Mutations in the IL2RG gene cause approximately 30 percent of severe combined immunodeficiency disorder (SCID) cases in humans. These mutations result in alterations to a protein component of cytokine receptors that are essential for proper development of the immune system. The IL2RG gene is composed of eight exons and contains upstream and downstream sequences that are necessary for proper transcription and translation. Below are some of the mutations observed. For each, explain its likely influence on the IL2RG gene product (assume its length to be 375 amino acids).
Deletion in Exon 2, causing frameshift

Verified step by step guidance

1. Understand that a frameshift mutation caused by a deletion in Exon 2 will alter the reading frame of the mRNA from the point of mutation onward, changing the codon sequence.
2. Recall that the reading frame is read in triplets (codons), so a deletion not in multiples of three nucleotides shifts the frame, potentially introducing premature stop codons.
3. Predict that this frameshift will likely result in a truncated protein due to early stop codons, producing a shorter and usually nonfunctional IL2RG protein.
4. Consider that the altered amino acid sequence downstream of the mutation will disrupt the normal structure and function of the cytokine receptor component encoded by IL2RG.
5. Conclude that this mutation will severely impair or abolish the function of the IL2RG protein, contributing to the SCID phenotype.

Key Concepts

Frameshift Mutation

A frameshift mutation occurs when nucleotides are inserted or deleted from the DNA sequence in numbers not divisible by three, altering the reading frame of the gene. This shift changes every amino acid downstream of the mutation, often resulting in a nonfunctional protein or premature stop codon. In the IL2RG gene, a frameshift in exon 2 would disrupt the normal protein sequence early on.

Gene Structure and Exons

Genes are composed of exons and introns; exons contain the coding sequences that are translated into proteins. The IL2RG gene has eight exons, each contributing specific amino acid sequences to the final protein. Mutations in early exons, like exon 2, can have a more severe impact on the protein product than mutations in later exons.

Protein Function in Immune Development

The IL2RG gene encodes a protein critical for cytokine receptor function, which is essential for immune cell development and signaling. Mutations that alter this protein’s structure can impair immune responses, leading to disorders like SCID. Understanding how mutations affect protein function helps explain disease mechanisms.