General pathology · Genetic disease
How a single gene causes disease: enzymes, receptors and structural proteins !
- Mechanism
An altered gene makes a protein that is missing, works badly or gets in the way; the kind of protein explains the disease and how it is inherited.
Updated 2026-11-01
What it is
The effect of a mutation depends on the protein the gene encodes. If it is an enzyme, its substrate builds up or its product is lacking; if it is a receptor, the signal fails to arrive; if it is a structural protein, the tissue loses strength. This reasoning explains why some diseases are recessive and others dominant.
Structure
- Gaucher: large macrophages with striated cytoplasm like ‘crumpled tissue paper’ in the spleen, liver and bone marrow.
- Tay-Sachs: neurons distended by vacuoles; on electron microscopy, cytoplasmic bodies in concentric layers (‘onion-skin’).
- Familial hypercholesterolaemia: tendon xanthomas (foamy, cholesterol-laden macrophages) in the Achilles tendon and the hand extensors.
Step by step
- A mutation reduces, removes or changes the protein the gene encodes.
- If the protein is an enzyme and half remains, the pathway usually works: heterozygous carriers are healthy.
- With no working enzyme, the substrate accumulates: in lysosomes it forms deposits that enlarge cells (Gaucher, Tay-Sachs).
- Or the end product is missing: without tyrosinase no melanin forms and albinism results.
- Or the substrate is diverted into a toxic side pathway: in phenylketonuria phenylketones form and harm the brain.
- If the protein is a receptor or a structural protein, half a dose or one abnormal component already causes disease: dominant inheritance.
Which protein fails and what happens
| Disease | Altered protein | Type of defect | Consequence | Inheritance |
|---|---|---|---|---|
| Phenylketonuria | Phenylalanine hydroxylase | Enzyme | Phenylalanine and toxic metabolites; intellectual disability if untreated | Autosomal recessive |
| Tay-Sachs disease | Hexosaminidase A | Lysosomal enzyme | GM2 ganglioside in neurons; cherry-red spot in the macula | Autosomal recessive |
| Gaucher disease | Glucocerebrosidase | Lysosomal enzyme | Glucocerebroside in macrophages; hepatosplenomegaly and bone lesions | Autosomal recessive |
| Familial hypercholesterolaemia | LDL receptor | Receptor | High LDL from birth, xanthomas and early atherosclerosis | Autosomal dominant |
| Marfan syndrome | Fibrillin-1 | Structural protein | Weak elastic fibres and excess TGF-β signalling: aorta, lens, skeleton | Autosomal dominant |
| Duchenne muscular dystrophy | Dystrophin | Structural protein | Muscle fibres tear with contraction and are replaced by fat and fibrosis | X-linked recessive |
| Cystic fibrosis | CFTR | Chloride channel | Thick secretions in the airways, pancreas and gut | Autosomal recessive |
Test yourself
Think of the answer, then tap the question to see it.
Why are most enzyme deficiencies inherited as recessive traits?
Because a single normal copy makes about half of the enzyme, which is enough to keep the pathway working.
Which mechanism lets one abnormal collagen copy cause severe osteogenesis imperfecta?
The dominant negative effect: the abnormal chain enters the triple helix and also ruins collagen built with the normal chain.
Which cell fills with stored material in Gaucher disease?
The macrophage, which accumulates glucocerebroside and looks like crumpled paper.
Why does the LDL receptor cause disease with only one altered copy?
Through haploinsufficiency: half the receptors cannot clear LDL from the blood, which is high from birth.
Related
- Mendelian inheritance: autosomal dominant, recessive and X-linked
- Intracellular accumulations: cholesterol, proteins, hyaline, glycogen
- Cystic fibrosis: from the CFTR channel to organ damage
Related conditions
- Familial hypercholesterolemia
- Marfan syndrome
- Gaucher disease
- Tay–Sachs disease
- Phenylketonuria (PKU)
- Niemann–Pick disease
- Hurler syndrome (mucopolysaccharidosis type I)
- Fabry disease
- Pompe disease (glycogen storage disease type II)
- Osteogenesis imperfecta
- Ehlers–Danlos syndrome
- Duchenne muscular dystrophy
- Cystic fibrosis
- Achondroplasia
Elsewhere in DurgiPedia
- Types of mutations
- Lysosomal storage diseases
- LDL receptor
- Fibrillin-1
- Phenylalanine and tyrosine metabolism
- Collagen synthesis
Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.
Sources: Familial hypercholesterolemia: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); Phenylketonuria: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); Gaucher disease: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); Tay-Sachs disease: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026).
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Representative model, for educational purposes only.