CNFN

Summary

CNFN (cornifelin, HGNC:30183) is a protein-coding gene on chromosome 19q13.2, encoding Cornifelin (Q9BYD5). Part of the insoluble cornified cell envelope (CE) of stratified squamous epithelia.

Predicted to be involved in keratinization. Located in cornified envelope.

Source: NCBI Gene 84518 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 16 total
• MANE Select transcript: NM_032488

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30183
Approved symbol	CNFN
Name	cornifelin
Location	19q13.2
Locus type	gene with protein product
Status	Approved
Aliases	PLAC8L2
Ensembl gene	ENSG00000105427
Ensembl biotype	protein_coding
OMIM	611764
Entrez	84518

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000222032, ENST00000597255

RefSeq mRNA: 1 — MANE Select: NM_032488 NM_032488

CCDS: CCDS12606

Canonical transcript exons

ENST00000222032 — 4 exons

Exon	Start	End
ENSE00000709266	42388926	42389039
ENSE00000709268	42387340	42387476
ENSE00000897489	42390240	42390297
ENSE00000952327	42387019	42387242

Expression profiles

Bgee: expression breadth ubiquitous, 177 present calls, max score 99.95.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 10.8064 / max 3425.8052, expressed in 141 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
181185	10.7972	141
181184	0.0091	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	99.95	gold quality
pharyngeal mucosa	UBERON:0000355	99.70	gold quality
gingiva	UBERON:0001828	99.59	gold quality
gingival epithelium	UBERON:0001949	99.54	gold quality
upper arm skin	UBERON:0004263	99.41	gold quality
buccal mucosa cell	CL:0002336	99.34	gold quality
esophagus mucosa	UBERON:0002469	99.30	gold quality
esophagus squamous epithelium	UBERON:0006920	99.23	gold quality
oral cavity	UBERON:0000167	99.22	gold quality
skin of abdomen	UBERON:0001416	98.94	gold quality
body of tongue	UBERON:0011876	98.68	gold quality
skin of leg	UBERON:0001511	98.63	gold quality
zone of skin	UBERON:0000014	98.36	gold quality
mammalian vulva	UBERON:0000997	98.02	gold quality
penis	UBERON:0000989	97.46	gold quality
upper leg skin	UBERON:0004262	96.47	gold quality
tongue	UBERON:0001723	95.70	gold quality
amniotic fluid	UBERON:0000173	92.63	gold quality
superior surface of tongue	UBERON:0007371	92.12	gold quality
vagina	UBERON:0000996	90.80	gold quality
skin of hip	UBERON:0001554	90.67	gold quality
nipple	UBERON:0002030	89.74	gold quality
esophagus	UBERON:0001043	85.98	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.27	gold quality
tonsil	UBERON:0002372	85.09	gold quality
mouth mucosa	UBERON:0003729	84.14	gold quality
minor salivary gland	UBERON:0001830	81.89	gold quality
pancreatic ductal cell	CL:0002079	80.32	silver quality
putamen	UBERON:0001874	80.21	gold quality
caudate nucleus	UBERON:0001873	78.89	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-HCAD-1	yes	23606.48
E-ANND-3	yes	20.05
E-MTAB-6142	no	29.13

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

16 targeting CNFN, 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-6748-5P	100.00	65.81	1057
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-6772-5P	99.94	67.01	577
HSA-MIR-4493	99.90	66.48	977
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-329-5P	99.27	68.11	1597
HSA-MIR-5701	98.97	69.54	1502
HSA-MIR-4456	97.50	64.88	1678
HSA-MIR-4296	96.35	63.55	1233
HSA-MIR-4265	96.18	64.68	557
HSA-MIR-4322	96.18	64.85	539
HSA-MIR-6796-5P	95.37	66.08	1120
HSA-MIR-3677-5P	93.16	64.62	393

Literature-anchored findings (GeneRIF, showing 1)

• Entorhinal cortex epigenome-wide association study highlights four novel loci showing differential methylation in Alzheimer’s disease. (PMID:37149695)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	cnfn	ENSDARG00000041115
mus_musculus	Cnfn	ENSMUSG00000063651
rattus_norvegicus	Cnfn	ENSRNOG00000020530

Paralogs (2): PLAC8 (ENSG00000145287), PLAC8L1 (ENSG00000173261)

Protein

Protein identifiers

Cornifelin — Q9BYD5 (reviewed: Q9BYD5)

All UniProt accessions (1): Q9BYD5

UniProt curated annotations — full annotation on UniProt →

Function. Part of the insoluble cornified cell envelope (CE) of stratified squamous epithelia.

Subunit / interactions. Directly or indirectly cross-linked to CE proteins loricin and involucrin (IVL).

Subcellular location. Cytoplasm.

Tissue specificity. Abundant in the cervix. Moderately abundant in the uterus and fetal skin. Expression is markedly increased in psoriatic skin (18.5 fold increase in comparison with normal skin) and its overexpression alters the protein composition of cornified cell envelope (CE), but does not affect keratinocyte differentiation. Expressed in the granular cell layer of epidermis in uninvolved psoriatic skin and in the psoriatic lesions it is found in the upper-spinous layer. Increased expression also seen in atopic dermatitis (14.3 fold increase in comparison with normal skin) and mycosis fungoides (4.6 fold increase in comparison with normal skin) and in both conditions expressed in the granular cell layer of epidermis.

Similarity. Belongs to the cornifelin family.

RefSeq proteins (1): NP_115877* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006461	PLAC_motif_containing	Family

Pfam: PF04749

UniProt features (1 total): chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BYD5-F1	85.22	0.53

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 44 (showing top): GOBP_EPITHELIUM_DEVELOPMENT, GCANCTGNY_MYOD_Q6, SP3_Q3, GOBP_EPIDERMAL_CELL_DIFFERENTIATION, KOYAMA_SEMA3B_TARGETS_UP, OCT1_06, GOBP_EPIDERMIS_DEVELOPMENT, GOBP_KERATINIZATION, GOBP_SKIN_DEVELOPMENT, GOCC_CORNIFIED_ENVELOPE, DODD_NASOPHARYNGEAL_CARCINOMA_DN, MIKKELSEN_MEF_HCP_WITH_H3K27ME3, BRUINS_UVC_RESPONSE_VIA_TP53_GROUP_D, SNACANNNYSYAGA_UNKNOWN, GOBP_KERATINOCYTE_DIFFERENTIATION

GO Biological Process (1): keratinization (GO:0031424)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (2): cornified envelope (GO:0001533), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
keratinocyte differentiation	1
multicellular organismal process	1
binding	1
plasma membrane	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1751 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CNFN	IVL	P07476	823
CNFN	LORICRIN	P23490	785
CNFN	KRTDAP	P60985	668
CNFN	TGM3	Q08188	604
CNFN	LCE3D	Q9BYE3	583
CNFN	ZNF574	Q6ZN55	549
CNFN	SPRR2A	P35326	544
CNFN	SPRR2E	P22531	542
CNFN	SPRR2G	Q9BYE4	512
CNFN	KRT80	Q6KB66	503
CNFN	SPRR3	Q9UBC9	498
CNFN	TMEM145	Q8NBT3	480
CNFN	PAFAH1B3	Q15102	463
CNFN	LCN2	P30150	462
CNFN	ACTG2	P12718	451

IntAct

49 interactions, top by confidence:

A	B	Type	Score
FAM222B	CNFN	psi-mi:“MI:0915”(physical association)	0.560
HR	CNFN	psi-mi:“MI:0915”(physical association)	0.560
HOXA1	CNFN	psi-mi:“MI:0915”(physical association)	0.560
CNFN	TCF7L2	psi-mi:“MI:0915”(physical association)	0.560
CNFN	SLC12A4	psi-mi:“MI:0915”(physical association)	0.560
CNFN	ZNF581	psi-mi:“MI:0915”(physical association)	0.560
VGLL3	CNFN	psi-mi:“MI:0915”(physical association)	0.560
ZNF414	CNFN	psi-mi:“MI:0915”(physical association)	0.560
CCDC120	CNFN	psi-mi:“MI:0915”(physical association)	0.560
CREB5	CNFN	psi-mi:“MI:0915”(physical association)	0.560
TFAP2D	CNFN	psi-mi:“MI:0915”(physical association)	0.560
EVX2	CNFN	psi-mi:“MI:0915”(physical association)	0.560
KPRP	CNFN	psi-mi:“MI:0915”(physical association)	0.560
TLE5	CNFN	psi-mi:“MI:0915”(physical association)	0.560
HOXB5	CNFN	psi-mi:“MI:0915”(physical association)	0.560
WDR25	CNFN	psi-mi:“MI:0915”(physical association)	0.560
WDR25	CNFN	psi-mi:“MI:0915”(physical association)	0.000
CREB5	CNFN	psi-mi:“MI:0915”(physical association)	0.000
TFAP2D	CNFN	psi-mi:“MI:0915”(physical association)	0.000
EVX2	CNFN	psi-mi:“MI:0915”(physical association)	0.000
KPRP	CNFN	psi-mi:“MI:0915”(physical association)	0.000
TLE5	CNFN	psi-mi:“MI:0915”(physical association)	0.000
FAM222B	CNFN	psi-mi:“MI:0915”(physical association)	0.000
HR	CNFN	psi-mi:“MI:0915”(physical association)	0.000
HOXA1	CNFN	psi-mi:“MI:0915”(physical association)	0.000
TCF7L2	CNFN	psi-mi:“MI:0915”(physical association)	0.000
SLC12A4	CNFN	psi-mi:“MI:0915”(physical association)	0.000
ZNF581	CNFN	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (18): CNFN (Two-hybrid), CNFN (Two-hybrid), HOXA1 (Two-hybrid), HOXB5 (Two-hybrid), SLC12A4 (Two-hybrid), ZNF414 (Two-hybrid), CREB5 (Two-hybrid), CCDC120 (Two-hybrid), TCF7L2 (Two-hybrid), HR (Two-hybrid), ZNF581 (Two-hybrid), FAM222B (Two-hybrid), EVX2 (Two-hybrid), WDR25 (Two-hybrid), KPRP (Two-hybrid)

ESM2 similar proteins: A0A1B0GVX0, A2ADU8, A2ADU9, A2Y075, A6QP72, O82232, P34655, P55017, P55018, P56508, P59158, P68178, P68179, Q0DKW8, Q0VBW2, Q22701, Q3ZCB2, Q53GD3, Q54RZ2, Q5REK4, Q5RJI2, Q5TYP8, Q66I68, Q6DK93, Q6DK99, Q6E1M8, Q6E213, Q6GMG8, Q6GZQ0, Q6NUC1, Q6P828, Q6PCW6, Q6ZPD8, Q8H5T6, Q8NG11, Q8QZY6, Q8S5M8, Q91VA1, Q9ARD5, Q9BYD5

Diamond homologs: A1L4L8, Q08EJ0, Q0VBW2, Q3ZCB2, Q5REK4, Q66I68, Q6DK93, Q6DK99, Q6NUC1, Q6PCW6, Q9BYD5, Q9JI48, Q9NZF1, D9HP27, Q9M9A5, D9HP19, D9HP23, D9HP26, P0CW97, Q9LQU2, Q9LQU4, D9HP25, Q9LS43, B4FF80, B6TYV8, B6TZ45, D9HP20, P0CW98, Q8S8T8, Q9LS44, Q9LS45, Q9M815, Q9SX24, Q9SX26

SIGNOR signaling

0 interactions.

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	13
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

595 predictions. Top by Δscore:

Variant	Effect	Δscore
19:42387239:AGCCC:A	acceptor_loss	1.0000
19:42387240:GCCCT:G	acceptor_loss	1.0000
19:42387241:CC:C	acceptor_gain	1.0000
19:42387242:CC:C	acceptor_gain	1.0000
19:42387242:CCTAG:C	acceptor_loss	1.0000
19:42387243:C:CC	acceptor_gain	1.0000
19:42387244:T:G	acceptor_loss	1.0000
19:42388924:A:AC	donor_gain	1.0000
19:42388925:C:CC	donor_gain	1.0000
19:42388925:CAGA:C	donor_gain	1.0000
19:42389035:CATAG:C	acceptor_gain	1.0000
19:42389037:TAG:T	acceptor_gain	1.0000
19:42389040:C:CC	acceptor_gain	1.0000
19:42390236:CTACC:C	donor_loss	1.0000
19:42390237:TA:T	donor_loss	1.0000
19:42390238:AC:A	donor_loss	1.0000
19:42387238:GAGCC:G	acceptor_gain	0.9900
19:42387239:AGCC:A	acceptor_gain	0.9900
19:42387240:GCC:G	acceptor_gain	0.9900
19:42387241:CCC:C	acceptor_gain	0.9900
19:42387335:CGCA:C	donor_loss	0.9900
19:42387336:GCAC:G	donor_loss	0.9900
19:42387337:CA:C	donor_loss	0.9900
19:42387338:A:AT	donor_loss	0.9900
19:42387339:C:CG	donor_loss	0.9900
19:42387583:A:T	acceptor_gain	0.9900
19:42388920:AC:A	donor_loss	0.9900
19:42388921:CTCA:C	donor_loss	0.9900
19:42388922:T:TG	donor_loss	0.9900
19:42388924:A:AT	donor_loss	0.9900

AlphaMissense

729 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:42388966:C:A	W24C	0.997
19:42388966:C:G	W24C	0.997
19:42387344:A:G	I82T	0.994
19:42387175:C:G	R106P	0.993
19:42387226:T:A	D89V	0.992
19:42387353:C:G	R79P	0.991
19:42387372:G:T	R73S	0.991
19:42388968:A:G	W24R	0.991
19:42388968:A:T	W24R	0.991
19:42387359:C:G	R77P	0.990
19:42387467:C:T	G41D	0.990
19:42387226:T:G	D89A	0.989
19:42387344:A:C	I82S	0.988
19:42387169:A:G	L108P	0.987
19:42387179:C:G	A105P	0.987
19:42387206:A:G	C96R	0.987
19:42387227:C:G	D89H	0.987
19:42387183:C:A	Q103H	0.985
19:42387183:C:G	Q103H	0.985
19:42387371:C:G	R73P	0.984
19:42387197:A:G	C99R	0.983
19:42387224:A:G	W90R	0.982
19:42387224:A:T	W90R	0.982
19:42387360:G:C	R77G	0.982
19:42387468:C:G	G41R	0.982
19:42387172:T:A	E107V	0.981
19:42387225:G:C	D89E	0.981
19:42387225:G:T	D89E	0.981
19:42387242:C:G	G84R	0.980
19:42387344:A:T	I82N	0.980

dbSNP variants (sampled 300 via entrez): RS1001460275 (19:42389342 G>A,C,T), RS1001939798 (19:42387675 T>C), RS1001956793 (19:42392163 A>G), RS1002347447 (19:42388240 C>A), RS1002535368 (19:42389344 C>T), RS1003013405 (19:42390862 C>G,T), RS1003132554 (19:42390676 G>C,T), RS1003997612 (19:42389666 G>A,T), RS1004619950 (19:42389322 G>A), RS1004694982 (19:42389003 G>A), RS1005293678 (19:42391917 C>T), RS1006294828 (19:42390647 G>A), RS1006338426 (19:42390733 T>A), RS1006362959 (19:42390977 G>A), RS1006368462 (19:42390330 G>A)

Disease associations

OMIM: gene MIM:611764 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

37 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression, increases methylation	4
Particulate Matter	decreases expression, increases abundance, increases expression	3
mercuric bromide	decreases expression, affects cotreatment	2
Air Pollutants	decreases expression, increases abundance, increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tetrachlorodibenzodioxin	increases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
urushiol	increases expression	1
methylmercuric chloride	decreases expression	1
sodium arsenate	decreases expression, increases abundance	1
sulforaphane	decreases expression	1
hydroquinone	increases expression	1
CGP 52608	affects binding, increases reaction	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
nutlin 3	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	affects cotreatment, increases expression	1
(+)-JQ1 compound	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Temozolomide	increases expression	1
Arsenic	decreases expression, increases abundance	1
Atrazine	increases expression	1
Benzalkonium Compounds	increases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Camptothecin	increases expression	1
Cisplatin	affects cotreatment, increases expression	1
Dactinomycin	affects cotreatment, increases expression	1
Diazinon	increases methylation	1
Nickel	increases expression	1

Clinical trials (associated diseases)

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