RAB18

RAB18, member RAS oncogene family, the group of RAB, member RAS oncogene GTPases

Basic information

Region (hg38): 10:27504174-27545117

Links

ENSG00000099246 ∙ NCBI:22931 ∙ OMIM:602207 ∙ HGNC:14244 ∙ Uniprot:Q9NP72 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Warburg micro syndrome 3 (Definitive), mode of inheritance: AR
• Warburg micro syndrome 3 (Strong), mode of inheritance: AR
• Warburg micro syndrome (Supportive), mode of inheritance: AR
• Warburg micro syndrome (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Warburg micro syndrome 3	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	Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic	21473985

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RAB18 gene.

• not_provided (43 variants)
• Inborn_genetic_diseases (22 variants)
• Warburg_micro_syndrome_3 (19 variants)
• RAB18-related_disorder (8 variants)
• not_specified (8 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RAB18 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000021252.5. 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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	15		16
missense	2	1	32	2	1	38
nonsense						0
start loss						0
frameshift	1	2	1			4
splice donor/acceptor (+/-2bp)			1			1
Total	3	3	35	17	1

Highest pathogenic variant AF is 0.00000805922

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RAB18	protein_coding	protein_coding	ENST00000356940	7	37947

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.910	0.0898	125697	0	6	125703	0.0000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.39	68	109	0.625	0.00000511	1342
Missense in Polyphen		25	42.709	0.58536		539
Synonymous	-0.297	42	39.6	1.06	0.00000198	382
Loss of Function	2.96	1	12.2	0.0823	6.10e-7	147

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000123	0.000123
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000264	0.0000264
Middle Eastern	0.0000544	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Plays a role in apical endocytosis/recycling. May be implicated in transport between the plasma membrane and early endosomes. Plays a key role in eye and brain development and neurodegeneration. {ECO:0000269|PubMed:21473985}.
• Pathway: Neutrophil degranulation;Vesicle-mediated transport;Membrane Trafficking;Post-translational protein modification;Metabolism of proteins;Innate Immune System;Immune System;Rab regulation of trafficking;COPI-independent Golgi-to-ER retrograde traffic;Golgi-to-ER retrograde transport;RAB GEFs exchange GTP for GDP on RABs;RAB geranylgeranylation;Intra-Golgi and retrograde Golgi-to-ER traffic (Consensus)

Recessive Scores

• pRec: 0.110

Intolerance Scores

• loftool: 0.541
• rvis_EVS: 0.1
• rvis_percentile_EVS: 61.28

Haploinsufficiency Scores

• pHI: 0.192
• hipred: Y
• hipred_score: 0.580
• ghis: 0.564

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: H
• gene_indispensability_pred: E
• gene_indispensability_score: 0.961

Mouse Genome Informatics

• Gene name: Rab18
• Phenotype: cellular 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); growth/size/body region phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); endocrine/exocrine gland phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); 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); reproductive system phenotype

Zebrafish Information Network

• Gene name: rab18b
• Affected structure: iridophore
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: eye development;intracellular protein transport;small GTPase mediated signal transduction;brain development;Rab protein signal transduction;lipid droplet organization;neutrophil degranulation;import into nucleus;endoplasmic reticulum tubular network organization
• Cellular component: endoplasmic reticulum membrane;Golgi apparatus;cytosol;plasma membrane;secretory granule membrane;synapse;endoplasmic reticulum tubular network
• Molecular function: GTPase activity;protein binding;GTP binding;GDP binding