RAB11B

protein-coding

RAB11B, member RAS oncogene family, the group of RAB, member RAS oncogene GTPases

Gene summary

The Ras superfamily of small GTP-binding proteins, which includes the Ras (see MIM 190020), Ral (see MIM 179550), Rho (see MIM 165390), Rap (see MIM 179520), and Rab (see MIM 179508) families, is involved in controlling a diverse set of essential cellular functions. The Rab family, including RAB11B, appears to play a critical role in regulating exocytotic and endocytotic pathways (summary by Zhu et al., 1994 [PubMed 7811277]).[supplied by OMIM, Nov 2010]

MANE transcript

NM_004218.4

Inheritance

ClinVar variants

P:7U:77B:106

Top phenotype

Neurodevelopmental disorder with ataxic gait, absent speech, and decreased cortical white matter

gnomAD constraint

pLI —, LoF o/e 0.2

Max pathogenic AF

—

Genomic locus

chr19:8,389,981-8,404,434

External References & Databases

Ensembl (ENSG00000185236)

Transcript & Mutation Effects

hg38 • Region Span ~14.5 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurodevelopmental disorder with ataxic gait, absent speech, and decreased cortical white matterMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0060624

Submitter: Ambry Genetics

neurodevelopmental disorder with ataxic gait, absent speech, and decreased cortical white matterSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0060624

Submitter: Labcorp Genetics (formerly Invitae)

neurodevelopmental disorder with ataxic gait, absent speech, and decreased cortical white matterSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0060624

Submitter: G2P

neurodevelopmental disorder with ataxic gait, absent speech, and decreased cortical white matterSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0060624

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Neurodevelopmental disorder with ataxic gait, absent speech, and decreased cortical white matterAD

Manifestation: Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic

Intervention: General

Rationale: 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

Refs: 29106825

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to RAB11B variants in ClinVar

6 Conditions Cataloged

not providedTotal: 235

Inborn genetic diseasesTotal: 17

Neurodevelopmental disorder with ataxic gait, absent speech, and decreased cortical white matterTotal: 17

not specifiedTotal: 16

RAB11B-related disorderTotal: 13

Neurodevelopmental abnormalityTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004218.4. 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				77 clinvar	5 clinvar	82
missense	1 clinvar	6 clinvar	69 clinvar	20 clinvar	3 clinvar	99
nonsense						0
start loss						0
frameshift			2 clinvar	1 clinvar		3
splice donor/acceptor (+/-2bp)			6 clinvar			6
Total	1	6	77	98	8	190

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 23 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004218.4	RefSeq	NP_004209.2	5	MANE Select
ENST00000328024.11	Ensembl	ENSP00000333547.5	5	MANE Select
ENST00000594216.1	Ensembl	ENSP00000471148.1	4	Standard
ENST00000594216.2	Ensembl	ENSP00000471148.1	4	Standard

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)
AMPK signaling pathway - Homo sapiens (human)
Focal Adhesion-PI3K-Akt-mTOR-signaling pathway
Vesicle-mediated transport

Biological Process

receptor recycling
intracellular protein transport
exocytosis
melanosome transport
Rab protein signal transduction

Molecular Function

GTPase activity
protein binding
GTP binding
GDP binding
myosin V binding

Cellular Component

endosome
cytosol
synaptic vesicle
cell junction
phagocytic vesicle membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000328024
Coding exons: 5
Length: 14454
Individuals with no LoFs: 125678
Homozygous LoFs: 0
Heterozygous LoFs: 2
Defined: 125680
p: 0.00000796

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.48	67	154	0.436	0.0000109	1410
Missense (PolyPhen)		18	69.219	0.26004		631
Synonymous	-0.181	71	69.1	1.03	0.00000551	419
Loss of Function	2.31	2	9.80	0.204	5.15e-7	108

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.0000088	0.0000088	rare
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 plays a role in endocytic recycling, regulating apical recycling of several transmembrane proteins including cystic fibrosis transmembrane conductance regulator/CFTR, epithelial sodium channel/ENaC, potassium voltage- gated channel, and voltage-dependent L-type calcium channel. May also regulate constitutive and regulated secretion, like insulin granule exocytosis. Required for melanosome transport and release from melanocytes. Also regulates V-ATPase intracellular transport in response to extracellular acidosis. {ECO:0000269|PubMed:14627637, ECO:0000269|PubMed:19029296, ECO:0000269|PubMed:19244346, ECO:0000269|PubMed:20717956, ECO:0000269|PubMed:21248079, ECO:0000269|PubMed:22129970}.;
Disease: DISEASE: Neurodevelopmental disorder with ataxic gait, absent speech, and decreased cortical white matter (NDAGSCW) [MIM:617807]: An autosomal dominant neurodevelopmental disorder apparent in infancy and characterized by severe intellectual disability with absent speech, epilepsy, and hypotonia. Additionally, visual problems, musculoskeletal abnormalities, and microcephaly can be present. Brain imaging shows decreased cortical white matter, often with decreased cerebellar white matter, thin corpus callosum, and thin brainstem. {ECO:0000269|PubMed:29106825}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.113

Intolerance Scores

LoFtool: 0.0603
RVIS EVS: -0.27
RVIS percentile EVS: 33.97

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.983

Gene Damage Prediction

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