LCE2B

Summary

LCE2B (late cornified envelope 2B, HGNC:16610) is a protein-coding gene on chromosome 1q21.3, encoding Late cornified envelope protein 2B (O14633). Precursors of the cornified envelope of the stratum corneum.

This gene is one of the at least 20 genes expressed during epidermal differentiation and located on chromosomal band 1q21. This gene is involved in epidermal differentiation, and it is expressed at high levels in normal and psoriatic skin, but not in cultured keratinocytes or in any other tested cell types or tissues.

Source: NCBI Gene 26239 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 33 total
• MANE Select transcript: NM_014357

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16610
Approved symbol	LCE2B
Name	late cornified envelope 2B
Location	1q21.3
Locus type	gene with protein product
Status	Approved
Aliases	LEP10, XP5
Ensembl gene	ENSG00000159455
Ensembl biotype	protein_coding
OMIM	612610
Entrez	26239

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000368780

RefSeq mRNA: 1 — MANE Select: NM_014357 NM_014357

CCDS: CCDS1020

Canonical transcript exons

ENST00000368780 — 2 exons

Exon	Start	End
ENSE00001447948	152686824	152687397
ENSE00001762977	152686123	152686156

Expression profiles

Bgee: expression breadth ubiquitous, 130 present calls, max score 99.36.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
upper arm skin	UBERON:0004263	99.36	gold quality
upper leg skin	UBERON:0004262	99.28	gold quality
skin of leg	UBERON:0001511	97.47	gold quality
zone of skin	UBERON:0000014	96.08	gold quality
skin of abdomen	UBERON:0001416	94.52	gold quality
nipple	UBERON:0002030	93.55	gold quality
skin of hip	UBERON:0001554	92.05	gold quality
penis	UBERON:0000989	90.90	gold quality
mammalian vulva	UBERON:0000997	81.36	gold quality
endometrium epithelium	UBERON:0004811	80.90	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.39	silver quality
Brodmann (1909) area 10	UBERON:0013541	70.07	gold quality
paraflocculus	UBERON:0005351	66.81	gold quality
frontal pole	UBERON:0002795	66.30	gold quality
middle frontal gyrus	UBERON:0002702	66.06	gold quality
hair follicle	UBERON:0002073	57.94	silver quality
decidua	UBERON:0002450	56.55	gold quality
amniotic fluid	UBERON:0000173	55.74	silver quality
thymus	UBERON:0002370	52.21	gold quality
quadriceps femoris	UBERON:0001377	52.12	gold quality
cervix epithelium	UBERON:0004801	52.01	silver quality
right adrenal gland cortex	UBERON:0035827	51.87	gold quality
gastrocnemius	UBERON:0001388	51.70	gold quality
oviduct epithelium	UBERON:0004804	51.16	silver quality
vastus lateralis	UBERON:0001379	51.12	gold quality
layer of synovial tissue	UBERON:0007616	50.38	gold quality
metanephric glomerulus	UBERON:0004736	49.35	gold quality
epithelial cell of pancreas	CL:0000083	49.33	gold quality
Brodmann (1909) area 46	UBERON:0006483	49.30	gold quality
blood vessel layer	UBERON:0004797	49.29	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

17 targeting LCE2B, 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-4795-3P	100.00	74.62	4024
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-4503	99.85	71.45	1869
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-766-5P	99.47	67.91	2225
HSA-MIR-302A-5P	99.39	68.21	1913
HSA-MIR-2116-5P	99.32	69.34	1273
HSA-MIR-3125	99.14	68.49	2269
HSA-MIR-3916	98.99	68.04	2155
HSA-MIR-6859-5P	98.99	68.07	2049
HSA-MIR-4711-5P	98.89	68.00	965
HSA-MIR-4266	98.53	67.29	1035
HSA-MIR-924	97.78	66.21	681
HSA-MIR-5702	96.68	68.21	958
HSA-MIR-4790-3P	96.63	67.08	806

Literature-anchored findings (GeneRIF, showing 2)

• XP5 is part of a cluster of genes (LEP genes) whose proteins incorporate into keratinocyte cornified envelopes. Strong skin expression confirmed. (PMID:11698679)
• paper describing nomenclature changes and expression in range of tissues and in response to UV (PMID:15854049)

Cross-species orthologs

0 orthologs

Paralogs (20): 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), LCE2D (ENSG00000187223), LCE3B (ENSG00000187238), KPLCE (ENSG00000198854), PRR9 (ENSG00000203783), LELP1 (ENSG00000203784), LCE1F (ENSG00000240386), LCE3C (ENSG00000244057)

Protein

Protein identifiers

Late cornified envelope protein 2B — O14633 (reviewed: O14633)

Alternative names: Late envelope protein 10, Skin-specific protein Xp5, Small proline-rich-like epidermal differentiation complex protein 1B

All UniProt accessions (1): O14633

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_055172* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR028205	LCE	Family

Pfam: PF14672

UniProt features (6 total): compositionally biased region 2, sequence variant 2, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O14633-F1	52.78	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: 61 (showing top): GOBP_EPITHELIUM_DEVELOPMENT, MODULE_45, GOBP_EPIDERMAL_CELL_DIFFERENTIATION, MODULE_379, GOBP_EPIDERMIS_DEVELOPMENT, MODULE_88, MODULE_242, GOBP_KERATINIZATION, GOBP_SKIN_DEVELOPMENT, chr1q21, MODULE_104, MODULE_55, MODULE_220, MODULE_153, MODULE_181

GO Biological Process (2): epidermis development (GO:0008544), keratinization (GO:0031424)

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
tissue development	1
keratinocyte differentiation	1
multicellular organismal process	1
protein binding	1
binding	1

Protein interactions and networks

STRING

434 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LCE2B	LCE1B	Q5T7P3	752
LCE2B	LCE1F	Q5T754	670
LCE2B	LCE1C	Q5T751	623
LCE2B	LCE6A	A0A183	598
LCE2B	LCE3E	Q5T5B0	595
LCE2B	LCE5A	Q5TCM9	582
LCE2B	LCE3D	Q9BYE3	582
LCE2B	LCE1D	Q5T752	578
LCE2B	LCE1A	Q5T7P2	577
LCE2B	SPRR2G	Q9BYE4	571
LCE2B	LCE1E	Q5T753	571
LCE2B	SPRR2A	P35326	520
LCE2B	LCE3A	Q5TA76	512
LCE2B	CDSN	Q15517	509
LCE2B	LCE4A	Q5TA78	505

IntAct

244 interactions, top by confidence:

A	B	Type	Score
LCE2B	LCE1F	psi-mi:“MI:0915”(physical association)	0.630
LCE2B	NOTCH2NLC	psi-mi:“MI:0915”(physical association)	0.600
LCE2B	LCE2C	psi-mi:“MI:0915”(physical association)	0.600
LCE2B	GUCD1	psi-mi:“MI:0915”(physical association)	0.600
LCE2B	KRTAP17-1	psi-mi:“MI:0915”(physical association)	0.600
LCE2B	PLA2G10	psi-mi:“MI:0915”(physical association)	0.600
CYSRT1	LCE2B	psi-mi:“MI:0915”(physical association)	0.560
LCE2B	KRTAP9-2	psi-mi:“MI:0915”(physical association)	0.560
KRTAP6-3	LCE2B	psi-mi:“MI:0915”(physical association)	0.560
LCE2B	KRTAP4-4	psi-mi:“MI:0915”(physical association)	0.560
LCE2B	NR4A3	psi-mi:“MI:0915”(physical association)	0.560
LCE2B	KRTAP4-2	psi-mi:“MI:0915”(physical association)	0.560
LCE2B	KRTAP9-8	psi-mi:“MI:0915”(physical association)	0.560
LCE2B	RGS17	psi-mi:“MI:0915”(physical association)	0.560
LCE2B	KRTAP1-1	psi-mi:“MI:0915”(physical association)	0.560
LCE2B	KRTAP10-8	psi-mi:“MI:0915”(physical association)	0.560
LCE2B	LCE1E	psi-mi:“MI:0915”(physical association)	0.560
LCE2B	KRTAP4-12	psi-mi:“MI:0915”(physical association)	0.560
LCE2B	ADAMTSL4	psi-mi:“MI:0915”(physical association)	0.560
LCE2B	KRTAP5-9	psi-mi:“MI:0915”(physical association)	0.560
LCE2B	KRTAP12-3	psi-mi:“MI:0915”(physical association)	0.560
LCE2B	KRTAP5-7	psi-mi:“MI:0915”(physical association)	0.560
LCE2B	KRTAP10-7	psi-mi:“MI:0915”(physical association)	0.560
LCE2B	KRTAP9-3	psi-mi:“MI:0915”(physical association)	0.560
LCE2B	HOXA1	psi-mi:“MI:0915”(physical association)	0.560
LCE2B	RGS20	psi-mi:“MI:0915”(physical association)	0.560
KRTAP1-3	LCE2B	psi-mi:“MI:0915”(physical association)	0.560
LCE2B	MDFI	psi-mi:“MI:0915”(physical association)	0.560
LCE2B	NECTIN2	psi-mi:“MI:0915”(physical association)	0.560
LCE2B	LCE4A	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (82): LCE2B (Two-hybrid), LCE2B (Two-hybrid), LCE2B (Two-hybrid), LCE2B (Two-hybrid), LCE2B (Two-hybrid), LCE2B (Two-hybrid), LCE2B (Two-hybrid), LCE2B (Two-hybrid), LCE2B (Two-hybrid), LCE2B (Two-hybrid), LCE2B (Two-hybrid), LCE2B (Two-hybrid), LCE2B (Two-hybrid), LCE2B (Two-hybrid), LCE2B (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 62 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	38	42.3×	1e-55
Formation of the cornified envelope	13	22.8×	2e-13

GO biological processes:

GO term	Partners	Fold	FDR
keratinization	15	85.6×	1e-23

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	30
Likely benign	1
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

216 predictions. Top by Δscore:

Variant	Effect	Δscore
1:152686155:GG:G	donor_gain	0.9900
1:152686156:GG:G	donor_gain	0.9900
1:152686157:G:GA	donor_loss	0.9800
1:152686158:TGAGT:T	donor_loss	0.9800
1:152686159:GAGTG:G	donor_loss	0.9800
1:152686157:G:GG	donor_gain	0.9600
1:152686160:AGTGG:A	donor_loss	0.9600
1:152686822:A:AG	acceptor_gain	0.9600
1:152686823:G:GG	acceptor_gain	0.9600
1:152686818:TTTCA:T	acceptor_loss	0.9500
1:152686819:TTCA:T	acceptor_loss	0.9500
1:152686820:TCAGG:T	acceptor_loss	0.9500
1:152686821:CA:C	acceptor_loss	0.9500
1:152686822:A:AC	acceptor_loss	0.9500
1:152686823:G:A	acceptor_loss	0.9500
1:152686152:CCAGG:C	donor_gain	0.9400
1:152686823:GGTT:G	acceptor_gain	0.9400
1:152686153:CAGG:C	donor_gain	0.9300
1:152686154:AGG:A	donor_gain	0.9300
1:152686155:GGG:G	donor_gain	0.9300
1:152687268:G:A	acceptor_gain	0.9300
1:152686822:AGGTT:A	acceptor_gain	0.9100
1:152686823:GGTTG:G	acceptor_gain	0.9100
1:152687266:ATG:A	acceptor_gain	0.9000
1:152686183:GGGTA:G	donor_gain	0.8800
1:152687267:T:TA	acceptor_gain	0.8600
1:152686157:G:A	donor_gain	0.8500
1:152686127:G:T	donor_gain	0.8400
1:152686180:GAGGG:G	donor_gain	0.8300
1:152686623:G:GT	donor_gain	0.8200

AlphaMissense

718 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:152687084:T:C	F81L	0.836
1:152687086:C:A	F81L	0.836
1:152687086:C:G	F81L	0.836
1:152686912:A:C	K23N	0.749
1:152686912:A:T	K23N	0.749
1:152686855:G:C	Q4H	0.722
1:152686855:G:T	Q4H	0.722
1:152686858:A:C	Q5H	0.715
1:152686858:A:T	Q5H	0.715
1:152687063:A:C	S74R	0.694
1:152687065:C:A	S74R	0.694
1:152687065:C:G	S74R	0.694
1:152686864:G:C	Q7H	0.676
1:152686864:G:T	Q7H	0.676
1:152686888:G:C	K15N	0.664
1:152686888:G:T	K15N	0.664
1:152686889:T:C	C16R	0.664
1:152686871:T:C	C10R	0.643
1:152686900:G:C	K19N	0.639
1:152686900:G:T	K19N	0.639
1:152686873:C:G	C10W	0.613
1:152687171:T:C	C110R	0.598
1:152686850:T:C	C3R	0.596
1:152686910:A:G	K23E	0.592
1:152686911:A:T	K23I	0.589
1:152687069:C:G	H76D	0.589
1:152687173:C:G	C110W	0.585
1:152687054:T:C	C71R	0.580
1:152686924:G:C	K27N	0.578
1:152686924:G:T	K27N	0.578

dbSNP variants (sampled 300 via entrez): RS1000921925 (1:152687709 A>G), RS1002226025 (1:152686064 C>T), RS1002996541 (1:152685019 T>C,G), RS1003260103 (1:152684881 C>A), RS1005022904 (1:152687273 G>A,T), RS1005726613 (1:152685244 C>T), RS1005769442 (1:152686339 T>C), RS1005822035 (1:152686213 A>T), RS1006022734 (1:152686342 CTG>C), RS1006108023 (1:152687230 G>A,C), RS1006697815 (1:152684245 A>G), RS1006961160 (1:152684428 G>A), RS1008224693 (1:152687689 A>G), RS1008234571 (1:152687465 G>A,C,T), RS1008883051 (1:152687506 A>G)

Disease associations

OMIM: gene MIM:612610 | 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

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
hydroquinone	increases expression	2
Arsenic	affects methylation, decreases expression, increases abundance	2
Sodium Dodecyl Sulfate	increases expression	2
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
sodium arsenate	decreases expression, increases abundance	1
manganese chloride	increases expression	1
CGP 52608	affects binding, increases reaction	1
Resveratrol	affects cotreatment, decreases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Cadmium	decreases expression, increases abundance	1
Endosulfan	increases expression	1
Manganese	increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Tetrachlorodibenzodioxin	increases expression	1
Tretinoin	decreases expression	1
Aflatoxin B1	decreases methylation	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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