NPNT nephronectin [Homo sapiens (human)] - Gene

Summary

Official Symbol: NPNTprovided by HGNC
Official Full Name: nephronectinprovided by HGNC
Primary source: HGNC:HGNC:27405
See related: Ensembl:ENSG00000168743 MIM:610306; AllianceGenome:HGNC:27405
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: POEM; EGFL6L
Summary: Predicted to enable integrin binding activity. Predicted to be involved in several processes, including cell-cell adhesion mediated by integrin; positive regulation of ERK1 and ERK2 cascade; and positive regulation of alkaline phosphatase activity. Predicted to act upstream of or within positive regulation of transforming growth factor beta receptor signaling pathway. Located in collagen-containing extracellular matrix and extracellular exosome. [provided by Alliance of Genome Resources, Dec 2024]
Expression: Biased expression in thyroid (RPKM 91.1), lung (RPKM 60.2) and 10 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 4q24

Exon count:: 15

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	4	NC_000004.12 (105895471..105971671)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	4	NC_060928.1 (109206597..109282798)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	4	NC_000004.11 (106816628..106892828)

Chromosome 4 - NC_000004.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

LncRNA ADAMTS9-AS1 inhibits the stemness of lung adenocarcinoma cells by regulating miR-5009-3p/NPNT axis.
Title: LncRNA ADAMTS9-AS1 inhibits the stemness of lung adenocarcinoma cells by regulating miR-5009-3p/NPNT axis.
Missense Variants in <i>GFRA1</i> and <i>NPNT</i> Are Associated with Congenital Anomalies of the Kidney and Urinary Tract.
Title: Missense Variants in GFRA1 and NPNT Are Associated with Congenital Anomalies of the Kidney and Urinary Tract.
A null founder variant in NPNT, encoding nephronectin, causes autosomal recessive renal agenesis.
Title: A null founder variant in NPNT, encoding nephronectin, causes autosomal recessive renal agenesis.
Integrated analysis identified NPNT as a potential key regulator in tumor metastasis of hepatocellular carcinoma.
Title: Integrated analysis identified NPNT as a potential key regulator in tumor metastasis of hepatocellular carcinoma.
Glomerular Endothelial Cell-Derived microRNA-192 Regulates Nephronectin Expression in Idiopathic Membranous Glomerulonephritis.
Title: Glomerular Endothelial Cell-Derived microRNA-192 Regulates Nephronectin Expression in Idiopathic Membranous Glomerulonephritis.
A Biallelic Frameshift Mutation in Nephronectin Causes Bilateral Renal Agenesis in Humans.
Title: A Biallelic Frameshift Mutation in Nephronectin Causes Bilateral Renal Agenesis in Humans.
Nephronectin is a prognostic biomarker and promotes gastric cancer cell proliferation, migration and invasion.
Title: Nephronectin is a prognostic biomarker and promotes gastric cancer cell proliferation, migration and invasion.
Serum Npnt was found to be higher in silicosis patients compared to healthy volunteers and seems to play a role in the progression of fibrosis with other cytokines. [review]
Title: Role of Nephronectin in Pathophysiology of Silicosis.
Biopsies from patients with focal segmental glomerulosclerosis and membranous nephropathy had increased miR-378a-3p expression and reduced glomerular levels of NPNT.
Title: Podocytes regulate the glomerular basement membrane protein nephronectin by means of miR-378a-3p in glomerular diseases.
Nephronectin (NPNT), a member of the epidermal growth factor (EGF) repeat superfamily proteins and a homologue of EGFL6, is expressed in osteoblasts. Intriguingly, the gene expression of NPNT is reduced in the bone of osteoporosis patients.
Title: NPNT is Expressed by Osteoblasts and Mediates Angiogenesis via the Activation of Extracellular Signal-regulated Kinase.

Submit: New GeneRIF Correction See all GeneRIFs (15)

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

EBI GWAS Catalog

Description
Genome-wide joint meta-analysis of SNP and SNP-by-smoking interaction identifies novel loci for pulmonary function. EBI GWAS Catalog EBI GWAS CatalogPubMed
Meta-analyses of genome-wide association studies identify multiple loci associated with pulmonary function. 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

NoName (e-PCR)
- UniSTS:484445

STS-N22230 (e-PCR)
- UniSTS:76195

G20746 (e-PCR)
- UniSTS:4017

A006E27 (e-PCR)
- UniSTS:4018

SHGC-81233 (e-PCR)
- UniSTS:102369

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables calcium ion binding	IEA Inferred from Electronic Annotation more info
enables extracellular matrix structural constituent	RCA inferred from Reviewed Computational Analysis more info	PubMed
enables integrin binding	ISS Inferred from Sequence or Structural Similarity more info	PubMed
enables integrin binding	NAS Non-traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
involved_in branching involved in ureteric bud morphogenesis	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in cell-cell adhesion mediated by integrin	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in cell-matrix adhesion	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in cellular response to tumor necrosis factor	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in establishment of protein localization	IEA Inferred from Electronic Annotation more info
involved_in extracellular matrix organization	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in pilomotor reflex	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of ERK1 and ERK2 cascade	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in positive regulation of cell-substrate adhesion	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in positive regulation of osteoblast differentiation	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in positive regulation of smooth muscle contraction	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of transcription by RNA polymerase II	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of transforming growth factor beta receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in smooth muscle cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in transforming growth factor beta receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in ureteric bud development	ISS Inferred from Sequence or Structural Similarity more info	PubMed

Component	Evidence Code	Pubs
located_in basement membrane	IEA Inferred from Electronic Annotation more info
located_in collagen-containing extracellular matrix	HDA more info	PubMed
located_in collagen-containing extracellular matrix	ISS Inferred from Sequence or Structural Similarity more info
located_in extracellular exosome	HDA more info	PubMed
located_in extracellular region	ISS Inferred from Sequence or Structural Similarity more info	PubMed
located_in membrane	IEA Inferred from Electronic Annotation more info
located_in smooth muscle contractile fiber	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: nephronectin

Names: preosteoblast EGF-like repeat protein with MAM domain

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.

mRNA and Protein(s)

NM_001033047.3 → NP_001028219.1 nephronectin isoform B precursor

See identical proteins and their annotated locations for NP_001028219.1

Status: VALIDATED

Description

Transcript Variant: This variant (2) lacks an in-frame exon in the 5' coding region, compared to variant 1, and encodes a shorter protein (isoform B), compared to isoform A. This variant is also known as isoform 1.

Source sequence(s)

AC109361, AK290029, AK295772, AW607534

Consensus CDS

CCDS34046.1

UniProtKB/Swiss-Prot

A6NFT9, A8K1W4, B4DIT4, B4DYK3, B4E2H7, B4E3H2, D6RCA1, E9PCK8, E9PCQ1, E9PE64, E9PF04, Q6UXI9

UniProtKB/TrEMBL

D6RH31

Related

ENSP00000369323.2, ENST00000379987.7

Conserved Domains (5) summary

cd06263
Location:422 → 561

MAM; Meprin, A5 protein, and protein tyrosine phosphatase Mu (MAM) domain. MAM is an extracellular domain which mediates protein-protein interactions and is found in a diverse set of proteins, many of which are known to function in cell adhesion. Members ...

pfam00629
Location:422 → 563

MAM; MAM domain, meprin/A5/mu

pfam12662
Location:150 → 172

cEGF; Complement Clr-like EGF-like

pfam12947
Location:218 → 253

EGF_3; EGF domain

cl00057
Location:164 → 204

vWFA; Von Willebrand factor type A (vWA) domain was originally found in the blood coagulation protein von Willebrand factor (vWF). Typically, the vWA domain is made up of approximately 200 amino acid residues folded into a classic a/b para-rossmann type of ...
NM_001184690.2 → NP_001171619.1 nephronectin isoform A precursor

Status: VALIDATED

Description

Transcript Variant: This variant (1) encodes a protein (isoform A) of 582 amino acids.

Source sequence(s)

AC109361, AK295772, AW607534

Consensus CDS

CCDS54784.1

UniProtKB/TrEMBL

D6RH31

Related

ENSP00000402884.2, ENST00000453617.6

Conserved Domains (6) summary

cd06263
Location:439 → 578

MAM; Meprin, A5 protein, and protein tyrosine phosphatase Mu (MAM) domain. MAM is an extracellular domain which mediates protein-protein interactions and is found in a diverse set of proteins, many of which are known to function in cell adhesion. Members ...

pfam00629
Location:439 → 580

MAM; MAM domain, meprin/A5/mu

pfam07645
Location:186 → 218

EGF_CA; Calcium-binding EGF domain

pfam12662
Location:167 → 189

cEGF; Complement Clr-like EGF-like

pfam12947
Location:235 → 270

EGF_3; EGF domain

cl00057
Location:100 → 142

vWFA; Von Willebrand factor type A (vWA) domain was originally found in the blood coagulation protein von Willebrand factor (vWF). Typically, the vWA domain is made up of approximately 200 amino acid residues folded into a classic a/b para-rossmann type of ...
NM_001184691.2 → NP_001171620.1 nephronectin isoform C precursor

Status: VALIDATED

Description

Transcript Variant: This variant (3) has multiple differences in the presence/absence of in-frame exons in the 5' coding region, compared to variant 1, and encodes a longer protein (isoform C), compared to isoform A.

Source sequence(s)

AC109361, AK295772, AK302477, AW607534

Consensus CDS

CCDS54785.1

UniProtKB/TrEMBL

D6RH31

Related

ENSP00000389252.2, ENST00000427316.6

Conserved Domains (6) summary

cd06263
Location:452 → 591

MAM; Meprin, A5 protein, and protein tyrosine phosphatase Mu (MAM) domain. MAM is an extracellular domain which mediates protein-protein interactions and is found in a diverse set of proteins, many of which are known to function in cell adhesion. Members ...

pfam00629
Location:452 → 593

MAM; MAM domain, meprin/A5/mu

pfam07645
Location:199 → 231

EGF_CA; Calcium-binding EGF domain

pfam12662
Location:180 → 202

cEGF; Complement Clr-like EGF-like

pfam12947
Location:248 → 283

EGF_3; EGF domain

pfam14670
Location:123 → 157

FXa_inhibition; Coagulation Factor Xa inhibitory site
NM_001184692.2 → NP_001171621.1 nephronectin isoform D precursor

Status: VALIDATED

Description

Transcript Variant: This variant (4) lacks multiple in-frame exons in the coding region, compared to variant 1, and encodes a shorter protein (isoform D), compared to isoform A.

Source sequence(s)

AC109361, AK304279, AK304721, AW607534

Consensus CDS

CCDS54787.1

UniProtKB/TrEMBL

D6RH31

Related

ENSP00000422044.1, ENST00000514622.5

Conserved Domains (5) summary

cd06263
Location:393 → 532

MAM; Meprin, A5 protein, and protein tyrosine phosphatase Mu (MAM) domain. MAM is an extracellular domain which mediates protein-protein interactions and is found in a diverse set of proteins, many of which are known to function in cell adhesion. Members ...

pfam00629
Location:393 → 534

MAM; MAM domain, meprin/A5/mu

pfam12662
Location:150 → 172

cEGF; Complement Clr-like EGF-like

pfam12947
Location:218 → 253

EGF_3; EGF domain

cl00057
Location:164 → 204

vWFA; Von Willebrand factor type A (vWA) domain was originally found in the blood coagulation protein von Willebrand factor (vWF). Typically, the vWA domain is made up of approximately 200 amino acid residues folded into a classic a/b para-rossmann type of ...
NM_001184693.2 → NP_001171622.1 nephronectin isoform E precursor

Status: VALIDATED

Description

Transcript Variant: This variant (5) has multiple differences in the presence/absence of in-frame exons in the coding region, compared to variant 1, and encodes a shorter protein (isoform E), compared to isoform A.

Source sequence(s)

AC109361, AK295772, AK304721, AW607534

Consensus CDS

CCDS54786.1

UniProtKB/TrEMBL

D6RH31

Related

ENSP00000422474.1, ENST00000506666.5

Conserved Domains (6) summary

cd06263
Location:423 → 562

MAM; Meprin, A5 protein, and protein tyrosine phosphatase Mu (MAM) domain. MAM is an extracellular domain which mediates protein-protein interactions and is found in a diverse set of proteins, many of which are known to function in cell adhesion. Members ...

pfam00629
Location:423 → 564

MAM; MAM domain, meprin/A5/mu

pfam12662
Location:180 → 202

cEGF; Complement Clr-like EGF-like

pfam12947
Location:248 → 283

EGF_3; EGF domain

pfam14670
Location:123 → 157

FXa_inhibition; Coagulation Factor Xa inhibitory site

cl00057
Location:194 → 234

vWFA; Von Willebrand factor type A (vWA) domain was originally found in the blood coagulation protein von Willebrand factor (vWF). Typically, the vWA domain is made up of approximately 200 amino acid residues folded into a classic a/b para-rossmann type of ...

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000004.12 Reference GRCh38.p14 Primary Assembly

Range

105895471..105971671

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011531820.3 → XP_011530122.1 nephronectin isoform X1

UniProtKB/TrEMBL

D6RH31

Conserved Domains (6) summary

cd06263
Location:470 → 609

MAM; Meprin, A5 protein, and protein tyrosine phosphatase Mu (MAM) domain. MAM is an extracellular domain which mediates protein-protein interactions and is found in a diverse set of proteins, many of which are known to function in cell adhesion. Members ...

pfam00629
Location:470 → 611

MAM; MAM domain, meprin/A5/mu

pfam07645
Location:217 → 249

EGF_CA; Calcium-binding EGF domain

pfam12662
Location:198 → 220

cEGF; Complement Clr-like EGF-like

pfam12947
Location:266 → 301

EGF_3; EGF domain

pfam14670
Location:141 → 175

FXa_inhibition; Coagulation Factor Xa inhibitory site
XM_017007984.2 → XP_016863473.1 nephronectin isoform X9

UniProtKB/TrEMBL

H0YAK9
XM_011531823.3 → XP_011530125.1 nephronectin isoform X4

UniProtKB/TrEMBL

D6RH31

Conserved Domains (6) summary

cd06263
Location:441 → 580

MAM; Meprin, A5 protein, and protein tyrosine phosphatase Mu (MAM) domain. MAM is an extracellular domain which mediates protein-protein interactions and is found in a diverse set of proteins, many of which are known to function in cell adhesion. Members ...

pfam00629
Location:441 → 582

MAM; MAM domain, meprin/A5/mu

pfam07645
Location:217 → 249

EGF_CA; Calcium-binding EGF domain

pfam12662
Location:198 → 220

cEGF; Complement Clr-like EGF-like

pfam12947
Location:266 → 301

EGF_3; EGF domain

pfam14670
Location:141 → 175

FXa_inhibition; Coagulation Factor Xa inhibitory site
XM_011531824.3 → XP_011530126.1 nephronectin isoform X5

UniProtKB/TrEMBL

D6RH31

Conserved Domains (6) summary

cd06263
Location:440 → 579

MAM; Meprin, A5 protein, and protein tyrosine phosphatase Mu (MAM) domain. MAM is an extracellular domain which mediates protein-protein interactions and is found in a diverse set of proteins, many of which are known to function in cell adhesion. Members ...

pfam00629
Location:440 → 581

MAM; MAM domain, meprin/A5/mu

pfam07645
Location:187 → 219

EGF_CA; Calcium-binding EGF domain

pfam12662
Location:168 → 190

cEGF; Complement Clr-like EGF-like

pfam12947
Location:236 → 271

EGF_3; EGF domain

cl00057
Location:101 → 143

vWFA; Von Willebrand factor type A (vWA) domain was originally found in the blood coagulation protein von Willebrand factor (vWF). Typically, the vWA domain is made up of approximately 200 amino acid residues folded into a classic a/b para-rossmann type of ...
XM_047449983.1 → XP_047305939.1 nephronectin isoform X7

UniProtKB/TrEMBL

D6RH31
XM_011531822.3 → XP_011530124.1 nephronectin isoform X3

UniProtKB/TrEMBL

D6RH31

Conserved Domains (6) summary

cd06263
Location:453 → 592

MAM; Meprin, A5 protein, and protein tyrosine phosphatase Mu (MAM) domain. MAM is an extracellular domain which mediates protein-protein interactions and is found in a diverse set of proteins, many of which are known to function in cell adhesion. Members ...

pfam00629
Location:453 → 594

MAM; MAM domain, meprin/A5/mu

pfam07645
Location:200 → 232

EGF_CA; Calcium-binding EGF domain

pfam12662
Location:181 → 203

cEGF; Complement Clr-like EGF-like

pfam12947
Location:249 → 284

EGF_3; EGF domain

pfam14670
Location:124 → 158

FXa_inhibition; Coagulation Factor Xa inhibitory site
XM_011531825.3 → XP_011530127.1 nephronectin isoform X6

UniProtKB/TrEMBL

D6RH31

Conserved Domains (5) summary

cd06263
Location:423 → 562

MAM; Meprin, A5 protein, and protein tyrosine phosphatase Mu (MAM) domain. MAM is an extracellular domain which mediates protein-protein interactions and is found in a diverse set of proteins, many of which are known to function in cell adhesion. Members ...

pfam00629
Location:423 → 564

MAM; MAM domain, meprin/A5/mu

pfam12662
Location:151 → 173

cEGF; Complement Clr-like EGF-like

pfam12947
Location:219 → 254

EGF_3; EGF domain

cl00057
Location:165 → 205

vWFA; Von Willebrand factor type A (vWA) domain was originally found in the blood coagulation protein von Willebrand factor (vWF). Typically, the vWA domain is made up of approximately 200 amino acid residues folded into a classic a/b para-rossmann type of ...
XM_005262888.5 → XP_005262945.1 nephronectin isoform X2

UniProtKB/TrEMBL

D6RH31

Related

ENSP00000426146.1, ENST00000503451.5

Conserved Domains (6) summary

cd06263
Location:469 → 608

MAM; Meprin, A5 protein, and protein tyrosine phosphatase Mu (MAM) domain. MAM is an extracellular domain which mediates protein-protein interactions and is found in a diverse set of proteins, many of which are known to function in cell adhesion. Members ...

pfam00629
Location:469 → 610

MAM; MAM domain, meprin/A5/mu

pfam07645
Location:216 → 248

EGF_CA; Calcium-binding EGF domain

pfam12662
Location:197 → 219

cEGF; Complement Clr-like EGF-like

pfam12947
Location:265 → 300

EGF_3; EGF domain

pfam14670
Location:140 → 174

FXa_inhibition; Coagulation Factor Xa inhibitory site
XM_047449985.1 → XP_047305941.1 nephronectin isoform X10

UniProtKB/TrEMBL

H0YAK9
XM_047449984.1 → XP_047305940.1 nephronectin isoform X8

UniProtKB/TrEMBL

D6RH31
XM_047449987.1 → XP_047305943.1 nephronectin isoform X12

UniProtKB/TrEMBL

H0YAK9

Related

ENSP00000427507.1, ENST00000514837.1
XM_047449988.1 → XP_047305944.1 nephronectin isoform X13

UniProtKB/TrEMBL

H0YAK9
XM_047449986.1 → XP_047305942.1 nephronectin isoform X11

Alternate T2T-CHM13v2.0

Genomic

NC_060928.1 Alternate T2T-CHM13v2.0

Range

109206597..109282798

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054349545.1 → XP_054205520.1 nephronectin isoform X1

UniProtKB/TrEMBL

D6RH31
XM_054349553.1 → XP_054205528.1 nephronectin isoform X9

UniProtKB/TrEMBL

H0YAK9
XM_054349548.1 → XP_054205523.1 nephronectin isoform X4

UniProtKB/TrEMBL

D6RH31
XM_054349549.1 → XP_054205524.1 nephronectin isoform X5

UniProtKB/TrEMBL

D6RH31
XM_054349551.1 → XP_054205526.1 nephronectin isoform X7

UniProtKB/TrEMBL

D6RH31
XM_054349547.1 → XP_054205522.1 nephronectin isoform X3

UniProtKB/TrEMBL

D6RH31
XM_054349550.1 → XP_054205525.1 nephronectin isoform X6

UniProtKB/TrEMBL

D6RH31
XM_054349546.1 → XP_054205521.1 nephronectin isoform X2

UniProtKB/TrEMBL

D6RH31
XM_054349554.1 → XP_054205529.1 nephronectin isoform X10

UniProtKB/TrEMBL

H0YAK9
XM_054349552.1 → XP_054205527.1 nephronectin isoform X8

UniProtKB/TrEMBL

D6RH31
XM_054349556.1 → XP_054205531.1 nephronectin isoform X12

UniProtKB/TrEMBL

H0YAK9
XM_054349557.1 → XP_054205532.1 nephronectin isoform X13

UniProtKB/TrEMBL

H0YAK9
XM_054349555.1 → XP_054205530.1 nephronectin isoform X11

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

NM_198278.1: Suppressed sequence

Description

NM_198278.1: This RefSeq was suppressed temporarily based on the calculation that the annotated protein was shorter than a protein or proteins from a putative ortholog.