Seroatlas · Human Serome Atlas

NPHP1

Nephrocystin-1

Also known as: JBTS4, NPH1, NPHP1_HUMAN, SLSN1

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

Protein identityUniProt · HPA

UniProt accession: O15259
Gene: NPHP1
Ensembl: ENSG00000144061
Chromosome: 2
Canonical length: 732 aa
Protein class: Disease related genes, Human disease related genes, Predicted intracellular proteins

OverviewNCBI Gene

This gene encodes a protein with src homology domain 3 (SH3) patterns. This protein interacts with Crk-associated substrate, and it appears to function in the control of cell division, as well as in cell-cell and cell-matrix adhesion signaling, likely as part of a multifunctional complex localized in actin- and microtubule-based structures. Mutations in this gene cause familial juvenile nephronophthisis type 1, a kidney disorder involving both tubules and glomeruli. Defects in this gene are also associated with Senior-Loken syndrome type 1, also referred to as juvenile nephronophthisis with Leber amaurosis, which is characterized by kidney and eye disease, and with Joubert syndrome type 4, which is characterized by cerebellar ataxia, oculomotor apraxia, psychomotor delay and neonatal breathing abnormalities, sometimes including retinal dystrophy and renal disease. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

732 residues, UniProt reviewed canonical sequence.

>O15259|NPHP1
     1  MLARRQRDPL QALRRRNQEL KQQVDSLLSE SQLKEALEPN KRQHIYQRCI QLKQAIDENK
    61  NALQKLSKAD ESAPVANYNQ RKEEEHTLLD KLTQQLQGLA VTISRENITE VGAPTEEEEE
   121  SESEDSEDSG GEEEDAEEEE EEKEENESHK WSTGEEYIAV GDFTAQQVGD LTFKKGEILL
   181  VIEKKPDGWW IAKDAKGNEG LVPRTYLEPY SEEEEGQESS EEGSEEDVEA VDETADGAEV
   241  KQRTDPHWSA VQKAISEAGI FCLVNHVSFC YLIVLMRNRM ETVEDTNGSE TGFRAWNVQS
   301  RGRIFLVSKP VLQINTVDVL TTMGAIPAGF RPSTLSQLLE EGNQFRANYF LQPELMPSQL
   361  AFRDLMWDAT EGTIRSRPSR ISLILTLWSC KMIPLPGMSI QVLSRHVRLC LFDGNKVLSN
   421  IHTVRATWQP KKPKTWTFSP QVTRILPCLL DGDCFIRSNS ASPDLGILFE LGISYIRNST
   481  GERGELSCGW VFLKLFDASG VPIPAKTYEL FLNGGTPYEK GIEVDPSISR RAHGSVFYQI
   541  MTMRRQPQLL VKLRSLNRRS RNVLSLLPET LIGNMCSIHL LIFYRQILGD VLLKDRMSLQ
   601  STDLISHPML ATFPMLLEQP DVMDALRSSW AGKESTLKRS EKRDKEFLKS TFLLVYHDCV
   661  LPLLHSTRLP PFRWAEEETE TARWKVITDF LKQNQENQGA LQALLSPDGV HEPFDLSEQT
   721  YDFLGEMRKN AV

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against NPHP1 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): 0.36
Highest tissue expression: 36 nTPM

Expression across tissuesHPA

Tissue

choroid plexus: 36 nTPM
skeletal muscle: 34 nTPM
testis: 23 nTPM
fallopian tube: 16 nTPM
parathyroid gland: 16 nTPM
pituitary gland: 12 nTPM

Single-cell type

myonuclei: 568 nCPM
respiratory ciliated cells: 339 nCPM
ependymal cells: 313 nCPM
late primary spermatocytes: 289 nCPM
endometrial ciliated cells: 240 nCPM
fallopian tube ciliated cells: 230 nCPM

Immune cell

naive B-cell: 1.5 nTPM
NK-cell: 1.1 nTPM
memory B-cell: 0.8 nTPM
MAIT T-cell: 0.5 nTPM
naive CD4 T-cell: 0.5 nTPM
basophil: 0.3 nTPM

Brain region

choroid plexus: 17 nTPM
midbrain: 6.3 nTPM
medulla oblongata: 5.5 nTPM
hypothalamus: 5.3 nTPM
basal ganglia: 3.7 nTPM
cerebral cortex: 3.6 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about NPHP1.

Disease | AllUniProt

Conditions NPHP1 is implicated in, by any mechanism.

Nephronophthisis 1 (NPHP1) MIM:256100
Senior-Loken syndrome 1 (SLSN1) MIM:266900
Joubert syndrome 4 (JBTS4) MIM:609583

Disease | GeneticClinVar

151 pathogenic / likely-pathogenic of 1,052 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

Joubert syndrome with renal defect
Nephronophthisis
Nephronophthisis 1
Senior-Loken syndrome 1
NPHP1-related disorder

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): 0.98
gnomAD pLI: 0
gnomAD missense Z: 0.23
DepMap mean gene effect: -0.12
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

structural molecule activity

Cellular components

Protein domainsUniProt · Pfam · InterPro

SH3 domain
SH3-like domain superfamily
SH3 domain
Nephrocystin-1, SH3 domain
Nephrocystin-1

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of NPHP1 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 NPHP1 as an antibody target. Whether an autoantibody or antibody against NPHP1 could matter depends on whether native NPHP1 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

NPHP1 is annotated at the cell surface, where native NPHP1 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 NPHP1 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

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