CHML
protein-codingCHM like Rab escort protein
Gene summary
The product of the CHML gene supports geranylgeranylation of most Rab proteins and may substitute for REP-1 in tissues other than retina. CHML is localized close to the gene for Usher syndrome type II. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~11.5 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to CHML variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001381853.1. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | ||||
| missense | 98 | 11 | 109 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 98 | 12 | 0 | 110 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001368782.1 | 1 | MANE Select | |
| Ensembl | ENSP00000355511.1 | 1 | MANE Select | |
| RefSeq | NP_001368783.1 | 1 | Standard | |
| RefSeq | NP_001812.2 | 1 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Vesicle-mediated transport
- Membrane Trafficking
- Post-translational protein modification
- Metabolism of proteins
- Rab regulation of trafficking
Biological Process
- intracellular protein transport
- small GTPase mediated signal transduction
- protein geranylgeranylation
- positive regulation of GTPase activity
- post-translational protein modification
Molecular Function
- GDP-dissociation inhibitor activity
- GTPase activator activity
- Rab GTPase binding
Cellular Component
- nucleus
- nucleoplasm
- cytosol
- Rab-protein geranylgeranyltransferase complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000366553
- Coding exons
- 1
- Length
- 7078
- Individuals with no LoFs
- 0
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 0
- Defined
- 0
- p
- 0.00
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.0429 | 342 | 340 | 1.01 | 0.0000168 | 4325 |
| Missense (PolyPhen) | 86 | 107.14 | 0.80266 | 1390 | ||
| Synonymous | -0.950 | 141 | 127 | 1.11 | 0.00000683 | 1253 |
| Loss of Function | 1.86 | 10 | 18.7 | 0.535 | 8.89e-7 | 284 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Substrate-binding subunit (component A) of the Rab geranylgeranyltransferase (GGTase) complex. Binds unprenylated Rab proteins and presents the substrate peptide to the catalytic component B. The component A is thought to be regenerated by transferring its prenylated Rab back to the donor membrane. Less effective than CHM in supporting prenylation of Rab3 family. {ECO:0000269|PubMed:12356470, ECO:0000269|PubMed:15186776, ECO:0000269|PubMed:8294464}.;
Intolerance Scores
- LoFtool
- 0.220
- RVIS EVS
- -0.38
- RVIS percentile EVS
- 28.11
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.357
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |