1C	KRTAP4-5	psi-mi:“MI:0915”(physical association)	0.560
LCE1C	TRIM42	psi-mi:“MI:0915”(physical association)	0.560
LCE1C	CHIC2	psi-mi:“MI:0915”(physical association)	0.560
KRTAP12-4	LCE1C	psi-mi:“MI:0915”(physical association)	0.560
LCE1C	KRTAP9-3	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-8	LCE1C	psi-mi:“MI:0915”(physical association)	0.560
LCE1C	LCE3A	psi-mi:“MI:0915”(physical association)	0.560
LCE1C		psi-mi:“MI:0915”(physical association)	0.560
LCE1C	VASN	psi-mi:“MI:0915”(physical association)	0.560
LCE1C	NTN4	psi-mi:“MI:0915”(physical association)	0.560
KRTAP12-1	LCE1C	psi-mi:“MI:0915”(physical association)	0.560
LCE1C	LCE5A	psi-mi:“MI:0915”(physical association)	0.560
	LCE1C	psi-mi:“MI:0915”(physical association)	0.560
VWC2	LCE1C	psi-mi:“MI:0915”(physical association)	0.560
KRTAP12-3	LCE1C	psi-mi:“MI:0915”(physical association)	0.560
LCE1C	LCE1B	psi-mi:“MI:0915”(physical association)	0.560
LCE1C	ADAMTSL4	psi-mi:“MI:0915”(physical association)	0.560
LCE1C	LCE2C	psi-mi:“MI:0915”(physical association)	0.560
LCE1C	SPRED2	psi-mi:“MI:0915”(physical association)	0.560
POU4F2	LCE1C	psi-mi:“MI:0915”(physical association)	0.560
LCE1C	KRTAP4-12	psi-mi:“MI:0915”(physical association)	0.560
LCE1C	KRTAP4-2	psi-mi:“MI:0915”(physical association)	0.560
LCE1C	GUCD1	psi-mi:“MI:0915”(physical association)	0.560
KRTAP5-9	LCE1C	psi-mi:“MI:0915”(physical association)	0.560
LCE1C	KRTAP5-6	psi-mi:“MI:0915”(physical association)	0.560
LCE2B	LCE1C	psi-mi:“MI:0915”(physical association)	0.560
LCE1C	KRTAP5-3	psi-mi:“MI:0915”(physical association)	0.560
LCE1C	LCE1A	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (76): LCE1C (Two-hybrid), LCE1C (Two-hybrid), LCE1C (Two-hybrid), LCE1C (Two-hybrid), LCE1C (Two-hybrid), LCE1C (Two-hybrid), LCE1C (Two-hybrid), LCE1C (Two-hybrid), LCE1C (Two-hybrid), LCE1C (Two-hybrid), LCE1C (Two-hybrid), LCE1C (Two-hybrid), LCE1C (Two-hybrid), LCE1C (Two-hybrid), LCE1C (Two-hybrid)

ESM2 similar proteins: A0A286YEV6, A0A286YEX9, A0A286YEY9, A0A286YF01, A0A286YF46, A0A286YF60, A0A286YF77, A0A286YFB4, A0A286YFG1, O14633, P02438, P05687, P05688, P08131, P08175, P0DSO2, P20730, Q01642, Q01643, Q01644, Q01645, Q07627, Q3LI58, Q3LI59, Q3V2C1, Q5T750, Q5T751, Q5T752, Q5T754, Q5TA77, Q5TA78, Q5TA79, Q5TA81, Q5TA82, Q5TCM9, Q9BQ66, Q9BYP8, Q9BYQ5, Q9BYQ6, Q9BYQ7

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 64 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	30	37.1×	2e-40
Formation of the cornified envelope	12	23.4×	3e-12

GO biological processes:

GO term	Partners	Fold	FDR
hair cycle	5	95.5×	3e-07
keratinization	13	62.1×	4e-18

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	15
Likely benign	2
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

248 predictions. Top by Δscore:

Variant	Effect	Δscore
1:152805433:A:AC	donor_gain	0.9400
1:152805434:C:CC	donor_gain	0.9400
1:152805264:C:A	donor_gain	0.8800
1:152805375:G:C	donor_gain	0.8600
1:152805421:A:AC	donor_gain	0.8600
1:152805422:C:CC	donor_gain	0.8600
1:152805452:CTG:C	donor_gain	0.8600
1:152805263:T:TA	donor_gain	0.8500
1:152805374:A:AC	donor_gain	0.8500
1:152805230:A:AC	donor_gain	0.8400
1:152805231:C:CC	donor_gain	0.8400
1:152805282:C:A	donor_gain	0.8400
1:152805258:C:CT	donor_gain	0.8200
1:152805423:T:C	donor_gain	0.8200
1:152805451:A:AC	donor_gain	0.8200
1:152805452:C:CC	donor_gain	0.8200
1:152805231:CGG:C	donor_gain	0.8100
1:152805231:CGGCG:C	donor_gain	0.8100
1:152805259:C:CT	donor_gain	0.8000
1:152805332:T:TA	donor_gain	0.7800
1:152805435:T:C	donor_gain	0.7600
1:152805257:G:C	donor_gain	0.7300
1:152805281:T:TA	donor_gain	0.7300
1:152804865:CG:C	acceptor_gain	0.7100
1:152805222:TGGG:T	donor_gain	0.7000
1:152805345:C:CC	acceptor_gain	0.6700
1:152804863:CACG:C	acceptor_gain	0.6600
1:152805447:TGG:T	donor_gain	0.6600
1:152804867:C:CC	acceptor_gain	0.6500
1:152805087:T:TA	donor_gain	0.6500

AlphaMissense

771 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:152805461:G:C	S6R	0.843
1:152805461:G:T	S6R	0.843
1:152805463:T:G	S6R	0.843
1:152805451:A:G	C10R	0.797
1:152805472:A:G	C3R	0.793
1:152805245:G:C	S78R	0.785
1:152805245:G:T	S78R	0.785
1:152805247:T:G	S78R	0.785
1:152805467:C:A	Q4H	0.785
1:152805467:C:G	Q4H	0.785
1:152805449:G:C	C10W	0.776
1:152805256:A:G	C75R	0.765
1:152805127:A:G	C118R	0.741
1:152805422:C:A	K19N	0.732
1:152805422:C:G	K19N	0.732
1:152805434:C:A	K15N	0.720
1:152805434:C:G	K15N	0.720
1:152805272:A:C	S69R	0.718
1:152805272:A:T	S69R	0.718
1:152805274:T:G	S69R	0.718
1:152805410:C:A	K23N	0.717
1:152805410:C:G	K23N	0.717
1:152805433:A:G	C16R	0.707
1:152805394:A:G	C29R	0.706
1:152805458:C:A	Q7H	0.706
1:152805458:C:G	Q7H	0.706
1:152805125:G:C	C118W	0.703
1:152805395:C:A	K28N	0.701
1:152805395:C:G	K28N	0.701
1:152805380:A:C	C33W	0.697

dbSNP variants (sampled 300 via entrez): RS1000140142 (1:152808227 T>C,G), RS1001337437 (1:152806166 G>T), RS1002178744 (1:152806482 G>C), RS1003163145 (1:152807155 A>G,T), RS1003416090 (1:152807446 C>T), RS1003446431 (1:152808383 A>C), RS1003906538 (1:152808639 C>T), RS1005220640 (1:152808361 G>A,C), RS1005433474 (1:152808404 A>G), RS1006103974 (1:152805593 T>A,C,G), RS1006512045 (1:152804817 A>T), RS1006691627 (1:152804333 A>G), RS1006741174 (1:152807225 T>C), RS1007407107 (1:152804689 C>T), RS1008862118 (1:152806499 A>G)

Disease associations

OMIM: gene MIM:612605 | 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_82	Asthma	5.000000e-27
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

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
propionaldehyde	increases expression	1
sodium arsenate	decreases expression, increases abundance	1
butyraldehyde	increases expression	1
tobacco tar	decreases reaction, increases expression	1
diallyl disulfide	decreases reaction, increases expression	1
nutlin 3	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Arsenic	decreases expression, increases abundance	1
Benzo(a)pyrene	increases methylation	1
Cadmium	decreases expression, increases abundance	1
Camptothecin	increases expression	1
Dactinomycin	affects cotreatment, increases expression	1
Formaldehyde	decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Tetrachlorodibenzodioxin	increases expression	1
Aflatoxin B1	decreases methylation	1
Sodium Selenite	increases expression	1
Cadmium Chloride	decreases expression, increases abundance	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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