NPHP3

nephrocystin 3, the group of Cilia and flagella associated|Tetratricopeptide repeat domain containing

Basic information

Region (hg38): 3:132680609-132722432

Links

ENSG00000113971 ∙ NCBI:27031 ∙ OMIM:608002 ∙ HGNC:7907 ∙ Uniprot:Q7Z494 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• nephronophthisis (Definitive), mode of inheritance: AR
• nephronophthisis 3 (Strong), mode of inheritance: AR
• NPHP3-related Meckel-like syndrome (Supportive), mode of inheritance: AR
• Senior-Loken syndrome (Supportive), mode of inheritance: AR
• late-onset nephronophthisis (Supportive), mode of inheritance: AR
• nephronophthisis 2 (Supportive), mode of inheritance: AR
• renal-hepatic-pancreatic dysplasia (Supportive), mode of inheritance: AR
• nephronophthisis 3 (Definitive), mode of inheritance: AR
• Senior-Loken syndrome (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Nephronophthisis 3; Meckel syndrome, type 7; Renal-hepatic-pancreatic dysplasia 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	Gastrointestinal; Hematologic; Musculoskeletal; Renal	8874114; 12872122; 18371931; 19303681; 19177160; 20007846; 21068128; 21642631;21866095
Liver-kidney transplantation has been described

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NPHP3 gene.

• Nephronophthisis (977 variants)
• Nephronophthisis_3 (370 variants)
• Renal-hepatic-pancreatic_dysplasia_1 (357 variants)
• NPHP3-related_Meckel-like_syndrome (356 variants)
• not_provided (312 variants)
• Inborn_genetic_diseases (132 variants)
• NPHP3-related_disorder (111 variants)
• not_specified (63 variants)
• Kidney_disorder (18 variants)
• Joubert_syndrome_and_related_disorders (11 variants)
• Meckel-Gruber_syndrome (6 variants)
• Retinal_dystrophy (5 variants)
• Optic_atrophy (3 variants)
• Congenital_anomaly_of_kidney_and_urinary_tract (2 variants)
• Renal-hepatic-pancreatic_dysplasia (2 variants)
• Fibrotic_kidney_disease (2 variants)
• Multiple_renal_cysts (2 variants)
• Anhydramnios (2 variants)
• Enlarged_kidney (2 variants)
• Atypical_hemolytic-uremic_syndrome (1 variants)
• Renal_dysplasia_and_retinal_aplasia (1 variants)
• Leber_congenital_amaurosis (1 variants)
• Joubert_syndrome (1 variants)
• See_cases (1 variants)
• Polycystic_kidney_disease (1 variants)
• Bardet-Biedl_syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NPHP3 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000153240.5. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous		1	14	238	4	257
missense	2	15	591	26	1	635
nonsense	37	16	1			54
start loss		1	1			2
frameshift	40	31	3			74
splice donor/acceptor (+/-2bp)	6	23	4			33
Total	85	87	614	264	5

Highest pathogenic variant AF is 0.00023482004

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NPHP3	protein_coding	protein_coding	ENST00000337331	27	164318

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
		125511	0	237	125748	0.000943

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.864	627	691	0.908	0.0000352	8672
Missense in Polyphen		179	205.57	0.87075		2578
Synonymous	1.41	228	257	0.888	0.0000129	2522
Loss of Function	4.10	38	76.7	0.495	0.00000398	923

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00134	0.00134
Ashkenazi Jewish	0.000198	0.000198
East Asian	0.00163	0.00163
Finnish	0.000139	0.000139
European (Non-Finnish)	0.00120	0.00119
Middle Eastern	0.00163	0.00163
South Asian	0.000751	0.000752
Other	0.000992	0.000978

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Required for normal ciliary development and function. Inhibits disheveled-1-induced canonical Wnt-signaling activity and may also play a role in the control of non-canonical Wnt signaling which regulates planar cell polarity. Probably acts as a molecular switch between different Wnt signaling pathways. Required for proper convergent extension cell movements. {ECO:0000269|PubMed:18371931}.
• Disease: DISEASE: Renal-hepatic-pancreatic dysplasia 1 (RHPD1) [MIM:208540]: A disease characterized by cystic malformations of the kidneys, liver, and pancreas. The pathological findings consist of multicystic dysplastic kidneys, dilated and dysgenetic bile ducts, a dysplastic pancreas with dilated ducts, cysts, fibrosis and inflammatory infiltrates. {ECO:0000269|PubMed:18371931}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Meckel syndrome 7 (MKS7) [MIM:267010]: A disorder characterized by a combination of renal cysts and variably associated features including developmental anomalies of the central nervous system (typically encephalocele), hepatic ductal dysplasia and cysts, and polydactyly. {ECO:0000269|PubMed:18371931}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Trafficking of myristoylated proteins to the cilium;Cargo trafficking to the periciliary membrane;Cilium Assembly;Organelle biogenesis and maintenance (Consensus)

Recessive Scores

• pRec: 0.196

Intolerance Scores

• loftool: 0.153
• rvis_EVS: -1.01
• rvis_percentile_EVS: 8.2

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.747

Gene Damage Prediction

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

Zebrafish Information Network

• Gene name: nphp3
• Affected structure: trunk
• Phenotype tag: abnormal
• Phenotype quality: curved ventral

Gene ontology

• Biological process: kidney development;heart looping;atrial septum development;determination of left/right symmetry;Wnt signaling pathway;lung development;determination of pancreatic left/right asymmetry;photoreceptor cell maintenance;maintenance of animal organ identity;convergent extension involved in gastrulation;cilium assembly;epithelial cilium movement involved in determination of left/right asymmetry;kidney morphogenesis;determination of intestine left/right asymmetry;determination of stomach left/right asymmetry;determination of liver left/right asymmetry;ureter development;negative regulation of canonical Wnt signaling pathway;regulation of Wnt signaling pathway, planar cell polarity pathway;regulation of planar cell polarity pathway involved in neural tube closure
• Cellular component: cytosol;cilium
• Molecular function: protein binding