NPHS1

Protein identityUniProt · HPA

UniProt accession

O60500

Gene

NPHS1

Ensembl

ENSG00000161270

Chromosome

19

Canonical length

1241 aa

Protein class

Disease related genes, Human disease related genes, Plasma proteins, Potential drug targets, Predicted intracellular proteins, Predicted membrane proteins, Transporters

OverviewNCBI Gene

This gene encodes a member of the immunoglobulin family of cell adhesion molecules that functions in the glomerular filtration barrier in the kidney. The gene is primarily expressed in renal tissues, and the protein is a type-1 transmembrane protein found at the slit diaphragm of glomerular podocytes. The slit diaphragm is thought to function as an ultrafilter to exclude albumin and other plasma macromolecules in the formation of urine. Mutations in this gene result in Finnish-type congenital nephrosis 1, characterized by severe proteinuria and loss of the slit diaphragm and foot processes.[provided by RefSeq, Oct 2009]

Canonical amino-acid sequenceUniProt

1241 residues, UniProt reviewed canonical sequence.

>O60500|NPHS1
     1  MALGTTLRAS LLLLGLLTEG LAQLAIPASV PRGFWALPEN LTVVEGASVE LRCGVSTPGS
    61  AVQWAKDGLL LGPDPRIPGF PRYRLEGDPA RGEFHLHIEA CDLSDDAEYE CQVGRSEMGP
   121  ELVSPRVILS ILVPPKLLLL TPEAGTMVTW VAGQEYVVNC VSGDAKPAPD ITILLSGQTI
   181  SDISANVNEG SQQKLFTVEA TARVTPRSSD NRQLLVCEAS SPALEAPIKA SFTVNVLFPP
   241  GPPVIEWPGL DEGHVRAGQS LELPCVARGG NPLATLQWLK NGQPVSTAWG TEHTQAVARS
   301  VLVMTVRPED HGAQLSCEAH NSVSAGTQEH GITLQVTFPP SAIIILGSAS QTENKNVTLS
   361  CVSKSSRPRV LLRWWLGWRQ LLPMEETVMD GLHGGHISMS NLTFLARRED NGLTLTCEAF
   421  SEAFTKETFK KSLILNVKYP AQKLWIEGPP EGQKLRAGTR VRLVCLAIGG NPEPSLMWYK
   481  DSRTVTESRL PQESRRVHLG SVEKSGSTFS RELVLVTGPS DNQAKFTCKA GQLSASTQLA
   541  VQFPPTNVTI LANASALRPG DALNLTCVSV SSNPPVNLSW DKEGERLEGV AAPPRRAPFK
   601  GSAAARSVLL QVSSRDHGQR VTCRAHSAEL RETVSSFYRL NVLYRPEFLG EQVLVVTAVE
   661  QGEALLPVSV SANPAPEAFN WTFRGYRLSP AGGPRHRILS SGALHLWNVT RADDGLYQLH
   721  CQNSEGTAEA RLRLDVHYAP TIRALQDPTE VNVGGSVDIV CTVDANPILP GMFNWERLGE
   781  DEEDQSLDDM EKISRGPTGR LRIHHAKLAQ AGAYQCIVDN GVAPPARRLL RLVVRFAPQV
   841  EHPTPLTKVA AAGDSTSSAT LHCRARGVPN IVFTWTKNGV PLDLQDPRYT EHTYHQGGVH
   901  SSLLTIANVS AAQDYALFTC TATNALGSDQ TNIQLVSISR PDPPSGLKVV SLTPHSVGLE
   961  WKPGFDGGLP QRFCIRYEAL GTPGFHYVDV VPPQATTFTL TGLQPSTRYR VWLLASNALG
  1021  DSGLADKGTQ LPITTPGLHQ PSGEPEDQLP TEPPSGPSGL PLLPVLFALG GLLLLSNASC
  1081  VGGVLWQRRL RRLAEGISEK TEAGSEEDRV RNEYEESQWT GERDTQSSTV STTEAEPYYR
  1141  SLRDFSPQLP PTQEEVSYSR GFTGEDEDMA FPGHLYDEVE RTYPPSGAWG PLYDEVQMGP
  1201  WDLHWPEDTY QDPRGIYDQV AGDLDTLEPD SLPFELRGHL V

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against NPHS1 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)

0.38

Highest tissue expression

40 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about NPHS1.

Disease | AllUniProt

Conditions NPHS1 is implicated in, by any mechanism.

• Nephrotic syndrome 1 (NPHS1) MIM:256300

Disease | GeneticClinVar

467 pathogenic / likely-pathogenic of 2,137 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Finnish congenital nephrotic syndrome
• Nephrotic syndrome
• NPHS1-related disorder
• Focal segmental glomerulosclerosis
• Congenital nephrotic syndrome

Disease | AutoantibodyPubMed

Conditions in which antibodies against NPHS1 are reported. Each links to that disease's full target list.

• Nephrotic Syndrome 26
• Proteinuria 6
• Kidney Diseases 5

Showing 3 of 5 — disease pages carrying at least 10 antigens.

ReferencesPubMed · IEDB

Publications for NPHS1 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.

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)

0.7

gnomAD pLI

0

gnomAD missense Z

0.41

DepMap mean gene effect

-0.12

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 2% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• cell-cell adhesion
• gene expression
• glomerular basement membrane development
• JNK cascade
• myoblast fusion
• podocyte development
• positive regulation of actin filament polymerization
• protein localization to synapse
• skeletal muscle tissue development
• slit diaphragm assembly

Molecular functions

• cell adhesion molecule binding
• myosin binding

Cellular components

• cell projection
• cell-cell junction
• extracellular exosome
• focal adhesion
• plasma membrane
• slit diaphragm

Protein domainsUniProt · Pfam · InterPro

• Immunoglobulin subtype 2
• Immunoglobulin domain subtype
• Fibronectin type III
• Immunoglobulin-like domain
• Immunoglobulin I-set
• Immunoglobulin V-set domain
• CD80-like, immunoglobulin C2-set
• Immunoglobulin-like fold
• Fibronectin type III superfamily
• Immunoglobulin-like domain superfamily
• Cellular adhesion and signaling domain-containing protein
• Fibronectin type III domain
• Immunoglobulin I-set domain
• Immunoglobulin V-set domain
• CD80-like C2-set immunoglobulin domain
• Immunoglobulin domain

KeywordsUniProt

• Cell adhesion
• Cell membrane
• Developmental protein
• Disulfide bond
• Glycoprotein
• Immunoglobulin domain
• Membrane
• Myogenesis
• Phosphoprotein
• Repeat
• Signal
• Transmembrane
• Transmembrane helix

InteractionsUniProt · HPA

Protein binding partners of NPHS1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• CD2AP
• DDN
• KIRREL3
• MAGI1
• NPHS2
• KIRREL2