Seroatlas · Human Serome Atlas

NHERF4

Na(+)/H(+) exchange regulatory cofactor NHE-RF4

Also known as: FLJ22756, IKEPP, NHRF4_HUMAN, PDZD3, PDZK2

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

Protein identityUniProt · HPA

UniProt accession
Q86UT5
Gene
NHERF4
Ensembl
ENSG00000172367
Chromosome
11
Canonical length
571 aa
Protein class
Predicted intracellular proteins

OverviewNCBI Gene

Guanylyl cyclase C (GCC, or GUCY2C; MIM 601330) produces cGMP following the binding of either endogenous ligands or heat-stable enterotoxins secreted by E. coli and other enteric bacteria. Activation of GCC initiates a signaling cascade that leads to phosphorylation of the cystic fibrosis transmembrane conductance regulator (CFTR; MIM 602421), followed by a net efflux of ions and water into the intestinal lumen. IKEPP is a regulatory protein that associates with GCC and regulates the amount of cGMP produced following receptor stimulation (Scott et al., 2002 [PubMed 11950846]).[supplied by OMIM, Mar 2008]

Canonical amino-acid sequenceUniProt

571 residues, UniProt reviewed canonical sequence.

>Q86UT5|NHERF4
     1  MVTPSPPGNH SLSLEAPRLH TASDLLGNHS LGLPLITALV GSRDRRGRVF SPVPVPLPTN
    61  PTTQHPTRQK LPSTLSGHRV CQAHGEPVLG LCPLLPLFCC PPHPPDPWSL ERPRFCLLSK
   121  EEGKSFGFHL QQELGRAGHV VCRVDPGTSA QRQGLQEGDR ILAVNNDVVE HEDYAVVVRR
   181  IRASSPRVLL TVLARHAHDV ARAQLGEDAH LCPTLGPGVR PRLCHIVKDE GGFGFSVTHG
   241  NQGPFWLVLS TGGAAERAGV PPGARLLEVN GVSVEKFTHN QLTRKLWQSG QQVTLLVAGP
   301  EVEEQCRQLG LPLAAPLAEG WALPTKPRCL HLEKGPQGFG FLLREEKGLD GRPGQFLWEV
   361  DPGLPAKKAG MQAGDRLVAV AGESVEGLGH EETVSRIQGQ GSCVSLTVVD PEADRFFSMV
   421  RLSPLLFLEN TEAPASPRGS SSASLVETED PSLEDTSVPS VPLGSRQCFL YPGPGGSYGF
   481  RLSCVASGPR LFISQVTPGG SAARAGLQVG DVILEVNGYP VGGQNDLERL QQLPEAEPPL
   541  CLKLAARSLR GLEAWIPPGA AEDWALASDL L

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against NHERF4 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
0
Mean surface accessibility (rSASA)
0.4
Highest tissue expression
18 nTPM

Expression across tissuesHPA

Tissue

  • small intestine: 18 nTPM
  • kidney: 18 nTPM
  • duodenum: 16 nTPM
  • colon: 11 nTPM
  • rectum: 5.8 nTPM
  • gallbladder: 2.6 nTPM

Single-cell type

  • colonocytes: 109 nCPM
  • enterocytes: 104 nCPM
  • proximal tubule cells: 78 nCPM
  • foveolar cells: 39 nCPM
  • enteric transient amplifying cells: 27 nCPM
  • enteric stem cells: 26 nCPM

Immune cell

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

Brain region

  • medulla oblongata: 0.2 nTPM
  • midbrain: 0.2 nTPM
  • cerebellum: 0.1 nTPM
  • choroid plexus: 0.1 nTPM
  • hypothalamus: 0.1 nTPM
  • spinal cord: 0.1 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)
1.27
gnomAD pLI
0
DepMap mean gene effect
-0.08
DepMap dependency class
selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of NHERF4 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads NHERF4 as an antibody target. Whether an autoantibody or antibody against NHERF4 could matter depends on whether native NHERF4 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

NHERF4 is annotated at the cell surface, where native NHERF4 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 NHERF4 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

Canonical record: https://seroatlas.com/gene/NHERF4. Study-independent annotations aggregated from UniProt, Human Protein Atlas, PubMed, IEDB, Pfam, InterPro, Gene Ontology, AlphaFold, gnomAD, DepMap, ClinVar, TCGA. Catalog release seroatlas-reviewed-human-uniprot-20260313.

Seroatlas is the reference for exploring autoantibody and antibody serology at the human-protein level: the autoreactome and human serome, multiplex serology (HuProt, HuScan, VirScan, PhIP-Seq).

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