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CHM

CHM Rab escort protein

The CHM gene contains instructions for making Rab escort protein-1 (REP-1), a crucial protein involved in cellular trafficking. The CHM gene encodes Rab escort protein-1 (REP-1), which is vital for intracellular transport processes.

Chromosome Xq21.2 Various HGNC:1940 Tier C
CHM Xq21.2 p arm q arm X

CHM is located on the long (q) arm of chromosome X, at band Xq21.2. Arm ratio per GRCh38 - banding schematic.

Explore chromosome X in the library →

Available at Jeen Health

Clinical tests that include this

Carrier Screening panel
CHM is 1 of 1,008 genes on this panel
Expanded carrier screening for recessive and X-linked conditions

Overview

The CHM gene provides the blueprint for Rab escort protein-1 (REP-1), a protein found in all tissues of the body. REP-1 is essential for orchestrating the precise movement of other proteins and cellular components within cells. When REP-1 does not function correctly, these important cellular transport mechanisms can be disrupted, leading to specific inherited clinical conditions.

What the gene does

Rab escort protein-1, encoded by CHM, serves as a molecular chaperone that facilitates the proper positioning of Rab proteins within cells. Initially, REP-1 binds to a Rab protein and supports a necessary chemical modification. Subsequently, the escort protein delivers its cargo to the appropriate membrane surface of a cellular organelle. At these membrane sites, Rab proteins coordinate the trafficking of various cellular structures and molecules, ensuring proper intracellular communication. Upon successful delivery, REP-1 detaches and returns to escort additional Rab proteins, thereby maintaining continuous cellular transport operations. Disruption of this system through loss of functional REP-1 can compromise cellular health.

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Chromosome location

The CHM gene is located on the long arm of the X chromosome at position Xq21.2. The specific chromosomal address aids in mapping the gene within the human genome and is significant for understanding its X-linked inheritance patterns, particularly for conditions like Choroideremia.

Protein structure

The CHM gene produces a protein composed of 653 amino acids. A specific segment of this protein, spanning amino acids 606-653, is identified as a disordered region, suggesting it may possess structural flexibility or lack a stable three-dimensional form.

Key variants

Genetic changes within the CHM gene can affect either the production or the function of Rab escort protein-1 (REP-1). Over 140 different types of variants have been identified in the CHM gene. Most of these genetic alterations lead to the creation of a shortened, non-functional REP-1 protein. Other gene mutations result in a decrease in the protein's function or delete part or all of the gene.

The table below shows the top 10 pathogenic or likely-pathogenic variants currently classified in ClinVar for CHM.
View all on ClinVar →

Sample of pathogenic variants

10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.

Variant (HGVS) Protein change Classification Evidence Associated condition
c.1166+1G>A
single nucleotide variant
 - Pathogenic ★★☆☆ Choroideremia
c.1244+1G>A
single nucleotide variant
 - Pathogenic ★★☆☆ Retinal dystrophy
c.1512T>A
single nucleotide variant
 p.Tyr504Ter Pathogenic ★★☆☆ Choroideremia
c.189+1G>A
single nucleotide variant
 - Pathogenic ★★☆☆ Retinal dystrophy
c.49+1G>A
single nucleotide variant
 - Pathogenic ★★☆☆ not provided
c.940+1G>A
single nucleotide variant
 - Pathogenic ★★☆☆ Retinal dystrophy
c.117-546_126delinsAA
Indel
 - Pathogenic ★☆☆☆ Choroideremia
c.1176dup
Duplication
 p.Val393fs Pathogenic ★☆☆☆ Choroideremia
c.1348dup
Duplication
 p.Arg450fs Pathogenic ★☆☆☆ not provided
c.625C>T
single nucleotide variant
 p.Gln209Ter Pathogenic ★☆☆☆ Paediatric disorders

Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.

Associated conditions

Pathogenic variants in the CHM gene are primarily linked to Choroideremia, an X-linked recessive condition affecting vision. The impaired function of REP-1 in intracellular trafficking is a central factor in the development of this disorder. Nearly all identified mutations lead to production of abnormally small, non-functional REP-1 protein, whilst others reduce protein function or involve deletions of gene segments.

UK clinical status

The CHM gene is included in several national genomic testing panels within the UK NHS. It is listed on the Panel DDG2P and the Panel Retinal disorders (R32), highlighting its clinical relevance for both developmental disorders and specific eye conditions within the NHS Genomic Medicine Service.

Green-listed
High evidence · clinically actionable in NHS testing
Included in NHS GMS signed-off panels
Retinal disorders · R32 NHS GMS → DDG2P NHS GMS →
NHS Genomic Medicine Service Jeen carrier screening

Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory

Frequently asked questions

What is the main function of the CHM gene?

The CHM gene provides instructions for creating Rab escort protein-1 (REP-1). This protein is essential for directing Rab proteins to specific cell membranes, which in turn helps manage the movement of proteins and organelles within cells.

What condition is associated with variants in the CHM gene?

Pathogenic variants in the CHM gene are primarily linked to Choroideremia, a progressive inherited eye disorder that leads to severe vision loss.

How does REP-1 dysfunction lead to Choroideremia?

When REP-1 is non-functional or absent due to CHM gene variants, Rab proteins cannot be properly transported to cell membranes. This disrupts crucial intracellular trafficking processes, particularly affecting the health and function of retinal cells, leading to symptoms of Choroideremia.

References

  1. Garcia-Hoyos M, Lorda-Sanchez I, Gómez-Garre P. New type of mutations in three spanish families with choroideremia. Investigative ophthalmology & visual science. 2008. PMID: 18385043
  2. Yip SP, Cheung TS, Chu MY. Novel truncating mutations of the CHM gene in Chinese patients with choroideremia. Molecular vision. 2007. PMID: 18087237
  3. MacDonald IM, Sereda C, McTaggart K. Choroideremia gene testing. Expert review of molecular diagnostics. 2004. PMID: 15225095
  4. Preising M, Ayuso C. Rab escort protein 1 (REP1) in intracellular traffic: a functional and pathophysiological overview. Ophthalmic genetics. 2004. PMID: 15370541
  5. van den Hurk JA, van de Pol DJ, Wissinger B. Novel types of mutation in the choroideremia ( CHM) gene: a full-length L1 insertion and an intronic mutation activating a cryptic exon. Human genetics. 2003. PMID: 12827496
  6. McTaggart KE, Tran M, Mah DY. Mutational analysis of patients with the diagnosis of choroideremia. Human mutation. 2002. PMID: 12203991
⚠ Draft content. This page has been flagged for manual clinical review and may contain gaps or inaccuracies. Speak with a qualified healthcare professional before acting on any information here.
Educational content. This page is not medical or genetic advice, is not individually reviewed by a clinician for each reader, and should not replace a consultation with a qualified healthcare professional or genetic counsellor. If you are considering genetic testing or acting on a test result, book a consultation.
Data sources Last updated 17 July 2026. Content compiled from HGNC · MedlinePlus Genetics · ClinGen · Genomics England PanelApp · NHS National Genomic Test Directory · ClinVar · UniProt · AlphaFold .