NPHS2 NPHS2 stomatin family member, podocin [Homo sapiens (human)] - Gene

Summary

Official Symbol: NPHS2provided by HGNC
Official Full Name: NPHS2 stomatin family member, podocinprovided by HGNC
Primary source: HGNC:HGNC:13394
See related: Ensembl:ENSG00000116218 MIM:604766
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: PDCN; SRN1
Summary: This gene encodes a protein that plays a role in the regulation of glomerular permeability. Mutations in this gene cause steroid-resistant nephrotic syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]
Expression: Restricted expression toward kidney (RPKM 45.3) See more
Orthologs: mouse all

Genomic context

Location:: 1q25.2

Exon count:: 8

Annotation release	Status	Assembly	Chr	Location
109.20200815	current	GRCh38.p13 (GCF_000001405.39)	1	NC_000001.11 (179550539..179575987, complement)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	1	NC_000001.10 (179519674..179545086, complement)

Chromosome 1 - NC_000001.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

ULK-1 with EGFR can predict early impairment in DN while PDCN can highlight progressive diabetic nephropathy (DN) risk EGFR and PDCN may interact synergistically with ULK-1 in autophagy dysregulation as a pathogenic mechanism of DN induction and progression.
Title: Epidermal growth factor receptor and podocin predict nephropathy progression in type 2 diabetic patients through interaction with the autophagy influencer ULK-1.
Haplotype analysis suggests a single mutation origin for V260E and it was associated with a decline in kidney function over a 60-month period (p = 0.026). The V260E variant is a good predictor of autosomal recessive SRNS in black South African children and could provide useful information in a clinical setting.
Title: The podocin V260E mutation predicts steroid resistant nephrotic syndrome in black South African children with focal segmental glomerulosclerosis.
Study identified three different polymorphisms in the NPHS2 gene in 7 patients with focal segmental glomerulosclerosis but none was detected in the Iranian cohort with steroid-resistant nephrotic syndrome.
Title: TRPC6 and NPHS2 gene variants in adult patients with steroid-resistant nephrotic syndrome in North-West of Iran.
The NPHS2 variant has been previously reported as likely pathogenic (rs61747728) and associated with Nephrotic Syndrome, was also found in Alport syndrome patients.
Title: Non-collagen genes role in digenic Alport syndrome.
Focal and segmental glomerulosclerosis pediatric patients express less podocin and more uPAR than controls.
Title: Podocin and uPAR are good biomarkers in cases of Focal and segmental glomerulosclerosis in pediatric renal biopsies.
It seems that NPHS2, especially exons 4 and 5, should be considered as the first step in genetic evaluation of Iranian patients of Nephrotic syndrome.
Title: Molecular Genetic Analysis of Steroid Resistant Nephrotic Syndrome, Detection of a Novel Mutation.
In this article, we review the emerging knowledge about the NPHS2 gene and translate these findings from the bench to practical advice for the clinical bedside
Title: Nephrotic Syndrome With Mutations in NPHS2: The Role of R229Q and Implications for Genetic Counseling.
Study show that a rare p.R229Q association can be considered pathogenic if the variant in trans affects the 270-351 residues and alters but does not disrupt the oligomerization, its p.R229Q association is found in a family with slowly progressing focal segmental glomerulosclerosis, but is expected to be rare in the general population. More than 15% of the p.R229Q association identified in patients are benign. [review]
Title: The mutation-dependent pathogenicity of NPHS2 p.R229Q: A guide for clinical assessment.
Results found that in addition to mutations in COL4A5 type IV collagen gene, nephrin and podocin polymorphisms aggravated kidney damage, leading to focal segmental glomerulosclerosis (FSGS) with ruptures of the basement membrane and early renal failure. This study suggests a synergistic role for genes encoding basement membrane and slit diaphragm proteins as a cause of kidney injury due to FSGS.
Title: Kidney Injury by Variants in the <i>COL4A5</i> Gene Aggravated by Polymorphisms in Slit Diaphragm Genes Causes Focal Segmental Glomerulosclerosis.
Pathogenic and likely pathogenic mutations in NPHS1, NPHS2, PLCE1 genes were identified by genetic testing of South Indian children with steroid resistant nephrotic syndrome.
Title: Targeted gene panel for genetic testing of south Indian children with steroid resistant nephrotic syndrome.

Submit: New GeneRIF Correction See all GeneRIFs (120)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Nephrotic syndrome, idiopathic, steroid-resistant MedGen: CN034406 OMIM: 600995 GeneReviews: Not available	Compare labs

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

NPHS2__6070 (e-PCR)
- UniSTS:463643

PMC151634P1 (e-PCR)
- UniSTS:271156

PMC151634P2 (e-PCR)
- UniSTS:271157

RH92018 (e-PCR)
- UniSTS:88117

PMC151634P3 (e-PCR)
- UniSTS:271158

PMC151634P4 (e-PCR)
- UniSTS:271159

PMC151634P5 (e-PCR)
- UniSTS:271160

D1S1640 (e-PCR)
- UniSTS:16039

Homology

Homologs of the NPHS2 gene: The NPHS2 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, and frog.
Orthologs from Annotation Pipeline: 251 organisms have orthologs with human gene NPHS2
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
actin cytoskeleton reorganization	IDA Inferred from Direct Assay more info	PubMed
excretion	TAS Traceable Author Statement more info	PubMed
metanephric glomerular visceral epithelial cell development	IEP Inferred from Expression Pattern more info	PubMed

Component	Evidence Code	Pubs
cell-cell junction	IDA Inferred from Direct Assay more info	PubMed
endoplasmic reticulum	IEA Inferred from Electronic Annotation more info
extracellular exosome	HDA more info	PubMed
integral component of plasma membrane	TAS Traceable Author Statement more info	PubMed
intrinsic component of the cytoplasmic side of the plasma membrane	IDA Inferred from Direct Assay more info	PubMed
membrane raft	IDA Inferred from Direct Assay more info	PubMed
plasma membrane	IBA Inferred from Biological aspect of Ancestor more info	PubMed
plasma membrane	TAS Traceable Author Statement more info
protein-containing complex	IDA Inferred from Direct Assay more info	PubMed
colocalizes_with slit diaphragm	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: podocin

Names: NPHS2, podocin; nephrosis 2, idiopathic, steroid-resistant (podocin)

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_007535.1 RefSeqGene

Range

4998..30411

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_887

mRNA and Protein(s)

NM_001297575.2 → NP_001284504.1 podocin isoform 2

See identical proteins and their annotated locations for NP_001284504.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an alternate in-frame exon, compared to variant 1. The encoded isoform (2) is shorter than isoform 1.

Source sequence(s)

AL160286, BC029141, BI831348, BX095913

Consensus CDS

CCDS72988.1

UniProtKB/Swiss-Prot

Q9NP85

Related

ENSP00000356588.4, ENST00000367616.4

Conserved Domains (1) summary

cl19107
Location:122 → 276

SPFH_like; core domain of the SPFH (stomatin, prohibitin, flotillin, and HflK/C) superfamily
NM_014625.4 → NP_055440.1 podocin isoform 1

See identical proteins and their annotated locations for NP_055440.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).

Source sequence(s)

AJ279254, AL160286, BC029141, BX095913

Consensus CDS

CCDS1331.1

UniProtKB/Swiss-Prot

Q9NP85

Related

ENSP00000356587.4, ENST00000367615.9

Conserved Domains (2) summary

smart00244
Location:123 → 287

PHB; prohibitin homologues

cd08827
Location:122 → 344

SPFH_podocin; Podocin, a subgroup of the stomatin-like proteins (slipins) family; belonging to the SPFH (stomatin, prohibitin, flotillin, and HflK/C) superfamily

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.20200815

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p13 Primary Assembly

Genomic

NC_000001.11 Reference GRCh38.p13 Primary Assembly

Range

179550539..179575987 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_017002298.1 → XP_016857787.1 podocin isoform X2
XM_005245483.3 → XP_005245540.1 podocin isoform X1

Conserved Domains (2) summary

smart00244
Location:90 → 228

PHB; prohibitin homologues

cl19107
Location:92 → 285

SPFH_like; core domain of the SPFH (stomatin, prohibitin, flotillin, and HflK/C) superfamily
XM_017002299.1 → XP_016857788.1 podocin isoform X3