CHM

CHM Rab escort protein, the group of MicroRNA protein coding host genes

Basic information

Region (hg38): X:85861180-86047561

Previous symbols: [ "TCD", "DXS540" ]

Links

ENSG00000188419

∙ NCBI:1121 ∙ OMIM:300390 ∙ HGNC:1940 ∙ Uniprot:P24386 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

choroideremia (Definitive), mode of inheritance: XL
choroideremia (Strong), mode of inheritance: XL
choroideremia (Supportive), mode of inheritance: XL
choroideremia (Definitive), mode of inheritance: XL
choroideremia (Definitive), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Choiroideremia	XL	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Ophthalmologic	2886237; 1302003; 1598901; 8477262; 7981671; 12827496; 19764077; 20301511; 22965595; 24913019

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CHM gene.

not_provided (761 variants)
Choroideremia (158 variants)
Retinal_dystrophy (92 variants)
Inborn_genetic_diseases (50 variants)
not_specified (8 variants)
CHM-related_disorder (8 variants)
Retinitis_pigmentosa (3 variants)
Choroideremia,_Salla_type (1 variants)
Night_blindness (1 variants)
Chorioretinal_atrophy (1 variants)
Abnormality_of_the_eye (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CHM gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000390.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous	2 clinvar	2 clinvar	4 clinvar	188 clinvar	18 clinvar	214
missense	5 clinvar	4 clinvar	188 clinvar	26 clinvar	10 clinvar	233
nonsense	85 clinvar	14 clinvar	1 clinvar			100
start loss	1	3				4
frameshift	108 clinvar	21 clinvar	1 clinvar			130
splice donor/acceptor (+/-2bp)	46 clinvar	15 clinvar	1 clinvar			62
Total	247	59	195	214	28

Highest pathogenic variant AF is 0.00000896957

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CHM	protein_coding	protein_coding	ENST00000357749	15	186382

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.999	0.00101	125140	1	1	125142	0.00000799

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.793	195	229	0.852	0.0000161	4300
Missense in Polyphen		71	91.524	0.77576		1819
Synonymous	-1.20	95	81.3	1.17	0.00000585	1195
Loss of Function	4.39	1	24.4	0.0410	0.00000189	446

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000366	0.0000366
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.0000599	0.0000328
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: 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 prenylate Rab proteins; this alternative pathway is proposed to be the predominant pathway for Rab protein geranylgeranylation. {ECO:0000269|PubMed:18532927, ECO:0000269|PubMed:7957092}.;
Disease: DISEASE: Choroideremia (CHM) [MIM:303100]: An X-linked recessive disease characterized by a slowly progressive degeneration of the choroid, photoreceptors, and retinal pigment epithelium. Affected males develop night blindness in their teenage years followed by loss of peripheral vision and complete blindness at middle age. Carrier females are generally asymptomatic but funduscopic examination often shows patchy areas of chorioretinal atrophy. {ECO:0000269|PubMed:19427510, ECO:0000269|PubMed:21905166, ECO:0000269|PubMed:7951216}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: Gene expression (Transcription);Vesicle-mediated transport;Membrane Trafficking;Generic Transcription Pathway;Post-translational protein modification;Metabolism of proteins;TP53 Regulates Transcription of Cell Death Genes;RNA Polymerase II Transcription;TP53 regulates transcription of several additional cell death genes whose specific roles in p53-dependent apoptosis remain uncertain;Rab regulation of trafficking;Transcriptional Regulation by TP53;RAB GEFs exchange GTP for GDP on RABs;RAB geranylgeranylation (Consensus)

Recessive Scores

pRec: 0.245

Intolerance Scores

loftool
rvis_EVS: 0.17
rvis_percentile_EVS: 65.96

Haploinsufficiency Scores

pHI: 0.133
hipred: Y
hipred_score: 0.633
ghis: 0.599

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: N
gene_indispensability_score: 0.0770

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

Gene name: Chm
Phenotype: growth/size/body region phenotype; homeostasis/metabolism phenotype; embryo phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); pigmentation phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); vision/eye phenotype;

Zebrafish Information Network

Gene name: chm
Affected structure: neuromast hair cell
Phenotype tag: abnormal
Phenotype quality: decreased amount

Gene ontology

Biological process: protein targeting to membrane;small GTPase mediated signal transduction;visual perception;protein geranylgeranylation;regulation of apoptotic process;positive regulation of GTPase activity;post-translational protein modification
Cellular component: cytosol;Rab-protein geranylgeranyltransferase complex
Molecular function: Rab geranylgeranyltransferase activity;GDP-dissociation inhibitor activity;GTPase activator activity;Rab GTPase binding