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O60500

- NPHN_HUMAN

UniProt

O60500 - NPHN_HUMAN

Protein

Nephrin

Gene

NPHS1

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 138 (01 Oct 2014)
      Sequence version 1 (01 Aug 1998)
      Previous versions | rss
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    Functioni

    Seems to play a role in the development or function of the kidney glomerular filtration barrier. Regulates glomerular vascular permeability. May anchor the podocyte slit diaphragm to the actin cytoskeleton. Plays a role in skeletal muscle formation through regulation of myoblast fusion By similarity.By similarity

    GO - Molecular functioni

    1. myosin binding Source: UniProtKB
    2. protein binding Source: IntAct

    GO - Biological processi

    1. cell adhesion Source: ProtInc
    2. excretion Source: ProtInc
    3. glomerular basement membrane development Source: UniProtKB
    4. glomerular visceral epithelial cell development Source: UniProtKB
    5. JNK cascade Source: Ensembl
    6. myoblast fusion Source: Ensembl
    7. positive regulation of actin filament polymerization Source: Ensembl
    8. regulation of excretion Source: Ensembl
    9. skeletal muscle tissue development Source: Ensembl

    Keywords - Molecular functioni

    Developmental protein

    Keywords - Biological processi

    Cell adhesion, Myogenesis

    Enzyme and pathway databases

    ReactomeiREACT_23832. Nephrin interactions.
    SignaLinkiO60500.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Nephrin
    Alternative name(s):
    Renal glomerulus-specific cell adhesion receptor
    Gene namesi
    Name:NPHS1
    Synonyms:NPHN
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 19

    Organism-specific databases

    HGNCiHGNC:7908. NPHS1.

    Subcellular locationi

    Cell membrane Curated; Single-pass type I membrane protein Curated
    Note: Predominantly located at podocyte slit diaphragm between podocyte foot processes. Also associated with podocyte apical plasma membrane.2 Publications

    GO - Cellular componenti

    1. cell projection Source: Ensembl
    2. extracellular vesicular exosome Source: UniProt
    3. integral component of plasma membrane Source: ProtInc
    4. membrane raft Source: Ensembl
    5. plasma membrane Source: UniProtKB
    6. protein complex Source: Ensembl
    7. slit diaphragm Source: UniProtKB

    Keywords - Cellular componenti

    Cell membrane, Membrane

    Pathology & Biotechi

    Involvement in diseasei

    Nephrotic syndrome 1 (NPHS1) [MIM:256300]: A form of nephrotic syndrome, a renal disease clinically characterized by severe proteinuria, resulting in complications such as hypoalbuminemia, hyperlipidemia and edema. Kidney biopsies show non-specific histologic changes such as focal segmental glomerulosclerosis and diffuse mesangial proliferation. Some affected individuals have an inherited steroid-resistant form and progress to end-stage renal failure.9 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti64 – 641W → S in NPHS1; lack of protein expression on the cell surface. 2 Publications
    VAR_013029
    Natural varianti96 – 961L → V in NPHS1. 1 Publication
    VAR_064194
    Natural varianti107 – 1071A → T in NPHS1. 1 Publication
    VAR_064195
    Natural varianti107 – 1071A → V in NPHS1. 1 Publication
    VAR_064196
    Natural varianti167 – 1671P → L in NPHS1. 1 Publication
    VAR_064197
    Natural varianti171 – 1711I → N in NPHS1; lack of protein expression on the cell surface. 2 Publications
    VAR_013031
    Natural varianti172 – 1721Missing in NPHS1. 3 Publications
    VAR_013032
    Natural varianti173 – 1731I → N in NPHS1; lack of protein expression on the cell surface. 2 Publications
    VAR_013033
    Natural varianti205 – 2073TPR → I in NPHS1.
    VAR_013034
    Natural varianti256 – 2561R → W in NPHS1. 1 Publication
    VAR_064198
    Natural varianti265 – 2651C → R in NPHS1. 1 Publication
    VAR_064200
    Natural varianti270 – 2701G → C in NPHS1; lack of protein expression on the cell surface. 2 Publications
    VAR_013035
    Natural varianti299 – 2991R → C in NPHS1. 1 Publication
    VAR_064201
    Natural varianti340 – 3401P → H in NPHS1. 1 Publication
    VAR_064202
    Natural varianti347 – 3471G → E in NPHS1. 1 Publication
    VAR_064203
    Natural varianti350 – 3501S → P in NPHS1; lack of protein expression on the cell surface. 3 Publications
    VAR_013036
    Natural varianti366 – 3661S → R in NPHS1; lack of protein expression on the cell surface; the mutant protein is retained in the endoplasmic reticulum. 3 Publications
    VAR_013037
    Natural varianti367 – 3671R → C in NPHS1; lack of protein expression on the cell surface. 4 Publications
    VAR_013038
    Natural varianti368 – 3681P → L in NPHS1. 1 Publication
    VAR_064204
    Natural varianti368 – 3681P → S in NPHS1; lack of protein expression on the cell surface. 2 Publications
    VAR_013039
    Natural varianti376 – 3761L → V in NPHS1; does not affect protein expression on the cell surface. 2 Publications
    VAR_013040
    Natural varianti379 – 3791R → W in NPHS1. 1 Publication
    VAR_064205
    Natural varianti407 – 4071R → W in NPHS1. 1 Publication
    VAR_064206
    Natural varianti408 – 4081R → Q in NPHS1; uncertain pathological significance; does not affect protein expression on the cell surface. 3 Publications
    Corresponds to variant rs33950747 [ dbSNP | Ensembl ].
    VAR_013041
    Natural varianti412 – 4121G → C in NPHS1. 1 Publication
    VAR_064207
    Natural varianti417 – 4171C → F in NPHS1. 1 Publication
    VAR_064208
    Natural varianti460 – 4601R → Q in NPHS1. 3 Publications
    VAR_064209
    Natural varianti465 – 4651C → Y in NPHS1; lack of protein expression on the cell surface. 2 Publications
    VAR_013043
    Natural varianti519 – 5191P → S in NPHS1. 1 Publication
    VAR_064210
    Natural varianti528 – 5281C → F in NPHS1; lack of protein expression on the cell surface. 2 Publications
    VAR_013044
    Natural varianti558 – 5581R → C in NPHS1. 2 Publications
    VAR_064211
    Natural varianti569 – 5691S → R in NPHS1. 1 Publication
    VAR_064212
    Natural varianti572 – 5721S → N in NPHS1. 1 Publication
    VAR_064213
    Natural varianti575 – 5751P → Q in NPHS1. 1 Publication
    VAR_064214
    Natural varianti586 – 5861R → G in NPHS1. 1 Publication
    VAR_064215
    Natural varianti587 – 5871L → R in NPHS1. 1 Publication
    VAR_064216
    Natural varianti610 – 6101L → Q in NPHS1; lack of protein expression on the cell surface. 2 Publications
    VAR_013045
    Natural varianti623 – 6231C → F in NPHS1; lack of protein expression on the cell surface. 3 Publications
    VAR_013046
    Natural varianti673 – 6731N → K in NPHS1. 1 Publication
    Corresponds to variant rs191807913 [ dbSNP | Ensembl ].
    VAR_064218
    Natural varianti681 – 6811W → C in NPHS1. 1 Publication
    VAR_064219
    Natural varianti709 – 7091V → G in NPHS1. 1 Publication
    VAR_064220
    Natural varianti724 – 7241S → C in NPHS1; does not affect protein expression on the cell surface. 2 Publications
    VAR_013047
    Natural varianti739 – 7391A → V in NPHS1. 1 Publication
    VAR_064222
    Natural varianti742 – 7421I → T in NPHS1. 1 Publication
    VAR_067252
    Natural varianti743 – 7431R → C in NPHS1; does not affect protein expression on the cell surface. 3 Publications
    VAR_013048
    Natural varianti802 – 8021R → P in NPHS1; lack of protein expression on the cell surface. 2 Publications
    VAR_013050
    Natural varianti802 – 8021R → W in NPHS1; lack of protein expression on the cell surface. 2 Publications
    VAR_013049
    Natural varianti806 – 8061A → D in NPHS1; lack of protein expression on the cell surface. 2 Publications
    VAR_013051
    Natural varianti819 – 8191D → V in NPHS1. 2 Publications
    VAR_013052
    Natural varianti822 – 8221V → M in NPHS1. 1 Publication
    VAR_064223
    Natural varianti831 – 8311R → C in NPHS1; lack of protein expression on the cell surface. 1 Publication
    VAR_013053
    Natural varianti832 – 8321L → P in NPHS1; the mutant protein is retained in the endoplasmic reticulum. 1 Publication
    VAR_064224
    Natural varianti834 – 8341V → F in NPHS1. 1 Publication
    VAR_064225
    Natural varianti910 – 9101S → P in NPHS1. 1 Publication
    VAR_064227
    Natural varianti976 – 9761R → S in NPHS1. 2 Publications
    VAR_064228
    Natural varianti1140 – 11401R → C in NPHS1; does not affect protein expression on the cell surface. 2 Publications
    VAR_013055

    Keywords - Diseasei

    Disease mutation

    Organism-specific databases

    MIMi256300. phenotype.
    Orphaneti839. Congenital nephrotic syndrome, Finnish type.
    93214. Familial idiopathic steroid-resistant nephrotic syndrome with diffuse mesangial proliferation.
    93213. Familial idiopathic steroid-resistant nephrotic syndrome with focal segmental hyalinosis.
    93216. Familial idiopathic steroid-resistant nephrotic syndrome with minimal changes.
    PharmGKBiPA31709.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 2222Sequence AnalysisAdd
    BLAST
    Chaini23 – 12411219NephrinPRO_0000015052Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi40 – 401N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi53 ↔ 111PROSITE-ProRule annotation
    Disulfide bondi160 ↔ 217PROSITE-ProRule annotation
    Disulfide bondi265 ↔ 317PROSITE-ProRule annotation
    Glycosylationi356 – 3561N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi361 ↔ 417PROSITE-ProRule annotation
    Glycosylationi401 – 4011N-linked (GlcNAc...)Sequence Analysis
    Modified residuei432 – 4321Phosphoserine1 Publication
    Disulfide bondi465 ↔ 528PROSITE-ProRule annotation
    Glycosylationi547 – 5471N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi553 – 5531N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi564 – 5641N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi567 ↔ 623PROSITE-ProRule annotation
    Glycosylationi577 – 5771N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi680 – 6801N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi708 – 7081N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi761 ↔ 816PROSITE-ProRule annotation
    Disulfide bondi863 ↔ 920PROSITE-ProRule annotation
    Glycosylationi908 – 9081N-linked (GlcNAc...)Sequence Analysis
    Modified residuei1193 – 11931Phosphotyrosine; by FYNBy similarity

    Post-translational modificationi

    Phosphorylated at Tyr-1193 by FYN, leading to the recruitment and activation of phospholipase C-gamma-1/PLCG1.By similarity

    Keywords - PTMi

    Disulfide bond, Glycoprotein, Phosphoprotein

    Proteomic databases

    PaxDbiO60500.
    PRIDEiO60500.

    PTM databases

    PhosphoSiteiO60500.

    Expressioni

    Tissue specificityi

    Specifically expressed in podocytes of kidney glomeruli.

    Developmental stagei

    In 23-week-old embryo found in epithelial podocytes of the periphery of mature and developing glomeruli.

    Gene expression databases

    BgeeiO60500.
    CleanExiHS_NPHS1.
    GenevestigatoriO60500.

    Organism-specific databases

    HPAiCAB035555.

    Interactioni

    Subunit structurei

    Interacts with CD2AP (via C-terminal domain). Interacts with MAGI1 (via PDZ 2 and 3 domains) forming a tripartite complex with IGSF5/JAM4. Interacts with DDN; the interaction is direct. Self-associates (via the Ig-like domains). Also interacts (via the Ig-like domains) with KIRREL/NEPH1 and KIRREL2; the interaction with KIRREL is dependent on KIRREL glycosylation. Forms a complex with ACTN4, CASK, IQGAP1, MAGI2, SPTAN1 and SPTBN1 By similarity. Interacts with NPHS2.By similarity1 Publication

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    IQGAP1P469405EBI-996920,EBI-297509
    NCK1P163333EBI-996920,EBI-389883

    Protein-protein interaction databases

    BioGridi110928. 17 interactions.
    IntActiO60500. 7 interactions.
    STRINGi9606.ENSP00000368190.

    Structurei

    3D structure databases

    ProteinModelPortaliO60500.
    SMRiO60500. Positions 32-1022.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini23 – 10551033ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini1077 – 1241165CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei1056 – 107621HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini27 – 130104Ig-like C2-type 1Add
    BLAST
    Domaini143 – 23492Ig-like C2-type 2Add
    BLAST
    Domaini242 – 33392Ig-like C2-type 3Add
    BLAST
    Domaini340 – 43495Ig-like C2-type 4Add
    BLAST
    Domaini440 – 540101Ig-like C2-type 5Add
    BLAST
    Domaini544 – 63592Ig-like C2-type 6Add
    BLAST
    Domaini740 – 83293Ig-like C2-type 7Add
    BLAST
    Domaini838 – 939102Ig-like C2-type 8Add
    BLAST
    Domaini943 – 103896Fibronectin type-IIIPROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni1160 – 124182Binds to NPHS2Add
    BLAST

    Sequence similaritiesi

    Belongs to the immunoglobulin superfamily.Curated
    Contains 1 fibronectin type-III domain.PROSITE-ProRule annotation

    Keywords - Domaini

    Immunoglobulin domain, Repeat, Signal, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiNOG251936.
    HOGENOMiHOG000113844.
    HOVERGENiHBG031752.
    InParanoidiO60500.
    OMAiNVNEGSQ.
    OrthoDBiEOG7RBZ7J.
    PhylomeDBiO60500.
    TreeFamiTF327139.

    Family and domain databases

    Gene3Di2.60.40.10. 10 hits.
    InterProiIPR013162. CD80_C2-set.
    IPR003961. Fibronectin_type3.
    IPR007110. Ig-like_dom.
    IPR013783. Ig-like_fold.
    IPR013098. Ig_I-set.
    IPR003599. Ig_sub.
    IPR003598. Ig_sub2.
    IPR013106. Ig_V-set.
    [Graphical view]
    PfamiPF08205. C2-set_2. 5 hits.
    PF00041. fn3. 1 hit.
    PF07679. I-set. 1 hit.
    PF07686. V-set. 1 hit.
    [Graphical view]
    SMARTiSM00060. FN3. 1 hit.
    SM00409. IG. 5 hits.
    SM00408. IGc2. 1 hit.
    [Graphical view]
    SUPFAMiSSF49265. SSF49265. 1 hit.
    PROSITEiPS50853. FN3. 1 hit.
    PS50835. IG_LIKE. 7 hits.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: O60500-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MALGTTLRAS LLLLGLLTEG LAQLAIPASV PRGFWALPEN LTVVEGASVE     50
    LRCGVSTPGS AVQWAKDGLL LGPDPRIPGF PRYRLEGDPA RGEFHLHIEA 100
    CDLSDDAEYE CQVGRSEMGP ELVSPRVILS ILVPPKLLLL TPEAGTMVTW 150
    VAGQEYVVNC VSGDAKPAPD ITILLSGQTI SDISANVNEG SQQKLFTVEA 200
    TARVTPRSSD NRQLLVCEAS SPALEAPIKA SFTVNVLFPP GPPVIEWPGL 250
    DEGHVRAGQS LELPCVARGG NPLATLQWLK NGQPVSTAWG TEHTQAVARS 300
    VLVMTVRPED HGAQLSCEAH NSVSAGTQEH GITLQVTFPP SAIIILGSAS 350
    QTENKNVTLS CVSKSSRPRV LLRWWLGWRQ LLPMEETVMD GLHGGHISMS 400
    NLTFLARRED NGLTLTCEAF SEAFTKETFK KSLILNVKYP AQKLWIEGPP 450
    EGQKLRAGTR VRLVCLAIGG NPEPSLMWYK DSRTVTESRL PQESRRVHLG 500
    SVEKSGSTFS RELVLVTGPS DNQAKFTCKA GQLSASTQLA VQFPPTNVTI 550
    LANASALRPG DALNLTCVSV SSNPPVNLSW DKEGERLEGV AAPPRRAPFK 600
    GSAAARSVLL QVSSRDHGQR VTCRAHSAEL RETVSSFYRL NVLYRPEFLG 650
    EQVLVVTAVE QGEALLPVSV SANPAPEAFN WTFRGYRLSP AGGPRHRILS 700
    SGALHLWNVT RADDGLYQLH CQNSEGTAEA RLRLDVHYAP TIRALQDPTE 750
    VNVGGSVDIV CTVDANPILP GMFNWERLGE DEEDQSLDDM EKISRGPTGR 800
    LRIHHAKLAQ AGAYQCIVDN GVAPPARRLL RLVVRFAPQV EHPTPLTKVA 850
    AAGDSTSSAT LHCRARGVPN IVFTWTKNGV PLDLQDPRYT EHTYHQGGVH 900
    SSLLTIANVS AAQDYALFTC TATNALGSDQ TNIQLVSISR PDPPSGLKVV 950
    SLTPHSVGLE WKPGFDGGLP QRFCIRYEAL GTPGFHYVDV VPPQATTFTL 1000
    TGLQPSTRYR VWLLASNALG DSGLADKGTQ LPITTPGLHQ PSGEPEDQLP 1050
    TEPPSGPSGL PLLPVLFALG GLLLLSNASC VGGVLWQRRL RRLAEGISEK 1100
    TEAGSEEDRV RNEYEESQWT GERDTQSSTV STTEAEPYYR SLRDFSPQLP 1150
    PTQEEVSYSR GFTGEDEDMA FPGHLYDEVE RTYPPSGAWG PLYDEVQMGP 1200
    WDLHWPEDTY QDPRGIYDQV AGDLDTLEPD SLPFELRGHL V 1241
    Length:1,241
    Mass (Da):134,742
    Last modified:August 1, 1998 - v1
    Checksum:i7F5AFAF078BCF532
    GO
    Isoform 2 (identifier: O60500-2) [UniParc]FASTAAdd to Basket

    Also known as: Alpha

    The sequence of this isoform differs from the canonical sequence as follows:
         1056-1095: Missing.

    Show »
    Length:1,201
    Mass (Da):130,546
    Checksum:i189283B140D831DF
    GO

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti64 – 641W → S in NPHS1; lack of protein expression on the cell surface. 2 Publications
    VAR_013029
    Natural varianti96 – 961L → V in NPHS1. 1 Publication
    VAR_064194
    Natural varianti107 – 1071A → T in NPHS1. 1 Publication
    VAR_064195
    Natural varianti107 – 1071A → V in NPHS1. 1 Publication
    VAR_064196
    Natural varianti117 – 1171E → K.4 Publications
    Corresponds to variant rs3814995 [ dbSNP | Ensembl ].
    VAR_013030
    Natural varianti167 – 1671P → L in NPHS1. 1 Publication
    VAR_064197
    Natural varianti171 – 1711I → N in NPHS1; lack of protein expression on the cell surface. 2 Publications
    VAR_013031
    Natural varianti172 – 1721Missing in NPHS1. 3 Publications
    VAR_013032
    Natural varianti173 – 1731I → N in NPHS1; lack of protein expression on the cell surface. 2 Publications
    VAR_013033
    Natural varianti205 – 2073TPR → I in NPHS1.
    VAR_013034
    Natural varianti233 – 2331T → A.
    Corresponds to variant rs35238405 [ dbSNP | Ensembl ].
    VAR_049970
    Natural varianti256 – 2561R → W in NPHS1. 1 Publication
    VAR_064198
    Natural varianti264 – 2641P → R Found in patients with nephrotic syndrome; unknown pathological significance. 1 Publication
    Corresponds to variant rs34982899 [ dbSNP | Ensembl ].
    VAR_064199
    Natural varianti265 – 2651C → R in NPHS1. 1 Publication
    VAR_064200
    Natural varianti270 – 2701G → C in NPHS1; lack of protein expression on the cell surface. 2 Publications
    VAR_013035
    Natural varianti299 – 2991R → C in NPHS1. 1 Publication
    VAR_064201
    Natural varianti340 – 3401P → H in NPHS1. 1 Publication
    VAR_064202
    Natural varianti347 – 3471G → E in NPHS1. 1 Publication
    VAR_064203
    Natural varianti350 – 3501S → P in NPHS1; lack of protein expression on the cell surface. 3 Publications
    VAR_013036
    Natural varianti366 – 3661S → R in NPHS1; lack of protein expression on the cell surface; the mutant protein is retained in the endoplasmic reticulum. 3 Publications
    VAR_013037
    Natural varianti367 – 3671R → C in NPHS1; lack of protein expression on the cell surface. 4 Publications
    VAR_013038
    Natural varianti368 – 3681P → L in NPHS1. 1 Publication
    VAR_064204
    Natural varianti368 – 3681P → S in NPHS1; lack of protein expression on the cell surface. 2 Publications
    VAR_013039
    Natural varianti376 – 3761L → V in NPHS1; does not affect protein expression on the cell surface. 2 Publications
    VAR_013040
    Natural varianti379 – 3791R → W in NPHS1. 1 Publication
    VAR_064205
    Natural varianti392 – 3921L → P.
    Corresponds to variant rs34320609 [ dbSNP | Ensembl ].
    VAR_049971
    Natural varianti407 – 4071R → W in NPHS1. 1 Publication
    VAR_064206
    Natural varianti408 – 4081R → Q in NPHS1; uncertain pathological significance; does not affect protein expression on the cell surface. 3 Publications
    Corresponds to variant rs33950747 [ dbSNP | Ensembl ].
    VAR_013041
    Natural varianti412 – 4121G → C in NPHS1. 1 Publication
    VAR_064207
    Natural varianti417 – 4171C → F in NPHS1. 1 Publication
    VAR_064208
    Natural varianti447 – 4471E → K.2 Publications
    Corresponds to variant rs28939695 [ dbSNP | Ensembl ].
    VAR_013042
    Natural varianti460 – 4601R → Q in NPHS1. 3 Publications
    VAR_064209
    Natural varianti465 – 4651C → Y in NPHS1; lack of protein expression on the cell surface. 2 Publications
    VAR_013043
    Natural varianti519 – 5191P → S in NPHS1. 1 Publication
    VAR_064210
    Natural varianti528 – 5281C → F in NPHS1; lack of protein expression on the cell surface. 2 Publications
    VAR_013044
    Natural varianti558 – 5581R → C in NPHS1. 2 Publications
    VAR_064211
    Natural varianti569 – 5691S → R in NPHS1. 1 Publication
    VAR_064212
    Natural varianti572 – 5721S → N in NPHS1. 1 Publication
    VAR_064213
    Natural varianti575 – 5751P → Q in NPHS1. 1 Publication
    VAR_064214
    Natural varianti586 – 5861R → G in NPHS1. 1 Publication
    VAR_064215
    Natural varianti587 – 5871L → R in NPHS1. 1 Publication
    VAR_064216
    Natural varianti610 – 6101L → Q in NPHS1; lack of protein expression on the cell surface. 2 Publications
    VAR_013045
    Natural varianti617 – 6171H → R Found in patients with nephrotic syndrome; unknown pathological significance. 1 Publication
    VAR_064217
    Natural varianti623 – 6231C → F in NPHS1; lack of protein expression on the cell surface. 3 Publications
    VAR_013046
    Natural varianti673 – 6731N → K in NPHS1. 1 Publication
    Corresponds to variant rs191807913 [ dbSNP | Ensembl ].
    VAR_064218
    Natural varianti681 – 6811W → C in NPHS1. 1 Publication
    VAR_064219
    Natural varianti709 – 7091V → G in NPHS1. 1 Publication
    VAR_064220
    Natural varianti724 – 7241S → C in NPHS1; does not affect protein expression on the cell surface. 2 Publications
    VAR_013047
    Natural varianti725 – 7251E → D Found in patients with nephrotic syndrome; unknown pathological significance. 1 Publication
    VAR_064221
    Natural varianti739 – 7391A → V in NPHS1. 1 Publication
    VAR_064222
    Natural varianti742 – 7421I → T in NPHS1. 1 Publication
    VAR_067252
    Natural varianti743 – 7431R → C in NPHS1; does not affect protein expression on the cell surface. 3 Publications
    VAR_013048
    Natural varianti802 – 8021R → P in NPHS1; lack of protein expression on the cell surface. 2 Publications
    VAR_013050
    Natural varianti802 – 8021R → W in NPHS1; lack of protein expression on the cell surface. 2 Publications
    VAR_013049
    Natural varianti806 – 8061A → D in NPHS1; lack of protein expression on the cell surface. 2 Publications
    VAR_013051
    Natural varianti819 – 8191D → V in NPHS1. 2 Publications
    VAR_013052
    Natural varianti822 – 8221V → M in NPHS1. 1 Publication
    VAR_064223
    Natural varianti831 – 8311R → C in NPHS1; lack of protein expression on the cell surface. 1 Publication
    VAR_013053
    Natural varianti832 – 8321L → P in NPHS1; the mutant protein is retained in the endoplasmic reticulum. 1 Publication
    VAR_064224
    Natural varianti834 – 8341V → F in NPHS1. 1 Publication
    VAR_064225
    Natural varianti851 – 8511A → V Found in patients with nephrotic syndrome; unknown pathological significance. 1 Publication
    VAR_064226
    Natural varianti910 – 9101S → P in NPHS1. 1 Publication
    VAR_064227
    Natural varianti976 – 9761R → S in NPHS1. 2 Publications
    VAR_064228
    Natural varianti991 – 9911V → L.
    Corresponds to variant rs34736717 [ dbSNP | Ensembl ].
    VAR_049972
    Natural varianti1077 – 10771N → S.2 Publications
    Corresponds to variant rs4806213 [ dbSNP | Ensembl ].
    VAR_013054
    Natural varianti1140 – 11401R → C in NPHS1; does not affect protein expression on the cell surface. 2 Publications
    VAR_013055

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1056 – 109540Missing in isoform 2. 1 PublicationVSP_002598Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF035835 mRNA. Translation: AAC39687.1.
    EU642886 mRNA. Translation: ACH99862.1.
    AF190637 mRNA. Translation: AAG17141.1.
    AC002133 Genomic DNA. No translation available.
    AF126957 mRNA. Translation: AAF36451.1.
    CCDSiCCDS32996.1. [O60500-1]
    PIRiT37190.
    RefSeqiNP_004637.1. NM_004646.3. [O60500-1]
    UniGeneiHs.122186.

    Genome annotation databases

    EnsembliENST00000353632; ENSP00000343634; ENSG00000161270. [O60500-2]
    ENST00000378910; ENSP00000368190; ENSG00000161270. [O60500-1]
    GeneIDi4868.
    KEGGihsa:4868.
    UCSCiuc002oby.3. human. [O60500-1]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF035835 mRNA. Translation: AAC39687.1 .
    EU642886 mRNA. Translation: ACH99862.1 .
    AF190637 mRNA. Translation: AAG17141.1 .
    AC002133 Genomic DNA. No translation available.
    AF126957 mRNA. Translation: AAF36451.1 .
    CCDSi CCDS32996.1. [O60500-1 ]
    PIRi T37190.
    RefSeqi NP_004637.1. NM_004646.3. [O60500-1 ]
    UniGenei Hs.122186.

    3D structure databases

    ProteinModelPortali O60500.
    SMRi O60500. Positions 32-1022.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 110928. 17 interactions.
    IntActi O60500. 7 interactions.
    STRINGi 9606.ENSP00000368190.

    PTM databases

    PhosphoSitei O60500.

    Proteomic databases

    PaxDbi O60500.
    PRIDEi O60500.

    Protocols and materials databases

    DNASUi 4868.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000353632 ; ENSP00000343634 ; ENSG00000161270 . [O60500-2 ]
    ENST00000378910 ; ENSP00000368190 ; ENSG00000161270 . [O60500-1 ]
    GeneIDi 4868.
    KEGGi hsa:4868.
    UCSCi uc002oby.3. human. [O60500-1 ]

    Organism-specific databases

    CTDi 4868.
    GeneCardsi GC19M036316.
    HGNCi HGNC:7908. NPHS1.
    HPAi CAB035555.
    MIMi 256300. phenotype.
    602716. gene.
    neXtProti NX_O60500.
    Orphaneti 839. Congenital nephrotic syndrome, Finnish type.
    93214. Familial idiopathic steroid-resistant nephrotic syndrome with diffuse mesangial proliferation.
    93213. Familial idiopathic steroid-resistant nephrotic syndrome with focal segmental hyalinosis.
    93216. Familial idiopathic steroid-resistant nephrotic syndrome with minimal changes.
    PharmGKBi PA31709.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG251936.
    HOGENOMi HOG000113844.
    HOVERGENi HBG031752.
    InParanoidi O60500.
    OMAi NVNEGSQ.
    OrthoDBi EOG7RBZ7J.
    PhylomeDBi O60500.
    TreeFami TF327139.

    Enzyme and pathway databases

    Reactomei REACT_23832. Nephrin interactions.
    SignaLinki O60500.

    Miscellaneous databases

    GeneWikii Nephrin.
    GenomeRNAii 4868.
    NextBioi 18748.
    PROi O60500.
    SOURCEi Search...

    Gene expression databases

    Bgeei O60500.
    CleanExi HS_NPHS1.
    Genevestigatori O60500.

    Family and domain databases

    Gene3Di 2.60.40.10. 10 hits.
    InterProi IPR013162. CD80_C2-set.
    IPR003961. Fibronectin_type3.
    IPR007110. Ig-like_dom.
    IPR013783. Ig-like_fold.
    IPR013098. Ig_I-set.
    IPR003599. Ig_sub.
    IPR003598. Ig_sub2.
    IPR013106. Ig_V-set.
    [Graphical view ]
    Pfami PF08205. C2-set_2. 5 hits.
    PF00041. fn3. 1 hit.
    PF07679. I-set. 1 hit.
    PF07686. V-set. 1 hit.
    [Graphical view ]
    SMARTi SM00060. FN3. 1 hit.
    SM00409. IG. 5 hits.
    SM00408. IGc2. 1 hit.
    [Graphical view ]
    SUPFAMi SSF49265. SSF49265. 1 hit.
    PROSITEi PS50853. FN3. 1 hit.
    PS50835. IG_LIKE. 7 hits.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Positionally cloned gene for a novel glomerular protein -- nephrin --is mutated in congenital nephrotic syndrome."
      Kestilae M., Lenkkeri U., Maennikkoe M., Lamerdin J.E., McCready P., Putaala H., Ruotsalainen V., Morita T., Nissinen M., Herva R., Kashtan C.E., Peltonen L., Holmberg C., Olsen A., Tryggvason K.
      Mol. Cell 1:575-582(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INVOLVEMENT IN NPHS1.
    2. "Novel human pathological mutations. Gene symbol: NPHS1. Disease: congenital nephrotic syndrome, Finnish type."
      Tikhomirov E., Voznesenskaya T., Tsygin A.
      Hum. Genet. 125:334-334(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT LYS-117.
    3. "Human nephrin (NPHS1) cDNA sequence."
      Grunkemeyer J.A., Kumar N., Kalluri R.
      Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    4. "The DNA sequence and biology of human chromosome 19."
      Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V.
      , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M.
      Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    5. "Nephrin localizes at the podocyte filtration slit area and is characteristically spliced in the human kidney."
      Holthoefer H., Ahola H., Solin M.-L., Wang S.-X., Palmen T., Luimula P., Miettinen A., Kerjaschki D.
      Am. J. Pathol. 155:1681-1687(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1032-1134 (ISOFORM 2), SUBCELLULAR LOCATION.
    6. Cited for: SUBCELLULAR LOCATION.
    7. "Interaction with podocin facilitates nephrin signaling."
      Huber T.B., Kottgen M., Schilling B., Walz G., Benzing T.
      J. Biol. Chem. 276:41543-41546(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH NPHS2.
    8. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-432, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Platelet.
    9. "Structure of the gene for congenital nephrotic syndrome of the Finnish type (NPHS1) and characterization of mutations."
      Lenkkeri U., Maennikkoe M., McCready P., Lamerdin J., Gribouval O., Niaudet P.M., Antignac C.K., Kashtan C.E., Homberg C., Olsen A., Kestilae M., Tryggvason K.
      Am. J. Hum. Genet. 64:51-61(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS LYS-117 AND SER-1077, VARIANTS NPHS1 SER-64; ASN-171; THR-172 DEL; ASN-173; 205-THR--ARG-207 DELINS ILE; CYS-270; PRO-350; ARG-366; CYS-367; SER-368; VAL-376; GLN-408; TYR-465; PHE-528; GLN-610; PHE-623; CYS-724; CYS-743; TRP-802; PRO-802; ASP-806; CYS-831 AND CYS-1140.
    10. "Novel mutation in the nephrin gene of a Japanese patient with congenital nephrotic syndrome of the Finnish type."
      Aya K., Tanaka H., Seino Y.
      Kidney Int. 57:401-404(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT NPHS1 VAL-819, VARIANT LYS-447.
    11. "Defective nephrin trafficking caused by missense mutations in the NPHS1 gene: insight into the mechanisms of congenital nephrotic syndrome."
      Liu L., Done S.C., Khoshnoodi J., Bertorello A., Wartiovaara J., Berggren P.O., Tryggvason K.
      Hum. Mol. Genet. 10:2637-2644(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: CHARACTERIZATION OF VARIANTS NPHS1 SER-64; ASN-171; ASN-173; CYS-270; PRO-350; ARG-366; CYS-367; SER-368; VAL-376; GLN-408; TYR-465; PHE-528; GLN-610; PHE-623; CYS-724; CYS-743; TRP-802; PRO-802; ASP-806; CYS-831 AND CYS-1140.
    12. "Mutation spectrum in the nephrin gene (NPHS1) in congenital nephrotic syndrome."
      Beltcheva O., Martin P., Lenkkeri U., Tryggvason K.
      Hum. Mutat. 17:368-373(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS NPHS1 SER-64; ASN-171; THR-172 DEL; ASN-173; CYS-270; PRO-350; ARG-366; CYS-367; LEU-368; SER-368; VAL-376; TRP-379; GLN-408; PHE-417; GLN-460; TYR-465; PHE-528; CYS-558; GLN-610; PHE-623; CYS-724; VAL-739; CYS-743; TRP-802; PRO-802; ASP-806; VAL-819 AND PHE-834, VARIANTS LYS-117; ARG-264; LYS-447; ARG-617; ASP-725; VAL-851 AND SER-1077.
    13. Cited for: VARIANTS NPHS1 ARG-265 AND MET-822.
    14. Cited for: VARIANTS NPHS1 VAL-96; THR-107; GLN-460; GLN-575; PRO-832 AND SER-976, CHARACTERIZATION OF VARIANT NPHS1 PRO-832.
    15. "Thirteen novel NPHS1 mutations in a large cohort of children with congenital nephrotic syndrome."
      Heeringa S.F., Vlangos C.N., Chernin G., Hinkes B., Gbadegesin R., Liu J., Hoskins B.E., Ozaltin F., Hildebrandt F.
      Nephrol. Dial. Transplant. 23:3527-3533(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS NPHS1 TRP-256; CYS-367; CYS-412; SER-519; ARG-569 AND GLY-709.
    16. Cited for: VARIANTS NPHS1 VAL-107; LEU-167; THR-172 DEL; 205-THR--ARG-207 DELINS ILE; CYS-299; HIS-340; GLU-347; PRO-350; ARG-366; CYS-367; TRP-407; GLN-408; GLN-460; CYS-558; ASN-572; GLY-586; ARG-587; PHE-623; LYS-673; CYS-681; CYS-743; PRO-910; SER-976 AND CYS-1140.
    17. "Two novel NPHS1 mutations in a Chinese family with congenital nephrotic syndrome."
      Wu L.Q., Hu J.J., Xue J.J., Liang D.S.
      Genet. Mol. Res. 10:2517-2522(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT NPHS1 THR-742, VARIANT LYS-117.

    Entry informationi

    Entry nameiNPHN_HUMAN
    AccessioniPrimary (citable) accession number: O60500
    Secondary accession number(s): A6NDH2, C3RX61
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: April 16, 2002
    Last sequence update: August 1, 1998
    Last modified: October 1, 2014
    This is version 138 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 19
      Human chromosome 19: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3