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FAM161A
FAM161 centrosomal protein A
FAM161A is located on the short (p) arm of chromosome 2, at band 2p15. Arm ratio per GRCh38 - banding schematic.
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Overview
FAM161A, short for FAM161 centrosomal protein A, resides on chromosome 2 at band 2p15 and encodes a 660-amino acid protein essential for retinal photoreceptor health. The protein localises to the centrosome and the connecting cilium, a specialised structure that links the inner and outer segments of rod and cone photoreceptors. This ciliary region is vital for transporting proteins and maintaining the organisation required for phototransduction, the process by which light is converted into electrical signals. When FAM161A function is impaired, photoreceptors gradually deteriorate, resulting in progressive retinal degeneration and vision loss. The gene is recognised in UK clinical genomics pathways for retinal disorders, reflecting its clinical relevance in inherited eye disease.
What the gene does
The FAM161A protein operates primarily at the centrosome and the photoreceptor connecting cilium, where it supports the structural framework necessary for ciliary assembly and maintenance. Research suggests that FAM161A interacts with other ciliary proteins to coordinate the architecture of the connecting cilium, which serves as a critical transport hub between the photoreceptor inner segment (containing the cell nucleus and biosynthetic machinery) and the outer segment (housing the light-sensitive discs). Evidence indicates that FAM161A plays a role in anchoring and organising ciliary components, ensuring that newly synthesised proteins reach the outer segment efficiently. Disruption of FAM161A function compromises ciliary integrity, impairing the delivery of essential proteins for phototransduction and disc renewal. Over time, this leads to photoreceptor cell death, beginning typically with rod cells and progressing to cones, manifesting clinically as night blindness followed by progressive loss of peripheral and central vision.
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Chromosome location
FAM161A is located on the short arm of chromosome 2 at cytogenetic band 2p15. This region of the genome contains multiple genes, and the FAM161A locus itself spans several thousand base pairs. The gene comprises multiple exons that are transcribed and spliced to produce the mature messenger RNA encoding the 660-amino acid protein. Structural details regarding total exon count have not been comprehensively catalogued in all public databases, but the genomic organisation supports alternative splicing mechanisms typical of centrosomal and ciliary genes.
Protein structure
The FAM161A protein contains several coiled-coil domains distributed along its length, including predicted coiled-coil regions at amino acids 93-120, 296-320, and 522-552. Coiled-coil motifs commonly mediate protein-protein interactions, suggesting that FAM161A engages with binding partners through these structural elements. A functionally significant region spanning amino acids 341-525 is required for interaction with CFAP418, a ciliary protein implicated in ciliary assembly and function. The carboxy-terminal portion of FAM161A, from amino acids 605-660, is predicted to be disordered, a feature that may confer flexibility for dynamic interactions within the ciliary environment. Together, these structural features position FAM161A as a scaffold protein, coordinating multiple binding partners to maintain ciliary organisation in photoreceptors.
Key variants
Pathogenic variants in FAM161A are distributed across the gene and include nonsense, frameshift, and missense changes that disrupt protein function. Loss-of-function variants typically lead to absent or severely truncated protein, abolishing ciliary localisation and scaffolding activity. Missense variants affecting conserved residues within coiled-coil domains or the CFAP418-binding region can impair protein interactions critical for ciliary integrity. The clinical severity and progression of retinal degeneration may vary depending on the specific variant and whether residual protein function is retained.
Sample of pathogenic variants
10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.
| Variant (HGVS) | Protein change | Classification | Evidence | Associated condition |
|---|---|---|---|---|
c.1138C>T | p.Arg380Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Retinitis pigmentosa 28 |
c.1150dup | p.Thr384fs | Pathogenic/Likely pathogenic | ★★☆☆ | Retinitis pigmentosa 28 |
c.1250dup | p.Leu418fs | Pathogenic/Likely pathogenic | ★★☆☆ | Retinitis pigmentosa 28 |
c.1405del | p.Arg469fs | Pathogenic | ★★☆☆ | Retinal dystrophy |
c.1753_1756del | - | Pathogenic | ★★☆☆ | Retinitis pigmentosa 28 |
c.1804_1805del | p.Glu602fs | Pathogenic/Likely pathogenic | ★★☆☆ | Retinitis pigmentosa 28 |
c.1928C>G | p.Ser643Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Retinitis pigmentosa 28 |
c.238G>T | p.Glu80Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Retinitis pigmentosa 28 |
c.690del | p.Glu231fs | Pathogenic | ★★☆☆ | Retinal dystrophy |
c.760G>T | p.Glu254Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Retinitis pigmentosa 28 |
Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.
Associated conditions
Pathogenic variants in FAM161A are causative of autosomal recessive retinal dystrophy, characterised by progressive degeneration of photoreceptor cells. Affected individuals typically present with night blindness in childhood or adolescence, reflecting early rod photoreceptor dysfunction, followed by gradual constriction of the visual field and eventual central vision loss as cone photoreceptors deteriorate. The phenotype overlaps with retinitis pigmentosa and related inherited retinal dystrophies. Clinical findings include retinal pigmentary changes, attenuated retinal vessels, and progressive loss of photoreceptor and retinal pigment epithelium function on electroretinography and imaging studies.
No disease links recorded for this gene in our reference set.
UK clinical status
FAM161A is listed on the NHS Genomic Medicine Service PanelApp under the Retinal disorders panel (green classification, version R32) and the Developmental Disorders Genotype-to-Phenotype (DDG2P) panel (green classification). Green classification indicates strong evidence supporting the gene-disease relationship, meaning that FAM161A testing is appropriate in the context of inherited retinal disease within NHS genomic diagnostic pathways. Individuals with clinical features consistent with retinal dystrophy may be offered genetic testing that includes FAM161A as part of a multi-gene panel for retinal disorders.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What does the FAM161A protein do in the eye?
The FAM161A protein is located in the connecting cilium of photoreceptor cells, where it helps organise the structural framework required for transporting proteins between the inner and outer segments. This transport is essential for maintaining the light-sensing machinery of rods and cones.
How is FAM161A-related retinal dystrophy inherited?
FAM161A-related retinal dystrophy follows an autosomal recessive inheritance pattern, meaning an individual must inherit two pathogenic variants (one from each parent) to develop the condition. Carriers with one pathogenic variant typically have normal vision.
Is FAM161A testing available through the NHS?
Yes, FAM161A is included in NHS genomic testing panels for retinal disorders. Individuals with clinical features of inherited retinal dystrophy may be eligible for multi-gene panel testing that includes FAM161A, following referral to a clinical genetics or ophthalmology service.