RAB11B

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

Basic information

Region (hg38): 19:8389981-8404434

Links

ENSG00000185236 ∙ NCBI:9230 ∙ OMIM:604198 ∙ HGNC:9761 ∙ Uniprot:Q15907 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intellectual disability, autosomal dominant 40 (Strong), mode of inheritance: AD
• neurodevelopmental disorder with ataxic gait, absent speech, and decreased cortical white matter (Strong), mode of inheritance: AD
• neurodevelopmental disorder with ataxic gait, absent speech, and decreased cortical white matter (Moderate), mode of inheritance: AD
• neurodevelopmental disorder with ataxic gait, absent speech, and decreased cortical white matter (Moderate), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neurodevelopmental disorder with ataxic gait, absent speech, and decreased cortical white matter	AD	General	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	Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic	29106825

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RAB11B gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RAB11B gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				62	6	68
missense		3	47	11	3	64
nonsense						0
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)			2			2
splice region			7	9	7	23
non coding			1	30	12	43
Total	0	3	51	103	21

Variants in RAB11B

This is a list of pathogenic ClinVar variants found in the RAB11B region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
19-8390114-T-G			Benign (May 24, 2021)
19-8390422-G-T			Likely benign (Dec 31, 2022)
19-8390423-A-G			Uncertain significance (May 30, 2023)
19-8390427-G-A			Benign (Dec 02, 2022)
19-8390428-G-A			Benign/Likely benign (Nov 01, 2024)
19-8390431-C-G			Uncertain significance (Oct 12, 2021)
19-8390435-G-A			Likely benign (Oct 03, 2023)
19-8390446-C-T			Likely benign (Jul 26, 2023)
19-8390449-A-G		RAB11B-related disorder	Likely benign (Apr 14, 2023)
19-8390450-T-C			Uncertain significance (Mar 22, 2023)
19-8390459-GC-G			Uncertain significance (May 03, 2023)
19-8390462-G-C			Uncertain significance (Jun 24, 2021)
19-8390462-G-T		RAB11B-related disorder	Benign (Feb 01, 2024)
19-8390463-C-T		RAB11B-related disorder	Benign (Jan 28, 2024)
19-8390465-G-A			Likely benign (Aug 31, 2022)
19-8390466-G-A			Likely benign (Jun 29, 2023)
19-8390469-G-T			Benign (Jan 22, 2024)
19-8390471-G-A			Likely benign (Sep 22, 2022)
19-8390471-G-T			Likely benign (Aug 19, 2021)
19-8399769-G-A			Benign (May 14, 2021)
19-8399848-C-T			Likely benign (Nov 27, 2023)
19-8399849-G-A			Likely benign (Oct 18, 2023)
19-8399852-T-C			Likely benign (Oct 21, 2022)
19-8399854-C-T			Likely benign (Jan 01, 2023)
19-8399855-C-T			Likely benign (Jul 07, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RAB11B	protein_coding	protein_coding	ENST00000328024	5	14454

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.444	0.550	125678	0	2	125680	0.00000796

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.48	67	154	0.436	0.0000109	1410
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.00000880	0.00000880
Middle Eastern	0.0000544	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

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.
• Pathway: 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;TBC/RABGAPs;Membrane Trafficking;Post-translational protein modification;Metabolism of proteins;Rab regulation of trafficking;RAB geranylgeranylation (Consensus)

Recessive Scores

• pRec: 0.113

Intolerance Scores

• loftool: 0.0603
• rvis_EVS: -0.27
• rvis_percentile_EVS: 33.97

Haploinsufficiency Scores

• pHI: 0.335
• hipred: Y
• hipred_score: 0.749
• ghis: 0.638

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.983

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Rab11b

Gene ontology

• Biological process: receptor recycling;intracellular protein transport;exocytosis;melanosome transport;Rab protein signal transduction;transferrin transport;insulin secretion involved in cellular response to glucose stimulus;post-translational protein modification;regulation of anion transport;constitutive secretory pathway;regulated exocytosis;transcytosis;cellular response to acidic pH;establishment of protein localization to membrane;retrograde transport, endosome to plasma membrane;regulation of protein localization to cell surface;regulation of endocytic recycling
• Cellular component: endosome;cytosol;synaptic vesicle;cell junction;phagocytic vesicle membrane;phagocytic vesicle;recycling endosome;recycling endosome membrane;extracellular exosome;anchored component of synaptic vesicle membrane
• Molecular function: GTPase activity;protein binding;GTP binding;GDP binding;myosin V binding;cadherin binding