On this page
SDCCAG8
SHH signaling and ciliogenesis regulator SDCCAG8
SDCCAG8 is located on the long (q) arm of chromosome 1, at band 1q43-q44. Arm ratio per GRCh38 - banding schematic.
Explore chromosome 1 in the library →Available at Jeen Health
Clinical tests that include this
Overview
SDCCAG8 (SHH signalling and ciliogenesis regulator SDCCAG8) is located on chromosome 1 at position q43-q44 and encodes a 713-amino acid protein essential for primary cilium formation. Primary cilia are sensory organelles that project from the cell surface and coordinate developmental pathways including Sonic Hedgehog (SHH) signalling, which guides tissue patterning during embryonic development. The SDCCAG8 protein localises to the centrosome and ciliary transition zone, where it helps recruit and organise other structural components required for cilium assembly. Pathogenic variants in SDCCAG8 follow an autosomal recessive inheritance pattern, meaning both gene copies must carry changes for clinical manifestations to occur. This gene is recognised across multiple NHS Genomic Medicine Service panels for ciliopathies affecting the kidney, retina, and other organ systems.
What the gene does
The SDCCAG8 protein functions as a scaffolding component at the base of primary cilia, where it organises the transition zone - a specialised region that controls which molecules enter and exit the cilium. By recruiting other proteins to this location, SDCCAG8 helps establish the cilium's structural integrity and enables the organelle to detect and relay external signals into the cell interior. This includes supporting Sonic Hedgehog pathway signalling, a cascade critical for embryonic patterning, limb development, and neuronal differentiation. The protein also participates in maintaining genomic stability during cell division by ensuring proper centrosome function, the structure from which cilia emerge. When SDCCAG8 is absent or non-functional, cilia either fail to form or remain too short and disorganised to transmit signals effectively. This disrupts multiple developmental processes that depend on ciliary sensing, including kidney tubule formation, photoreceptor structure in the retina, and hypothalamic pathways that regulate appetite and metabolism.
Video: Genetics 101
Chromosome location
SDCCAG8 is positioned on the long arm of chromosome 1 at the cytogenetic band 1q43-q44. This region lies near the chromosomal terminus and contains a cluster of genes implicated in developmental regulation. The precise genomic coordinates and exon structure contribute to the gene's susceptibility to certain classes of pathogenic variants, including deletions affecting multiple neighbouring genes.
Protein structure
The SDCCAG8 protein comprises 713 amino acids with a domain organisation characterised by extended coiled-coil regions that mediate protein-protein interactions. A coiled coil spanning amino acids 129-175 is followed by disordered regions at positions 194-215, which provide structural flexibility. A second coiled coil extends from amino acids 223-273, and a third large coiled-coil domain occupies amino acids 348-707, forming much of the protein's C-terminal half. This C-terminal region (amino acids 216-713) is sufficient for homodimerisation, enabling SDCCAG8 molecules to pair with one another. The segment from amino acids 533-713 specifically mediates interaction with OFD1, another ciliopathy-associated protein that colocalises to the centrosome and transition zone. Disordered regions at amino acids 84-103 likely confer adaptability for binding partners during cilium assembly. These structural features position SDCCAG8 as a central hub for organising multi-protein complexes at the ciliary base.
Key variants
Pathogenic variants in SDCCAG8 are distributed across the gene's coding sequence, with many affecting the extended coiled-coil domains that mediate protein interactions. Missense changes, nonsense variants leading to premature termination, and small deletions or insertions causing frameshifts have all been reported. Because SDCCAG8-related conditions follow autosomal recessive inheritance, affected individuals typically carry two pathogenic variants - one inherited from each parent. Carrier parents are generally unaffected. The specific combination of variants may influence the severity and range of clinical features observed.
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.1147C>T | p.Gln383Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Senior-Loken syndrome 7 |
c.1556_1557del | p.Glu519fs | Pathogenic/Likely pathogenic | ★★☆☆ | Senior-Loken syndrome 7 |
c.397G>T | p.Glu133Ter | Pathogenic | ★★☆☆ | Inborn genetic diseases |
c.506_507del | p.Gln169fs | Pathogenic/Likely pathogenic | ★★☆☆ | Senior-Loken syndrome 7 |
c.511G>T | p.Glu171Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Senior-Loken syndrome 7 |
c.523G>T | p.Glu175Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Bardet-Biedl syndrome 16 |
c.696T>G | p.Tyr232Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Senior-Loken syndrome 7 |
c.784G>T | p.Glu262Ter | Pathogenic | ★★☆☆ | Senior-Loken syndrome 7 |
c.849_852del | p.Leu282_Cys283insTer | Pathogenic | ★★☆☆ | Senior-Loken syndrome 7 |
c.985dup | p.Thr329fs | Pathogenic/Likely pathogenic | ★★☆☆ | Senior-Loken syndrome 7 |
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 SDCCAG8 cause a spectrum of ciliopathies, with Bardet-Biedl syndrome being the most commonly recognised presentation. Bardet-Biedl syndrome is characterised by progressive vision loss due to retinal degeneration, kidney abnormalities, extra fingers or toes, obesity typically beginning in childhood, and learning difficulties of variable severity. Some individuals present with features overlapping other ciliopathies, including senior Løken syndrome (kidney disease with retinal dystrophy) or nephronophthisis (a form of cystic kidney disease). The range of clinical features reflects the widespread importance of primary cilia across multiple organ systems during development and throughout life.
No disease links recorded for this gene in our reference set.
Inheritance pattern
Conditions caused by pathogenic SDCCAG8 variants typically follow autosomal recessive inheritance.
When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.
UK clinical status
SDCCAG8 holds green (high-evidence) classification across multiple NHS Genomic Medicine Service gene panels, reflecting robust clinical and research evidence linking it to inherited disease. It appears on the Bardet Biedl syndrome panel (R107), the Fetal anomalies panel (R21), the Intellectual disability panel (R29), and the Retinal disorders panel (R32), among others. Green status on the Rare multisystem ciliopathy disorders panel, Renal ciliopathies panel, and Ophthalmological ciliopathies panel confirms its broad relevance to conditions affecting cilia-dependent processes. Inclusion on the Severe early-onset obesity panel (R149) recognises the metabolic features associated with ciliary dysfunction in hypothalamic pathways. The gene is also listed in the Developmental Disorders Genotype-Phenotype Database (DDG2P), supporting its role in early-onset developmental conditions.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What does it mean to be a carrier of an SDCCAG8 variant?
Carriers have one pathogenic variant in SDCCAG8 and one typical copy. They generally do not develop ciliopathy features themselves. If both parents are carriers, each pregnancy has a 25% chance of inheriting both variants and being affected, a 50% chance of being a carrier, and a 25% chance of inheriting two typical copies.
How do SDCCAG8 variants cause such diverse symptoms?
Primary cilia are present on nearly all cell types and serve distinct sensing roles in different tissues. In the retina, cilia support photoreceptor structure; in the kidney, they detect fluid flow; in the hypothalamus, they help regulate appetite. Disrupting cilium assembly therefore affects multiple organ systems simultaneously.
Are all SDCCAG8-related conditions the same?
No. While Bardet-Biedl syndrome is the most recognised presentation, some individuals have features overlapping with other ciliopathies such as nephronophthisis or senior Løken syndrome. The specific variants and additional genetic or environmental factors may influence which features predominate.