INVS

inversin, the group of Ankyrin repeat domain containing

Basic information

Region (hg38): 9:100099243-100302175

Previous symbols: [ "NPHP2" ]

Links

ENSG00000119509

∙ NCBI:27130 ∙ OMIM:243305 ∙ HGNC:17870 ∙ Uniprot:Q9Y283 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

nephronophthisis 2 (Definitive), mode of inheritance: AR
Senior-Loken syndrome (Supportive), mode of inheritance: AR
nephronophthisis 2 (Supportive), mode of inheritance: AR
nephronophthisis 2 (Strong), mode of inheritance: AR
nephronophthisis 2 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Nephronophthisis 2	AR	General		Gastrointestinal; Neurologic; Renal	2702088; 9792867; 12872123; 19177160; 20798123; 23559409

ClinVar

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

Nephronophthisis (840 variants)
Infantile_nephronophthisis (266 variants)
not_provided (153 variants)
Inborn_genetic_diseases (134 variants)
INVS-related_disorder (74 variants)
not_specified (30 variants)
Retinal_dystrophy (5 variants)
Kidney_disorder (5 variants)
Kidney_failure (2 variants)
Optic_atrophy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the INVS gene is commonly pathogenic or not. These statistics are base on transcript: NM_000014425.5. 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	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous		1 clinvar	8 clinvar	296 clinvar	2 clinvar	307
missense		1 clinvar	424 clinvar	21 clinvar		446
nonsense	33 clinvar	13 clinvar	2 clinvar			48
start loss						0
frameshift	34 clinvar	19 clinvar	7 clinvar			60
splice donor/acceptor (+/-2bp)	3 clinvar	16 clinvar				19
Total	70	50	441	317	2

Highest pathogenic variant AF is 0.000094867

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
INVS	protein_coding	protein_coding	ENST00000262457	16	201745

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
5.55e-18	0.728	125615	0	133	125748	0.000529

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.07	502	574	0.874	0.0000309	6960
Missense in Polyphen		131	181.79	0.72062		2250
Synonymous	0.649	204	216	0.944	0.0000117	2112
Loss of Function	2.02	35	50.5	0.693	0.00000293	581

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000886	0.000886
Ashkenazi Jewish	0.000498	0.000496
East Asian	0.000598	0.000598
Finnish	0.00	0.00
European (Non-Finnish)	0.000618	0.000615
Middle Eastern	0.000598	0.000598
South Asian	0.000523	0.000457
Other	0.00131	0.00130

dbNSFP

Source: dbNSFP

Function: FUNCTION: Required for normal renal development and establishment of left-right axis. Probably acts as a molecular switch between different Wnt signaling pathways. Inhibits the canonical Wnt pathway by targeting cytoplasmic disheveled (DVL1) for degradation by the ubiquitin-proteasome. This suggests that it is required in renal development to oppose the repression of terminal differentiation of tubular epithelial cells by Wnt signaling. Involved in the organization of apical junctions in kidney cells together with NPHP1, NPHP4 and RPGRIP1L/NPHP8 (By similarity). Does not seem to be strictly required for ciliogenesis (By similarity). {ECO:0000250, ECO:0000269|PubMed:15852005, ECO:0000269|PubMed:18371931}.;
Disease: DISEASE: Nephronophthisis 2 (NPHP2) [MIM:602088]: An autosomal recessive disorder resulting in end-stage renal disease. It is characterized by early onset and rapid progression. Phenotypic manifestations include enlarged kidneys, chronic tubulo- interstitial nephritis, anemia, hyperkalemic metabolic acidosis. Some patients also display situs inversus. Pathologically, it differs from later-onset nephronophthisis by the absence of medullary cysts and thickened tubular basement membranes, and by the presence of cortical microcysts. {ECO:0000269|PubMed:12872123}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: Wnt signaling pathway - Homo sapiens (human);Wnt Signaling in Kidney Disease;Wnt Signaling Pathway (Consensus)

Recessive Scores

pRec: 0.215

Intolerance Scores

loftool: 0.912
rvis_EVS: -0.57
rvis_percentile_EVS: 19.04

Haploinsufficiency Scores

pHI: 0.509
hipred: Y
hipred_score: 0.706
ghis: 0.567

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.831

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Invs
Phenotype: liver/biliary system phenotype; respiratory system phenotype; embryo 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); hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); digestive/alimentary phenotype; renal/urinary system phenotype; cellular phenotype; immune system phenotype; homeostasis/metabolism phenotype; endocrine/exocrine gland phenotype; growth/size/body region phenotype;

Zebrafish Information Network

Gene name: invs
Affected structure: pronephric proximal convoluted tubule
Phenotype tag: abnormal
Phenotype quality: increased diameter

Gene ontology

Biological process: multicellular organism development;Wnt signaling pathway;negative regulation of canonical Wnt signaling pathway
Cellular component: nucleus;cytoplasm;spindle;microtubule;cilium;membrane
Molecular function: protein binding;calmodulin binding