TSPAN12

Last update 08 May 2025

Basic Info

Synonyms

NET-2, NET2, Tetraspan NET-2

+ [6]

Introduction

Regulator of cell surface receptor signal transduction. Plays a central role in retinal vascularization by regulating norrin (NDP) signal transduction. Acts in concert with norrin (NDP) to promote FZD4 multimerization and subsequent activation of FZD4, leading to promote accumulation of beta-catenin (CTNNB1) and stimulate LEF/TCF-mediated transcriptional programs. Suprisingly, it only activates the norrin (NDP)-dependent activation of FZD4, while it does not activate the Wnt-dependent activation of FZD4, suggesting the existence of a Wnt-independent signaling that also promote accumulation the beta-catenin (CTNNB1) (By similarity). Acts as a regulator of membrane proteinases such as ADAM10 and MMP14/MT1-MMP. Activates ADAM10-dependent cleavage activity of amyloid precursor protein (APP). Activates MMP14/MT1-MMP-dependent cleavage activity.

100 Clinical Results associated with TSPAN12

100 Translational Medicine associated with TSPAN12

0 Patents (Medical) associated with TSPAN12

184

Literatures (Medical) associated with TSPAN12

16 Apr 2025·RETINAL Cases & Brief Reports

Impact of neonatal family screening in early-onset management of TSPAN 12 positive Familial Exudative Vitreoretinopathy- a case report

Article

Author: Shettigar, Manoj P. ; Agarwal, Komal ; Belenje, Akash ; Jalali, Subhadra

Purpose:To report a case of Familial Exudative Vitreoretinopathy (FEVR) where both the mother and the daughter had the same genetic mutation in TSPAN 12, and the daughter had treatable retinal detachment at birth.Methods:This is an interventional case report.Results:A 28-year-old primi gravida, a known case of FEVR presented to our OPD in the first trimester. Targeted Imaging for Fetal Anomalies (TIFFA scan) ruled out any anomalies. A planned near-term but early elective delivery was done at the 36th week of gestational age, and the child was brought for early neonatal screening for FEVR at ten days of age. The birth weight was 3.6 kg. Fundus evaluation showed bilateral disc and arcade drag due to a highly vascular temporal peripheral tractional retinal detachment. Diagnosis of bilateral FEVR - Stage 3A retinal detachment was made. A bilateral lens-sparing vitrectomy with endolaser was performed to mitigate the traction onto the retina. The child did well postoperatively. Genetic testing of the mother and the child showed the same TSPAN12 (c.738G>A) gene mutation.Conclusion:Surgical success in FEVR can hinge on the timely screening of the new family member. Progression of FEVR to more advanced stages may be prevented with laser photocoagulation and prompt surgery whenever indicated. It is imperative to educate FEVR patients about the risk to the next generation and the importance of good antenatal monitoring, early delivery, and immediate postnatal ophthalmic fundoscopic examination of newborns.

07 Feb 2025·Investigative Ophthalmology & Visual Science

Gene Variant Spectrum in Probands With Familial Exudative Vitreoretinopathy Using an Expanded Panel

Article

Author: Nightingale, Mathew ; Gillett, Roxanne ; Clark, Ian H. ; Gaston, Daniel ; Wallace, Karin ; Traboulsi, Elias I. ; Lyons, Christopher J. ; Bedard, Karen ; Beis, M. Jill ; Mackley, Michael P. ; Robitaille, Johane M. ; Levin, Alex V. ; van der Ende, Sarah ; Muni, Rajeev H. ; McMaster, Christopher R. ; Héon, Élise ; Leblanc, Marissa A.

PurposeTo investigate the gene variant spectrum in patients with familial exudative vitreoretinopathy (FEVR).MethodsProbands clinically diagnosed with FEVR and their relatives were enrolled and clinical information and DNA collected. An expanded FEVR panel was used, including six recognized FEVR genes (FZD4, NDP, LRP5, TSPAN12, ZNF408, and CTNNB1) and 19 genes previously associated with ocular features overlapping FEVR (FEVR-associated genes). Variants identified using targeted next-generation sequencing and/or Sanger sequencing were analyzed and classified using the American College of Medical Genetics and Clinical Genome Resource Sequence Variant Interpretation (ClinGen SVI) working group recommendations to detect disease-causing variants (DCVs).ResultsAnalyses of data from a cohort of 94 probands provided a molecular diagnosis for 39 (41.5%) probands: 34 (87.2%) had a single DCV, whereas 5 (12.8%) harbored more than 1 DCV. Of 41 total DCVs in solved probands, 33 (80.5%) were in 4 of the 6 recognized genes, LRP5, FZD4, TSPAN12, and NDP, whereas 8 were found in FEVR-associated genes, 6 in KIF11, and 2 (LAMA1 and DOCK6) each in association with a KIF11 DCV. Reanalyzing variants using the latest criteria impacted the variant classification in five probands (5.3%), changing variants that were once deemed likely pathogenic to variants of uncertain significance.ConclusionsThe expanded FEVR gene panel detected DCVs in nearly one-half of our cohort. Including the criteria used in classification will improve transparency of variant calls as more data become available. Four FEVR genes account for most cases, and the role of rare FEVR genes and candidate genes requires further study.

04 Feb 2025·Investigative Ophthalmology & Visual Science

Genotype–Phenotype Spectrum of eyeGENE Patients With Familial Exudative Vitreoretinopathy: Novel Variants in Norrin/β-Catenin Signaling Pathway Genes

Article

Author: Guan, Bin ; Goetz, Kerry E. ; Tumminia, Santa J. ; Hufnagel, Robert B. ; Ullah, Ehsan ; Reeves, Melissa J. ; Yousaf, Sairah ; Yaylacıoğlu Tuncay, Fulya

PurposeTo report the variants and genotype-phenotype correlations in patients with familial exudative vitreoretinopathy (FEVR) included in the eyeGENE database.MethodsA retrospective study was conducted in a cohort of 122 eyeGENE patients from 114 families with FEVR. Clinical details and genetic test results were provided by referring clinicians and clinical laboratories in the eyeGENE network, respectively. Genotype and phenotype information was reviewed, and reported variants were reclassified.ResultsGenetic test reports of 50 probands revealed 52 variants in the four genes of the Norrin/β-catenin signaling pathway: LRP5, FZD4, TSPAN12, and NDP. Following variant reclassification, 35 of the reported variants were interpreted as pathogenic or likely pathogenic (12 in LRP5, 11 in FZD4, seven in TSPAN12 and five in NDP), providing a conclusive test result for nearly one-third (32%) of the probands. Among the reported variants, 18 were novel (34.6%) and two-thirds were missense. Retinal detachment was reported less in patients with variants in TSPAN12 (P = 0.017). One-third of the patients (33.3%) with an FZD4 variant had asymmetric findings. In contrast, asymmetry was less pronounced in patients with variants in TSPAN12 (11.1%).ConclusionsThis was one of the largest cohorts reviewed from North America, expanding the variant spectrum in FEVR. Among the eyeGENE FEVR patients, disease-associated variants in Norrin/β-catenin signaling pathway genes can explain one-third of the cohort. LRP5 and FZD4 variants were the most common. The genotype-phenotype correlations supported the phenotypic variability in FEVR.

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TSPAN12

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