RAB25

protein-coding

RAB25, member RAS oncogene family, the group of RAB, member RAS oncogene GTPases

Gene summary

The protein encoded by this gene is a member of the RAS superfamily of small GTPases. The encoded protein is involved in membrane trafficking and cell survival. This gene has been found to be a tumor suppressor and an oncogene, depending on the context. Two variants, one protein-coding and the other not, have been found for this gene. [provided by RefSeq, Nov 2015]

MANE transcript

NM_020387.4

Inheritance

—

ClinVar variants

U:36B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.95

Max pathogenic AF

—

Genomic locus

chr1:156,061,160-156,070,504

External References & Databases

Ensembl (ENSG00000132698)

Transcript & Mutation Effects

hg38 • Region Span ~9.3 kb

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GenCC 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 RAB25 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 35

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_020387.4. 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 clinvar	1 clinvar		2
missense			34 clinvar	1 clinvar		35
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	36	2	0	38

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 14 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_020387.4	RefSeq	NP_065120.2	5	MANE Select
ENST00000361084.10	Ensembl	ENSP00000354376.5	5	MANE Select
ENST00000876131.1	Ensembl	ENSP00000546190.1	5	Standard
ENST00000876131.2	Ensembl	ENSP00000546190.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Post-translational protein modification
Metabolism of proteins
RAB geranylgeranylation

Biological Process

epithelial cell morphogenesis
intracellular protein transport
exocytosis
positive regulation of cell population proliferation
positive regulation of epithelial cell migration

Molecular Function

GTPase activity
protein binding
GTP binding
myosin V binding

Cellular Component

endosome
pseudopodium
pseudopodium membrane
cytoplasmic vesicle
recycling endosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000361084
Coding exons: 5
Length: 9345
Individuals with no LoFs: 124457
Homozygous LoFs: 0
Heterozygous LoFs: 372
Defined: 124829
p: 0.00149

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.815	106	132	0.801	0.00000800	1367
Missense (PolyPhen)		55	62.08	0.88596		606
Synonymous	0.0632	54	54.6	0.989	0.00000320	448
Loss of Function	0.168	11	11.6	0.947	8.26e-7	106

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00052	0.00052	rare
Latino/Admixed American	0.0015	0.0014	notable
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00022	0.00022	rare
Finnish	0.0016	0.0016	notable
European (Non-Finnish)	0.0024	0.0023	notable
South Asian	0.00027	0.00026	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Involved in the regulation of cell survival. Promotes invasive migration of cells in which it functions to localize and maintain integrin alpha-V/beta-1 at the tips of extending pseudopodia (PubMed:17925226). Involved in the regulation of epithelial morphogenesis through the control of CLDN4 expression and localization at tight junctions (By similarity). May selectively regulate the apical recycling pathway. Together with MYO5B regulates transcytosis (By similarity). {ECO:0000250|UniProtKB:E2RQ15, ECO:0000250|UniProtKB:P46629, ECO:0000250|UniProtKB:Q9WTL2, ECO:0000269|PubMed:17925226}.;

Recessive Scores

pRec: 0.0925

Intolerance Scores

LoFtool: 0.600
RVIS EVS: 0.35
RVIS percentile EVS: 74.18

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.801

Gene Damage Prediction

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