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FAM126A
hyccin PI4KA lipid kinase complex subunit 1
FAM126A encodes hyccin, a protein critical for myelin formation in the nervous system and lens development in the eye. The FAM126A gene provides instructions for producing hyccin, a protein expressed throughout the nervous system where it participates in myelin sheath formation.
FAM126A is located on the short (p) arm of chromosome 7, at band 7p15.3. Arm ratio per GRCh38 - banding schematic.
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Clinical tests that include this
Overview
The FAM126A gene, also known as HYCC1, encodes a protein called hyccin that plays an essential role in the development and maintenance of the nervous system. Hyccin is particularly important for generating the protective myelin coating that surrounds nerve fibres and allows electrical signals to propagate efficiently. The protein is expressed throughout the nervous system and also functions in the lens of the eye, heart, and kidneys, though its precise roles in these tissues remain under investigation.
Pathogenic variants in FAM126A have been identified as the cause of hypomyelination and congenital cataract, a rare condition characterised by impaired myelin development in the brain and clouding of the eye lens present from birth. The gene is recognised across multiple NHS Genomic Medicine Service gene panels for neurological conditions, intellectual disability, and paediatric disorders, reflecting its clinical significance in inherited disease.
What the gene does
Research suggests that hyccin contributes to the production and structural integrity of myelin sheaths, which wrap around axons in both the central and peripheral nervous systems. These lipid-rich membranes serve as insulation, enabling nerve signals to travel rapidly and reliably along axons. When myelin development is compromised, nerve impulse transmission becomes slower and less efficient, resulting in neurological impairment.
Evidence indicates that hyccin may play a role in organising the cells that manufacture myelin, though the detailed molecular mechanisms remain an active area of investigation. The protein's widespread expression across neural tissues indicates it serves a broad function in nervous system development and maintenance. Hyccin is also active in the eye lens, where it appears to help maintain transparency, as well as in cardiac and kidney tissue where its specific contributions remain less well defined.
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Chromosome location
FAM126A is located on the short arm of chromosome 7 at position 7p15.3. This chromosomal region contains numerous genes involved in developmental processes and cellular signalling. The genomic organisation of FAM126A and its regulatory elements contribute to the tissue-specific expression pattern observed for hyccin protein, with particularly high expression in nervous system tissues and the lens.
Protein structure
The hyccin protein comprises 521 amino acids. Analysis of the protein sequence reveals two disordered regions spanning amino acids 355-413 and 501-521. These intrinsically disordered regions lack fixed three-dimensional structure under physiological conditions and may serve regulatory functions or provide flexible linkers between structured portions of the protein. Disordered regions in proteins often participate in protein-protein interactions and can undergo conformational changes in response to binding partners, suggesting that hyccin may interact with multiple cellular components during myelin formation.
Key variants
At least four variants in FAM126A have been identified in individuals with hypomyelination and congenital cataract. The majority of these genetic changes either remove substantial portions of the gene sequence or introduce premature termination signals during protein synthesis, preventing production of functional hyccin. One documented variant permits some protein production but likely generates a hyccin molecule with impaired function. The spectrum of identified variants demonstrates that loss of hyccin activity disrupts both nervous system myelin development and lens transparency.
No pathogenic or likely-pathogenic ClinVar variants recorded yet for this gene.
Associated conditions
Pathogenic variants in FAM126A cause hypomyelination and congenital cataract, a rare inherited condition affecting the nervous system and eyes. Individuals with this condition typically present with neurological features resulting from inadequate myelin formation in the brain and spinal cord, alongside opacity of the eye lens that is present from birth or develops during early infancy. The neurological manifestations can include developmental delay, intellectual disability, and motor difficulties. The condition demonstrates the dual importance of hyccin in both neural and ocular development, with clinical features reflecting dysfunction in both tissue types.
No disease links recorded for this gene in our reference set.
UK clinical status
FAM126A appears on multiple NHS Genomic Medicine Service gene panels with green (high evidence) classification, reflecting strong evidence for its role in human disease. The gene is included in panels for bilateral congenital or childhood onset cataracts, hereditary neuropathy, hereditary neuropathy or pain disorder, inherited white matter disorders, and intellectual disability. It also features in the Developmental Disorders Genotype to Phenotype (DDG2P) resource, the foetal anomalies panel, and the white matter disorders and cerebral calcification narrow panel. This breadth of panel membership underscores the gene's relevance to NHS genomic testing pathways for neurogenetic and developmental conditions.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What does the FAM126A gene do?
FAM126A encodes hyccin, a protein that supports the formation of myelin sheaths around nerve fibres in the nervous system. The protein is also active in the lens of the eye, where it contributes to maintaining transparency, though its functions in ocular tissue are less completely understood.
How do FAM126A variants cause disease?
Most pathogenic variants in FAM126A prevent production of functional hyccin protein, either by deleting portions of the gene or introducing premature stop signals. Loss of hyccin disrupts normal myelin formation in the nervous system and impairs lens development, leading to neurological dysfunction and congenital cataracts.
Is FAM126A testing available through the NHS?
Yes, FAM126A is included on multiple NHS Genomic Medicine Service gene panels with green classification, including panels for hereditary neuropathy, inherited white matter disorders, intellectual disability, and congenital cataracts. Testing may be available through appropriate NHS clinical genetics services when clinical features suggest a relevant condition.
References
- Ugur SA, Tolun A. A deletion in DRCTNNB1A associated with hypomyelination and juvenile onset cataract. European journal of human genetics : EJHG. 2008. PMID: 17928815
- Rossi A, Biancheri R, Zara F. Hypomyelination and congenital cataract: neuroimaging features of a novel inherited white matter disorder. AJNR. American journal of neuroradiology. 2008. PMID: 17974614
- Biancheri R, Zara F, Bruno C. Phenotypic characterization of hypomyelination and congenital cataract. Annals of neurology. 2007. PMID: 17683097
- Zara F, Biancheri R, Bruno C. Deficiency of hyccin, a newly identified membrane protein, causes hypomyelination and congenital cataract. Nature genetics. 2006. PMID: 16951682