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Genetic Archaeology
GENETIC ARCHAEOLOGY // PROFILE

CFTR

Cystic Fibrosis Transmembrane Conductance Regulator

CHR 7
7q31.2

Overview

CFTR encodes a chloride ion channel expressed in the epithelial cells of many organs. The protein regulates the transport of chloride and sodium ions across the cell membrane, which is essential for the production of normal mucus. Mutations lead to Cystic Fibrosis (Mucoviscidosis), the most common life-shortening hereditary disease in the Caucasian population.

📍 Chromosomal Position

7q31.2 (Chromosome 7)

🧬 Gene Category

Hereditary Diseases

🔬 Inheritance

Autosomal recessive

📊 Prevalence

~1:2,500 newborns (Europe), carrier frequency ~1:25

Function & Significance

The CFTR channel is an ATP-gated chloride channel found in the epithelial cells of the lungs, pancreas, intestine, sweat glands, and other organs. It regulates the composition of the mucus layer covering these surfaces.

In mutations in CFTR, chloride transport is disrupted. This leads to thick, sticky mucus that clogs the airways and promotes bacterial infections. In the pancreas, the mucus blocks digestive enzymes, leading to malabsorption and malnutrition.

🔬 The F508del Mutation

The F508del mutation (deletion of phenylalanine at position 508) is the most common CFTR mutation worldwide (~70% of all cystic fibrosis alleles). The mutated protein is not correctly folded and never reaches the cell surface. Modern CFTR modulators such as Trikafta® can partially restore the function of this defective protein.

Associated Diseases

  • 🫁 Cystic Fibrosis (Mucoviscidosis)

    Chronic lung disease, recurrent infections, pancreatic insufficiency

  • 🦠 Chronic Pseudomonas Infections

    Bacterial colonization of the lung that is difficult to treat

  • 🍽️ Pancreatic Insufficiency

    Digestive disorders due to missing enzymes

  • 👨 Male Infertility

    Congenital bilateral aplasia of the vas deferens (CBAVD)

🧬 Relevant SNPs

rs113993960
7:117559590
Allele 1

CTT

/

Allele 2

Significance: F508del – Most common mutation worldwide (~70% of all CF alleles). Deletion of 3 base pairs leads to the loss of phenylalanine at position 508.

rs75961395
7:117530953
Allele 1

G

/

Allele 2

A

Significance: R117H – Associated with milder disease courses or isolated CBAVD (male infertility). Clinical expression is variable.

rs80287110
7:117534363
Allele 1

G

/

Allele 2

A

Significance: G551D – “Gating mutation” where the channel is present at the cell surface but does not open. Responds very well to Ivacaftor (Kalydeco®).

⚕️ Clinical Significance

Cystic fibrosis is included in newborn screening in most countries (sweat test, genetic tests). Early diagnosis allows for timely therapy and significantly improves prognosis.

Modern Therapies: CFTR modulators such as Trikafta® (elexacaftor/tezacaftor/ivacaftor) have revolutionized treatment. They significantly improve lung function and quality of life. Therapy is mutation-specific – not all mutations respond to all medications.

Life Expectancy: Thanks to modern therapies, median life expectancy today is over 50 years (previously ~30 years).

📚 Data Sources

The information on this page is based on the following scientific sources:

  • OMIM: #602421 (CFTR), #219700 (Cystic Fibrosis)
  • dbSNP: rs113993960, rs75961395, rs80287110
  • ClinVar: Pathogenic CFTR variants
  • PubMed: Literature on cystic fibrosis and CFTR modulators
  • CFTR2: cftr2.org – Database for CFTR variants

Last Update: February 2026

Biological Function

The CFTR protein is a chloride channel in the cell membrane regulating the transport of chloride ions and water. It is particularly important in epithelial cells of the lung, pancreas, liver, and digestive tract. Mutations lead to malfunction of chloride transport, resulting in thick mucus in various organs.

Associated Conditions

Cystic Fibrosis (Mucoviscidosis) Congenital Bilateral Absence of the Vas Deferens (CBAVD) Chronic Pancreatitis
Molecular Analysis

Analyzed Markers

rs113993960 Pathogenic
Pos: 7:117559590 | Alleles: CTT/del

F508del - Most common mutation (70% of CF alleles)

rs121909013 Pathogenic
Pos: 7:117534318 | Alleles: G/A

G542X - Second most common mutation, stop codon

rs75961395 Pathogenic (Mild)
Pos: 7:117492120 | Alleles: G/A

R117H - Associated with milder or late-onset symptoms

rs80287110 Pathogenic
Pos: 7:117544039 | Alleles: G/A

G551D - 'Ivacaftor-sensitive' mutation