[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [General pathology](https://durgical.com/en/general-pathology/) › [Genetic disease](https://durgical.com/en/general-pathology/#a-genetic) › How a single gene causes disease: enzymes, receptors and structural proteins

[General pathology](https://durgical.com/en/general-pathology/) · [Genetic disease](https://durgical.com/en/general-pathology/#a-genetic)

# 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

## Key points

- Loss of function of an enzyme: usually recessive, because half of the enzyme is enough.
- Haploinsufficiency: half of the protein is not enough (LDL receptor in familial hypercholesterolaemia), dominant inheritance.
- Dominant negative effect: the abnormal protein spoils the complex it forms with the normal one (collagen in osteogenesis imperfecta, fibrillin in Marfan).
- Gain of function: the protein does something new or excessive (huntingtin in Huntington, activated FGFR3 in achondroplasia).
- Lysosomal storage diseases: an acid hydrolase is missing and its substrate piles up inside lysosomes.

## 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](https://durgical.com/en/conditions/phenylketonuria/) | Phenylalanine hydroxylase | Enzyme | Phenylalanine and toxic metabolites; intellectual disability if untreated | Autosomal recessive |
| [Tay-Sachs disease](https://durgical.com/en/conditions/tay-sachs-disease/) | Hexosaminidase A | Lysosomal enzyme | GM2 ganglioside in neurons; cherry-red spot in the macula | Autosomal recessive |
| [Gaucher disease](https://durgical.com/en/conditions/gaucher-disease/) | Glucocerebrosidase | Lysosomal enzyme | Glucocerebroside in macrophages; hepatosplenomegaly and bone lesions | Autosomal recessive |
| [Familial hypercholesterolaemia](https://durgical.com/en/conditions/familial-hypercholesterolemia/) | LDL receptor | Receptor | High LDL from birth, xanthomas and early atherosclerosis | Autosomal dominant |
| [Marfan syndrome](https://durgical.com/en/conditions/marfan-syndrome/) | Fibrillin-1 | Structural protein | Weak elastic fibres and excess TGF-β signalling: aorta, lens, skeleton | Autosomal dominant |
| [Duchenne muscular dystrophy](https://durgical.com/en/conditions/duchenne-muscular-dystrophy/) | Dystrophin | Structural protein | Muscle fibres tear with contraction and are replaced by fat and fibrosis | X-linked recessive |
| [Cystic fibrosis](https://durgical.com/en/conditions/cystic-fibrosis/) | CFTR | Chloride channel | Thick secretions in the airways, pancreas and gut | Autosomal recessive |

## Memory aid

Lose the enzyme and the storeroom overflows; break the receptor or the beam and one bad copy is enough to bring the house down.

## 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.

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## Related

- [Mendelian inheritance: autosomal dominant, recessive and X-linked](https://durgical.com/en/general-pathology/mendelian-inheritance-autosomal-dominant-recessive-and-x-linked/)
- [Intracellular accumulations: cholesterol, proteins, hyaline, glycogen](https://durgical.com/en/general-pathology/intracellular-accumulations-cholesterol-proteins-hyaline-glycogen/)
- [Cystic fibrosis: from the CFTR channel to organ damage](https://durgical.com/en/general-pathology/cystic-fibrosis-from-the-cftr-channel-to-organ-damage/)

## Related conditions

- [Familial hypercholesterolemia](https://durgical.com/en/conditions/familial-hypercholesterolemia/)
- [Marfan syndrome](https://durgical.com/en/conditions/marfan-syndrome/)
- [Gaucher disease](https://durgical.com/en/conditions/gaucher-disease/)
- [Tay–Sachs disease](https://durgical.com/en/conditions/tay-sachs-disease/)
- [Phenylketonuria (PKU)](https://durgical.com/en/conditions/phenylketonuria/)
- [Niemann–Pick disease](https://durgical.com/en/conditions/niemann-pick-disease/)
- [Hurler syndrome (mucopolysaccharidosis type I)](https://durgical.com/en/conditions/hurler-syndrome/)
- [Fabry disease](https://durgical.com/en/conditions/fabry-disease/)
- [Pompe disease (glycogen storage disease type II)](https://durgical.com/en/conditions/pompe-disease/)
- [Osteogenesis imperfecta](https://durgical.com/en/conditions/osteogenesis-imperfecta/)
- [Ehlers–Danlos syndrome](https://durgical.com/en/conditions/ehlers-danlos-syndrome/)
- [Duchenne muscular dystrophy](https://durgical.com/en/conditions/duchenne-muscular-dystrophy/)
- [Cystic fibrosis](https://durgical.com/en/conditions/cystic-fibrosis/)
- [Achondroplasia](https://durgical.com/en/conditions/achondroplasia/)

## Elsewhere in DurgiPedia

- [Types of mutations](https://durgical.com/en/biochemistry/topics/types-of-mutations/)
- [Lysosomal storage diseases](https://durgical.com/en/biochemistry/topics/lysosomal-storage-diseases/)
- [LDL receptor](https://durgical.com/en/biochemistry/enzymes/ldl-receptor/)
- [Fibrillin-1](https://durgical.com/en/biochemistry/enzymes/fibrillin-1/)
- [Phenylalanine and tyrosine metabolism](https://durgical.com/en/biochemistry/pathways/phenylalanine-and-tyrosine-metabolism/)
- [Collagen synthesis](https://durgical.com/en/biochemistry/topics/collagen-synthesis/)

[← All of general pathology](https://durgical.com/en/general-pathology/)

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](https://medlineplus.gov/genetics/condition/familial-hypercholesterolemia/) (MedlinePlus, US National Library of Medicine, 2026); [Phenylketonuria: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/phenylketonuria/) (MedlinePlus, US National Library of Medicine, 2026); [Gaucher disease: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/gaucher-disease/) (MedlinePlus, US National Library of Medicine, 2026); [Tay-Sachs disease: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/tay-sachs-disease/) (MedlinePlus, US National Library of Medicine, 2026).

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Representative model, for educational purposes only.

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Source: https://durgical.com/en/general-pathology/how-a-single-gene-causes-disease-enzymes-receptors-and-structural-proteins/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/general-pathology/how-a-single-gene-causes-disease-enzymes-receptors-and-structural-proteins/