Seroatlas · Human Serome Atlas

BEST4

Bestrophin-4

Also known as: BEST4_HUMAN, VMD2L2

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

Protein identityUniProt · HPA

UniProt accession: Q8NFU0
Gene: BEST4
Ensembl: ENSG00000142959
Chromosome: 1
Canonical length: 473 aa
Protein class: Predicted membrane proteins, Transporters

OverviewNCBI Gene

This gene is a member of the bestrophin gene family of anion channels. Bestrophin genes share a similar gene structure with highly conserved exon-intron boundaries, but with distinct 3' ends. Bestrophins are transmembrane proteins that contain a homologous region rich in aromatic residues, including an invariant arg-phe-pro motif. Mutation in one of the family members (bestrophin 1) is associated with vitelliform macular dystrophy. The bestrophin 4 gene is predominantly expressed in the colon. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

473 residues, UniProt reviewed canonical sequence.

>Q8NFU0|BEST4
     1  MTVSYTLKVA EARFGGFSGL LLRWRGSIYK LLYKEFLLFG ALYAVLSITY RLLLTQEQRY
    61  VYAQVARYCN RSADLIPLSF VLGFYVTLVV NRWWSQYTSI PLPDQLMCVI SASVHGVDQR
   121  GRLLRRTLIR YANLASVLVL RSVSTRVLKR FPTMEHVVDA GFMSQEERKK FESLKSDFNK
   181  YWVPCVWFTN LAAQARRDGR IRDDIALCLL LEELNKYRAK CSMLFHYDWI SIPLVYTQVV
   241  TIAVYSFFAL SLVGRQFVEP EAGAAKPQKL LKPGQEPAPA LGDPDMYVPL TTLLQFFFYA
   301  GWLKVAEQII NPFGEDDDDF ETNQLIDRNL QVSLLSVDEM YQNLPPAEKD QYWDEDQPQP
   361  PYTVATAAES LRPSFLGSTF NLRMSDDPEQ SLQVEASPGS GRPAPAAQTP LLGRFLGVGA
   421  PSPAISLRNF GRVRGTPRPP HLLRFRAEEG GDPEAAARIE EESAESGDEA LEP

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against BEST4 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: 4
Mean surface accessibility (rSASA): 0.42
Highest tissue expression: 21 nTPM

Expression across tissuesHPA

Tissue

colon: 21 nTPM
rectum: 15 nTPM
choroid plexus: 14 nTPM
duodenum: 8.6 nTPM
fallopian tube: 7.5 nTPM
small intestine: 6.6 nTPM

Single-cell type

colonocytes: 420 nCPM
enterocytes: 116 nCPM
epididymal efferent duct ciliated cells: 89 nCPM
respiratory ciliated cells: 67 nCPM
endometrial ciliated cells: 55 nCPM
ependymal cells: 40 nCPM

Immune cell

memory B-cell: 0.8 nTPM
memory CD8 T-cell: 0.7 nTPM
MAIT T-cell: 0.6 nTPM
memory CD4 T-cell: 0.6 nTPM
T-reg: 0.6 nTPM
naive B-cell: 0.5 nTPM

Brain region

choroid plexus: 37 nTPM
midbrain: 9 nTPM
cerebellum: 6.4 nTPM
medulla oblongata: 6.3 nTPM
hypothalamus: 5.5 nTPM
thalamus: 5.4 nTPM

ReferencesPubMed · IEDB

Publications for BEST4 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Reference: AutoantibodyPubMed

2 publications

Autoantibody discovery across monogenic, acquired, and COVID-19-associated autoimmunity with scalable PhIP-seq.
2022 · Elife · RCR 3.2 · 46 citations
Autoantibody discovery across monogenic, acquired, and COVID19-associated autoimmunity with scalable PhIP-Seq.
2022 · bioRxiv · RCR 0.4 · 5 citations

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

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): 0.89
gnomAD pLI: 0
gnomAD missense Z: 2.01
DepMap mean gene effect: -0.05
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

chloride transmembrane transport

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads BEST4 as an antibody target. Whether an autoantibody or antibody against BEST4 could matter depends on whether native BEST4 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

BEST4 is annotated at the cell surface, where native BEST4 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 BEST4 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

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