LCE2C

Summary

LCE2C (late cornified envelope 2C, HGNC:29460) is a protein-coding gene on chromosome 1q21.3, encoding Late cornified envelope protein 2C (Q5TA81). Precursors of the cornified envelope of the stratum. It is a common-essential gene (DepMap: required in 99.4% of cancer cell lines).

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

Source: NCBI Gene 353140 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 26 total
• Cancer dependency (DepMap): dependent in 99.4% of screened cell lines (common-essential)
• MANE Select transcript: NM_178429

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29460
Approved symbol	LCE2C
Name	late cornified envelope 2C
Location	1q21.3
Locus type	gene with protein product
Status	Approved
Aliases	LEP11
Ensembl gene	ENSG00000187180
Ensembl biotype	protein_coding
OMIM	612611
Entrez	353140

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000368783

RefSeq mRNA: 1 — MANE Select: NM_178429 NM_178429

CCDS: CCDS1019

Canonical transcript exons

ENST00000368783 — 2 exons

Exon	Start	End
ENSE00001447951	152675995	152676569
ENSE00003610153	152675279	152675328

Expression profiles

Bgee: expression breadth broad, 89 present calls, max score 95.85.

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	95.85	gold quality
zone of skin	UBERON:0000014	94.09	gold quality
skin of abdomen	UBERON:0001416	91.48	gold quality
lower esophagus mucosa	UBERON:0035834	54.48	gold quality
stromal cell of endometrium	CL:0002255	50.65	gold quality
apex of heart	UBERON:0002098	48.80	gold quality
right lung	UBERON:0002167	43.52	gold quality
right lobe of liver	UBERON:0001114	42.29	gold quality
gastrocnemius	UBERON:0001388	41.12	gold quality
tonsil	UBERON:0002372	40.94	gold quality
heart left ventricle	UBERON:0002084	39.41	gold quality
muscle of leg	UBERON:0001383	39.34	gold quality
skeletal muscle tissue	UBERON:0001134	37.89	gold quality
fundus of stomach	UBERON:0001160	37.77	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
popliteal artery	UBERON:0002250	37.10	gold quality
tibial artery	UBERON:0007610	36.95	gold quality
multicellular organism	UBERON:0000468	36.59	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
body of pancreas	UBERON:0001150	36.39	gold quality
blood	UBERON:0000178	36.27	gold quality
bone marrow cell	CL:0002092	36.16	gold quality
subcutaneous adipose tissue	UBERON:0002190	35.86	gold quality
liver	UBERON:0002107	35.76	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
heart	UBERON:0000948	35.45	gold quality
right adrenal gland cortex	UBERON:0035827	35.24	gold quality
muscle layer of sigmoid colon	UBERON:0035805	34.89	gold quality
right atrium auricular region	UBERON:0006631	34.79	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.15

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

24 targeting LCE2C, 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-12118	100.00	65.88	1270
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-609	99.82	64.26	505
HSA-MIR-766-5P	99.47	67.91	2225
HSA-MIR-3125	99.14	68.49	2269
HSA-MIR-4795-5P	99.11	66.90	876
HSA-MIR-3916	98.99	68.04	2155
HSA-MIR-6859-5P	98.99	68.07	2049
HSA-MIR-6819-5P	97.96	66.59	1071
HSA-MIR-924	97.78	66.21	681
HSA-MIR-6737-5P	97.75	66.54	1044
HSA-MIR-22-5P	97.67	68.92	1355
HSA-MIR-6812-5P	97.56	65.39	1059
HSA-MIR-5189-3P	97.52	66.33	487
HSA-MIR-3187-3P	97.38	65.80	904
HSA-MIR-921	97.09	66.45	562
HSA-MIR-5702	96.68	68.21	958
HSA-MIR-4790-3P	96.63	67.08	806
HSA-MIR-6747-5P	96.17	64.99	743
HSA-MIR-3174	94.63	63.64	577
HSA-MIR-4323	93.93	63.89	656

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.4% of screened cell lines, common-essential.

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), LCE2D (ENSG00000187223), LCE3B (ENSG00000187238), KPLCE (ENSG00000198854), PRR9 (ENSG00000203783), LELP1 (ENSG00000203784), LCE1F (ENSG00000240386), LCE3C (ENSG00000244057)

Protein

Protein identifiers

Late cornified envelope protein 2C — Q5TA81 (reviewed: Q5TA81)

Alternative names: Late envelope protein 11

All UniProt accessions (1): Q5TA81

UniProt curated annotations — full annotation on UniProt →

Function. Precursors of the cornified envelope of the stratum.

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. By calcium and UVB.

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

Similarity. Belongs to the LCE family.

RefSeq proteins (1): NP_848516* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR028205	LCE	Family

Pfam: PF14672

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

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5TA81-F1	54.03	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: 20 (showing top): GOBP_EPITHELIUM_DEVELOPMENT, GOBP_EPIDERMAL_CELL_DIFFERENTIATION, GOBP_EPIDERMIS_DEVELOPMENT, GOBP_KERATINIZATION, GOBP_SKIN_DEVELOPMENT, chr1q21, REACTOME_KERATINIZATION, REACTOME_FORMATION_OF_THE_CORNIFIED_ENVELOPE, GOBP_KERATINOCYTE_DIFFERENTIATION, GOBP_EPITHELIAL_CELL_DIFFERENTIATION, MIR4795_3P, MIR6891_5P, MIR12118, MIR3173_3P, MIR5702

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

332 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LCE2C	LCE3E	Q5T5B0	785
LCE2C	LCE1C	Q5T751	756
LCE2C	LCE1B	Q5T7P3	747
LCE2C	LCE3D	Q9BYE3	726
LCE2C	LCE1E	Q5T753	719
LCE2C	LCE1F	Q5T754	711
LCE2C	LCE6A	A0A183	710
LCE2C	SPRR2A	P35326	656
LCE2C	LCE1D	Q5T752	621
LCE2C	LCE1A	Q5T7P2	621
LCE2C	SPRR2G	Q9BYE4	615
LCE2C	LCE3C	Q5T5A8	576
LCE2C	LCE5A	Q5TCM9	542
LCE2C	SPRR2D	P22532	512
LCE2C	SPRR2E	P22531	506

IntAct

310 interactions, top by confidence:

A	B	Type	Score
BAG5	LCE2C	psi-mi:“MI:0915”(physical association)	0.560
STRA6	LCE2C	psi-mi:“MI:0915”(physical association)	0.560
TACSTD2	LCE2C	psi-mi:“MI:0915”(physical association)	0.560
LCE2C	LCE2D	psi-mi:“MI:0915”(physical association)	0.560
LCE2C	BAG5	psi-mi:“MI:0915”(physical association)	0.560
LCE2C	STRA6	psi-mi:“MI:0915”(physical association)	0.560
EFEMP1	LCE2C	psi-mi:“MI:0915”(physical association)	0.560
LCE1D	LCE2C	psi-mi:“MI:0915”(physical association)	0.560
CREB5	LCE2C	psi-mi:“MI:0915”(physical association)	0.560
LCE2C	KRTAP5-4	psi-mi:“MI:0915”(physical association)	0.560
LCE2C	KRTAP4-11	psi-mi:“MI:0915”(physical association)	0.560
LCE3A	LCE2C	psi-mi:“MI:0915”(physical association)	0.560
LCE2C	MACO1	psi-mi:“MI:0915”(physical association)	0.560
LCE1B	LCE2C	psi-mi:“MI:0915”(physical association)	0.560
LCE2C	KRTAP4-4	psi-mi:“MI:0915”(physical association)	0.560
LCE3B	LCE2C	psi-mi:“MI:0915”(physical association)	0.560
LCE1F	LCE2C	psi-mi:“MI:0915”(physical association)	0.560
OTX1	LCE2C	psi-mi:“MI:0915”(physical association)	0.560
KRTAP12-4	LCE2C	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-8	LCE2C	psi-mi:“MI:0915”(physical association)	0.560
TGFB1	LCE2C	psi-mi:“MI:0915”(physical association)	0.560
	LCE2C	psi-mi:“MI:0915”(physical association)	0.560
FAM221B	LCE2C	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-7	LCE2C	psi-mi:“MI:0915”(physical association)	0.560
LCE2C	XAGE3	psi-mi:“MI:0915”(physical association)	0.560
LCE2C	KRTAP5-2	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (88): LCE2C (Two-hybrid), LCE2C (Two-hybrid), LCE2C (Two-hybrid), LCE2C (Two-hybrid), LCE2C (Two-hybrid), LCE2C (Two-hybrid), LCE2C (Two-hybrid), LCE2C (Two-hybrid), LCE2C (Two-hybrid), LCE2C (Two-hybrid), LCE2C (Two-hybrid), LCE2C (Two-hybrid), LCE2C (Two-hybrid), LCE2C (Two-hybrid), LCE2C (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, Q5T753, Q5T7P3

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 84 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	41	34.6×	4e-54
Formation of the cornified envelope	14	18.6×	7e-13

GO biological processes:

GO term	Partners	Fold	FDR
hair cycle	5	85.1×	5e-07
keratinization	15	63.8×	3e-21

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	23
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

171 predictions. Top by Δscore:

Variant	Effect	Δscore
1:152675327:GG:G	donor_gain	0.9900
1:152675328:GG:G	donor_gain	0.9900
1:152675328:GGT:G	donor_loss	0.9800
1:152675329:G:C	donor_loss	0.9800
1:152675330:TGAGT:T	donor_loss	0.9800
1:152675331:GAGTG:G	donor_loss	0.9800
1:152675989:TTTCA:T	acceptor_loss	0.9800
1:152675990:TTCAG:T	acceptor_loss	0.9800
1:152675991:TCA:T	acceptor_loss	0.9800
1:152675992:CA:C	acceptor_loss	0.9800
1:152675993:A:C	acceptor_loss	0.9800
1:152675994:G:A	acceptor_loss	0.9800
1:152675329:G:GG	donor_gain	0.9600
1:152675332:AGTGG:A	donor_loss	0.9600
1:152676262:C:A	acceptor_gain	0.9300
1:152675994:GGTT:G	acceptor_gain	0.9200
1:152675324:CCAGG:C	donor_gain	0.9100
1:152675325:CAGG:C	donor_gain	0.9100
1:152675993:A:AG	acceptor_gain	0.9100
1:152675994:G:GG	acceptor_gain	0.9100
1:152675326:AGG:A	donor_gain	0.8900
1:152675327:GGG:G	donor_gain	0.8900
1:152675355:GGGTA:G	donor_gain	0.8700
1:152675299:G:T	donor_gain	0.8600
1:152675329:G:A	donor_gain	0.8600
1:152675993:AGGTT:A	acceptor_gain	0.8600
1:152675994:GGTTG:G	acceptor_gain	0.8600
1:152675352:GAGGG:G	donor_gain	0.8100
1:152675327:GGGT:G	donor_gain	0.8000
1:152675328:GGTG:G	donor_gain	0.8000

AlphaMissense

723 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:152676256:T:C	F81L	0.815
1:152676258:C:A	F81L	0.815
1:152676258:C:G	F81L	0.815
1:152676027:G:C	Q4H	0.730
1:152676027:G:T	Q4H	0.730
1:152676084:A:C	K23N	0.716
1:152676084:A:T	K23N	0.716
1:152676030:A:C	Q5H	0.693
1:152676030:A:T	Q5H	0.693
1:152676036:G:C	Q7H	0.663
1:152676036:G:T	Q7H	0.663
1:152676043:T:C	C10R	0.650
1:152676060:G:C	K15N	0.625
1:152676060:G:T	K15N	0.625
1:152676072:G:C	K19N	0.625
1:152676072:G:T	K19N	0.625
1:152676061:T:C	C16R	0.622
1:152676045:C:G	C10W	0.613
1:152676096:G:C	K27N	0.609
1:152676096:G:T	K27N	0.609
1:152676190:A:C	S59R	0.603
1:152676192:C:A	S59R	0.603
1:152676192:C:G	S59R	0.603
1:152676235:A:C	S74R	0.603
1:152676237:C:A	S74R	0.603
1:152676237:C:G	S74R	0.603
1:152676343:T:C	C110R	0.596
1:152676345:C:G	C110W	0.595
1:152676063:T:G	C16W	0.589
1:152676020:C:T	S2F	0.586

dbSNP variants (sampled 300 via entrez): RS1000094432 (1:152676975 G>T), RS1001340810 (1:152674258 T>A), RS1002974977 (1:152674119 C>T), RS1003048705 (1:152675061 C>A,T), RS1003305183 (1:152675072 G>A,C), RS1006426107 (1:152676851 G>A,T), RS1006457202 (1:152676663 G>T), RS1007059265 (1:152676641 T>A,C), RS1007103091 (1:152674771 A>G), RS1007836185 (1:152673635 T>C), RS1008102357 (1:152673792 A>T), RS1008586275 (1:152674782 C>T), RS1010261315 (1:152675222 G>A,C), RS1010347680 (1:152675055 A>G,T), RS1010733700 (1:152676943 G>A)

Disease associations

OMIM: gene MIM:612611 | 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
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

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

11 total (human), top 11 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenate	increases abundance, decreases expression	1
CGP 52608	affects binding, increases reaction	1
Resveratrol	affects cotreatment, decreases expression	1
Acetaminophen	increases expression	1
Arsenic	decreases expression, increases abundance	1
Benzo(a)pyrene	increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Aflatoxin B1	decreases methylation	1
Cadmium Chloride	increases expression	1
Copper Sulfate	increases expression	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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