RAB4A

protein-coding

RAB4A, member RAS oncogene family, the group of RAB, member RAS oncogene GTPases

Gene summary

This gene is a member of the largest group in the Ras superfamily of small GTPases, which regulate membrane trafficking. The encoded protein is associated with early endosomes and is involved in their sorting and recycling. The protein also plays a role in regulating the recycling of receptors from endosomes to the plasma membrane. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Dec 2012]

Previous symbols:

RAB4

MANE transcript

NM_004578.4

Inheritance

—

ClinVar variants

U:31

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.26

Max pathogenic AF

—

Genomic locus

chr1:229,271,062-229,305,894

External References & Databases

Ensembl (ENSG00000168118)

Transcript & Mutation Effects

hg38 • Region Span ~34.8 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 RAB4A variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 26

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004578.4. 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
missense			29 clinvar			29
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	31	0	0	31

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 32 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004578.4	RefSeq	NP_004569.2	7	MANE Select
ENST00000366690.5	Ensembl	ENSP00000355651.4	7	MANE Select
NM_001271998.2	RefSeq	NP_001258927.1	4	Standard
ENST00000618010.4	Ensembl	ENSP00000482077.1	4	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
rab4a	Danio rerio	Structure: vasculature Quality: malformed abnormal

Gene / Model

Organism

Observed Phenotype

rab4a

Danio rerio

Structure: vasculature

Quality: malformed

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Endocytosis - Homo sapiens (human)
VEGFA-VEGFR2 Signaling Pathway
Insulin Signaling
Vesicle-mediated transport
TBC/RABGAPs

Biological Process

phosphatidylinositol biosynthetic process
intracellular protein transport
antigen processing and presentation
regulation of endocytosis
Rab protein signal transduction

Molecular Function

ATPase activator activity
GTPase activity
protein binding
GTP binding
protein transporter activity

Cellular Component

endosome
cytosol
plasma membrane
cytoplasmic vesicle membrane
early endosome membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000366690
Coding exons: 7
Length: 34820
Individuals with no LoFs: 125725
Homozygous LoFs: 0
Heterozygous LoFs: 19
Defined: 125744
p: 0.0000756

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.28	84	124	0.676	0.00000736	1414
Missense (PolyPhen)		26	41.982	0.61931		476
Synonymous	-0.369	51	47.8	1.07	0.00000329	406
Loss of Function	2.71	4	15.5	0.258	0.00000101	169

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00041	0.00038	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000063	0.000062	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Protein transport. Probably involved in vesicular traffic (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.107

Intolerance Scores

LoFtool: 0.435
RVIS EVS: -0.12
RVIS percentile EVS: 44.54

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.915

Gene Damage Prediction

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