Human Disease Model Report: nephrotic syndrome, type 12

General Information

Name

nephrotic syndrome, type 12

FlyBase ID

FBhh0001483

Disease Ontology Term

nephrotic syndrome type 12

Parent Disease

nephrotic syndrome

OMIM

NEPHROTIC SYNDROME, TYPE 12; NPHS12

Overview

This report describes nephrotic syndrome, type 12, a subtype of nephrotic syndrome that exhibits autosomal recessive inheritance. The human gene implicated is NUP93, which encodes a critical component of the nuclear pore complex. There are two high-scoring fly orthologs, Dmel\Nup93-1 and Dmel\Nup93-2, for which classical alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated.

The human NUP93 gene has not been introduced into flies.

RNAi knockdown of either Dmel\Nup93-1 or Dmel\Nup93-2 in developing nephrocytes results in a significant reduction in the number of pericardial nephrocytes in adult flies, with surviving nephrocytes exhibiting an abnormal morphology.

[updated Nov. 2022 by FlyBase; FBrf0222196]

Disease Summary Information

Parent Disease Summary: nephrotic syndrome

Symptoms and phenotype

The nephrotic syndrome is characterized clinically by proteinuria, hypoalbuminemia, hyperlipidemia, and edema. Kidney biopsies show nonspecific histologic changes such as minimal change, focal segmental glomerulosclerosis (FSGS), and diffuse mesangial proliferation. Approximately 20% of affected individuals have an inherited steroid-resistant form and progress to end-stage renal failure (summary by Fuchshuber et al., 1996, pubmed:8606597). [From MIM:256300, 2016.06.13]

(OMIM, 2013-)

Specific Disease Summary: nephrotic syndrome, type 12

OMIM report

[NEPHROTIC SYNDROME, TYPE 12; NPHS12](https://omim.org/entry/616892)

Human gene(s) implicated

[NUCLEOPORIN, 93-KD; NUP93](https://omim.org/entry/614351)

Symptoms and phenotype

Nephrotic syndrome type 12 is an autosomal recessive renal disorder caused by defects in the renal glomerular filter. Affected individuals have onset of progressive renal failure in the first years of life. Renal biopsy typically shows focal segmental glomerulosclerosis (FSGS) (summary by Braun et al., 2016; pubmed:26878725). [from MIM:616892; 2022.11.04]

(OMIM, 2013-)

Genetics

Nephrotic syndrome type 12 is caused by homozygous or compound heterozygous mutation in the NUP93 gene on chromosome 16q13. [from MIM:616892; 2022.11.04]

(OMIM, 2013-)

Cellular phenotype and pathology

Molecular information

NUP93 is a critical subunit of the 120-million-Da nuclear pore complex, which functions in active transport of molecules between the nucleus and cytoplasm (Grandi et al., 1997; pubmed:9348540). [from MIM:614351; 2022.11.04]

(OMIM, 2013-)

External links

Gene2Function (human gene): NUP93
Gene Cards: NUP93
GeneReviews, NCBI Bookshelf: Congenital Nephrotic Syndrome
GeneReviews, NCBI Bookshelf: Genetic Steroid-Resistant Nephrotic Syndrome Overview
MedlinePlus (condition): Congenital nephrotic syndrome
MedlinePlus (gene): NUP93
MARRVEL (human gene): NUP93
NCBI MedGen: Congenital nephrotic syndrome
NCBI (Entrez) gene: NUP93; nucleoporin 93

Disease synonyms

NPHS12

paediatric onset SRNS

paediatric steroid-resistant nephrotic syndrome

pediatric onset SRNS

pediatric steroid-resistant nephrotic syndrome

SRNS

Related Diseases

Related human health report(s)

Related Specific Diseases

OMIM phenotypic series

Nephrotic syndrome

Disease

Associated Human gene(s)

Drosophila model

Human transgene in Drosophila

[NPHS1](https://omim.org/entry/256300)

[NPHS1](https://omim.org/entry/602716)

nephrotic syndrome, type 1

[NPHS2](https://omim.org/entry/600995)

[NPHS2](https://omim.org/entry/604766)

nephrotic syndrome, type 2

[NPHS3](https://omim.org/entry/610725)

[PLCE1](https://omim.org/entry/608414)

[NPHS4](https://omim.org/entry/256370)

[WT1](https://omim.org/entry/607102)

[NPHS5](https://omim.org/entry/614199)

[LAMB2](https://omim.org/entry/150325)

[NPHS6](https://omim.org/entry/614196)

[PTPRO](https://omim.org/entry/600579)

[NPHS7](https://omim.org/entry/615008)

[DGKE](https://omim.org/entry/601440)

[NPHS8](https://omim.org/entry/615244)

[ARHGDIA](https://omim.org/entry/601925)

[NPHS9](https://omim.org/entry/615573)

[COQ8B](https://omim.org/entry/615567)

nephrotic syndrome, type 9

[NPHS10](https://omim.org/entry/615861)

[EMP2](https://omim.org/entry/602334)

[NPHS11](https://omim.org/entry/616730)

[NUP107](https://omim.org/entry/607617)

[NPHS12](https://omim.org/entry/616892)

[NUP93](https://omim.org/entry/614351)

nephrotic syndrome, type 12

[NPHS13](https://omim.org/entry/616893)

[NUP205](https://omim.org/entry/614352)

[NPHS15](https://omim.org/entry/617609)

[MAGI2](https://omim.org/entry/606382)

[NPHS16](https://omim.org/entry/617783)

[KANK2](https://omim.org/entry/614610)

nephrotic syndrome, type 16

[NPHS17](https://omim.org/entry/618176)

[NUP85](https://omim.org/entry/170285)

[NPHS18](https://omim.org/entry/618177)

[NUP133](https://omim.org/entry/607613)

[NPHS19](https://omim.org/entry/618178)

[NUP160](https://omim.org/entry/607614)

nephrotic syndrome, type 19

[NPHS20](https://omim.org/entry/301028)

[TBC1D8B](https://omim.org/entry/301027)

nephrotic syndrome, type 20

[NPHS21](https://omim.org/entry/618594)

[AVIL](https://omim.org/entry/613397)

[NPHS22](https://omim.org/entry/619155)

[NOS1AP](https://omim.org/entry/605551)

[NPHS23](https://omim.org/entry/619201)

[KIRREL1](https://omim.org/entry/607428)

nephrotic syndrome, type 23

[RENI](https://omim.org/entry/617575)

[SGPL1](https://omim.org/entry/603729)

nephrotic syndrome, type 14

Ortholog Information

Human gene(s) in FlyBase

Human gene (HGNC)

Symbol / Name

NUP93; nucleoporin 93

D. melanogaster ortholog (based on DIOPT)

Dmel\Nup93-1

(DIOPT, 2013-)

Dmel\Nup93-2

(DIOPT, 2013-)

Comments on ortholog(s)

One to two (1 human to 2 Drosophila); there are two high-scoring Drosophila orthologs of human NUP93.

Other mammalian ortholog(s) used

D. melanogaster Gene Information (2)

Dmel\Nup93-1

Gene Snapshot

Nucleoporin 93kD-1 (Nup93-1) encodes a protein that directly interacts with the product of Nup154. However, the product of Nup93-1 is not necessary for the Nup154-dependent organization of the inner nuclear membrane proteins at the nuclear envelope. [Date last reviewed: 2019-03-14]

Molecular function (GO)

Cellular component (GO)

Gene Groups / Pathways

Comments on ortholog(s)

High-scoring ortholog of human NUP93 (2 Drosophila to 1 human); both Nup93-1 and Nup93-2 are high-scoring orthologs of human NUP93.

Orthologs and Alignments from DRSC

DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans

H. sapiens (Human)

Dmel\Nup93-2

Gene Snapshot

Contributions welcome

Molecular function (GO)

structural constituent of nuclear pore

Cellular component (GO)

Gene Groups / Pathways

Comments on ortholog(s)

High-scoring ortholog of human NUP93 (2 Drosophila to 1 human); both Nup93-2 and Nup93-1 are high-scoring orthologs of human NUP93.

Orthologs and Alignments from DRSC

DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans

H. sapiens (Human)

Other Genes Used: Viral, Bacterial, Synthetic (0)

Summary of Physical Interactions (12 groups)

Nup93-1

protein-protein

Interacting group

Assay

References

Nup93-1 - didum

pull down, anti tag western blot

(Finan et al., 2011)

Nup93-1 - E(z)

anti bait coimmunoprecipitation, western blot

(Gozalo et al., 2020)

Nup93-1 - jar

pull down, anti tag western blot

(Finan et al., 2011)

Nup93-1 - Nup54

proximity-dependent biotin identification, Identification by mass spectrometry

(Munafò et al., 2021)

Nup93-1 - Nup58

proximity-dependent biotin identification, Identification by mass spectrometry

(Munafò et al., 2021)

Nup93-1 - Nup154

pull down, western blot, autoradiography

(Busayavalasa et al., 2012)

Nup93-1 - Pc

anti bait coimmunoprecipitation, western blot

(Gozalo et al., 2020)

Nup93-1 - RfC4

two hybrid

(Hu et al., 2017.6.13)

Nup93-1 - RYBP

anti bait coimmunoprecipitation, western blot

(Gozalo et al., 2020)

Nup93-2

protein-protein

Interacting group

Assay

References

Nup93-2 - E(z)

anti bait coimmunoprecipitation, western blot

(Gozalo et al., 2020)

Nup93-2 - Pc

anti bait coimmunoprecipitation, western blot

(Gozalo et al., 2020)

Nup93-2 - RYBP

anti bait coimmunoprecipitation, western blot

(Gozalo et al., 2020)

Alleles Reported to Model Human Disease (Disease Ontology) (3 alleles)

Nup93-1

Models Based on Experimental Evidence ( 1 )

Allele

Disease

Evidence

References

Nup93-1^HMS00898

model of nephrotic syndrome type 12

CEC

(Bierzynska et al., 2022)

Modifiers Based on Experimental Evidence ( 1 )

Allele

Disease

Interaction

References

Nup93-1^JF01712

exacerbates C9orf72 frontotemporal dementia and/or amyotrophic lateral sclerosis

modeled by Zzzz\poly-PR^{25.UAS.Tag:FLAG}

(Boeynaems et al., 2016)

Nup93-2

Models Based on Experimental Evidence ( 1 )

Allele

Disease

Evidence

References

Nup93-2^HMC03310

model of nephrotic syndrome type 12

CEC

(Bierzynska et al., 2022)

Modifiers Based on Experimental Evidence ( 0 )

Allele

Disease

Interaction

References

Alleles Representing Disease-Implicated Variants

Genetic Tools, Stocks and Reagents

Sources of Stocks

Contact lab of origin for a reagent not available from a public stock center.

Bloomington Stock Center Disease Page

Related mammalian, viral, bacterial, or synthetic transgenes

Allele

Transgene

Publicly Available Stocks

Selected Drosophila transgenes

Allele

Transgene

Publicly Available Stocks

RNAi constructs available

Allele

Transgene

Publicly Available Stocks

Nup93-1^RNAi.UAS.cUa

P{UAS-Nup93-1.RNAi.U}

Nup93-1^GD7196

P{GD7196}

w¹¹¹⁸; P{GD7196}v16189/TM3

y¹ v¹; P{TRiP.JF01712}attP2/TM3, Sb¹

Nup93-1^HMS00850

P{TRiP.HMS00850}

y¹ sc^* v¹ sev²¹; P{TRiP.HMS00850}attP2

Nup93-1^HMS00898

P{TRiP.HMS00898}

y¹ sc^* v¹ sev²¹; P{TRiP.HMS00898}attP2

Nup93-2^GD12186

P{GD12186}

w¹¹¹⁸; P{GD12186}v22552

Nup93-2^HMC03310

P{TRiP.HMC03310}

y¹ sc^* v¹ sev²¹; P{TRiP.HMC03310}attP2

Selected Drosophila classical alleles

Allele

Allele class

Mutagen

Publicly Available Stocks

References (4)

Report Sections

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