PCDH12 (protocadherin 12)

Gene

• Entrez ID: 51294
• Gene name: Protocadherin 12
• Gene symbol: PCDH12
• Synonyms (NCBI Gene): DMJDS1, VE-cadherin-2, VECAD2
• Chromosome: 5
• Chromosome location: 5q31.3
• Summary: This gene belongs to the protocadherin gene family, a subfamily of the cadherin superfamily. The encoded protein consists of an extracellular domain containing 6 cadherin repeats, a transmembrane domain and a cytoplasmic tail that differs from those of th

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs370283860	G>A	Pathogenic	Coding sequence variant, stop gained
rs375346212	G>A,T	Pathogenic	Coding sequence variant, synonymous variant, stop gained
rs531630376	C>A	Likely-pathogenic	Coding sequence variant, stop gained
rs776111123	G>-,GG	Pathogenic	Coding sequence variant, frameshift variant
rs1199523766	C>-	Pathogenic	Frameshift variant, coding sequence variant
rs1596646165	AG>-	Pathogenic	Coding sequence variant, frameshift variant
rs1596646372	C>-	Pathogenic	Coding sequence variant, frameshift variant
rs1596646556	G>A	Pathogenic	Coding sequence variant, stop gained

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT1216729	hsa-miR-4432	CLIP-seq
MIRT1216730	hsa-miR-548u	CLIP-seq
MIRT1216731	hsa-miR-558	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0005509	Function	Calcium ion binding	IEA
GO:0005576	Component	Extracellular region	IEA
GO:0005886	Component	Plasma membrane	IBA
GO:0005886	Component	Plasma membrane	IEA
GO:0005886	Component	Plasma membrane	TAS	10380929, 10716726
GO:0005911	Component	Cell-cell junction	IEA
GO:0005977	Process	Glycogen metabolic process	IEA
GO:0007155	Process	Cell adhesion	IEA
GO:0007156	Process	Homophilic cell adhesion via plasma membrane adhesion molecules	IEA
GO:0007156	Process	Homophilic cell adhesion via plasma membrane adhesion molecules	IEA
GO:0008038	Process	Neuron recognition	TAS	10380929
GO:0016020	Component	Membrane	IEA
GO:0016339	Process	Calcium-dependent cell-cell adhesion via plasma membrane cell adhesion molecules	IBA
GO:0016339	Process	Calcium-dependent cell-cell adhesion via plasma membrane cell adhesion molecules	IEA
GO:0050839	Function	Cell adhesion molecule binding	IBA
GO:0060711	Process	Labyrinthine layer development	IEA
GO:0070062	Component	Extracellular exosome	HDA	23533145
GO:0070161	Component	Anchoring junction	IEA

Other IDs

• MIM: 605622
• HGNC: 8657
• e!Ensembl: ENSG00000113555

Protein

• UniProt ID: Q9NPG4
• Protein name: Protocadherin-12 (Vascular cadherin-2) (Vascular endothelial cadherin-2) (VE-cad-2) (VE-cadherin-2) [Cleaved into: Protocadherin-12, secreted form]
• Protein function: Cellular adhesion molecule that may play an important role in cell-cell interactions at interendothelial junctions (By similarity). Acts as a regulator of cell migration, probably via increasing cell-cell adhesion (PubMed:21402705). Promotes hom
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF08266	Cadherin_2	31 → 114	Cadherin-like	Domain
  PF00028	Cadherin	140 → 235	Cadherin domain	Domain
  PF00028	Cadherin	249 → 343	Cadherin domain	Domain
  PF00028	Cadherin	360 → 451	Cadherin domain	Domain
  PF00028	Cadherin	465 → 556	Cadherin domain	Domain
  PF00028	Cadherin	612 → 694	Cadherin domain	Domain

• Tissue specificity: TISSUE SPECIFICITY: Expressed in highly vascularized tissues including the heart and placenta, but most tissues contain a low level of expression (PubMed:11063261). Prominent expression in the spleen (PubMed:11063261). Present in villous and extravillous
• Sequence:

  MMQLLQLLLGLLGPGGYLFLLGDCQEVTTLTVKYQVSEEVPSGTVIGKLSQELGREERRR
  QAGAAFQVLQLPQALPIQVDSEEGLLSTGRRLDREQLCRQWDPCLVSFDVLATGDLALIH
  VEIQVLDINDHQPRFPKGEQELEISESASLRTRIPLDRALDPDTGPNTLHTYTLSPSEHF
  ALDVIVGPDETKHAELIVVKELDREIHSFFDLVLTAYDNGNPPKSGTSLVKVNVLDSNDN
  SPAFAESSLALEIQEDAAPGTLLIKLTATDPDQGPNGEVEFFLSKHMPPEVLDTFSIDAK
  TGQVILRRPLDYEKNPAYEVDVQARDLGPNPIPAHCKVLIKVLDVNDNIPSIHVTWASQP
  SLVSEALPKDSFIALVMADDLDSGHNGLVHCWLSQELGHFRLKRTNGNTYMLLTNATLDR
  EQWPKYTLTLLAQDQGLQPLSAKKQLSIQISDINDNAPVFEKSRYEVSTRENNLPSLHLI
  TIKAHDADLGINGKVSYRIQDSPVAHLVAIDSNTGEVTAQRSLNYEEMAGFEFQVIAEDS
  GQPMLASSVSVWVSLLDANDNAPEVVQPVLSDGKASLSVLVNASTGHLLVPIETPNGLGP
  AGTDTPPLATHSSRPFLLTTIVARDADSGANGEPLYSIRSGNEAHLFILNPHTGQLFVNV
  TNASSLIGSEWELEIVVEDQGSPPLQTRALLRVMFVTSVDHLRDSARKPGALSMSMLTVI
  CLAVLLGIFGLILALFMSICRTEKKDNRAYNCREAESTYRQQPKRPQKHIQKADIHLVPV
  LRGQAGEPCEVGQSHKDVDKEAMMEAGWDPCLQAPFHLTPTLYRTLRNQGNQGAPAESRE
  VLQDTVNLLFNHPRQRNASRENLNLPEPQPATGQPRSRPLKVAGSPTGRLAGDQGSEEAP
  QRPPASSATLRRQRHLNGKVSPEKESGPRQILRSLVRLSVAAFAERNPVEELTVDSPPVQ
  QISQLLSLLHQGQFQPKPNHRGNKYLAKPGGSRSAIPDTDGPSARAGGQTDPEQEEGPLD
  PEEDLSVKQLLEEELSSLLDPSTGLALDRLSAPDPAWMARLSLPLTTNYRDNVISPDAAA
  TEEPRTFQTFGKAEAPELSPTGTRLASTFVSEMSSLLEMLLEQRSSMPVEAASEALRRLS
  VCGRTLSLDLATSAASGMKVQGDPGGKTGTEGKSRGSSSSSRCL

• Sequence length: 1184

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Abnormal facial shape	Likely pathogenic	rs531630376	RCV000758009	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Cerebellar ataxia	Likely pathogenic	rs531630376	RCV000758009	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Coats disease	Likely pathogenic	rs531630376	RCV000758009	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Diencephalic-mesencephalic junction dysplasia	Pathogenic; Likely pathogenic	rs1175979418, rs148884293, rs1596646372, rs1199523766	RCV001842235 RCV004018303 RCV003312998 RCV003312999	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Diencephalic-mesencephalic junction dysplasia syndrome 1	Likely pathogenic; Pathogenic	rs1753211537, rs2126927387, rs1048025807, rs1175979418, rs1389877870, rs764897668, rs2126931148, rs765136839, rs2532556080, rs375346212, rs370283860, rs1596646372, rs776111123	RCV001332140 RCV001376160 RCV001784803 RCV002468643 RCV001843792 RCV005397204 RCV002226903 RCV002468758 RCV003493239 RCV000509062 RCV002470971 RCV000855436 RCV003141929	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Disorder of development or morphogenesis	Likely pathogenic	rs148884293	RCV005626877	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Dystonic disorder	Likely pathogenic	rs531630376	RCV000758009	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Adrenocortical carcinoma, hereditary	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cervical cancer	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Clear cell carcinoma of kidney	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DIENCEPHALIC MESENCEPHALIC JUNCTION DYSPLASIA	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
EXUDATIVE RETINOPATHY	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gastric cancer	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hepatocellular carcinoma	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Marshall syndrome	Conflicting classifications of pathogenicity	ClinVar Disgenet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Neurodevelopmental disorder	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NEURODEVELOPMENTAL DISORDERS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian cancer	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian serous cystadenocarcinoma	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PCDH12-related disorder	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine corpus endometrial carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Aicardi Goutieres syndrome	Aicardi goutieres syndrome	Pubtator	27164683	Associate	★☆☆☆☆ Found in Text Mining only
Athetoid cerebral palsy	Athetoid cerebral palsy	BEFREE	29556033		★☆☆☆☆ Found in Text Mining only
Bipolar Disorder	Bipolar Disorder	GWASCAT_DG	29064472		★☆☆☆☆ Found in Text Mining only
Blood Coagulation Disorders	Blood coagulation disorder	Pubtator	35005846	Associate	★☆☆☆☆ Found in Text Mining only
Blood Platelet Disorders	Platelet disorder	Pubtator	35005846	Associate	★☆☆☆☆ Found in Text Mining only
Brain Stem Neoplasms	Brain stem neoplasms	Pubtator	30178464	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Renal Cell	Renal cell carcinoma	Pubtator	31948514	Associate	★☆☆☆☆ Found in Text Mining only
Congenital microcephaly	Congenital Microcephaly	BEFREE	27164683		★☆☆☆☆ Found in Text Mining only
Developmental Disabilities	Development Disorder	BEFREE	27164683		★☆☆☆☆ Found in Text Mining only
Developmental Disabilities	Developmental disability	Pubtator	27164683	Associate	★☆☆☆☆ Found in Text Mining only
Epilepsy	Epilepsy	GENOMICS_ENGLAND_DG	18477666, 27164683, 29556033, 30459466		★☆☆☆☆ Found in Text Mining only
Epilepsy	Epilepsy	BEFREE	29556033		★☆☆☆☆ Found in Text Mining only
Exudative retinopathy	Exudative retinopathy	BEFREE	30459466		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Exudative retinopathy	Exudative retinopathy	CLINVAR_DG	30459466		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Fahr's disease	Fahr's disease	Pubtator	30178464	Associate	★☆☆☆☆ Found in Text Mining only
Generalized myoclonic seizures	Myoclonic Seizures	HPO_DG			★☆☆☆☆ Found in Text Mining only
Global developmental delay	Developmental Delay	HPO_DG			★☆☆☆☆ Found in Text Mining only
Heart Diseases	Heart disease	Pubtator	35005846	Associate	★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Mental retardation	GENOMICS_ENGLAND_DG	18477666, 27164683, 29556033, 30459466		★☆☆☆☆ Found in Text Mining only
Microcephaly	Microcephaly	GENOMICS_ENGLAND_DG	18477666, 27164683, 29556033, 30459466		★☆☆☆☆ Found in Text Mining only
Microcephaly	Microcephaly	BEFREE	27164683		★☆☆☆☆ Found in Text Mining only
Microcephaly	Microcephaly	Pubtator	27164683, 30178464	Associate	★☆☆☆☆ Found in Text Mining only
MICROCEPHALY, SEIZURES, SPASTICITY, AND BRAIN CALCIFICATIONS	MICROCEPHALY, SEIZURES, SPASTICITY, AND BRAIN CALCIFICATIONS	GENOMICS_ENGLAND_DG	18477666, 28804758		★☆☆☆☆ Found in Text Mining only
MICROCEPHALY, SEIZURES, SPASTICITY, AND BRAIN CALCIFICATIONS	MICROCEPHALY, SEIZURES, SPASTICITY, AND BRAIN CALCIFICATIONS	UNIPROT_DG	27164683, 28804758		★☆☆☆☆ Found in Text Mining only
MICROCEPHALY, SEIZURES, SPASTICITY, AND BRAIN CALCIFICATIONS	MICROCEPHALY, SEIZURES, SPASTICITY, AND BRAIN CALCIFICATIONS	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
Schizoaffective Disorder	Schizoaffective Disorder	GWASCAT_DG	29064472		★☆☆☆☆ Found in Text Mining only
Schizophrenia	Schizophrenia	GWASCAT_DG	29064472		★☆☆☆☆ Found in Text Mining only
Spastic Quadriplegia	Spastic Quadriplegia	HPO_DG			★☆☆☆☆ Found in Text Mining only