RAB27A

RAB27A, member RAS oncogene family, the group of RAB, member RAS oncogene GTPases

Basic information

Region (hg38): 15:55202966-55319113

Links

ENSG00000069974 ∙ NCBI:5873 ∙ OMIM:603868 ∙ HGNC:9766 ∙ Uniprot:P51159 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Griscelli syndrome type 2 (Strong), mode of inheritance: AR
• Griscelli syndrome type 2 (Supportive), mode of inheritance: AR
• Griscelli syndrome type 2 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Griscelli syndrome, type 2; Elejalde syndrome	AR	Allergy/Immunology/Infectious; Oncologic	Antiinfectious prophylaxis and early and aggressive treatment of infections can be beneficial; Surveillance for complications such as hemophagocytic lymphohistiocytosis to allow early medical treatment (with chemo-immunotherapy) may be beneficial in order to allow prompt medical treatment; HSCT has been described	Allergy/Immunology/Infectious; Dermatologic; Hematologic; Neurologic; Oncologic	707528; 7996360; 10835631; 12058346; 15452859; 17151879; 18350256; 18350256; 18397837; 18489042; 19030707; 19270433; 19953648; 20370853; 20591709; 21314004; 22111599; 23403622; 32374962

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RAB27A gene.

• Griscelli_syndrome_type_2 (215 variants)
• Inborn_genetic_diseases (28 variants)
• Autoinflammatory_syndrome (27 variants)
• not_provided (19 variants)
• RAB27A-related_disorder (9 variants)
• not_specified (8 variants)
• Griscelli_syndrome (2 variants)
• See_cases (2 variants)
• Multisystem_inflammatory_syndrome_in_children (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RAB27A gene is commonly pathogenic or not. These statistics are base on transcript: NM_000183235.3. 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	4	41	1	47
missense	8	14	74	5		101
nonsense	6	1				7
start loss		1	1			2
frameshift	14	5	1			20
splice donor/acceptor (+/-2bp)	4	2				6
Total	32	24	80	46	1

Highest pathogenic variant AF is 0.00017167562

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RAB27A	protein_coding	protein_coding	ENST00000396307	5	116148

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.00e-7	0.183	125686	0	62	125748	0.000247

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.515	135	119	1.13	0.00000610	1464
Missense in Polyphen		56	53.5	1.0467		670
Synonymous	0.766	37	43.4	0.852	0.00000230	407
Loss of Function	0.00696	10	10.0	0.998	5.10e-7	120

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000376	0.000376
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000272	0.000272
Finnish	0.00	0.00
European (Non-Finnish)	0.000291	0.000290
Middle Eastern	0.000272	0.000272
South Asian	0.000261	0.000261
Other	0.000326	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Plays a role in cytotoxic granule exocytosis in lymphocytes. Required for both granule maturation and granule docking and priming at the immunologic synapse. {ECO:0000269|PubMed:18812475}.
• Pathway: Deregulation of Rab and Rab Effector Genes in Bladder Cancer;Neutrophil degranulation;Vesicle-mediated transport;Membrane Trafficking;Post-translational protein modification;Metabolism of proteins;Innate Immune System;Immune System;Rab regulation of trafficking;RAB GEFs exchange GTP for GDP on RABs;RAB geranylgeranylation (Consensus)

Recessive Scores

• pRec: 0.390

Intolerance Scores

• loftool: 0.719
• rvis_EVS: -0.56
• rvis_percentile_EVS: 19.31

Haploinsufficiency Scores

• pHI: 0.722
• hipred: Y
• hipred_score: 0.579
• ghis: 0.596

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.139

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Rab27a
• Phenotype: cellular phenotype; homeostasis/metabolism 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; hematopoietic system phenotype; endocrine/exocrine gland phenotype; 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); immune system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; reproductive system phenotype

Gene ontology

• Biological process: protein targeting;intracellular protein transport;exocytosis;blood coagulation;positive regulation of gene expression;antigen processing and presentation;melanocyte differentiation;melanosome localization;melanosome transport;Rab protein signal transduction;multivesicular body organization;neutrophil degranulation;cytotoxic T cell degranulation;natural killer cell degranulation;positive regulation of exocytosis;synaptic vesicle transport;positive regulation of phagocytosis;multivesicular body sorting pathway;complement-dependent cytotoxicity;positive regulation of regulated secretory pathway;positive regulation of reactive oxygen species biosynthetic process;positive regulation of constitutive secretory pathway;exosomal secretion
• Cellular component: photoreceptor outer segment;extracellular region;lysosome;late endosome;Golgi apparatus;cytosol;apical plasma membrane;secretory granule;dendrite;secretory granule membrane;multivesicular body membrane;Weibel-Palade body;melanosome membrane;specific granule lumen;melanosome;synapse;extracellular exosome;exocytic vesicle
• Molecular function: GTPase activity;protein binding;GTP binding;GDP binding;protein domain specific binding;myosin V binding