NPHP4 nephrocystin 4 [Homo sapiens (human)] - Gene

Summary

Official Symbol: NPHP4provided by HGNC
Official Full Name: nephrocystin 4provided by HGNC
Primary source: HGNC:HGNC:19104
See related: Ensembl:ENSG00000131697 MIM:607215; AllianceGenome:HGNC:19104
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: POC10; SLSN4
Summary: This gene encodes a protein involved in renal tubular development and function. This protein interacts with nephrocystin, and belongs to a multifunctional complex that is localized to actin- and microtubule-based structures. Mutations in this gene are associated with nephronophthisis type 4, a renal disease, and with Senior-Loken syndrome type 4, a combination of nephronophthisis and retinitis pigmentosa. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2014]
Expression: Broad expression in testis (RPKM 3.4), thyroid (RPKM 2.6) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 1p36.31

Exon count:: 38

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	1	NC_000001.11 (5862811..5992425, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	1	NC_060925.1 (5387041..5518608, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	1	NC_000001.10 (5922871..6052485, 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?

A novel NPHP4 homozygous missense variant identified in infertile brothers with multiple morphological abnormalities of the sperm flagella.
Title: A novel NPHP4 homozygous missense variant identified in infertile brothers with multiple morphological abnormalities of the sperm flagella.
Association of Nephronophthisis 4 genetic variation with cardiorenal syndrome and cardiovascular events in Japanese general population: the Yamagata (Takahata) study.
Title: Association of Nephronophthisis 4 genetic variation with cardiorenal syndrome and cardiovascular events in Japanese general population: the Yamagata (Takahata) study.
SENIOR-LOKEN SYNDROME: A Case Series and Review of the Renoretinal Phenotype and Advances of Molecular Diagnosis.
Title: SENIOR-LØKEN SYNDROME: A Case Series and Review of the Renoretinal Phenotype and Advances of Molecular Diagnosis.
Adult-Diagnosed Nonsyndromic Nephronophthisis in Australian Families Caused by Biallelic NPHP4 Variants.
Title: Adult-Diagnosed Nonsyndromic Nephronophthisis in Australian Families Caused by Biallelic NPHP4 Variants.
Study provides evidence that KIF13B and NPHP4 are both required for establishment of a specialized caveolin-1 membrane microdomain at the ciliary transition zone, which is essential for Shh-induced accumulation of SMO in the primary cilium as well as for activation of GLI-mediated target gene expression.
Title: KIF13B establishes a CAV1-enriched microdomain at the ciliary transition zone to promote Sonic hedgehog signalling.
Inherited 3 deleterious mutations in two nephronophthisis genes, NPHP3 and NPHP4 cause unusually severe form of infantile nephronophthisis.
Title: A familial case of severe infantile nephronophthisis explained by oligogenic inheritance.
homozygous NPHP4 truncating mutation that expands the phenotypic spectrum of NPHP4-related nephronophthisis to also include cerebello-oculo-renal syndrome and abnormal spermatogenesis causing male infertility
Title: NPHP4 mutation is linked to cerebello-oculo-renal syndrome and male infertility.
The ciliary protein nephrocystin-4 translocates the canonical Wnt regulator Jade-1 to the nucleus to negatively regulate beta-catenin signaling.
Title: The ciliary protein nephrocystin-4 translocates the canonical Wnt regulator Jade-1 to the nucleus to negatively regulate β-catenin signaling.
NPHP4 mutations are associated with cardiac laterality defects and heterotaxy.
Title: NPHP4 variants are associated with pleiotropic heart malformations.
Identify NPHP4 as a negative regulator of the Hippo pathway and suggest that NPHP4 regulates cell proliferation through its effects on Hippo signaling.
Title: NPHP4, a cilia-associated protein, negatively regulates the Hippo pathway.

Submit: New GeneRIF Correction See all GeneRIFs (23)

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
Nephronophthisis 4 MedGen: C1847013 OMIM: 606966 GeneReviews: Nephronophthisis-Related Ciliopathies	not available
Senior-Loken syndrome 4 MedGen: C1846979 OMIM: 606996 GeneReviews: Not available	not available

EBI GWAS Catalog

Description
Common variants at ten loci influence QT interval duration in the QTGEN Study. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genetic association with overall survival of taxane-treated lung cancer patients - A genome-wide association study in human lymphoblastoid cell lines followed by a clinical association study. EBI GWAS Catalog EBI GWAS CatalogPubMed

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

D1S1323 (e-PCR)
- UniSTS:149520

RH119046 (e-PCR)
- UniSTS:138274

D1S1824E (e-PCR)
- UniSTS:15433

D1S3371 (e-PCR)
- UniSTS:82637

D1S253 (e-PCR)
- UniSTS:72145

DXS7419 (e-PCR)
- UniSTS:10733

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables structural molecule activity	NAS Non-traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
involved_in actin cytoskeleton organization	NAS Non-traceable Author Statement more info	PubMed
involved_in cell-cell adhesion	NAS Non-traceable Author Statement more info	PubMed
involved_in flagellated sperm motility	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of canonical Wnt signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of canonical Wnt signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in photoreceptor cell maintenance	IEA Inferred from Electronic Annotation more info
involved_in photoreceptor cell outer segment organization	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of bicellular tight junction assembly	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein localization to ciliary transition zone	IBA Inferred from Biological aspect of Ancestor more info
involved_in retina development in camera-type eye	IEA Inferred from Electronic Annotation more info
involved_in signal transduction	NAS Non-traceable Author Statement more info	PubMed
involved_in visual behavior	NAS Non-traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
located_in bicellular tight junction	IEA Inferred from Electronic Annotation more info
located_in cell-cell junction	IDA Inferred from Direct Assay more info	PubMed
located_in centriole	IEA Inferred from Electronic Annotation more info
located_in centrosome	IDA Inferred from Direct Assay more info	PubMed
is_active_in ciliary basal body	IBA Inferred from Biological aspect of Ancestor more info
is_active_in ciliary base	IBA Inferred from Biological aspect of Ancestor more info
is_active_in ciliary transition zone	IBA Inferred from Biological aspect of Ancestor more info
located_in cytosol	IDA Inferred from Direct Assay more info
located_in cytosol	TAS Traceable Author Statement more info
located_in intracellular membrane-bounded organelle	IDA Inferred from Direct Assay more info
is_active_in non-motile cilium	IBA Inferred from Biological aspect of Ancestor more info
located_in nuclear body	IDA Inferred from Direct Assay more info
located_in nucleoplasm	IDA Inferred from Direct Assay more info
located_in photoreceptor distal connecting cilium	IEA Inferred from Electronic Annotation more info
located_in ribbon synapse	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: nephrocystin-4

Names: POC10 centriolar protein homolog; nephroretinin

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_011724.2 RefSeqGene

Range

5047..134661

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001291593.2 → NP_001278522.1 nephrocystin-4 isoform b

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks three exons and uses an alternate splice site in the 5' region, and initiates translation at an alternate downstream start codon, compared to variant 1. The encoded isoform (b) has a distinct N-terminus and is shorter than isoform 1.

Source sequence(s)

AK124074, AK314326

UniProtKB/TrEMBL

B3KW36
NM_001291594.2 → NP_001278523.1 nephrocystin-4 isoform c

See identical proteins and their annotated locations for NP_001278523.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) lacks four exons in the 5' region, and initiates translation at an alternate downstream start codon, compared to variant 1. The encoded isoform (c) has a distinct N-terminus and is shorter than isoform 1.

Source sequence(s)

AK124074, AK314326, BC040520

UniProtKB/TrEMBL

B3KW36

Related

ENST00000478423.6
NM_015102.5 → NP_055917.1 nephrocystin-4 isoform a

See identical proteins and their annotated locations for NP_055917.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longest isoform (a).

Source sequence(s)

AF537130, AK314326, BU738621, R40620

Consensus CDS

CCDS44052.1

UniProtKB/Swiss-Prot

O75161, Q8IWC0

Related

ENSP00000367398.4, ENST00000378156.9

RNA

NR_111987.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (4) contains three alternate internal exons and uses an alternate splice site, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AL356693, BC040520, R40620

Related

ENST00000489180.6