LCE4A

Summary

LCE4A (late cornified envelope 4A, HGNC:16613) is a protein-coding gene on chromosome 1q21.3, encoding Late cornified envelope protein 4A (Q5TA78). Precursors of the cornified envelope of the stratum corneum.

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

Source: NCBI Gene 199834 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 18 total
• MANE Select transcript: NM_001387222

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16613
Approved symbol	LCE4A
Name	late cornified envelope 4A
Location	1q21.3
Locus type	gene with protein product
Status	Approved
Aliases	LEP8
Ensembl gene	ENSG00000187170
Ensembl biotype	protein_coding
OMIM	612618
Entrez	199834

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000368777

RefSeq mRNA: 2 — MANE Select: NM_001387222 NM_001387222, NM_178356

CCDS: CCDS1022

Canonical transcript exons

ENST00000368777 — 2 exons

Exon	Start	End
ENSE00001447942	152709055	152709434
ENSE00001447943	152708160	152708394

Expression profiles

Bgee: expression breadth broad, 12 present calls, max score 64.13.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	64.13	gold quality
skin of leg	UBERON:0001511	60.24	gold quality
zone of skin	UBERON:0000014	56.78	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	53.10	gold quality
skin of abdomen	UBERON:0001416	51.52	gold quality
colonic epithelium	UBERON:0000397	42.43	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
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
bone marrow	UBERON:0002371	31.74	gold quality
muscle tissue	UBERON:0002385	31.06	gold quality
sural nerve	UBERON:0015488	30.93	gold quality
monocyte	CL:0000576	29.97	gold quality
leukocyte	CL:0000738	29.75	gold quality
prefrontal cortex	UBERON:0000451	29.04	gold quality
tonsil	UBERON:0002372	28.88	gold quality
liver	UBERON:0002107	28.33	gold quality
duodenum	UBERON:0002114	28.14	gold quality
lymph node	UBERON:0000029	27.57	gold quality
islet of Langerhans	UBERON:0000006	26.55	gold quality
vermiform appendix	UBERON:0001154	26.42	gold quality
blood	UBERON:0000178	26.18	gold quality
gall bladder	UBERON:0002110	25.98	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	25.89	gold quality
placenta	UBERON:0001987	25.81	gold quality
urinary bladder	UBERON:0001255	25.72	gold quality
muscle of leg	UBERON:0001383	25.02	silver 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

Literature-anchored findings (GeneRIF, showing 2)

• paper describing nomenclature changes and expression in range of tissues and in response to UV (PMID:15854049)
• SNPs in LCE4A are associated with increased risk of candidemia. (PMID:25197941)

Cross-species orthologs

0 orthologs

Protein

Protein identifiers

Late cornified envelope protein 4A — Q5TA78 (reviewed: Q5TA78)

Alternative names: Late envelope protein 8, Small proline-rich-like epidermal differentiation complex protein 4A

All UniProt accessions (1): Q5TA78

UniProt curated annotations — full annotation on UniProt →

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

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.

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

Similarity. Belongs to the LCE family.

RefSeq proteins (2): NP_001374151, NP_848133 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR028205	LCE	Family

Pfam: PF14672

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

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5TA78-F1	54.24	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: 10 (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

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

236 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LCE4A	LCE5A	Q5TCM9	970
LCE4A	LCE1A	Q5T7P2	852
LCE4A	KPLCE	Q5T750	767
LCE4A	TAGAP	Q8N103	621
LCE4A	LCE2A	Q5TA79	574
LCE4A	LCE1F	Q5T754	506
LCE4A	LCE2B	O14633	505
LCE4A	LCE3A	Q5TA76	469
LCE4A	LCE2C	Q5TA81	449
LCE4A	OR5AS1	Q8N127	447
LCE4A	CD58	P19256	446
LCE4A	KPRP	Q5T749	432
LCE4A	LCE3C	Q5T5A8	430
LCE4A	LCE1D	Q5T752	419
LCE4A	LCE1C	Q5T751	419

IntAct

287 interactions, top by confidence:

A	B	Type	Score
LCE4A	KRTAP9-2	psi-mi:“MI:0915”(physical association)	0.740
KRTAP9-2	LCE4A	psi-mi:“MI:0915”(physical association)	0.740
RGS20	LCE4A	psi-mi:“MI:0915”(physical association)	0.720
LCE4A	KRTAP5-9	psi-mi:“MI:0915”(physical association)	0.720
HOXA1	LCE4A	psi-mi:“MI:0915”(physical association)	0.720
SMCP	LCE4A	psi-mi:“MI:0915”(physical association)	0.720
LCE4A	KRTAP10-7	psi-mi:“MI:0915”(physical association)	0.720
LCE4A	KRTAP10-8	psi-mi:“MI:0915”(physical association)	0.720
KRTAP10-9	LCE4A	psi-mi:“MI:0915”(physical association)	0.720
LCE4A	ADAMTSL4	psi-mi:“MI:0915”(physical association)	0.720
LCE4A	MDFI	psi-mi:“MI:0915”(physical association)	0.720
LCE4A	KRTAP4-12	psi-mi:“MI:0915”(physical association)	0.720
LCE4A	KRTAP4-2	psi-mi:“MI:0915”(physical association)	0.720
KRTAP3-2	LCE4A	psi-mi:“MI:0915”(physical association)	0.720
LCE4A	RGS20	psi-mi:“MI:0915”(physical association)	0.720
KRTAP10-7	LCE4A	psi-mi:“MI:0915”(physical association)	0.720
ADAMTSL4	LCE4A	psi-mi:“MI:0915”(physical association)	0.720
LCE4A	KRTAP10-9	psi-mi:“MI:0915”(physical association)	0.720

BioGRID (94): LCE4A (Two-hybrid), LCE4A (Two-hybrid), LCE4A (Two-hybrid), LCE4A (Two-hybrid), LCE4A (Two-hybrid), LCE4A (Two-hybrid), LCE4A (Two-hybrid), LCE4A (Two-hybrid), LCE4A (Two-hybrid), LCE4A (Two-hybrid), LCE4A (Two-hybrid), LCE4A (Two-hybrid), LCE4A (Two-hybrid), LCE4A (Two-hybrid), LCE4A (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

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 67 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	39.6×	2e-52
Formation of the cornified envelope	9	15.2×	1e-07

GO biological processes:

GO term	Partners	Fold	FDR
hair cycle	5	111.5×	6e-08
keratinization	7	39.0×	6e-08

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	18
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

142 predictions. Top by Δscore:

Variant	Effect	Δscore
1:152708365:G:GT	donor_gain	0.9900
1:152708365:G:T	donor_gain	0.9900
1:152708391:CACGG:C	donor_loss	0.9900
1:152708392:ACGG:A	donor_loss	0.9900
1:152708393:CGG:C	donor_loss	0.9900
1:152708395:GT:G	donor_loss	0.9900
1:152708395:G:GG	donor_gain	0.9800
1:152708396:T:A	donor_loss	0.9800
1:152708393:CG:C	donor_gain	0.9700
1:152708394:GG:G	donor_gain	0.9700
1:152708594:G:GT	donor_gain	0.9700
1:152708671:G:GT	donor_gain	0.9700
1:152709052:CAGGT:C	acceptor_loss	0.9700
1:152709053:AGG:A	acceptor_loss	0.9700
1:152708390:CCACG:C	donor_gain	0.9600
1:152708397:GAGTG:G	donor_loss	0.9600
1:152708235:C:T	donor_gain	0.9400
1:152708391:CACG:C	donor_gain	0.9400
1:152709054:GGTTT:G	acceptor_gain	0.9400
1:152708392:ACG:A	donor_gain	0.9200
1:152708568:G:GT	donor_gain	0.9100
1:152708568:G:T	donor_gain	0.9100
1:152708200:G:GT	donor_gain	0.9000
1:152708648:GTCC:G	donor_gain	0.9000
1:152708649:TCCT:T	donor_gain	0.9000
1:152708216:G:GT	donor_gain	0.8900
1:152708363:GGGAC:G	donor_gain	0.8900
1:152708364:GGACG:G	donor_gain	0.8900
1:152709053:A:AG	acceptor_gain	0.8900
1:152709054:G:GG	acceptor_gain	0.8900

AlphaMissense

645 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000287595 (1:152706903 C>T), RS1000506112 (1:152706744 T>C), RS1001316884 (1:152707906 A>T), RS1003023105 (1:152708757 T>C), RS1004207142 (1:152706273 T>G), RS1006350131 (1:152706526 G>A), RS1007059756 (1:152708135 A>G), RS1007542776 (1:152707867 T>C), RS1007797321 (1:152706848 A>G), RS1007845242 (1:152709584 T>A,G), RS1008132636 (1:152708170 G>A,C), RS1010669626 (1:152708705 A>G), RS1010946792 (1:152708399 G>A), RS1011036738 (1:152709763 A>G), RS1012325907 (1:152707185 A>G)

Disease associations

OMIM: gene MIM:612618 | 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	decreases expression, increases abundance	1
CGP 52608	affects binding, increases reaction	1
Resveratrol	affects cotreatment, decreases expression	1
Arsenic	decreases expression, increases abundance	1
Benzo(a)pyrene	increases methylation	1
Hydrogen Peroxide	affects expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Valproic Acid	decreases methylation	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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