Your joints are too flexible. Here's the genetic reason.

COL1A1 codes for type I collagen, the primary structural protein in your ligaments, tendons, and bones. It’s what gives these tissues their tensile strength. Think of it as the steel framework of your joints. When your body makes type I collagen, it assembles it into a network and then cross-links the chains together to create a stable structure.

The Sp1 site variant (rs1800012), present in approximately 15-20% of the population, weakens this cross-linking process. Your body may be making normal amounts of collagen, but the chains aren’t bonded together as tightly. This means your ligaments and tendons have reduced tensile strength and can stretch further than they should, allowing excessive joint movement.

In practice, this feels like joints that give way without warning. You reach for something and your shoulder slips. You walk on uneven ground and your ankle rolls. Your ligaments simply can’t hold your joints in their normal position, no matter how strong your muscles are. Physical therapy can’t fix loose cross-linking; your muscles can’t pull hard enough to compensate for structurally weak collagen.

COL11A1 codes for type XI collagen, a key component of cartilage. While type I collagen is your structural framework, type XI collagen maintains the integrity of the cartilage matrix that cushions your joints. It helps cartilage hold water, resist compression, and maintain its shape during movement.

Variants in COL11A1, present in roughly 20-30% of the population, reduce cartilage matrix integrity. This means your cartilage breaks down faster than normal, and your joints develop osteoarthritis earlier and more aggressively than they would otherwise. Even at a young age, your cartilage may show wear patterns similar to someone decades older.

With a COL11A1 variant, you often feel joint pain that’s worse with repeated motion. Your knee or hip aches after activity. You have trouble with stairs or uneven surfaces. Your joints feel less stable because the cartilage cushion is degrading, which forces your ligaments to work harder to stabilize the joint. Over time, as the cartilage thins, your hypermobility can actually worsen because there’s less structural support from the cartilage itself.

GDF5 codes for growth differentiation factor 5, a protein that shapes how your joints form during development. It tells your body how much cartilage to make, how to shape the joint surfaces, and how to position the bones relative to each other. It’s essentially a biological blueprint for joint architecture.

The rs143384 variant in GDF5, carried by approximately 40% of the population, reduces GDF5 expression. This means your joints may develop with slightly abnormal shapes or alignments, making them inherently less stable. Your joint surfaces may not fit together quite right, or the socket may be shallower than optimal. These subtle structural differences accumulate across multiple joints.

You feel this as generalized laxity. Your joints are loose across the board, not just in one direction. You have difficulty with certain movements that most people find easy. Your physical therapist notes that your joint alignment is “just slightly off” in ways that can’t be fully corrected with exercises. This is because the problem started before you were born, during skeletal development.

VDR codes for the vitamin D receptor, the protein that allows your cells to respond to vitamin D. When vitamin D binds to VDR, it signals your intestines to absorb calcium, and your bones to mineralize. Without functional VDR activity, your body can’t absorb calcium efficiently or build strong bone matrix, regardless of how much vitamin D or calcium you consume.

The BsmI, FokI, and TaqI variants in VDR are carried by 30-50% of the population. People with these variants have reduced calcium absorption and slower bone mineralization, meaning their bones stay softer and weaker longer. Even if your vitamin D levels look normal on a blood test, your bones may not be responding to that vitamin D properly.

This creates a vicious cycle with hypermobility. Weak bones + loose ligaments = severely unstable joints. Your bones don’t provide enough rigidity to anchor your ligaments, so your joints move excessively. Your hip socket is less mineralized. Your spine is less dense. Your ankle bones are weaker. Combined with collagen variants, this makes hypermobility much more severe and much harder to manage.

TNF codes for tumor necrosis factor-alpha, a powerful inflammatory molecule. In controlled amounts, TNF helps coordinate immune responses. But when TNF levels are chronically elevated, it activates osteoclasts, the cells that break down bone. Elevated TNF is one of the primary drivers of inflammatory bone loss.

The -308G>A variant (rs1800629) in TNF, carried by approximately 30% of the population, increases TNF production. People with this variant have chronically elevated TNF levels, which accelerates bone resorption and weakens the structural support for your joints. Your bones thin faster, your ligaments have less bony support, and your joints become more unstable.

With a TNF variant and hypermobility, you often develop early osteoarthritis, experience frequent inflammation and joint pain, and may struggle with autoimmune symptoms. Your body is essentially eating its own bone structure to feed inflammatory signals. No amount of calcium supplementation will help until you address the TNF-driven bone loss. You need to reduce TNF itself.

IL6 codes for interleukin-6, an inflammatory cytokine that signals osteoclasts to break down bone and activates the RANKL pathway, which specifically targets cartilage. When IL-6 levels are high, your body aggressively degrades cartilage matrix, leading to rapid joint degeneration.

The -174G>C variant (rs1800795) in IL6, present in roughly 40% of the population carrying the C allele, increases IL-6 production. People with this variant experience accelerated cartilage breakdown, meaning your joints develop osteoarthritis faster and more aggressively than the standard timeline. In combination with COL11A1 variants, this becomes severe.

You feel this as progressive joint pain and swelling, particularly after activity. Your joints feel hot. Inflammation comes and goes, but never quite resolves. Your hypermobility may feel worse on inflammatory days because the damaged cartilage provides even less structural support. Over time, the cartilage loss can paradoxically worsen hypermobility by eliminating the last bit of structural cushioning.