LCE1D

Summary

LCE1D (late cornified envelope 1D, HGNC:29465) is a protein-coding gene on chromosome 1q21.3, encoding Late cornified envelope protein 1D (Q5T752). Precursors of the cornified envelope of the stratum corneum.

Enables identical protein binding activity. Involved in cognition. Acts upstream of or within cellular response to calcium ion. Located in cornified envelope and perinuclear region of cytoplasm.

Source: NCBI Gene 353134 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 21 total
• MANE Select transcript: NM_178352

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29465
Approved symbol	LCE1D
Name	late cornified envelope 1D
Location	1q21.3
Locus type	gene with protein product
Status	Approved
Aliases	LEP4
Ensembl gene	ENSG00000172155
Ensembl biotype	protein_coding
OMIM	612606
Entrez	353134

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000326233

RefSeq mRNA: 1 — MANE Select: NM_178352 NM_178352

CCDS: CCDS1025

Canonical transcript exons

ENST00000326233 — 2 exons

Exon	Start	End
ENSE00001128966	152797773	152798181
ENSE00001447930	152796721	152796771

Expression profiles

Bgee: expression breadth broad, 53 present calls, max score 85.69.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.3034 / max 325.6900, expressed in 15 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
5318	0.3034	15

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
skin of leg	UBERON:0001511	85.69	gold quality
zone of skin	UBERON:0000014	82.62	gold quality
skin of abdomen	UBERON:0001416	78.24	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
skeletal muscle tissue	UBERON:0001134	36.92	gold quality
sural nerve	UBERON:0015488	36.80	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
fundus of stomach	UBERON:0001160	33.85	gold quality
muscle tissue	UBERON:0002385	33.66	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
muscle of leg	UBERON:0001383	31.10	gold quality
gastrocnemius	UBERON:0001388	31.10	gold quality
blood	UBERON:0000178	30.46	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
liver	UBERON:0002107	29.43	gold quality
multicellular organism	UBERON:0000468	29.00	gold quality
heart left ventricle	UBERON:0002084	28.47	gold quality
popliteal artery	UBERON:0002250	28.33	gold quality
tibial artery	UBERON:0007610	28.28	gold quality
duodenum	UBERON:0002114	28.14	gold quality
lymph node	UBERON:0000029	27.57	gold quality
right adrenal gland cortex	UBERON:0035827	27.07	silver quality
tonsil	UBERON:0002372	27.05	gold quality
pancreas	UBERON:0001264	26.96	gold quality
islet of Langerhans	UBERON:0000006	26.55	gold quality
vermiform appendix	UBERON:0001154	26.42	gold quality
body of pancreas	UBERON:0001150	26.20	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.49

Regulation

Is transcription factor: no

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), SPRR4 (ENSG00000184148), LCE3A (ENSG00000185962), LCE3E (ENSG00000185966), LCE5A (ENSG00000186207), 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 1D — Q5T752 (reviewed: Q5T752)

Alternative names: Late envelope protein 4

All UniProt accessions (1): Q5T752

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 UVB.

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

Similarity. Belongs to the LCE family.

RefSeq proteins (1): NP_848129* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR028205	LCE	Family

Pfam: PF14672

UniProt features (8 total): compositionally biased region 3, region of interest 2, sequence variant 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5T752-F1	53.13	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: 24 (showing top): GOBP_EPITHELIUM_DEVELOPMENT, GOBP_COGNITION, GOBP_RESPONSE_TO_METAL_ION, GOBP_EPIDERMAL_CELL_DIFFERENTIATION, GOBP_EPIDERMIS_DEVELOPMENT, GOBP_CELLULAR_RESPONSE_TO_CALCIUM_ION, GOBP_KERATINIZATION, GOBP_SKIN_DEVELOPMENT, GOBP_RESPONSE_TO_CALCIUM_ION, chr1q21, GOCC_CORNIFIED_ENVELOPE, REACTOME_KERATINIZATION, REACTOME_FORMATION_OF_THE_CORNIFIED_ENVELOPE, GOBP_KERATINOCYTE_DIFFERENTIATION, GSE14386_UNTREATED_VS_IFNA_TREATED_ACT_PBMC_MS_PATIENT_UP

GO Biological Process (4): keratinization (GO:0031424), cognition (GO:0050890), cellular response to calcium ion (GO:0071277), epidermis development (GO:0008544)

GO Molecular Function (2): identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (3): cornified envelope (GO:0001533), cytoplasm (GO:0005737), perinuclear region of cytoplasm (GO:0048471)

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
cellular anatomical structure	2
keratinocyte differentiation	1
multicellular organismal process	1
nervous system process	1
response to calcium ion	1
cellular response to metal ion	1
tissue development	1
protein binding	1
binding	1
plasma membrane	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

324 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LCE1D	LCE1E	Q5T753	986
LCE1D	LCE1B	Q5T7P3	788
LCE1D	LCE1A	Q5T7P2	785
LCE1D	LCE2D	Q5TA82	756
LCE1D	LCE1C	Q5T751	720
LCE1D	LCE1F	Q5T754	720
LCE1D	LCE2C	Q5TA81	621
LCE1D	LCE6A	A0A183	620
LCE1D	LCE5A	Q5TCM9	620
LCE1D	LCE2A	Q5TA79	583
LCE1D	LCE2B	O14633	578
LCE1D	LCE3C	Q5T5A8	570
LCE1D	IL37	Q9NZH6	508
LCE1D	LCE3E	Q5T5B0	507
LCE1D	LCE3A	Q5TA76	507

IntAct

198 interactions, top by confidence:

A	B	Type	Score
KRTAP1-5	LCE1D	psi-mi:“MI:0915”(physical association)	0.700
CYSRT1	LCE1D	psi-mi:“MI:0915”(physical association)	0.700
LCE1D	KRTAP1-5	psi-mi:“MI:0915”(physical association)	0.700
LCE1D	CYSRT1	psi-mi:“MI:0915”(physical association)	0.700
LCE1D	KRTAP5-11	psi-mi:“MI:0915”(physical association)	0.600
LCE1D	KRTAP9-3	psi-mi:“MI:0915”(physical association)	0.600
KRTAP9-3	LCE1D	psi-mi:“MI:0915”(physical association)	0.600
LCE1D	LCE2C	psi-mi:“MI:0915”(physical association)	0.560
LCE1D	KRTAP5-6	psi-mi:“MI:0915”(physical association)	0.560
LCE1D	UBE2I	psi-mi:“MI:0915”(physical association)	0.560
KRTAP4-1	LCE1D	psi-mi:“MI:0915”(physical association)	0.560
GRN	LCE1D	psi-mi:“MI:0915”(physical association)	0.560
LCE1D	LCE1B	psi-mi:“MI:0915”(physical association)	0.560
LCE1D	PCSK5	psi-mi:“MI:0915”(physical association)	0.560
LCE1D	MACO1	psi-mi:“MI:0915”(physical association)	0.560
NOTCH2NLC	LCE1D	psi-mi:“MI:0915”(physical association)	0.560
LCE1D	KRTAP5-4	psi-mi:“MI:0915”(physical association)	0.560
LCE1D	KRTAP9-8	psi-mi:“MI:0915”(physical association)	0.560
LCE1D	KRTAP4-4	psi-mi:“MI:0915”(physical association)	0.560
SPRY1	LCE1D	psi-mi:“MI:0915”(physical association)	0.560
ALPP	LCE1D	psi-mi:“MI:0915”(physical association)	0.560
LCE1D	MEOX2	psi-mi:“MI:0915”(physical association)	0.560
LCE1D	KRTAP2-4	psi-mi:“MI:0915”(physical association)	0.560
	LCE1D	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-8	LCE1D	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-7	LCE1D	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (72): LCE1D (Two-hybrid), LCE1D (Two-hybrid), LCE1D (Two-hybrid), LCE1D (Two-hybrid), LCE1D (Two-hybrid), LCE1D (Two-hybrid), LCE1D (Two-hybrid), LCE1D (Two-hybrid), LCE1D (Two-hybrid), LCE1D (Two-hybrid), LCE1D (Two-hybrid), LCE1D (Two-hybrid), LCE1D (Two-hybrid), LCE1D (Two-hybrid), LCE1D (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: Q5T751, Q5T752, Q5T753, Q5T754, Q5T7P2, Q5T7P3, Q5T5A8, Q5TA79

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 54 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	30	37.1×	1e-40
Formation of the cornified envelope	9	17.6×	6e-08

GO biological processes:

GO term	Partners	Fold	FDR
hair cycle	5	130.0×	5e-08
keratinization	9	58.5×	8e-12

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	17
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

145 predictions. Top by Δscore:

Variant	Effect	Δscore
1:152797771:A:AG	acceptor_gain	0.9600
1:152797772:G:GG	acceptor_gain	0.9600
1:152796769:CCGGT:C	donor_loss	0.9200
1:152796770:CGG:C	donor_loss	0.9200
1:152796771:GGTAA:G	donor_loss	0.9200
1:152796772:GTA:G	donor_loss	0.9200
1:152796773:T:G	donor_loss	0.9200
1:152796788:G:T	donor_gain	0.9000
1:152797767:CCTCA:C	acceptor_loss	0.9000
1:152797768:CTCA:C	acceptor_loss	0.9000
1:152797769:TCA:T	acceptor_loss	0.9000
1:152797770:CAGCT:C	acceptor_loss	0.9000
1:152797771:A:T	acceptor_loss	0.9000
1:152797772:G:GT	acceptor_loss	0.9000
1:152796772:G:GG	donor_gain	0.8900
1:152796811:G:T	donor_gain	0.8900
1:152797108:G:T	donor_gain	0.8100
1:152797772:GCT:G	acceptor_gain	0.8000
1:152797772:GCTC:G	acceptor_gain	0.7900
1:152797259:GGTG:G	donor_gain	0.7500
1:152797260:GTGG:G	donor_gain	0.7500
1:152797261:TGGT:T	donor_gain	0.7500
1:152797262:GGTG:G	donor_gain	0.7500
1:152797272:G:GT	donor_gain	0.7500
1:152797131:GGAC:G	donor_gain	0.7200
1:152797772:GCTCC:G	acceptor_gain	0.7200
1:152797772:GC:G	acceptor_gain	0.7000
1:152796767:CTCCG:C	donor_gain	0.6900
1:152797149:GGTT:G	donor_gain	0.6800
1:152796807:G:GT	donor_gain	0.6700

AlphaMissense

748 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:152797810:A:C	S6R	0.841
1:152797812:C:A	S6R	0.841
1:152797812:C:G	S6R	0.841
1:152797806:G:C	Q4H	0.820
1:152797806:G:T	Q4H	0.820
1:152798014:A:C	S74R	0.819
1:152798016:C:A	S74R	0.819
1:152798016:C:G	S74R	0.819
1:152797822:T:C	C10R	0.811
1:152797801:T:C	C3R	0.801
1:152797824:C:G	C10W	0.790
1:152797809:G:C	Q5H	0.775
1:152797809:G:T	Q5H	0.775
1:152798005:T:C	C71R	0.760
1:152798134:T:C	C114R	0.757
1:152797815:G:C	Q7H	0.754
1:152797815:G:T	Q7H	0.754
1:152797840:T:C	C16R	0.742
1:152797839:G:C	K15N	0.738
1:152797839:G:T	K15N	0.738
1:152798136:C:G	C114W	0.733
1:152797842:C:G	C16W	0.729
1:152797851:G:C	K19N	0.728
1:152797851:G:T	K19N	0.728
1:152797879:T:C	C29R	0.717
1:152797863:G:C	K23N	0.715
1:152797863:G:T	K23N	0.715
1:152797799:C:G	S2C	0.699
1:152797799:C:T	S2F	0.693
1:152797881:T:G	C29W	0.690

dbSNP variants (sampled 300 via entrez): RS1000603769 (1:152797592 C>T), RS1000974343 (1:152798398 G>C), RS1004712592 (1:152796529 C>G), RS1008108298 (1:152797494 A>G,T), RS1012015025 (1:152798504 G>A), RS1014324399 (1:152795445 C>A), RS1016880722 (1:152794739 C>T), RS1017182954 (1:152795568 G>A), RS1020582539 (1:152796709 C>T), RS1020591924 (1:152797504 A>G), RS1023115393 (1:152798530 G>A), RS1027920887 (1:152795791 C>T), RS1028223581 (1:152796588 A>G), RS1032535866 (1:152797685 T>A,C), RS1038177284 (1:152796567 G>A)

Disease associations

OMIM: gene MIM:612606 | 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
GCST007564_25	Asthma or allergic disease (pleiotropy)	5.000000e-09
GCST008916_82	Asthma	5.000000e-27
GCST008916_92	Asthma	6.000000e-16

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

16 total (human), top 16 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects expression, increases methylation	2
sodium arsenate	increases abundance, decreases expression	1
arsenite	decreases methylation	1
tobacco tar	decreases reaction, increases expression	1
diallyl disulfide	decreases reaction, increases expression	1
CGP 52608	increases reaction, affects binding	1
nutlin 3	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Acetaminophen	decreases expression	1
Arsenic	decreases expression, increases abundance	1
Cadmium	decreases expression, increases abundance	1
Dactinomycin	affects cotreatment, increases expression	1
Mustard Gas	increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Cadmium Chloride	decreases expression, increases abundance	1
Nanotubes, Carbon	increases expression	1

Clinical trials (associated diseases)

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