ArticlePLoS genetics2016
Mutations in the Heme Exporter FLVCR1 Cause Sensory Neurodegeneration with Loss of Pain Perception.
Article in PLoS genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 71 citations in OpenAlex.
- Expanding the ocular and genetic spectrum of FLVCR1-associated disease in a Chinese cohort.Documenta ophthalmologica. Advances in ophthalmology · 2026Article
- Exploiting porphyrin metabolism to inhibit angiogenesis.Angiogenesis · 2026Article
- Mitochondrial energetic failure underlies FLVCR1-related sensory neuropathy.Communications biology · 2026Article
- FLVCR1-related diseases: from clinical heterogeneity to mechanistic insights.Brain communications · 2026Review
- Comparative proteomics of HepG2 cells reveals NGLY1 as an important regulator of ferroptosis resistance and iron uptake.PloS one · 2025Article
- The Neural Palette of Heme: Altered Heme Homeostasis Underlies Defective Neurotransmission, Increased Oxidative Stress, and Disease Pathogenesis.Antioxidants (Basel, Switzerland) · 2024Review
- Dysregulation of FLVCR1a-dependent mitochondrial calcium handling in neural progenitors causes congenital hydrocephalus.Cell reports. Medicine · 2024Article
- Article
- Advance in Iron Metabolism, Oxidative Stress and Cellular Dysfunction in Experimental and Human Kidney Diseases.Antioxidants (Basel, Switzerland) · 2024Review
- Coexistence of Retinitis Pigmentosa and Ataxia in Patients with PHARC, PCARP, and Oliver-McFarlane Syndromes.International journal of molecular sciences · 2024Article
- Unearthing FLVCR1a: tracing the path to a vital cellular transporter.Cellular and molecular life sciences : CMLS · 2024Review
- Biallelic variation in the choline and ethanolamine transportermedRxiv : the preprint server for health sciences · 2024Article
- Mfsd7b facilitates choline transport and missense mutations affect choline transport function.Cellular and molecular life sciences : CMLS · 2023Article
- Genetic landscape of congenital insensitivity to pain and hereditary sensory and autonomic neuropathies.Brain : a journal of neurology · 2023Article
- Heme: The Lord of the Iron Ring.Antioxidants (Basel, Switzerland) · 2023Review
- Genetic pain loss disorders.Nature reviews. Disease primers · 2022Review
- Cryo-EM of CcsBA reveals the basis for cytochrome c biogenesis and heme transport.Nature chemical biology · 2022Article
- Distinct Mechanisms Account for In Vitro Activation and Sensitization of TRPV1 by the Porphyrin Hemin.International journal of molecular sciences · 2021Article
- FLVCR1 Predicts Poor Prognosis and Promotes Malignant Phenotype in Esophageal Squamous Cell CarcinomaFrontiers in oncology · 2021Article
- The ferroptosis and iron-metabolism signature robustly predicts clinical diagnosis, prognosis and immune microenvironment for hepatocellular carcinoma.Cell communication and signaling : CCS · 2020Article
Corrections and comments
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Authors and funding
14 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pain is necessary to alert us to actual or potential tissue damage. Specialized nerve cells in the body periphery, so called nociceptors, are fundamental to mediate pain perception and humans without pain perception are at permanent risk for injuries, burns and mutilations. Pain insensitivity can be caused by sensory neurodegeneration which is a hallmark of hereditary sensory and autonomic neuropathies (HSANs). Although mutations in several genes were previously associated with sensory neurodegeneration, the etiology of many cases remains unknown. Using next generation sequencing in patients with congenital loss of pain perception, we here identify bi-allelic mutations in the FLVCR1 (Feline Leukemia Virus subgroup C Receptor 1) gene, which encodes a broadly expressed heme exporter. Different FLVCR1 isoforms control the size of the cytosolic heme pool required to sustain metabolic activity of different cell types. Mutations in FLVCR1 have previously been linked to vision impairment and posterior column ataxia in humans, but not to HSAN. Using fibroblasts and lymphoblastoid cell lines from patients with sensory neurodegeneration, we here show that the FLVCR1-mutations reduce heme export activity, enhance oxidative stress and increase sensitivity to programmed cell death. Our data link heme metabolism to sensory neuron maintenance and suggest that intracellular heme overload causes early-onset degeneration of pain-sensing neurons in humans.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.