LCE2A

Summary

LCE2A (late cornified envelope 2A, HGNC:29469) is a protein-coding gene on chromosome 1q21.3, encoding Late cornified envelope protein 2A (Q5TA79). Precursors of the cornified envelope of the stratum corneum. It is a selective cancer dependency (DepMap: 34.5% of cell lines).

Predicted to be involved in keratinization.

Source: NCBI Gene 353139 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 27 total — 1 pathogenic
• Cancer dependency (DepMap): dependent in 34.5% of screened cell lines
• MANE Select transcript: NM_178428

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29469
Approved symbol	LCE2A
Name	late cornified envelope 2A
Location	1q21.3
Locus type	gene with protein product
Status	Approved
Aliases	LEP9
Ensembl gene	ENSG00000187173
Ensembl biotype	protein_coding
OMIM	612609
Entrez	353139

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000368779

RefSeq mRNA: 1 — MANE Select: NM_178428 NM_178428

CCDS: CCDS1021

Canonical transcript exons

ENST00000368779 — 2 exons

Exon	Start	End
ENSE00001447944	152698882	152699442
ENSE00001447945	152698345	152698394

Expression profiles

Bgee: expression breadth broad, 73 present calls, max score 92.51.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.6379 / max 277.6758, expressed in 86 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
5310	0.5835	75
5309	0.0544	22

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
skin of leg	UBERON:0001511	92.51	gold quality
zone of skin	UBERON:0000014	89.30	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.24	gold quality
skin of abdomen	UBERON:0001416	84.75	gold quality
stromal cell of endometrium	CL:0002255	82.67	gold quality
apex of heart	UBERON:0002098	41.85	silver quality
duodenum	UBERON:0002114	40.38	gold quality
mucosa of transverse colon	UBERON:0004991	37.88	silver quality
skeletal muscle tissue	UBERON:0001134	37.24	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
small intestine	UBERON:0002108	37.10	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
small intestine Peyer’s patch	UBERON:0003454	36.40	gold quality
bone marrow cell	CL:0002092	36.16	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
tonsil	UBERON:0002372	34.41	gold quality
muscle tissue	UBERON:0002385	33.90	gold quality
gastrocnemius	UBERON:0001388	33.40	gold quality
muscle of leg	UBERON:0001383	33.00	gold quality
heart left ventricle	UBERON:0002084	32.18	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
multicellular organism	UBERON:0000468	31.45	gold quality
blood	UBERON:0000178	31.29	gold quality
popliteal artery	UBERON:0002250	30.64	gold quality
right lung	UBERON:0002167	30.52	silver quality
tibial artery	UBERON:0007610	30.43	gold quality
intestine	UBERON:0000160	29.83	gold quality
heart	UBERON:0000948	29.76	gold quality
descending thoracic aorta	UBERON:0002345	29.27	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.98

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

21 targeting LCE2A, 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-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4679	99.76	69.19	1229
HSA-MIR-4428	99.73	66.41	1733
HSA-MIR-1276	99.36	68.18	1642
HSA-MIR-296-3P	99.21	66.56	474
HSA-MIR-4796-3P	99.08	68.38	1681
HSA-MIR-6814-5P	99.03	66.68	1273
HSA-MIR-5701	98.97	69.54	1502
HSA-MIR-3149	98.77	67.13	1639
HSA-MIR-330-5P	98.73	67.63	1788
HSA-MIR-326	98.25	66.44	1565
HSA-MIR-5691	98.23	67.02	1335
HSA-MIR-6805-3P	98.23	67.02	1334
HSA-MIR-4457	98.09	67.12	1274
HSA-MIR-10526-3P	97.86	64.97	1342
HSA-MIR-4690-3P	97.02	64.72	981
HSA-MIR-5685	97.02	64.34	1004
HSA-MIR-635	96.00	65.54	687
HSA-MIR-6774-5P	95.94	65.18	722
HSA-MIR-4772-5P	95.60	68.04	617

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 34.5% 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), LCE2C (ENSG00000187180), LCE2D (ENSG00000187223), LCE3B (ENSG00000187238), KPLCE (ENSG00000198854), PRR9 (ENSG00000203783), LELP1 (ENSG00000203784), LCE1F (ENSG00000240386), LCE3C (ENSG00000244057)

Protein

Protein identifiers

Late cornified envelope protein 2A — Q5TA79 (reviewed: Q5TA79)

Alternative names: Late envelope protein 9

All UniProt accessions (1): Q5TA79

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 calcium and UVB.

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

Similarity. Belongs to the LCE family.

RefSeq proteins (1): NP_848515* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR028205	LCE	Family

Pfam: PF14672

UniProt features (5 total): compositionally biased region 2, chain 1, region of interest 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5TA79-F1	53.97	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: 13 (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, MIR5196_5P, MIR4747_5P, MIR4796_3P

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

310 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LCE2A	LCE1C	Q5T751	764
LCE2A	LCE1B	Q5T7P3	725
LCE2A	SPRR4	Q96PI1	685
LCE2A	LCE1F	Q5T754	677
LCE2A	LCE6A	A0A183	675
LCE2A	LCE1A	Q5T7P2	620
LCE2A	LCE3E	Q5T5B0	620
LCE2A	LCE1D	Q5T752	583
LCE2A	LCE3A	Q5TA76	583
LCE2A	LCE1E	Q5T753	582
LCE2A	LCE4A	Q5TA78	574
LCE2A	LCE3C	Q5T5A8	571
LCE2A	SPRR2G	Q9BYE4	544
LCE2A	IVL	P07476	532
LCE2A	LCE5A	Q5TCM9	528

IntAct

192 interactions, top by confidence:

A	B	Type	Score
LCE2A	KRTAP5-9	psi-mi:“MI:0915”(physical association)	0.720
LCE2A	KRTAP10-5	psi-mi:“MI:0915”(physical association)	0.720
LCE2A	KRTAP10-8	psi-mi:“MI:0915”(physical association)	0.720
KRTAP10-9	LCE2A	psi-mi:“MI:0915”(physical association)	0.720
LCE2A	KRTAP9-2	psi-mi:“MI:0915”(physical association)	0.720
KRTAP4-2	LCE2A	psi-mi:“MI:0915”(physical association)	0.720
KRTAP10-5	LCE2A	psi-mi:“MI:0915”(physical association)	0.720
KRTAP10-8	LCE2A	psi-mi:“MI:0915”(physical association)	0.720
LCE2A	KRTAP10-9	psi-mi:“MI:0915”(physical association)	0.720
KRTAP9-2	LCE2A	psi-mi:“MI:0915”(physical association)	0.720
KRTAP5-9	LCE2A	psi-mi:“MI:0915”(physical association)	0.720
LCE2A	KRTAP4-2	psi-mi:“MI:0915”(physical association)	0.720
MEOX2	LCE2A	psi-mi:“MI:0915”(physical association)	0.560
SUMO1P1	LCE2A	psi-mi:“MI:0915”(physical association)	0.560
	LCE2A	psi-mi:“MI:0915”(physical association)	0.560
RGS20	LCE2A	psi-mi:“MI:0915”(physical association)	0.560
LCE2A	OTX1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (77): LCE2A (Two-hybrid), LCE2A (Two-hybrid), LCE2A (Two-hybrid), LCE2A (Two-hybrid), LCE2A (Two-hybrid), LCE2A (Two-hybrid), LCE2A (Two-hybrid), LCE2A (Two-hybrid), KRTAP10-7 (Two-hybrid), KRTAP10-9 (Two-hybrid), KRTAP10-5 (Two-hybrid), KRTAP10-8 (Two-hybrid), KRTAP10-3 (Two-hybrid), SUMO1P1 (Two-hybrid), LCE2A (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, Q5T751, Q5T752, Q5T753, Q5T754, Q5T7P2, Q5T7P3

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 51 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	29	39.4×	1e-40
Formation of the cornified envelope	7	15.0×	6e-06

GO biological processes:

GO term	Partners	Fold	FDR
keratinization	8	58.5×	1e-10

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	23
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
565180	GRCh37/hg19 1q21.3(chr1:150853044-154647786)x3	Pathogenic

SpliceAI

86 predictions. Top by Δscore:

Variant	Effect	Δscore
1:152698393:GG:G	donor_gain	0.9900
1:152698394:GG:G	donor_gain	0.9900
1:152698391:CAGGG:C	donor_loss	0.9500
1:152698396:T:A	donor_loss	0.9500
1:152698395:G:GG	donor_gain	0.9400
1:152698881:G:GA	acceptor_loss	0.9300
1:152698397:GAGTG:G	donor_loss	0.9000
1:152698868:ATTTC:A	acceptor_loss	0.8700
1:152698880:A:AG	acceptor_gain	0.8500
1:152698881:G:GG	acceptor_gain	0.8500
1:152699136:C:A	acceptor_gain	0.8500
1:152698390:CCAGG:C	donor_gain	0.8400
1:152698881:GGTT:G	acceptor_gain	0.8400
1:152698399:G:C	donor_loss	0.8100
1:152698391:CAGG:C	donor_gain	0.7900
1:152698398:A:AC	donor_loss	0.7900
1:152698872:C:A	acceptor_loss	0.7800
1:152698365:G:GT	donor_gain	0.7600
1:152698392:AGG:A	donor_gain	0.7600
1:152698393:GGG:G	donor_gain	0.7600
1:152698880:AGGTT:A	acceptor_gain	0.7600
1:152698881:GGTTG:G	acceptor_gain	0.7600
1:152698872:C:CA	acceptor_gain	0.7500
1:152698875:ATTTC:A	acceptor_loss	0.7100
1:152698869:T:G	acceptor_loss	0.6500
1:152698875:A:AG	acceptor_gain	0.6500
1:152698446:G:T	donor_gain	0.6300
1:152698877:TTCA:T	acceptor_gain	0.6200
1:152698880:A:C	acceptor_gain	0.6200
1:152699033:T:TA	acceptor_gain	0.5900

AlphaMissense

695 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:152699130:T:C	F77L	0.734
1:152699132:C:A	F77L	0.734
1:152699132:C:G	F77L	0.734
1:152698913:G:C	Q4H	0.670
1:152698913:G:T	Q4H	0.670
1:152698947:T:C	C16R	0.669
1:152699109:A:C	S70R	0.654
1:152699111:C:A	S70R	0.654
1:152699111:C:G	S70R	0.654
1:152698922:G:C	Q7H	0.639
1:152698922:G:T	Q7H	0.639
1:152698916:A:C	Q5H	0.633
1:152698916:A:T	Q5H	0.633
1:152699100:T:C	C67R	0.630
1:152699064:A:C	S55R	0.629
1:152699066:C:A	S55R	0.629
1:152699066:C:G	S55R	0.629
1:152698949:C:G	C16W	0.618
1:152698958:A:C	K19N	0.616
1:152698958:A:T	K19N	0.616
1:152698946:G:C	K15N	0.610
1:152698946:G:T	K15N	0.610
1:152698970:G:C	K23N	0.605
1:152698970:G:T	K23N	0.605
1:152698929:T:C	C10R	0.599
1:152699115:C:G	H72D	0.577

dbSNP variants (sampled 300 via entrez): RS1000646603 (1:152697269 T>A), RS1001619636 (1:152696886 T>C), RS1001951846 (1:152698117 C>T), RS1002071245 (1:152697742 A>G), RS1003626354 (1:152699254 T>C), RS1004176811 (1:152698301 G>A), RS1004530946 (1:152699599 C>T), RS1005481908 (1:152699327 A>G), RS1005577308 (1:152699820 A>G), RS1007518994 (1:152698134 TG>T,TGG,TGGGG,TGGGGGG), RS1008495245 (1:152697446 T>C), RS1009215320 (1:152699785 A>G), RS1009760892 (1:152697714 T>C), RS1011630819 (1:152698568 C>A,T), RS1012524740 (1:152699298 C>T)

Disease associations

OMIM: gene MIM:612609 | 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

10 total (human), top 10 by PubMed support.

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

Clinical trials (associated diseases)

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