RAB23

RAB23, member RAS oncogene family, the group of RAB, member RAS oncogene GTPases

Basic information

Region (hg38): 6:57186991-57222307

Links

ENSG00000112210 ∙ NCBI:51715 ∙ OMIM:606144 ∙ HGNC:14263 ∙ Uniprot:Q9ULC3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• RAB23-related Carpenter syndrome (Definitive), mode of inheritance: AR
• RAB23-related Carpenter syndrome (Strong), mode of inheritance: AR
• Carpenter syndrome (Supportive), mode of inheritance: AR
• RAB23-related Carpenter syndrome (Strong), mode of inheritance: AR
• RAB23-related Carpenter syndrome (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Carpenter syndrome 1	AR	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	Audiologic/Otolaryngologic; Craniofacial; Dental; Endocrine; Genitourinary; Musculoskeletal; Neurologic	19974019; 5935752; 3322002; 17503333; 20358613; 21082653; 21412941

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RAB23 gene.

• Carpenter syndrome (145 variants)
• RAB23-related Carpenter syndrome (77 variants)
• not provided (22 variants)
• Inborn genetic diseases (13 variants)
• RAB23-related condition (12 variants)
• not specified (5 variants)
• Bladder exstrophy-epispadias-cloacal extrophy complex (1 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RAB23 gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	64	1	66
missense			31	1		32
nonsense	5	1				6
start loss			1			1
frameshift	6	1	1			8
inframe indel			1			1
splice donor/acceptor (+/-2bp)	1	4				5
splice region			1	18		19
non coding			36	27	13	76
Total	12	6	71	92	14

Highest pathogenic variant AF is 0.000361

Variants in RAB23

This is a list of pathogenic ClinVar variants found in the RAB23 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
6-57187131-T-C		RAB23-related Carpenter syndrome	Benign (Jan 13, 2018)
6-57187163-T-C		RAB23-related Carpenter syndrome	Uncertain significance (Jan 13, 2018)
6-57187272-A-G		RAB23-related Carpenter syndrome	Likely benign (Jan 13, 2018)
6-57187332-C-G		RAB23-related Carpenter syndrome	Uncertain significance (Jan 13, 2018)
6-57187428-G-A		RAB23-related Carpenter syndrome	Uncertain significance (Jan 13, 2018)
6-57187585-A-G		RAB23-related Carpenter syndrome	Uncertain significance (Jan 12, 2018)
6-57187692-G-T		RAB23-related Carpenter syndrome	Uncertain significance (Jan 13, 2018)
6-57187708-C-T		RAB23-related Carpenter syndrome	Uncertain significance (Feb 09, 2018)
6-57187780-C-T		RAB23-related Carpenter syndrome	Uncertain significance (Jan 13, 2018)
6-57187875-C-T		RAB23-related Carpenter syndrome	Uncertain significance (Jan 12, 2018)
6-57187976-T-C		RAB23-related Carpenter syndrome	Benign (Jan 12, 2018)
6-57188036-C-T		RAB23-related Carpenter syndrome	Benign (Jan 13, 2018)
6-57188120-G-T		RAB23-related Carpenter syndrome	Uncertain significance (Jan 12, 2018)
6-57188142-A-G		RAB23-related Carpenter syndrome	Uncertain significance (Jan 12, 2018)
6-57188188-A-G		RAB23-related Carpenter syndrome	Benign (Jan 13, 2018)
6-57188216-A-G		RAB23-related Carpenter syndrome	Uncertain significance (Jan 13, 2018)
6-57188394-T-C		RAB23-related Carpenter syndrome	Uncertain significance (Jan 13, 2018)
6-57188453-C-T		RAB23-related Carpenter syndrome	Uncertain significance (Jan 13, 2018)
6-57188644-T-C		RAB23-related Carpenter syndrome	Uncertain significance (Jan 12, 2018)
6-57188721-G-A		RAB23-related Carpenter syndrome	Benign (Jan 12, 2018)
6-57188755-A-G		RAB23-related Carpenter syndrome	Likely benign (Jan 13, 2018)
6-57188793-A-AATT		Carpenter syndrome	Uncertain significance (Jun 14, 2016)
6-57188925-A-C		RAB23-related Carpenter syndrome	Uncertain significance (Jan 13, 2018)
6-57188927-A-C		RAB23-related Carpenter syndrome	Uncertain significance (Jan 13, 2018)
6-57188967-T-C		RAB23-related Carpenter syndrome	Uncertain significance (Jan 12, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RAB23	protein_coding	protein_coding	ENST00000317483	6	33472

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00561	0.973	125652	0	81	125733	0.000322

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.318	112	122	0.919	0.00000585	1565
Missense in Polyphen		38	43.195	0.87972		552
Synonymous	0.0972	43	43.8	0.981	0.00000229	430
Loss of Function	2.02	6	14.2	0.422	8.37e-7	163

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000181	0.000119
Ashkenazi Jewish	0.000199	0.000198
East Asian	0.0000544	0.0000544
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000635	0.000624
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000328	0.0000327
Other	0.000327	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different set of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion. Together with SUFU, prevents nuclear import of GLI1, and thereby inhibits GLI1 transcription factor activity. Regulates GLI1 in differentiating chondrocytes. Likewise, regulates GLI3 proteolytic processing and modulates GLI2 and GLI3 transcription factor activity. Plays a role in autophagic vacuole assembly, and mediates defense against pathogens, such as S.aureus, by promoting their capture by autophagosomes that then merge with lysosomes. {ECO:0000269|PubMed:22365972, ECO:0000269|PubMed:22452336}.
• Disease: DISEASE: Carpenter syndrome 1 (CRPT1) [MIM:201000]: A rare autosomal recessive disorder characterized by acrocephaly with variable synostosis of the sagittal, lambdoid, and coronal sutures; peculiar facies; brachydactyly of the hands with syndactyly; preaxial polydactyly and syndactyly of the feet; congenital heart defects; growth retardation; mental retardation; hypogenitalism; and obesity. In addition, cerebral malformations, oral and dental abnormalities, coxa valga, genu valgum, hydronephrosis, precocious puberty, and hearing loss may be observed. {ECO:0000269|PubMed:17503333, ECO:0000269|PubMed:21412941}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: HH-Ncore;miR-targeted genes in lymphocytes - TarBase;Post-translational protein modification;Metabolism of proteins;RAB geranylgeranylation;Hedgehog signaling events mediated by Gli proteins (Consensus)

Recessive Scores

• pRec: 0.145

Intolerance Scores

• loftool: 0.458
• rvis_EVS: 0.13
• rvis_percentile_EVS: 63

Haploinsufficiency Scores

• pHI: 0.212
• hipred: N
• hipred_score: 0.444
• ghis: 0.562

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.747

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Rab23
• Phenotype: integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); skeleton phenotype; limbs/digits/tail 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; 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); embryo phenotype

Zebrafish Information Network

• Gene name: rab23
• Affected structure: determination of liver left/right asymmetry
• Phenotype tag: abnormal
• Phenotype quality: process quality

Gene ontology

• Biological process: autophagosome assembly;intracellular protein transport;cellular defense response;Rab protein signal transduction;negative regulation of protein import into nucleus;GTP metabolic process;cilium assembly;craniofacial suture morphogenesis
• Cellular component: cytoplasm;autophagosome;centrosome;cytosol;plasma membrane;endosome membrane;cell junction;phagocytic vesicle membrane;phagocytic vesicle
• Molecular function: GTPase activity;protein binding;GTP binding