LCE1F

Summary

LCE1F (late cornified envelope 1F, HGNC:29467) is a protein-coding gene on chromosome 1q21.3, encoding Late cornified envelope protein 1F (Q5T754). Precursors of the cornified envelope of the stratum corneum. It is a selective cancer dependency (DepMap: 88.2% of cell lines).

Enables identical protein binding activity. Predicted to be involved in keratinization.

Source: NCBI Gene 353137 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 25 total
• Cancer dependency (DepMap): dependent in 88.2% of screened cell lines
• MANE Select transcript: NM_178354

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29467
Approved symbol	LCE1F
Name	late cornified envelope 1F
Location	1q21.3
Locus type	gene with protein product
Status	Approved
Aliases	LEP6
Ensembl gene	ENSG00000240386
Ensembl biotype	protein_coding
OMIM	612608
Entrez	353137

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000334371

RefSeq mRNA: 1 — MANE Select: NM_178354 NM_178354

CCDS: CCDS1023

Canonical transcript exons

ENST00000334371 — 2 exons

Exon	Start	End
ENSE00001338824	152776350	152777024
ENSE00003919031	152775140	152775190

Expression profiles

Bgee: expression breadth broad, 82 present calls, max score 94.81.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0081 / max 6.7852, expressed in 3 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
5315	0.0081	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
skin of leg	UBERON:0001511	94.81	gold quality
zone of skin	UBERON:0000014	92.68	gold quality
skin of abdomen	UBERON:0001416	90.12	gold quality
lower esophagus mucosa	UBERON:0035834	47.32	silver quality
sural nerve	UBERON:0015488	41.24	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
skeletal muscle tissue	UBERON:0001134	36.90	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
bone marrow	UBERON:0002371	33.82	silver quality
muscle tissue	UBERON:0002385	33.65	gold quality
gastrocnemius	UBERON:0001388	33.52	gold quality
right lobe of liver	UBERON:0001114	33.36	silver quality
muscle of leg	UBERON:0001383	33.08	gold quality
heart left ventricle	UBERON:0002084	32.44	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
blood	UBERON:0000178	31.92	gold quality
multicellular organism	UBERON:0000468	31.87	gold quality
subcutaneous adipose tissue	UBERON:0002190	30.61	gold quality
muscle layer of sigmoid colon	UBERON:0035805	30.57	gold quality
tibial artery	UBERON:0007610	30.33	gold quality
popliteal artery	UBERON:0002250	30.22	gold quality
heart	UBERON:0000948	29.97	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	29.63	gold quality
minor salivary gland	UBERON:0001830	29.46	gold quality
saliva-secreting gland	UBERON:0001044	29.43	gold quality
descending thoracic aorta	UBERON:0002345	29.37	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.65

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

19 targeting LCE1F, 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-5002-5P	99.76	70.84	1763
HSA-MIR-10393-3P	99.72	66.56	961
HSA-MIR-6801-5P	99.72	66.50	981
HSA-MIR-6505-3P	99.34	67.39	1071
HSA-MIR-6814-5P	99.03	66.68	1273
HSA-MIR-455-3P	98.94	67.68	878
HSA-MIR-7977	98.65	66.18	2590
HSA-MIR-4782-5P	98.35	69.33	1474
HSA-MIR-5706	98.35	69.33	1463
HSA-MIR-4436B-3P	98.25	65.26	1494
HSA-MIR-6735-5P	98.24	65.36	1488
HSA-MIR-4423-3P	97.98	69.66	912
HSA-MIR-4257	97.86	68.05	1190
HSA-MIR-6879-5P	97.77	65.52	1521
HSA-MIR-1910-5P	97.42	66.36	844
HSA-MIR-6839-5P	96.74	68.29	1088
HSA-MIR-378J	96.44	66.20	1020
HSA-MIR-6828-3P	96.06	67.61	1155
HSA-MIR-6722-5P	93.60	64.28	59

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 88.2% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 1)

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

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), LCE3C (ENSG00000244057)

Protein

Protein identifiers

Late cornified envelope protein 1F — Q5T754 (reviewed: Q5T754)

Alternative names: Late envelope protein 6

All UniProt accessions (1): Q5T754

UniProt curated annotations — full annotation on UniProt →

Function. Precursors of the cornified envelope of the stratum corneum.

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. Expression is observed in the fibroblasts.

Induction. By UVB.

Miscellaneous. Belongs to the LCE cluster present on 1q21.

Similarity. Belongs to the LCE family.

RefSeq proteins (1): NP_848131* (*=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-Q5T754-F1	52.55	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: 19 (showing top): GOBP_EPITHELIUM_DEVELOPMENT, GOBP_EPIDERMAL_CELL_DIFFERENTIATION, GOBP_EPIDERMIS_DEVELOPMENT, AACTTT_UNKNOWN, GOBP_KERATINIZATION, GOBP_SKIN_DEVELOPMENT, chr1q21, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY, REACTOME_KERATINIZATION, REACTOME_FORMATION_OF_THE_CORNIFIED_ENVELOPE, GOBP_KERATINOCYTE_DIFFERENTIATION, GOBP_EPITHELIAL_CELL_DIFFERENTIATION, MIR6814_5P, WP_VITAMIN_D_RECEPTOR_PATHWAY, ZAK_PBMC_MRKAD5_HIV_1_GAG_POL_NEF_AGE_20_50YO_CORRELATED_WITH_CD8_T_CELL_RESPONSE_3DY_NEGATIVE

GO Biological Process (2): keratinization (GO:0031424), epidermis development (GO:0008544)

GO Molecular Function (2): identical protein binding (GO:0042802), 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
protein binding	1
binding	1

Protein interactions and networks

STRING

326 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LCE1F	LCE1D	Q5T752	720
LCE1F	LCE2C	Q5TA81	711
LCE1F	LCE1C	Q5T751	695
LCE1F	LCE1E	Q5T753	690
LCE1F	LCE2A	Q5TA79	677
LCE1F	LCE2B	O14633	670
LCE1F	LCE1A	Q5T7P2	669
LCE1F	LCE6A	A0A183	653
LCE1F	LCE1B	Q5T7P3	607
LCE1F	LCE3E	Q5T5B0	596
LCE1F	LCE2D	Q5TA82	582
LCE1F	OR8J1	Q8NGP2	580
LCE1F	LCE3A	Q5TA76	570
LCE1F	LCE3D	Q9BYE3	507
LCE1F	LCE4A	Q5TA78	506

IntAct

272 interactions, top by confidence:

A	B	Type	Score
LCE2B	LCE1F	psi-mi:“MI:0915”(physical association)	0.630
KRTAP12-3	LCE1F	psi-mi:“MI:0915”(physical association)	0.600
LCE1F	LCE2C	psi-mi:“MI:0915”(physical association)	0.560
LCE1F	KRTAP4-4	psi-mi:“MI:0915”(physical association)	0.560
LCE1F	MDFI	psi-mi:“MI:0915”(physical association)	0.560
LCE1F	KRTAP4-5	psi-mi:“MI:0915”(physical association)	0.560
KRTAP1-1	LCE1F	psi-mi:“MI:0915”(physical association)	0.560
LCE1F	KRTAP2-4	psi-mi:“MI:0915”(physical association)	0.560
LCE1E	LCE1F	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-6	LCE1F	psi-mi:“MI:0915”(physical association)	0.560
CYSRT1	LCE1F	psi-mi:“MI:0915”(physical association)	0.560
KRTAP5-9	LCE1F	psi-mi:“MI:0915”(physical association)	0.560
LCE1F	KRTAP5-2	psi-mi:“MI:0915”(physical association)	0.560
KRTAP12-2	LCE1F	psi-mi:“MI:0915”(physical association)	0.560
NOTCH2NLC	LCE1F	psi-mi:“MI:0915”(physical association)	0.560
LCE1F	KRTAP9-3	psi-mi:“MI:0915”(physical association)	0.560
LCE1F	KRTAP9-8	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-9	LCE1F	psi-mi:“MI:0915”(physical association)	0.560
KRTAP1-3	LCE1F	psi-mi:“MI:0915”(physical association)	0.560
LCE1F	ADAMTSL4	psi-mi:“MI:0915”(physical association)	0.560
LCE1F	KRTAP4-12	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-7	LCE1F	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-8	LCE1F	psi-mi:“MI:0915”(physical association)	0.560
RGS20	LCE1F	psi-mi:“MI:0915”(physical association)	0.560
LCE1D	LCE1F	psi-mi:“MI:0915”(physical association)	0.560
KRTAP6-3	LCE1F	psi-mi:“MI:0915”(physical association)	0.560
HOXA1	LCE1F	psi-mi:“MI:0915”(physical association)	0.560
LCE1F	LCE3B	psi-mi:“MI:0915”(physical association)	0.560
LCE1F	KRTAP9-2	psi-mi:“MI:0915”(physical association)	0.560
LCE1F	LCE1F	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (92): LCE1F (Two-hybrid), LCE1F (Two-hybrid), LCE1F (Two-hybrid), LCE1F (Two-hybrid), LCE1F (Two-hybrid), LCE1F (Two-hybrid), LCE1F (Two-hybrid), LCE1F (Two-hybrid), LCE1F (Two-hybrid), LCE1F (Two-hybrid), LCE1F (Two-hybrid), LCE1F (Two-hybrid), LCE1F (Two-hybrid), LCE1F (Two-hybrid), LCE1F (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: 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 70 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	37	38.2×	5e-51
Formation of the cornified envelope	10	16.3×	2e-08

GO biological processes:

GO term	Partners	Fold	FDR
keratinization	11	58.5×	5e-15

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	20
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

106 predictions. Top by Δscore:

Variant	Effect	Δscore
1:152776452:G:GT	donor_gain	0.9300
1:152776416:G:GG	donor_gain	0.9100
1:152776475:C:CG	donor_gain	0.8800
1:152776564:G:GA	donor_gain	0.8700
1:152776395:GCA:G	donor_gain	0.8500
1:152776475:C:G	donor_gain	0.8500
1:152776563:T:TA	donor_gain	0.8400
1:152776415:A:AG	donor_gain	0.8300
1:152776398:G:GG	donor_gain	0.8100
1:152776428:G:GG	donor_gain	0.8000
1:152776397:A:AG	donor_gain	0.7900
1:152776427:A:AG	donor_gain	0.7900
1:152776617:GC:G	donor_gain	0.7700
1:152776616:GGC:G	donor_gain	0.7400
1:152776617:GCG:G	donor_gain	0.7400
1:152776498:T:A	acceptor_gain	0.7300
1:152776505:GC:G	acceptor_gain	0.7200
1:152776504:A:AG	acceptor_gain	0.7000
1:152776505:G:GG	acceptor_gain	0.7000
1:152776619:G:GG	donor_gain	0.6700
1:152776559:G:GT	donor_gain	0.6300
1:152776501:T:A	acceptor_gain	0.6200
1:152776505:GCGTC:G	acceptor_gain	0.6200
1:152776586:G:T	donor_gain	0.6200
1:152776520:GCTGC:G	donor_gain	0.6100
1:152776501:TGCA:T	acceptor_loss	0.5800
1:152776502:GCAGC:G	acceptor_loss	0.5800
1:152776503:CA:C	acceptor_loss	0.5800
1:152776400:GCC:G	donor_gain	0.5700
1:152776536:C:G	donor_gain	0.5600

AlphaMissense

768 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:152776387:A:C	S6R	0.867
1:152776389:C:A	S6R	0.867
1:152776389:C:G	S6R	0.867
1:152776399:T:C	C10R	0.853
1:152776401:C:G	C10W	0.839
1:152776603:A:C	S78R	0.839
1:152776605:C:A	S78R	0.839
1:152776605:C:G	S78R	0.839
1:152776378:T:C	C3R	0.835
1:152776594:T:C	C75R	0.816
1:152776383:G:C	Q4H	0.803
1:152776383:G:T	Q4H	0.803
1:152776576:A:C	S69R	0.778
1:152776578:C:A	S69R	0.778
1:152776578:C:G	S69R	0.778
1:152776428:G:C	K19N	0.769
1:152776428:G:T	K19N	0.769
1:152776417:T:C	C16R	0.766
1:152776470:T:G	C33W	0.752
1:152776419:C:G	C16W	0.749
1:152776723:T:C	C118R	0.746
1:152776431:C:G	C20W	0.744
1:152776416:G:C	K15N	0.740
1:152776416:G:T	K15N	0.740
1:152776440:G:C	K23N	0.739
1:152776440:G:T	K23N	0.739
1:152776456:T:C	C29R	0.736
1:152776392:G:C	Q7H	0.735
1:152776392:G:T	Q7H	0.735
1:152776458:C:G	C29W	0.733

dbSNP variants (sampled 300 via entrez): RS1000530232 (1:152777340 T>G), RS1000598468 (1:152776112 T>C), RS1000848176 (1:152773835 A>C,G), RS1001149765 (1:152774059 G>A,T), RS1001371814 (1:152776855 C>A,T), RS1001594341 (1:152776951 C>T), RS1003586480 (1:152773704 G>A,C), RS1004102918 (1:152775408 G>A,T), RS1004842802 (1:152774683 C>T), RS1004957285 (1:152774476 C>T), RS1005076097 (1:152774016 T>C), RS1005277631 (1:152775623 A>G,T), RS1005413001 (1:152775273 A>G), RS1005844635 (1:152773460 G>A), RS1005849014 (1:152777503 C>T)

Disease associations

OMIM: gene MIM:612608 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
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

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenate	decreases expression, increases abundance	1
sodium arsenite	increases expression	1
CGP 52608	increases reaction, affects binding	1
nutlin 3	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Arsenic	increases abundance, decreases expression	1
Benzo(a)pyrene	affects methylation	1
Camptothecin	increases expression	1
Cannabidiol	increases expression	1
Cisplatin	affects cotreatment, increases expression	1
Dactinomycin	increases expression, affects cotreatment	1
Plant Extracts	affects cotreatment, decreases expression	1
Tetrachlorodibenzodioxin	increases expression	1
Thiram	increases expression	1
Sodium Selenite	decreases expression	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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