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, in frame

Verified step by step guidance

1. Understand that the IL2RG gene codes for a protein of 375 amino acids, and the gene contains eight exons. Each exon contributes a specific portion of the amino acid sequence in the final protein.
2. Recognize that an "in-frame deletion" means nucleotides are deleted in multiples of three, so the reading frame downstream of the deletion remains unchanged. This results in the loss of one or more amino acids but does not cause a frameshift.
3. Since the deletion is in Exon 2, identify that the missing amino acids will be located early in the protein sequence, potentially affecting the protein's structure or function depending on the importance of that region.
4. Consider that the rest of the protein sequence after the deletion will be translated normally because the reading frame is preserved, so the protein will be shorter but not completely disrupted by a frameshift.
5. Evaluate the likely impact on protein function: the deletion may remove critical amino acids necessary for cytokine receptor activity, possibly reducing or abolishing function, but it will not cause a truncated protein due to premature stop codons caused by frameshifts.

Key Concepts

Gene Structure and Exons

Genes are composed of exons and introns; exons contain the coding sequences that are spliced together to form mRNA. Each exon contributes specific amino acid sequences to the final protein. Understanding which exon is affected by a mutation helps predict how the protein’s structure and function might change.

In-Frame Deletions

An in-frame deletion removes nucleotides in multiples of three, preserving the reading frame of the gene. This results in a protein missing certain amino acids but otherwise intact, potentially altering protein function depending on the deleted region’s importance.

Protein Function and Cytokine Receptors

The IL2RG gene encodes a protein critical for cytokine receptor complexes involved in immune cell development. Mutations affecting this protein can disrupt receptor assembly or signaling, leading to immune deficiencies like SCID by impairing immune system maturation.