LCE5A

Summary

LCE5A (late cornified envelope 5A, HGNC:16614) is a protein-coding gene on chromosome 1q21.3, encoding Late cornified envelope protein 5A (Q5TCM9). Precursors of the cornified envelope of the stratum corneum.

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

Source: NCBI Gene 254910 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 16 total
• MANE Select transcript: NM_178438

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16614
Approved symbol	LCE5A
Name	late cornified envelope 5A
Location	1q21.3
Locus type	gene with protein product
Status	Approved
Aliases	LEP18
Ensembl gene	ENSG00000186207
Ensembl biotype	protein_coding
OMIM	612619
Entrez	254910

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000334269

RefSeq mRNA: 1 — MANE Select: NM_178438 NM_178438

CCDS: CCDS1011

Canonical transcript exons

ENST00000334269 — 2 exons

Exon	Start	End
ENSE00001338723	152511514	152512177
ENSE00001447966	152510803	152510998

Expression profiles

Bgee: expression breadth broad, 81 present calls, max score 91.57.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2587 / max 366.4013, expressed in 5 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
5301	0.2587	5

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	91.57	gold quality
zone of skin	UBERON:0000014	89.24	gold quality
skin of abdomen	UBERON:0001416	85.97	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.08	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	59.96	gold quality
lower esophagus mucosa	UBERON:0035834	56.83	gold quality
cortical plate	UBERON:0005343	45.46	gold quality
bone marrow cell	CL:0002092	43.86	gold quality
esophagus mucosa	UBERON:0002469	41.86	gold quality
bone marrow	UBERON:0002371	40.88	gold quality
ventricular zone	UBERON:0003053	40.75	silver quality
vagina	UBERON:0000996	39.00	gold quality
right lung	UBERON:0002167	38.90	silver quality
left testis	UBERON:0004533	38.30	gold quality
granulocyte	CL:0000094	38.28	gold quality
blood	UBERON:0000178	37.90	gold quality
testis	UBERON:0000473	37.87	gold quality
ganglionic eminence	UBERON:0004023	37.59	silver quality
putamen	UBERON:0001874	37.55	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
skeletal muscle tissue	UBERON:0001134	36.83	gold quality
multicellular organism	UBERON:0000468	36.80	gold quality
right testis	UBERON:0004534	36.67	gold quality
gastrocnemius	UBERON:0001388	36.57	gold quality
nucleus accumbens	UBERON:0001882	36.36	gold quality
esophagus	UBERON:0001043	36.23	gold quality
sural nerve	UBERON:0015488	36.22	gold quality
anterior cingulate cortex	UBERON:0009835	35.82	gold quality
muscle of leg	UBERON:0001383	35.58	gold quality
amygdala	UBERON:0001876	35.56	gold quality

Single-cell (SCXA)

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

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

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

15 targeting LCE5A, 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-3910	99.95	71.13	2227
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-5093	99.67	69.26	2291
HSA-MIR-504-3P	99.30	67.18	1745
HSA-MIR-5701	98.97	69.54	1502
HSA-MIR-4755-3P	98.77	65.59	1915
HSA-MIR-4712-3P	98.52	65.39	822
HSA-MIR-654-3P	98.38	67.61	905
HSA-MIR-122-5P	97.23	64.92	1024
HSA-MIR-4268	94.45	64.09	819

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

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Lce1g	ENSMUSG00000027919
mus_musculus	Lce1e	ENSMUSG00000068889
rattus_norvegicus	Lce1g	ENSRNOG00000070872

Paralogs (20): LCE2B (ENSG00000159455), SPRR2G (ENSG00000159516), LCE3D (ENSG00000163202), SPRR3 (ENSG00000163209), SPRR1B (ENSG00000169469), SPRR1A (ENSG00000169474), LCE1D (ENSG00000172155), SPRR4 (ENSG00000184148), LCE3A (ENSG00000185962), LCE3E (ENSG00000185966), LCE1E (ENSG00000186226), LCE2A (ENSG00000187173), LCE2C (ENSG00000187180), LCE2D (ENSG00000187223), LCE3B (ENSG00000187238), KPLCE (ENSG00000198854), PRR9 (ENSG00000203783), LELP1 (ENSG00000203784), LCE1F (ENSG00000240386), LCE3C (ENSG00000244057)

Protein

Protein identifiers

Late cornified envelope protein 5A — Q5TCM9 (reviewed: Q5TCM9)

Alternative names: Late envelope protein 18, Small proline-rich-like epidermal differentiation complex protein 5A

All UniProt accessions (1): Q5TCM9

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. Expression is observed in the heart.

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

Similarity. Belongs to the LCE family.

RefSeq proteins (1): NP_848525* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR028205	LCE	Family

Pfam: PF14672

UniProt features (8 total): compositionally biased region 4, region of interest 2, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5TCM9-F1	53.12	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, GCANCTGNY_MYOD_Q6, GOBP_EPIDERMAL_CELL_DIFFERENTIATION, GOBP_EPIDERMIS_DEVELOPMENT, TATA_C, GOBP_KERATINIZATION, GOBP_SKIN_DEVELOPMENT, chr1q21, MARTENS_TRETINOIN_RESPONSE_UP, REACTOME_KERATINIZATION, REACTOME_FORMATION_OF_THE_CORNIFIED_ENVELOPE, GOBP_KERATINOCYTE_DIFFERENTIATION, GOBP_EPITHELIAL_CELL_DIFFERENTIATION, MIR6721_5P, TATA_01

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

314 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LCE5A	LCE4A	Q5TA78	970
LCE5A	LCE1A	Q5T7P2	910
LCE5A	LCE1D	Q5T752	620
LCE5A	LCE6A	A0A183	601
LCE5A	LCE2B	O14633	582
LCE5A	LCE1C	Q5T751	575
LCE5A	LCE3C	Q5T5A8	550
LCE5A	LCE2C	Q5TA81	542
LCE5A	LCE2D	Q5TA82	540
LCE5A	SPRR1B	P22528	535
LCE5A	LCE2A	Q5TA79	528
LCE5A	RPTN	Q6XPR3	518
LCE5A	LCE3E	Q5T5B0	505
LCE5A	LCE1F	Q5T754	505
LCE5A	KCTD6	Q8NC69	475

IntAct

250 interactions, top by confidence:

A	B	Type	Score
LCE5A	KRTAP4-12	psi-mi:“MI:0915”(physical association)	0.600
LCE5A	LCE5A	psi-mi:“MI:0915”(physical association)	0.600
LCE5A	KRTAP5-3	psi-mi:“MI:0915”(physical association)	0.600
LCE5A	KRTAP5-4	psi-mi:“MI:0915”(physical association)	0.600
KRTAP10-9	LCE5A	psi-mi:“MI:0915”(physical association)	0.600
LCE5A	UBE2I	psi-mi:“MI:0915”(physical association)	0.560
NUTF2	LCE5A	psi-mi:“MI:0915”(physical association)	0.560
RGS20	LCE5A	psi-mi:“MI:0915”(physical association)	0.560
KRTAP5-9	LCE5A	psi-mi:“MI:0915”(physical association)	0.560
NOTCH2NLC	LCE5A	psi-mi:“MI:0915”(physical association)	0.560
LCE5A	KRTAP9-2	psi-mi:“MI:0915”(physical association)	0.560
LCE5A	PLSCR2	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-8	LCE5A	psi-mi:“MI:0915”(physical association)	0.560
KRTAP1-3	LCE5A	psi-mi:“MI:0915”(physical association)	0.560
KRTAP1-1	LCE5A	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-7	LCE5A	psi-mi:“MI:0915”(physical association)	0.560
KRTAP6-3	LCE5A	psi-mi:“MI:0915”(physical association)	0.560
CYSRT1	LCE5A	psi-mi:“MI:0915”(physical association)	0.560
KRTAP4-1	LCE5A	psi-mi:“MI:0915”(physical association)	0.560
HOXA1	LCE5A	psi-mi:“MI:0915”(physical association)	0.560
LCE5A	PLSCR3	psi-mi:“MI:0915”(physical association)	0.560
LCE2C	LCE5A	psi-mi:“MI:0915”(physical association)	0.560
KRTAP12-3	LCE5A	psi-mi:“MI:0915”(physical association)	0.560
LCE5A	KRTAP4-4	psi-mi:“MI:0915”(physical association)	0.560
LCE5A	KRTAP9-3	psi-mi:“MI:0915”(physical association)	0.560
LCE5A	RGS17	psi-mi:“MI:0915”(physical association)	0.560
LCE5A	NECTIN2	psi-mi:“MI:0915”(physical association)	0.560
LCE5A	CHIC2	psi-mi:“MI:0915”(physical association)	0.560
LCE5A	KRTAP5-11	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (90): LCE5A (Synthetic Lethality), LCE5A (Two-hybrid), LCE5A (Two-hybrid), LCE5A (Two-hybrid), LCE5A (Two-hybrid), LCE5A (Two-hybrid), LCE5A (Two-hybrid), LCE5A (Two-hybrid), LCE5A (Two-hybrid), LCE5A (Two-hybrid), LCE5A (Two-hybrid), LCE5A (Two-hybrid), LCE5A (Two-hybrid), LCE5A (Two-hybrid), LCE5A (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 63 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	33	37.5×	4e-45
Formation of the cornified envelope	8	14.3×	2e-06

GO biological processes:

GO term	Partners	Fold	FDR
hair cycle	5	111.5×	6e-08
keratinization	10	55.7×	2e-13

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	12
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

146 predictions. Top by Δscore:

Variant	Effect	Δscore
1:152511513:GCTTT:G	acceptor_gain	0.9900
1:152510947:GA:G	donor_gain	0.9700
1:152510969:G:T	donor_gain	0.9600
1:152511512:A:AG	acceptor_gain	0.9600
1:152511513:G:GG	acceptor_gain	0.9600
1:152511502:ATT:A	acceptor_loss	0.9400
1:152511504:T:A	acceptor_loss	0.9400
1:152511512:AGC:A	acceptor_loss	0.9400
1:152510969:G:GT	donor_gain	0.9300
1:152511503:T:G	acceptor_loss	0.9300
1:152510957:G:GT	donor_gain	0.9000
1:152510970:A:T	donor_gain	0.9000
1:152511513:GCT:G	acceptor_gain	0.9000
1:152511580:T:G	donor_gain	0.9000
1:152510953:G:GT	donor_gain	0.8800
1:152510996:AAG:A	donor_loss	0.8700
1:152511000:T:G	donor_loss	0.8700
1:152511507:CTTT:C	acceptor_loss	0.8600
1:152511499:T:A	acceptor_loss	0.8500
1:152511505:GTCTT:G	acceptor_loss	0.8500
1:152511506:TCTTT:T	acceptor_loss	0.8500
1:152511002:GGTAA:G	donor_loss	0.8400
1:152511513:GC:G	acceptor_gain	0.8400
1:152511513:GCTT:G	acceptor_gain	0.8400
1:152510920:TTG:T	donor_gain	0.8100
1:152511510:TCAGC:T	acceptor_gain	0.8000
1:152511511:CAGCT:C	acceptor_gain	0.7900
1:152510919:GT:G	donor_gain	0.7800
1:152511003:G:C	donor_loss	0.7600
1:152511611:C:G	donor_gain	0.7600

AlphaMissense

767 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:152511546:G:C	Q4H	0.740
1:152511546:G:T	Q4H	0.740
1:152511550:A:C	S6R	0.737
1:152511552:C:A	S6R	0.737
1:152511552:C:G	S6R	0.737
1:152511555:G:C	Q7H	0.696
1:152511555:G:T	Q7H	0.696
1:152511541:T:C	C3R	0.664
1:152511562:T:C	C10R	0.664
1:152511564:C:G	C10W	0.663
1:152511591:A:C	K19N	0.661
1:152511591:A:T	K19N	0.661
1:152511616:T:C	C28R	0.633
1:152511579:A:C	K15N	0.629
1:152511579:A:T	K15N	0.629
1:152511549:G:C	Q5H	0.623
1:152511549:G:T	Q5H	0.623
1:152511618:T:G	C28W	0.621
1:152511543:C:G	C3W	0.594
1:152511580:T:C	C16R	0.591
1:152511582:T:G	C16W	0.586
1:152511603:G:C	K23N	0.586
1:152511603:G:T	K23N	0.586
1:152511615:G:C	K27N	0.586
1:152511615:G:T	K27N	0.586
1:152511558:G:C	Q8H	0.581
1:152511558:G:T	Q8H	0.581
1:152511592:T:C	C20R	0.569
1:152511742:A:C	S70R	0.565
1:152511744:C:A	S70R	0.565

dbSNP variants (sampled 300 via entrez): RS1000956174 (1:152512157 A>C,G), RS1001385005 (1:152508889 G>A), RS1001505755 (1:152509261 G>A,C), RS1001623251 (1:152509387 G>A), RS1001696735 (1:152509804 A>G), RS1002334269 (1:152509962 A>T), RS1004125421 (1:152510352 G>A,C), RS1005264269 (1:152510212 T>C), RS1005293645 (1:152510566 T>C,G), RS1007633468 (1:152509065 CA>C), RS1008462569 (1:152512122 T>C), RS1008847890 (1:152511947 T>A,C), RS1008860855 (1:152510686 A>C), RS1009752316 (1:152509631 C>G,T), RS1009878173 (1:152510909 C>T)

Disease associations

OMIM: gene MIM:612619 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST000519_10	Hair morphology	4.000000e-06
GCST002740_5	Inflammatory skin disease	2.000000e-12
GCST003180_3	Atopic march	9.000000e-11
GCST007563_33	Allergic disease (asthma, hay fever or eczema)	3.000000e-11
GCST007564_24	Asthma or allergic disease (pleiotropy)	5.000000e-12
GCST008916_75	Asthma	2.000000e-08
GCST008916_82	Asthma	5.000000e-27
GCST008916_88	Asthma	1.000000e-25
GCST012462_1	Asthma and eczema	2.000000e-06
GCST012489_17	Heel bone mineral density x serum urate levels interaction	6.000000e-11

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0005038	hair morphology
EFO:0007755	atopic march
EFO:0004531	urate measurement
EFO:0009270	heel bone mineral density

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

5 total (human), top 5 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Resveratrol	affects cotreatment, decreases expression	1
Benzo(a)pyrene	increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Aflatoxin B1	decreases expression	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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