RAB11A

protein-coding

RAB11A, member RAS oncogene family, the group of RAB, member RAS oncogene GTPases

Gene summary

The protein encoded by this gene belongs to the Rab family of the small GTPase superfamily. It is associated with both constitutive and regulated secretory pathways, and may be involved in protein transport. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2011]

MANE transcript

NM_004663.5

Inheritance

ClinVar variants

P:3U:56B:43

Top phenotype

neurodevelopmental disorder

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr15:65,726,054-65,891,989

External References & Databases

Ensembl (ENSG00000103769)

Transcript & Mutation Effects

hg38 • Region Span ~165.9 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurodevelopmental disorderSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0700092

Submitter: G2P

neurodevelopmental disorderSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0700092

Submitter: PanelApp Australia

complex neurodevelopmental disorder with motor featuresMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0100516

Submitter: ClinGen

*RAB11A* was first reported in relation to autosomal dominant complex neurodevelopmental disorder with motor features in 2017 (McRae et al., PMID:28135719, Hamden et al., PMID:29100083). This disease is a complex neurodevelopmental disorder that involves more than one phenotype associated with the central nervous system, including but not limited to intellectual disability, developmental delay. Other variable features include seizures, gait disturbances, motor disability, hypotonia, magnetic resonance imaging abnormalities, visual anomalies, dysmorphisms, early adrenarche, and obesity. At least 15 unique missense variants that have been reported in 19 probands in six publications (PMIDs: 28135719, 29100083, 33875846, 39181022, 40225156, 40959816) are included in this curation. Most of the variants are reported to be *de novo* occurrences. The mechanism of pathogenicity appears to be gain-of-function (PMID: 40959816). This gene-disease relationship is also supported by experimental evidence, including the biochemical function of *RAB11A* as a part of the family of small GTPases, Rab, that regulates intercellular trafficking. Evidence also demonstrates distinct expression patterns of RAB11A in the developing cortex, and a zebrafish model shows reduced central nervous system area in mutants (PMIDs: 39883192, 40959816). Of note, an individual with intellectual disability, seizures, and motor disorders was found to have a homozygous nonsense variant in *RAB11A* along with a homozygous pathogenic LAMA2 variant. Variants in LAMA2 have been associated with autosomal recessive muscular dystrophy. This individual was not scored. In summary, there is moderate evidence supporting the relationship between RAB11A and autosomal dominant complex neurodevelopmental disorder with motor features. While more evidence is needed to establish this relationship definitively, no convincing contradictory evidence has emerged. This classification was approved by the ClinGen Cerebral Palsy GCEP on the meeting date December 15, 2025 (SOP Version 11).

autosomal dominant non-syndromic intellectual disabilitySUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0015802

Submitter: Orphanet

neurodevelopmental disorderSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0700092

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to RAB11A variants in ClinVar

11 Conditions Cataloged

not providedTotal: 116

not specifiedTotal: 19

RAB11A-related disorderTotal: 8

EEG abnormalityTotal: 1

Precocious puberty in femalesTotal: 1

Coarse facial featuresTotal: 1

Primary microcephalyTotal: 1

Mild intellectual disabilityTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004663.5. 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			2 clinvar	35 clinvar		37
missense		3 clinvar	47 clinvar	7 clinvar	1 clinvar	58
nonsense			3 clinvar			3
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	3	56	42	1	102

Highest pathogenic variant AF is 6.841115e-7

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 28 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004663.5	RefSeq	NP_004654.1	5	MANE Select
ENST00000261890.7	Ensembl	ENSP00000261890.2	5	MANE Select
NM_001206836.2	RefSeq	NP_001193765.1	5	Standard
ENST00000564910.5	Ensembl	ENSP00000455567.1	5	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
rab11a	Danio rerio	Structure: vasculature Quality: malformed abnormal

Gene / Model

Organism

Observed Phenotype

rab11a

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)
Vasopressin-regulated water reabsorption - Homo sapiens (human)
Endocrine and other factor-regulated calcium reabsorption - Homo sapiens (human)
Pancreatic secretion - Homo sapiens (human)
NOTCH-Ncore

Biological Process

renal water homeostasis
intracellular protein transport
exocytosis
mitotic metaphase plate congression
positive regulation of epithelial cell migration

Molecular Function

GTPase activity
protein binding
GTP binding
microtubule binding
syntaxin binding

Cellular Component

spindle pole
endosome
multivesicular body
Golgi apparatus
trans-Golgi network

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000261890
Coding exons: 5
Length: 165938
Individuals with no LoFs: 125729
Homozygous LoFs: 0
Heterozygous LoFs: 1
Defined: 125730
p: 0.00000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.09	27	124	0.218	0.00000656	1411
Missense (PolyPhen)		5	48.82	0.10242		602
Synonymous	-0.364	43	40.1	1.07	0.00000193	418
Loss of Function	3.50	0	14.3	0.00	0.00000107	126

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

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. That Rab regulates endocytic recycling. Acts as a major regulator of membrane delivery during cytokinesis. Together with MYO5B and RAB8A participates in epithelial cell polarization. Together with RAB3IP, RAB8A, the exocyst complex, PARD3, PRKCI, ANXA2, CDC42 and DNMBP promotes transcytosis of PODXL to the apical membrane initiation sites (AMIS), apical surface formation and lumenogenesis. Together with MYO5B participates in CFTR trafficking to the plasma membrane and TF (Transferrin) recycling in nonpolarized cells. Required in a complex with MYO5B and RAB11FIP2 for the transport of NPC1L1 to the plasma membrane. Participates in the sorting and basolateral transport of CDH1 from the Golgi apparatus to the plasma membrane. Regulates the recycling of FCGRT (receptor of Fc region of monomeric Ig G) to basolateral membranes. May also play a role in melanosome transport and release from melanocytes. {ECO:0000269|PubMed:15601896, ECO:0000269|PubMed:15689490, ECO:0000269|PubMed:17462998, ECO:0000269|PubMed:19542231, ECO:0000269|PubMed:20890297, ECO:0000269|PubMed:21282656}.;

Recessive Scores

pRec: 0.260

Intolerance Scores

LoFtool: 0.173
RVIS EVS: -0.05
RVIS percentile EVS: 49.39

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.998

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Low	Low	Low
Primary Immunodeficiency	Low	Low	Low
Cancer	Low	Low	Low