NDP

norrin cystine knot growth factor NDP, the group of Receptor ligands

Basic information

Region (hg38): X:43948775-43973395

Previous symbols: [ "EVR2" ]

Links

ENSG00000124479 ∙ NCBI:4693 ∙ OMIM:300658 ∙ HGNC:7678 ∙ Uniprot:Q00604 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Norrie disease (Definitive), mode of inheritance: XLR
• Norrie disease (Definitive), mode of inheritance: XL
• Norrie disease (Supportive), mode of inheritance: XL
• exudative vitreoretinopathy (Supportive), mode of inheritance: AD
• persistent hyperplastic primary vitreous (Supportive), mode of inheritance: AD
• Norrie disease (Strong), mode of inheritance: XL
• Norrie disease (Definitive), mode of inheritance: XL
• exudative vitreoretinopathy 2, X-linked (Definitive), mode of inheritance: XL
• exudative vitreoretinopathy 2, X-linked (Strong), mode of inheritance: XL
• Norrie disease (Definitive), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Norrie disease; Exudative vitreoretinopathy, 2, X-linked	XL	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	Ophthalmologic	95062; 1303235; 1307245; 1642288; 8252044; 8457509; 8110678; 7662640; 7814011; 7795608; 7627181; 8990009; 17325173; 17334993; 20301506; 20491809; 20679667; 21179243; 21960066; 22563645; 22674248

ClinVar

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

• not provided (113 variants)
• Atrophia bulborum hereditaria (17 variants)
• Inborn genetic diseases (7 variants)
• not specified (4 variants)
• Exudative vitreoretinopathy 2, X-linked (4 variants)
• Retinal detachment (1 variants)
• Exudative vitreoretinopathy, X-linked (1 variants)
• Short lingual frenulum;Nystagmus;Persistent hyperplastic primary vitreous;High myopia (1 variants)
• History of neurodevelopmental disorder (1 variants)
• Hearing impairment (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NDP 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			1	17	2	20
missense	5	13	30	1	1	50
nonsense	8	4				12
start loss	1					1
frameshift	6	4	1			11
inframe indel		1				1
splice donor/acceptor (+/-2bp)	1					1
splice region			2	2		4
non coding			2	7	7	16
Total	21	22	34	25	10

Variants in NDP

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

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

Position	Type	Phenotype	Significance	ClinVar
X-43949084-A-G		not specified	Likely benign (-)
X-43949605-G-GGAAAA			Uncertain significance (Aug 28, 2019)
X-43949785-C-T		History of neurodevelopmental disorder	Conflicting classifications of pathogenicity (Dec 23, 2018)
X-43949789-G-C		not specified	Benign (Apr 25, 2019)
X-43949796-G-T			Uncertain significance (Mar 05, 2019)
X-43949808-G-T			Likely pathogenic (Jul 18, 2019)
X-43949812-T-C			Uncertain significance (Oct 05, 2023)
X-43949813-C-A			Likely pathogenic (Aug 19, 2022)
X-43949814-C-T			Benign (Jan 06, 2024)
X-43949816-C-T			Conflicting classifications of pathogenicity (Aug 23, 2023)
X-43949817-G-A			Likely benign (Oct 02, 2023)
X-43949817-G-T		Atrophia bulborum hereditaria	Pathogenic (Jul 28, 2023)
X-43949831-G-A		Exudative vitreoretinopathy 2, X-linked	Pathogenic (Apr 27, 2023)
X-43949833-A-T			Likely pathogenic (Oct 22, 2023)
X-43949836-T-C			Uncertain significance (Feb 23, 2015)
X-43949838-C-A			Likely benign (Jan 28, 2022)
X-43949839-C-A		Exudative vitreoretinopathy 2, X-linked	Pathogenic (Sep 01, 1996)
X-43949840-G-A		Exudative vitreoretinopathy 2, X-linked • Atrophia bulborum hereditaria	Pathogenic/Likely pathogenic (Jul 12, 2023)
X-43949846-T-G		Atrophia bulborum hereditaria	Likely pathogenic (May 25, 2021)
X-43949855-G-A			Uncertain significance (Nov 13, 2022)
X-43949858-G-A			Pathogenic (Dec 30, 2023)
X-43949861-T-TG			Pathogenic (Jul 03, 2022)
X-43949862-GC-G			Likely pathogenic (Jul 01, 2021)
X-43949862-G-GC			Likely pathogenic (Jun 17, 2021)
X-43949863-C-T			Likely pathogenic (Aug 19, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NDP	protein_coding	protein_coding	ENST00000378062	2	24729

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.650	0.326	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.969	31	50.4	0.616	0.00000330	855
Missense in Polyphen		5	22.881	0.21853		392
Synonymous	-0.757	26	21.5	1.21	0.00000144	272
Loss of Function	1.71	0	3.39	0.00	2.12e-7	55

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Activates the canonical Wnt signaling pathway through FZD4 and LRP5 coreceptor. Plays a central role in retinal vascularization by acting as a ligand for FZD4 that signals via stabilizing beta-catenin (CTNNB1) and activating LEF/TCF-mediated transcriptional programs. Acts in concert with TSPAN12 to activate FZD4 independently of the Wnt-dependent activation of FZD4, suggesting the existence of a Wnt-independent signaling that also promote accumulation the beta-catenin (CTNNB1). May be involved in a pathway that regulates neural cell differentiation and proliferation. Possible role in neuroectodermal cell-cell interaction.
• Disease: DISEASE: Vitreoretinopathy, exudative 2 (EVR2) [MIM:305390]: A disorder of the retinal vasculature characterized by an abrupt cessation of growth of peripheral capillaries, leading to an avascular peripheral retina. This may lead to compensatory retinal neovascularization, which is thought to be induced by hypoxia from the initial avascular insult. New vessels are prone to leakage and rupture causing exudates and bleeding, followed by scarring, retinal detachment and blindness. Clinical features can be highly variable, even within the same family. Patients with mild forms of the disease are asymptomatic, and their only disease related abnormality is an arc of avascular retina in the extreme temporal periphery. {ECO:0000269|PubMed:16163268, ECO:0000269|PubMed:16970763, ECO:0000269|PubMed:17296899, ECO:0000269|PubMed:17325173, ECO:0000269|PubMed:8252044, ECO:0000269|PubMed:8946107, ECO:0000269|PubMed:9143917}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: GPCR signaling-G alpha q;GPCR signaling-cholera toxin;GPCR signaling-pertussis toxin;GPCR signaling-G alpha s Epac and ERK;GPCR signaling-G alpha s PKA and ERK;GPCR signaling-G alpha i (Consensus)

Recessive Scores

• pRec: 0.479

Intolerance Scores

• rvis_EVS: 0.28
• rvis_percentile_EVS: 70.87

Haploinsufficiency Scores

• pHI: 0.414
• hipred: Y
• hipred_score: 0.722
• ghis: 0.526

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.234

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ndp
• 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); pigmentation phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hearing/vestibular/ear phenotype; vision/eye phenotype; skeleton phenotype

Zebrafish Information Network

• Gene name: ndp
• Affected structure: ocular blood vessel
• Phenotype tag: abnormal
• Phenotype quality: decreased area

Gene ontology

• Biological process: placenta development;vacuole organization;signal transduction;cell-cell signaling;nervous system development;visual perception;sensory perception of sound;cell population proliferation;regulation of signaling receptor activity;Wnt signaling pathway;extracellular matrix-cell signaling;positive regulation of transcription, DNA-templated;positive regulation of DNA-binding transcription factor activity;canonical Wnt signaling pathway;retina vasculature morphogenesis in camera-type eye
• Cellular component: extracellular space;cell surface;collagen-containing extracellular matrix
• Molecular function: frizzled binding;cytokine activity;protein binding;growth factor activity;protein homodimerization activity