Seroatlas · Human Serome Atlas

PCDHGA4

Protocadherin gamma-A4

Also known as: PCDG4_HUMAN, PCDH-GAMMA-A4

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession: Q9Y5G9
Gene: PCDHGA4
Ensembl: ENSG00000262576
Chromosome: 5
Canonical length: 962 aa
Protein class: Predicted membrane proteins
Subcellular location: Nucleoplasm,Vesicles,Plasma membrane,Cytosol

OverviewNCBI Gene

This gene is a member of the protocadherin gamma gene cluster, one of three related clusters tandemly linked on chromosome five. These gene clusters have an immunoglobulin-like organization, suggesting that a novel mechanism may be involved in their regulation and expression. The gamma gene cluster includes 22 genes divided into 3 subfamilies. Subfamily A contains 12 genes, subfamily B contains 7 genes and 2 pseudogenes, and the more distantly related subfamily C contains 3 genes. The tandem array of 22 large, variable region exons are followed by a constant region, containing 3 exons shared by all genes in the cluster. Each variable region exon encodes the extracellular region, which includes 6 cadherin ectodomains and a transmembrane region. The constant region exons encode the common cytoplasmic region. These neural cadherin-like cell adhesion proteins most likely play a critical role in the establishment and function of specific cell-cell connections in the brain. Alternative splicing has been described for the gamma cluster genes. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

962 residues, UniProt reviewed canonical sequence.

>Q9Y5G9|PCDHGA4
     1  MHFILDPEDP GAPQASTEGK PKHRRLRGGV VMAAPPARPD HTRLLQICLL LGVLVEIRAE
    61  QILYSVFEEQ EEGSVVGNIA KDLGLAPREL AERGVRIVSR GRTQLFALNP RSGTLVTAGR
   121  IDREELCDRS PNCVTNLEIL LEDTVKILRV EVEIIDVNDN PPSFGTEQRE IKVAENENPG
   181  ARFPLPEAFD PDVGVNSLQG YQLNSNGYFS LDVQSGADGI KYPELVLERA LDREEEAVHH
   241  LVLTAFDGGD PVRSGTARIL IILVDTNDNA PVFTQPEYHV SVRENVPVGT RLLTVKATDP
   301  DEGANGDVTY SFRKVRDKIS QLFQLNSLSG DITILGGLDY EDSGFYDIDV EAHDGPGLRA
   361  RSKVLVTVLD ENDNAPEVTV TSLTSSVQES SSPGTVIALF NVHDSDSGGN GLVTCSIPDN
   421  LPFTLEKTYG NYYRLLTHRT LDREEVSEYN ITVTATDQGT PPLSTETHIS LQVMDINDNP
   481  PTFPHASYSA YIPENNPRGA SILSMTAQDP DSGDNARITY SLAEDTFQGA PLSSYVSINS
   541  NTGILYALCS FDYEQFRDLQ LLMTASDSGD PPLSSNVSLS LFVLDQNDNV PEILYPTFPT
   601  DGSTGVELAP RSADSGYLVT KVVAVDRDSG QNAWLSYSLL KSSEPGLFAV GLHTGEVRTA
   661  RALLDRDALK QRLVVVVQDH GQPPLSATVT LTVAVADSIP DVLADLGSLK PSADPDDSGL
   721  TLYLVVAVAA VSCVFLAFVT VLLALKLRRW HKSRLLHAEG SRLAGVPASH FVGVDGVRAF
   781  LQTYSHEVSL TADSRKSHLI FSQPSYADTL ISRESCEKSE PLLITQDLLE TKGDPNLQQA
   841  PPNTDWRFSQ AQRPGTSGSQ NGDDTGTWPN NQFDTEMLQA MILASASEAA DGSSTLGGGA
   901  GTMGLSARYG PQFTLQHVPD YRQNVYIPGS NATLTNAAGK RDGKAPAGGN GNKKKSGKKE
   961  KK

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against PCDHGA4 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability: Cell surface
Secreted: No
Transmembrane segments: 1
Mean surface accessibility (rSASA): 0.43
Highest tissue expression: 3.2 nTPM

Expression across tissuesHPA

Tissue

cerebral cortex: 3.2 nTPM
basal ganglia: 2.1 nTPM
parathyroid gland: 2.1 nTPM
blood vessel: 2 nTPM
pancreas: 2 nTPM
cerebellum: 1.9 nTPM

Single-cell type

ependymal cells: 1 nCPM
astrocytes: 0.8 nCPM
bergmann glia: 0.7 nCPM
choroid plexus epithelial cells: 0.4 nCPM
brain excitatory neurons: 0.3 nCPM
brain inhibitory neurons: 0.3 nCPM

Immune cell

MAIT T-cell: 0.2 nTPM
basophil: 0 nTPM
classical monocyte: 0 nTPM
eosinophil: 0 nTPM
gdT-cell: 0 nTPM
intermediate monocyte: 0 nTPM

Brain region

cerebellum: 14 nTPM
hippocampal formation: 12 nTPM
midbrain: 12 nTPM
white matter: 11 nTPM
medulla oblongata: 11 nTPM
spinal cord: 11 nTPM

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance): 1.18
gnomAD pLI: 0
gnomAD missense Z: 0.48
DepMap mean gene effect: -0.11
DepMap dependency class: selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

Cellular components

plasma membrane

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads PCDHGA4 as an antibody target. Whether an autoantibody or antibody against PCDHGA4 could matter depends on whether native PCDHGA4 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

PCDHGA4 is annotated at the cell surface, where native PCDHGA4 is exposed to circulating antibodies and is a prime autoantibody target that could block, deplete, or overstimulate it.

Annotation status

The present source text does not explicitly label PCDHGA4 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

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