NPHS1

NPHS1 adhesion molecule, nephrin, the group of Fibronectin type III domain containing|V-set domain containing|C2-set domain containing

Basic information

Region (hg38): 19:35825371-35869287

Links

ENSG00000161270 ∙ NCBI:4868 ∙ OMIM:602716 ∙ HGNC:7908 ∙ Uniprot:O60500 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• congenital nephrotic syndrome, Finnish type (Definitive), mode of inheritance: AR
• congenital nephrotic syndrome, Finnish type (Definitive), mode of inheritance: AR
• familial idiopathic steroid-resistant nephrotic syndrome (Supportive), mode of inheritance: AD
• congenital nephrotic syndrome, Finnish type (Supportive), mode of inheritance: AR
• congenital nephrotic syndrome, Finnish type (Strong), mode of inheritance: AR
• congenital nephrotic syndrome, Finnish type (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Nephrotic syndrome, type 1	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Renal	6384451; 9660941; 10577936; 17413422; 17290294; 20650908; 20798252; 21125408; 22009864; 22565185; 22584503; 22653594
Medical therapy to control bacterial infections, along with renal transplantation, can be beneficial

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NPHS1 gene.

• not provided (1151 variants)
• Finnish congenital nephrotic syndrome (493 variants)
• Congenital nephrotic syndrome (136 variants)
• not specified (60 variants)
• Inborn genetic diseases (45 variants)
• Focal segmental glomerulosclerosis (43 variants)
• Nephrotic syndrome (21 variants)
• NPHS1-related condition (11 variants)
• Kidney disorder (8 variants)
• Proteinuria (5 variants)
• Infantile Nephrotic syndrome (3 variants)
• Familial idiopathic steroid-resistant nephrotic syndrome (2 variants)
• - (2 variants)
• Microscopic hematuria (2 variants)
• Atypical hemolytic-uremic syndrome (2 variants)
• Glomerulonephritis (1 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NPHS1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			6	458	10	474
missense	10	37	162	44	7	260
nonsense	36	27	1			64
start loss	1					1
frameshift	63	84	2			149
inframe indel	1		7			8
splice donor/acceptor (+/-2bp)	8	54	3			65
splice region		3	5	95	2	105
non coding			34	126	35	195
Total	119	202	215	628	52

Highest pathogenic variant AF is 0.000847

Variants in NPHS1

This is a list of pathogenic ClinVar variants found in the NPHS1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
19-35825395-T-G		Congenital nephrotic syndrome	Benign (Jan 12, 2018)
19-35825403-C-A		Congenital nephrotic syndrome	Uncertain significance (Jan 13, 2018)
19-35825474-G-A		Congenital nephrotic syndrome	Uncertain significance (Jan 13, 2018)
19-35825493-C-T		Congenital nephrotic syndrome	Uncertain significance (Jan 12, 2018)
19-35825494-G-A		Congenital nephrotic syndrome	Uncertain significance (Jan 12, 2018)
19-35825552-C-T		Congenital nephrotic syndrome	Uncertain significance (Jan 12, 2018)
19-35825556-C-A		Congenital nephrotic syndrome	Uncertain significance (Jan 13, 2018)
19-35825626-T-C		Congenital nephrotic syndrome	Uncertain significance (Mar 16, 2018)
19-35825649-A-G		Congenital nephrotic syndrome	Uncertain significance (Jan 13, 2018)
19-35825749-G-A		Congenital nephrotic syndrome	Uncertain significance (Jan 12, 2018)
19-35825754-A-G		Congenital nephrotic syndrome	Uncertain significance (Jan 12, 2018)
19-35825755-T-A		Congenital nephrotic syndrome	Uncertain significance (Jan 12, 2018)
19-35825757-A-G		Congenital nephrotic syndrome	Uncertain significance (Jan 13, 2018)
19-35825763-G-A		Congenital nephrotic syndrome	Uncertain significance (Jan 13, 2018)
19-35825808-T-C		Congenital nephrotic syndrome	Likely benign (Jan 12, 2018)
19-35825905-C-T		Congenital nephrotic syndrome	Uncertain significance (Jan 13, 2018)
19-35825976-C-T		Congenital nephrotic syndrome	Likely benign (Jan 13, 2018)
19-35825985-G-A		Congenital nephrotic syndrome	Uncertain significance (Jan 12, 2018)
19-35826026-A-G		Finnish congenital nephrotic syndrome	Uncertain significance (Jun 14, 2016)
19-35826031-C-T		Congenital nephrotic syndrome	Uncertain significance (Apr 27, 2017)
19-35826057-T-C		Congenital nephrotic syndrome	Benign (Apr 28, 2017)
19-35826095-G-A		Congenital nephrotic syndrome	Uncertain significance (Jan 12, 2018)
19-35826227-G-A		Congenital nephrotic syndrome	Uncertain significance (Jan 13, 2018)
19-35826242-C-A		Congenital nephrotic syndrome	Uncertain significance (Jan 13, 2018)
19-35826242-C-T		Congenital nephrotic syndrome	Uncertain significance (Jan 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NPHS1	protein_coding	protein_coding	ENST00000378910	29	43324

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.54e-14	1.00	125254	0	494	125748	0.00197

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.408	698	729	0.957	0.0000436	7848
Missense in Polyphen		198	224.96	0.88016		2563
Synonymous	-1.04	346	322	1.07	0.0000209	2677
Loss of Function	3.53	33	63.4	0.521	0.00000335	677

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00143	0.00141
Ashkenazi Jewish	0.000102	0.0000992
East Asian	0.000493	0.000489
Finnish	0.0122	0.0121
European (Non-Finnish)	0.00130	0.00128
Middle Eastern	0.000493	0.000489
South Asian	0.00115	0.000980
Other	0.00164	0.00163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: 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). {ECO:0000250|UniProtKB:Q9QZS7, ECO:0000250|UniProtKB:Q9R044}.
• Disease: DISEASE: 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. {ECO:0000269|PubMed:10652016, ECO:0000269|PubMed:11317351, ECO:0000269|PubMed:11726550, ECO:0000269|PubMed:17290294, ECO:0000269|PubMed:18503012, ECO:0000269|PubMed:18614772, ECO:0000269|PubMed:20172850, ECO:0000269|PubMed:20798252, ECO:0000269|PubMed:22009864, ECO:0000269|PubMed:22565185, ECO:0000269|PubMed:22732337, ECO:0000269|PubMed:25804400, ECO:0000269|PubMed:26560236, ECO:0000269|PubMed:9660941, ECO:0000269|PubMed:9915943}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Primary Focal Segmental Glomerulosclerosis FSGS;Nephrin family interactions;Cell-Cell communication;Nephrin/Neph1 signaling in the kidney podocyte (Consensus)

Recessive Scores

• pRec: 0.535

Intolerance Scores

• loftool: 0.574
• rvis_EVS: 0.68
• rvis_percentile_EVS: 84.95

Haploinsufficiency Scores

• hipred: Y
• hipred_score: 0.723
• ghis: 0.416

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.999

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	High
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Nphs1
• Phenotype: homeostasis/metabolism phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; renal/urinary system phenotype

Zebrafish Information Network

• Gene name: nphs1
• Affected structure: skeletal muscle cell
• Phenotype tag: abnormal
• Phenotype quality: mislocalised

Gene ontology

• Biological process: cell adhesion;JNK cascade;skeletal muscle tissue development;myoblast fusion;excretion;positive regulation of actin filament polymerization;glomerular basement membrane development;protein localization to synapse;regulation of excretion;glomerular visceral epithelial cell development
• Cellular component: plasma membrane;integral component of plasma membrane;slit diaphragm;cell projection;extracellular exosome
• Molecular function: protein binding;myosin binding