LCE2D

Summary

LCE2D (late cornified envelope 2D, HGNC:16518) is a protein-coding gene on chromosome 1q21.3, encoding Late cornified envelope protein 2D (Q5TA82). Precursors of the cornified envelope of the stratum corneum.

Predicted to be involved in keratinization.

Source: NCBI Gene 353141 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 23 total
• MANE Select transcript: NM_178430

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16518
Approved symbol	LCE2D
Name	late cornified envelope 2D
Location	1q21.3
Locus type	gene with protein product
Status	Approved
Aliases	LEP12
Ensembl gene	ENSG00000187223
Ensembl biotype	protein_coding
OMIM	612612
Entrez	353141

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000368784

RefSeq mRNA: 1 — MANE Select: NM_178430 NM_178430

CCDS: CCDS1018

Canonical transcript exons

ENST00000368784 — 2 exons

Exon	Start	End
ENSE00001447953	152664085	152664659
ENSE00001636694	152663380	152663429

Expression profiles

Bgee: expression breadth broad, 70 present calls, max score 93.68.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0569 / max 54.2817, expressed in 7 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
5308	0.0569	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
skin of leg	UBERON:0001511	93.68	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	93.57	gold quality
zone of skin	UBERON:0000014	91.24	gold quality
skin of abdomen	UBERON:0001416	87.70	gold quality
right lobe of liver	UBERON:0001114	48.31	gold quality
liver	UBERON:0002107	41.72	silver quality
stromal cell of endometrium	CL:0002255	41.60	silver quality
tonsil	UBERON:0002372	41.40	gold quality
mucosa of transverse colon	UBERON:0004991	37.90	silver quality
skeletal muscle tissue	UBERON:0001134	37.54	gold quality
colonic epithelium	UBERON:0000397	37.20	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
mucosa of stomach	UBERON:0001199	35.74	silver quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
gastrocnemius	UBERON:0001388	35.06	gold quality
adult mammalian kidney	UBERON:0000082	34.78	gold quality
right adrenal gland cortex	UBERON:0035827	34.60	gold quality
muscle of leg	UBERON:0001383	34.47	gold quality
muscle tissue	UBERON:0002385	34.12	gold quality
fundus of stomach	UBERON:0001160	33.40	gold quality
bone marrow	UBERON:0002371	33.26	gold quality
blood	UBERON:0000178	32.67	gold quality
multicellular organism	UBERON:0000468	32.39	gold quality
descending thoracic aorta	UBERON:0002345	32.22	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
kidney	UBERON:0002113	31.84	gold quality
popliteal artery	UBERON:0002250	31.59	gold quality
tibial artery	UBERON:0007610	31.56	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.14

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

25 targeting LCE2D, 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-4481	100.00	66.42	1669
HSA-MIR-4500	99.99	72.72	2367
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-556-3P	99.74	68.75	1203
HSA-MIR-4428	99.73	66.41	1733
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-488-3P	99.61	68.79	1731
HSA-MIR-657	99.48	66.02	848
HSA-MIR-7155-5P	98.65	66.14	1290
HSA-MIR-4700-5P	98.63	67.43	1915
HSA-MIR-3179	98.22	65.90	1445
HSA-MIR-924	97.78	66.21	681
HSA-MIR-6783-5P	97.67	67.21	1528
HSA-MIR-5702	96.68	68.21	958
HSA-MIR-1238-5P	94.82	67.52	493
HSA-MIR-4758-5P	94.82	67.06	499

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

Protein

Protein identifiers

Late cornified envelope protein 2D — Q5TA82 (reviewed: Q5TA82)

Alternative names: Late envelope protein 12, Small proline-rich-like epidermal differentiation complex protein 1A

All UniProt accessions (1): Q5TA82

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.

Induction. By calcium and UVB.

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

Similarity. Belongs to the LCE family.

RefSeq proteins (1): NP_848517* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR028205	LCE	Family

Pfam: PF14672

UniProt features (2 total): chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5TA82-F1	53.74	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: 14 (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, MIR488_3P, MIR6783_5P, MIR4428, MIR1238_5P_MIR4758_5P

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

350 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LCE2D	LCE1C	Q5T751	780
LCE2D	LCE3E	Q5T5B0	761
LCE2D	LCE1D	Q5T752	756
LCE2D	LCE3D	Q9BYE3	729
LCE2D	LCE6A	A0A183	727
LCE2D	LCE1E	Q5T753	725
LCE2D	SPRR2A	P35326	656
LCE2D	LCE1B	Q5T7P3	620
LCE2D	LCE1A	Q5T7P2	583
LCE2D	LCE1F	Q5T754	582
LCE2D	LCE3C	Q5T5A8	571
LCE2D	SPRR2G	Q9BYE4	545
LCE2D	LCE5A	Q5TCM9	540
LCE2D	IL37	Q9NZH6	505
LCE2D	SPRR2D	P22532	503

IntAct

199 interactions, top by confidence:

A	B	Type	Score
SPRY1	LCE2D	psi-mi:“MI:0915”(physical association)	0.780
LCE2D	SPRY1	psi-mi:“MI:0915”(physical association)	0.780
LCE2D	GLRX3	psi-mi:“MI:0915”(physical association)	0.720
OTX1	LCE2D	psi-mi:“MI:0915”(physical association)	0.720
LCE2D	KRTAP10-8	psi-mi:“MI:0915”(physical association)	0.720
LCE2D	KRTAP10-9	psi-mi:“MI:0915”(physical association)	0.720
ADAMTSL4	LCE2D	psi-mi:“MI:0915”(physical association)	0.720
LCE2D	KRTAP4-12	psi-mi:“MI:0915”(physical association)	0.720
KRTAP10-8	LCE2D	psi-mi:“MI:0915”(physical association)	0.720
LCE2D	ADAMTSL4	psi-mi:“MI:0915”(physical association)	0.720
KRTAP10-9	LCE2D	psi-mi:“MI:0915”(physical association)	0.720
GLRX3	LCE2D	psi-mi:“MI:0915”(physical association)	0.720
LCE2D	OTX1	psi-mi:“MI:0915”(physical association)	0.720

BioGRID (82): LCE2D (Two-hybrid), LCE2D (Two-hybrid), LCE2D (Two-hybrid), LCE2D (Two-hybrid), LCE2D (Two-hybrid), LCE2D (Two-hybrid), LCE2D (Two-hybrid), LCE2D (Two-hybrid), LCE2D (Two-hybrid), LCE2D (Two-hybrid), KRTAP10-9 (Two-hybrid), KRTAP10-5 (Two-hybrid), KRTAP10-8 (Two-hybrid), NOTCH2NL (Two-hybrid), SUMO1P1 (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 55 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	27	35.0×	2e-35
Formation of the cornified envelope	7	14.3×	1e-05

GO biological processes:

GO term	Partners	Fold	FDR
keratinization	8	52.0×	5e-10

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	21
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

142 predictions. Top by Δscore:

Variant	Effect	Δscore
1:152663428:GG:G	donor_gain	0.9300
1:152663429:GG:G	donor_gain	0.9300
1:152664530:G:A	acceptor_gain	0.9000
1:152664079:TTTTA:T	acceptor_loss	0.8700
1:152664080:TTTA:T	acceptor_loss	0.8700
1:152664081:TTA:T	acceptor_loss	0.8700
1:152664082:TA:T	acceptor_loss	0.8700
1:152664084:G:GT	acceptor_loss	0.8700
1:152663429:GGTGA:G	donor_loss	0.8500
1:152663431:T:A	donor_loss	0.8500
1:152663433:A:AC	donor_loss	0.8400
1:152663883:G:GT	donor_gain	0.8400
1:152664524:A:AG	acceptor_gain	0.8400
1:152663430:G:GG	donor_gain	0.8100
1:152663400:G:T	donor_gain	0.8000
1:152664073:A:AG	acceptor_loss	0.8000
1:152664076:A:AG	acceptor_loss	0.8000
1:152664084:GGTT:G	acceptor_gain	0.8000
1:152664078:CTTTT:C	acceptor_loss	0.7900
1:152664529:T:TA	acceptor_gain	0.7900
1:152664528:ATG:A	acceptor_gain	0.7800
1:152664074:T:G	acceptor_loss	0.7300
1:152663470:T:TA	donor_gain	0.7200
1:152663471:A:AA	donor_gain	0.7200
1:152664083:A:AG	acceptor_gain	0.7200
1:152664084:G:GG	acceptor_gain	0.7200
1:152663461:T:TG	donor_gain	0.6900
1:152663460:ATT:A	donor_gain	0.6800
1:152663975:ACT:A	donor_gain	0.6800
1:152664352:C:A	acceptor_gain	0.6600

AlphaMissense

722 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:152664346:T:C	F81L	0.821
1:152664348:C:A	F81L	0.821
1:152664348:C:G	F81L	0.821
1:152664117:G:C	Q4H	0.773
1:152664117:G:T	Q4H	0.773
1:152664174:A:C	K23N	0.765
1:152664174:A:T	K23N	0.765
1:152664325:A:C	S74R	0.754
1:152664327:C:A	S74R	0.754
1:152664327:C:G	S74R	0.754
1:152664150:A:C	K15N	0.750
1:152664150:A:T	K15N	0.750
1:152664133:T:C	C10R	0.744
1:152664151:T:C	C16R	0.730
1:152664120:A:C	Q5H	0.717
1:152664120:A:T	Q5H	0.717
1:152664316:T:C	C71R	0.715
1:152664126:G:C	Q7H	0.712
1:152664126:G:T	Q7H	0.712
1:152664135:C:G	C10W	0.702
1:152664162:G:C	K19N	0.694
1:152664162:G:T	K19N	0.694
1:152664153:T:G	C16W	0.684
1:152664123:C:A	N6K	0.676
1:152664123:C:G	N6K	0.676
1:152664331:C:G	H76D	0.669
1:152664172:A:G	K23E	0.665
1:152664112:T:C	C3R	0.659
1:152664336:G:C	R77S	0.643
1:152664336:G:T	R77S	0.643

dbSNP variants (sampled 300 via entrez): RS1000623580 (1:152663787 G>A), RS1000853703 (1:152663223 T>A), RS1001325119 (1:152662942 A>G), RS1001779880 (1:152663199 C>T), RS1002639724 (1:152664895 G>A,C), RS1004193399 (1:152664740 G>A), RS1004768349 (1:152662347 T>G), RS1005408366 (1:152662202 T>C,G), RS1005876539 (1:152661970 A>G), RS1005982591 (1:152662536 GT>G), RS1007965558 (1:152663529 C>T), RS1008043194 (1:152662314 A>G), RS1008502554 (1:152663943 A>T), RS1009450855 (1:152661686 G>A), RS1012353241 (1:152663286 A>T)

Disease associations

OMIM: gene MIM:612612 | 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

9 total (human), top 9 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenate	increases abundance, decreases expression	1
CGP 52608	affects binding, increases reaction	1
Arsenic	decreases expression, increases abundance	1
Benzo(a)pyrene	increases methylation	1
Valproic Acid	decreases methylation	1
Aflatoxin B1	decreases methylation	1
Sodium Selenite	increases expression	1
Cadmium Chloride	increases expression	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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