PCDH20

Summary

PCDH20 (protocadherin 20, HGNC:14257) is a protein-coding gene on chromosome 13q21.2, encoding Protocadherin-20 (Q8N6Y1). Potential calcium-dependent cell-adhesion protein.

This gene belongs to the protocadherin gene family, a subfamily of the cadherin superfamily. This gene encodes a protein which contains 6 extracellular cadherin domains, a transmembrane domain and a cytoplasmic tail differing from those of the classical cadherins. Although its specific function is undetermined, the cadherin-related neuronal receptor is thought to play a role in the establishment and function of specific cell-cell connections in the brain.

Source: NCBI Gene 64881 — RefSeq curated summary.

At a glance

• GWAS associations: 11
• Clinical variants (ClinVar): 142 total
• MANE Select transcript: NM_022843

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14257
Approved symbol	PCDH20
Name	protocadherin 20
Location	13q21.2
Locus type	gene with protein product
Status	Approved
Aliases	PCDH13, FLJ22218
Ensembl gene	ENSG00000280165
Ensembl biotype	protein_coding
OMIM	614449
Entrez	64881

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000409204

RefSeq mRNA: 1 — MANE Select: NM_022843 NM_022843

CCDS: CCDS9442

Canonical transcript exons

ENST00000409204 — 2 exons

Exon	Start	End
ENSE00003344703	61409685	61413966
ENSE00003978334	61415027	61415849

Expression profiles

Bgee: expression breadth ubiquitous, 119 present calls, max score 78.87.

FANTOM5 (CAGE): breadth broad, TPM avg 1.2682 / max 93.4066, expressed in 388 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
137468	1.2501	387
137469	0.0181	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
superior frontal gyrus	UBERON:0002661	78.87	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.49	gold quality
prefrontal cortex	UBERON:0000451	77.55	gold quality
Ammon’s horn	UBERON:0001954	75.62	gold quality
popliteal artery	UBERON:0002250	75.42	gold quality
tibial artery	UBERON:0007610	75.37	gold quality
calcaneal tendon	UBERON:0003701	74.74	gold quality
Brodmann (1909) area 9	UBERON:0013540	73.20	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	72.73	gold quality
cerebral cortex	UBERON:0000956	72.69	gold quality
anterior cingulate cortex	UBERON:0009835	72.67	gold quality
frontal cortex	UBERON:0001870	72.42	gold quality
lower esophagus muscularis layer	UBERON:0035833	72.38	gold quality
lower esophagus	UBERON:0013473	72.30	gold quality
descending thoracic aorta	UBERON:0002345	72.15	gold quality
islet of Langerhans	UBERON:0000006	71.38	gold quality
smooth muscle tissue	UBERON:0001135	71.32	gold quality
thoracic aorta	UBERON:0001515	71.25	gold quality
ascending aorta	UBERON:0001496	70.54	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	70.02	gold quality
temporal lobe	UBERON:0001871	69.65	gold quality
right atrium auricular region	UBERON:0006631	69.64	gold quality
amygdala	UBERON:0001876	69.53	gold quality
mucosa of transverse colon	UBERON:0004991	69.18	gold quality
caudate nucleus	UBERON:0001873	69.05	gold quality
putamen	UBERON:0001874	68.15	gold quality
nucleus accumbens	UBERON:0001882	67.51	gold quality
hypothalamus	UBERON:0001898	66.90	gold quality
endometrium	UBERON:0001295	66.51	gold quality
primary visual cortex	UBERON:0002436	66.41	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-GEOD-81383	yes	302.55
E-ANND-3	no	0.94

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

170 targeting PCDH20, 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-5011-5P	100.00	83.46	5820
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548N	99.98	71.94	4170
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784

Literature-anchored findings (GeneRIF, showing 7)

• In conclusion, these data here strongly suggested that PCDH20 may act as a candidate tumour suppressor in hepatocellular carcinoma. (PMID:24910204)
• Study shows that PCDH20 expression is downregulated in nasopharyngeal carcinoma cells (NPC) and identified it as a functional tumor suppressor and an important antagonist of Wnt/beta-catenin signaling and EMT, with frequent epigenetic inactivation in NPC. (PMID:25736877)
• Genome-wide association analysis on normal hearing function identifies PCDH20 and SLC28A3 as good candidates for modulatory genes in the auditory system. [meta-analysis] (PMID:26188009)
• low expression of PCDH20 was found to be associated with poor OS in HCC patients; hence, this protein represents a promising potential prognostic biomarker (PMID:27935871)
• Low PCDH20 expression is associated with hypopharyngeal squamous cell carcinoma through the Wnt/beta-catenin signalling pathway. (PMID:31450490)
• Protocadherin 20 promotes ferroptosis by suppressing the expression of Sirtuin 1 and promoting the acetylation of nuclear factor erythroid 2-related factor 2 in hepatocellular carcinoma. (PMID:36641129)
• Protocadherin 20 maintains intestinal barrier function to protect against Crohn’s disease by targeting ATF6. (PMID:37407995)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	pcdh20	ENSDARG00000036424
mus_musculus	Pcdh20	ENSMUSG00000050505
rattus_norvegicus	Pcdh20	ENSRNOG00000013306

Paralogs (33): CDH1 (ENSG00000039068), CDH10 (ENSG00000040731), CDH3 (ENSG00000062038), CDH19 (ENSG00000071991), CDHR2 (ENSG00000074276), CDH17 (ENSG00000079112), CDH7 (ENSG00000081138), PCDH11Y (ENSG00000099715), CDHR5 (ENSG00000099834), CDH20 (ENSG00000101542), PCDH11X (ENSG00000102290), CDH23 (ENSG00000107736), CDH9 (ENSG00000113100), CDH6 (ENSG00000113361), CDH26 (ENSG00000124215), CDHR3 (ENSG00000128536), CDH15 (ENSG00000129910), CDH24 (ENSG00000139880), CDH11 (ENSG00000140937), CDH13 (ENSG00000140945), CDH18 (ENSG00000145526), CDHR1 (ENSG00000148600), CDH22 (ENSG00000149654), CDH8 (ENSG00000150394), CDH12 (ENSG00000154162), PCDH1 (ENSG00000156453), DCHS1 (ENSG00000166341), PCDH7 (ENSG00000169851), CDH2 (ENSG00000170558), CDH4 (ENSG00000179242), CDH5 (ENSG00000179776), PCDH9 (ENSG00000184226), DCHS2 (ENSG00000197410)

Protein

Protein identifiers

Protocadherin-20 — Q8N6Y1 (reviewed: Q8N6Y1)

Alternative names: Protocadherin-13

All UniProt accessions (1): Q8N6Y1

UniProt curated annotations — full annotation on UniProt →

Function. Potential calcium-dependent cell-adhesion protein.

Subcellular location. Cell membrane.

RefSeq proteins (1): NP_073754* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002126	Cadherin-like_dom	Domain
IPR015919	Cadherin-like_sf	Homologous_superfamily
IPR020894	Cadherin_CS	Conserved_site
IPR050174	Protocadherin/Cadherin-CA	Family

Pfam: PF00028

UniProt features (21 total): glycosylation site 8, domain 6, topological domain 2, signal peptide 1, chain 1, sequence variant 1, sequence conflict 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N6Y1-F1	77.99	0.47

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Glycosylation sites (8): 135, 326, 332, 680, 748, 803, 844, 849

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 111 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_DN, GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_DN, chr13q21, TGCACTT_MIR519C_MIR519B_MIR519A, ZHAN_MULTIPLE_MYELOMA_CD1_UP, GOBP_CELL_CELL_ADHESION, TAKEDA_TARGETS_OF_NUP98_HOXA9_FUSION_10D_UP, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_DN, TGTTTAC_MIR30A5P_MIR30C_MIR30D_MIR30B_MIR30E5P, VECCHI_GASTRIC_CANCER_EARLY_DN, OCT1_B, TAKEDA_TARGETS_OF_NUP98_HOXA9_FUSION_16D_UP, ZHAN_MULTIPLE_MYELOMA_CD1_VS_CD2_UP, TGGAAA_NFAT_Q4_01, NUYTTEN_EZH2_TARGETS_DN

GO Biological Process (2): cell adhesion (GO:0007155), homophilic cell-cell adhesion (GO:0007156)

GO Molecular Function (3): RNA binding (GO:0003723), calcium ion binding (GO:0005509), cell adhesion molecule binding (GO:0050839)

GO Cellular Component (2): plasma membrane (GO:0005886), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular process	1
cell-cell adhesion	1
nucleic acid binding	1
metal ion binding	1
protein binding	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

718 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PCDH20	CHODL	Q9H9P2	473
PCDH20	SLC28A3	Q9HAS3	406
PCDH20	BRICD5	Q6PL45	397
PCDH20	EEIG2	Q5T8I3	375
PCDH20	OR4X1	Q8NH49	367
PCDH20	CENPA	P49450	353
PCDH20	JPH3	Q8WXH2	350
PCDH20	TRIOBP	Q9H2D6	345
PCDH20	TAFA4	Q96LR4	328
PCDH20	PCDH9	Q9HC56	323
PCDH20	PCDHB16	Q9NRJ7	321
PCDH20	PAX5	Q02548	315
PCDH20	SULF2	Q8IWU5	311
PCDH20	SCAPER	Q9BY12	302
PCDH20	GRM7	Q14831	290

IntAct

29 interactions, top by confidence:

A	B	Type	Score
MGAT4C	GXYLT2	psi-mi:“MI:0914”(association)	0.530
PRSS37	MANBA	psi-mi:“MI:0914”(association)	0.530
DCDC2B	HSPA8	psi-mi:“MI:0914”(association)	0.530
PCDHGB1	FAM171A2	psi-mi:“MI:0914”(association)	0.530
CMA1	MANBA	psi-mi:“MI:0914”(association)	0.530
PPIAL4G	ACTB	psi-mi:“MI:0914”(association)	0.530
DKKL1	VWA8	psi-mi:“MI:0914”(association)	0.350
PCDHGB1	FAM171A2	psi-mi:“MI:0914”(association)	0.350
SIRT6	HDAC3	psi-mi:“MI:0914”(association)	0.350
PCDH20		psi-mi:“MI:0914”(association)	0.350
FCGR1A	PCDH17	psi-mi:“MI:0914”(association)	0.350
PPIAL4G	PPIAL4D	psi-mi:“MI:0914”(association)	0.350
C2orf48	PCDH7	psi-mi:“MI:0914”(association)	0.350
CEACAM21	MET	psi-mi:“MI:0914”(association)	0.350
VPS35	ILVBL	psi-mi:“MI:0914”(association)	0.350
SPSB4	CCDC85C	psi-mi:“MI:0914”(association)	0.350
DHFR2	MANBA	psi-mi:“MI:0914”(association)	0.350
PCDH20	PCDH17	psi-mi:“MI:0914”(association)	0.350
UCN3	PCDH7	psi-mi:“MI:0914”(association)	0.350
LAG3	PCDH7	psi-mi:“MI:0914”(association)	0.350
DCANP1	IDE	psi-mi:“MI:0914”(association)	0.350
PCDH20	B4GALT5	psi-mi:“MI:0914”(association)	0.350
PCDH20	MAP3K7	psi-mi:“MI:0914”(association)	0.350
PCDH20	CAPN5	psi-mi:“MI:0914”(association)	0.350

BioGRID (103): PCDH20 (Affinity Capture-MS), PCDH20 (Affinity Capture-MS), PCDH20 (Affinity Capture-MS), PCDH20 (Affinity Capture-MS), PCDH20 (Affinity Capture-MS), PCDH20 (Affinity Capture-MS), CCDC51 (Affinity Capture-MS), SUPT7L (Affinity Capture-MS), LTBP1 (Affinity Capture-MS), PCDH17 (Affinity Capture-MS), CBX6 (Affinity Capture-MS), TAF5L (Affinity Capture-MS), MAP3K7 (Affinity Capture-MS), CELSR3 (Affinity Capture-MS), TAF9B (Affinity Capture-MS)

ESM2 similar proteins: A7MB46, F8W3X3, O14917, O35902, O54800, O97799, P05622, P16234, P20786, P26618, P26619, P32926, P35546, P55286, P55289, P79749, P97291, Q05030, Q08DJ5, Q13634, Q14126, Q28889, Q5RJH3, Q68SP4, Q6KEQ9, Q6W3B0, Q6WXV7, Q6WYY1, Q6X862, Q71M42, Q7TMD7, Q7TSF0, Q7YRU7, Q80TF3, Q86SJ6, Q8AXC6, Q8AXC7, Q8BIZ0, Q8N6Y1, Q8TAB3

Diamond homologs: B2KI42, B4USZ0, F1PAA9, F1QSQ0, H2EQR6, O18926, O55075, O93319, P08641, P09803, P10287, P12830, P19534, P19535, P22223, P24503, P30944, P33145, P33146, P33148, P33150, P33152, P33545, P39038, P55280, P55283, P55285, P55288, P55290, P55291, P55292, P55849, P55850, P58365, P59862, P97326, Q01107, Q02487, Q08554, Q08DJ5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	131
Likely benign	8
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

599 predictions. Top by Δscore:

Variant	Effect	Δscore
13:61413651:C:CA	donor_gain	0.9900
13:61413940:C:CT	acceptor_gain	0.9900
13:61413940:C:T	acceptor_gain	0.9900
13:61413942:C:CT	acceptor_gain	0.9800
13:61413943:G:T	acceptor_gain	0.9800
13:61414520:T:TA	donor_gain	0.9800
13:61414892:C:CA	donor_gain	0.9800
13:61415020:CCCTT:C	donor_loss	0.9800
13:61415021:CCTTA:C	donor_loss	0.9800
13:61415022:CTTA:C	donor_loss	0.9800
13:61415024:T:TG	donor_loss	0.9800
13:61415026:C:A	donor_loss	0.9800
13:61415026:CCGG:C	donor_gain	0.9800
13:61415025:A:AC	donor_gain	0.9700
13:61415026:C:CC	donor_gain	0.9700
13:61415035:T:TA	donor_gain	0.9700
13:61413560:A:T	acceptor_gain	0.9600
13:61415042:G:C	donor_gain	0.9600
13:61413973:T:C	acceptor_gain	0.9500
13:61413563:A:T	acceptor_gain	0.9300
13:61414917:C:A	donor_gain	0.9300
13:61413973:T:TC	acceptor_gain	0.9200
13:61414516:CA:C	donor_gain	0.9200
13:61413967:C:CC	acceptor_gain	0.8900
13:61414916:T:TA	donor_gain	0.8900
13:61415495:C:CC	acceptor_gain	0.8900
13:61413965:TG:T	acceptor_gain	0.8800
13:61415018:AAC:A	donor_gain	0.8800
13:61415493:TG:T	acceptor_gain	0.8700
13:61413764:TCAG:T	donor_gain	0.8400

AlphaMissense

6215 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
13:61411694:C:A	G802V	1.000
13:61411694:C:T	G802D	1.000
13:61411781:T:G	D773A	1.000
13:61411782:C:G	D773H	1.000
13:61411880:G:T	P740H	1.000
13:61411577:A:G	L841P	0.999
13:61411622:T:A	D826V	0.999
13:61411622:T:G	D826A	0.999
13:61411623:C:G	D826H	0.999
13:61411688:A:C	I804S	0.999
13:61411688:A:T	I804N	0.999
13:61411695:C:A	G802C	0.999
13:61411695:C:G	G802R	0.999
13:61411715:A:G	F795S	0.999
13:61411755:A:C	Y782D	0.999
13:61411767:C:G	A778P	0.999
13:61411780:G:C	D773E	0.999
13:61411780:G:T	D773E	0.999
13:61411781:T:A	D773V	0.999
13:61411781:T:C	D773G	0.999
13:61411787:T:A	D771V	0.999
13:61411788:C:G	D771H	0.999
13:61411793:G:T	A769D	0.999
13:61411799:A:T	V767D	0.999
13:61411889:T:A	D737V	0.999
13:61411889:T:G	D737A	0.999
13:61411890:C:G	D737H	0.999
13:61411891:A:C	N736K	0.999
13:61411891:A:T	N736K	0.999
13:61411892:T:A	N736I	0.999

dbSNP variants (sampled 300 via entrez): RS1000153815 (13:61414197 T>A), RS1000541028 (13:61412807 A>G), RS1002199737 (13:61417814 C>A,T), RS1002461188 (13:61412733 T>C), RS1002535293 (13:61416359 C>G), RS1002591045 (13:61409578 T>C), RS1002754711 (13:61409684 A>G), RS1003133346 (13:61409409 GTTAA>G), RS1004212906 (13:61415056 T>C), RS1004497085 (13:61414885 C>T), RS1005324443 (13:61417848 A>G,T), RS1005528583 (13:61411105 G>A), RS1006141513 (13:61417626 C>A,T), RS1006445568 (13:61411344 G>A), RS1006558536 (13:61410074 A>G)

Disease associations

OMIM: gene MIM:614449 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST000785_23	Longevity	1.000000e-06
GCST001226_1	Asthma	8.000000e-06
GCST001414_14	Phospholipid levels (plasma)	2.000000e-08
GCST001757_3	Schizophrenia	3.000000e-06
GCST002701_41	Verbal declarative memory	1.000000e-06
GCST002701_5	Verbal declarative memory	1.000000e-06
GCST003443_2	Response to carboplatin and paclitaxel in ovarian cancer (Caspase 3/7 EC50)	8.000000e-07
GCST007325_2	General risk tolerance (MTAG)	5.000000e-09
GCST009616_2	HDL cholesterol levels x thiazide or thiazide-like diuretics use interaction	4.000000e-07
GCST010566_9	Benign childhood epilepsy with centro-temporal spikes	5.000000e-06
GCST010988_470	Adult body size	7.000000e-09

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004874	memory performance
EFO:0006806	paragraph delayed recall measurement
EFO:0006952	cytotoxicity measurement
EFO:0008579	risk-taking behaviour
EFO:0004612	high density lipoprotein cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	9
mercuric bromide	increases expression, affects cotreatment	2
entinostat	increases expression, affects cotreatment	2
Panobinostat	increases expression, affects cotreatment	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tretinoin	increases expression	2
methylmercuric chloride	decreases expression	1
trichostatin A	increases expression	1
beta-lapachone	decreases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
2,2’,4,4’,5-brominated diphenyl ether	decreases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Temozolomide	increases expression	1
Zoledronic Acid	decreases expression	1
Arsenic Trioxide	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Boron Compounds	decreases expression	1
Cytarabine	decreases expression	1
Doxorubicin	decreases expression	1
Nickel	decreases expression	1
Niclosamide	decreases expression	1
Rotenone	decreases expression	1
Dronabinol	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Triclosan	decreases expression	1
8-Bromo Cyclic Adenosine Monophosphate	decreases expression	1
1-Methyl-4-phenylpyridinium	decreases expression	1
Cyclosporine	decreases expression	1

Clinical trials (associated diseases)

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