• 3
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
CHM (HGNC:1940) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
CHM Rab escort protein
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
TCD, DXS540
Alias symbols
REP-1
%HI
25.28(Read more about the DECIPHER Haploinsufficiency Index)
pLI
1(Read more about gnomAD pLI score)
LOEUF
0.19(Read more about gnomAD LOEUF score)
Cytoband
Xq21.2
Genomic Coordinates
GRCh37/hg19: chrX:85116185-85302562 NCBI Ensembl UCSC
GRCh38/hg38: chrX:85861180-86047558 NCBI Ensembl UCSC
MANE Select Transcript
NM_000390.4 ENST00000357749.7 (Read more about MANE Select)
Function
Substrate-binding subunit of the Rab geranylgeranyltransferase (GGTase) complex. Binds unprenylated Rab proteins and presents the substrate peptide to the catalytic component B composed of RABGGTA and RABGGTB, and remains bound to it after the geranylgeranyl transfer reaction. The component A is thought to be regenerated by transferring its prenylated Rab back to the donor membrane. Besides, a pre-formed complex consisting of CHM and the Rab GGTase dimer (RGGT or component B) can bind to and pre... (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-29081
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
Sufficient Evidence for Haploinsufficiency (3)
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Last Evaluated:
03/24/2021

Haploinsufficiency (HI) Score Details

HI Score:
3
HI Evidence Strength:
Sufficient Evidence for Haploinsufficiency (Disclaimer)
HI Disease:
HI Evidence:
  • PUBMED: 33538369
    Zeitz et al. (2021) describe a French cohort of 45 families, 25 of which carry novel variants, in the context of 822 previously reported choroideremia (CHM) families. Most of the variants represent loss‐of‐function variants with eleven families having large (i.e. ≥6 kb) genomic deletions; 18 small insertions, deletions or insertion deletions; 6 nonsense variants; 8 splice site variants; and 2 missense variants likely to affect splicing. Similarly, 822 previously published families carry mostly loss‐of‐function variants. These variants and other recurrent variants span all exons of CHM.
  • PUBMED: 27070432
    Sanchez-Alcudia et al. (2016) characterized 36 families with CHM and identified 28 different variants. Most of the families (31%, 22/36) carried hemizygous nucleotide substitutions that corresponded mostly to nonsense mutations (36%, 13/36), although splicing mutations (11%, 4/36), frameshift (11%, 4/36) and missense (3%, 1/36) variants were also identified. The remainder of the families (13/36) carried genomic deletions involving complete or partial deletion of the gene. Of note, a 455.6 kb deletion at chromosome region Xq21.2 (arr[GRCh37] Xq21.2(84847610–85303270)x0) exclusively encompassing the entire CHM gene was detected. A de novo previously described translocation was also found.
HI Evidence Comments:
Choroideremia (CHM) is characterized by progressive chorioretinal degeneration in affected males and milder signs in carrier females. A recent study (PMID: 31181178) has shown female carriers of choroideremia can present with a wide range of clinical phenotypes and disease severity, from mild to severe disease similar to males. Symptoms in affected individuals evolve from night blindness to peripheral visual field loss, with central vision preserved until late in life.
NOTE:

The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.

Triplosensitivity (TS) Score Details

TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)
NOTE:

The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.

Genomic View

Select assembly: (NC_000023.10) (NC_000023.11)