RAB39B

RAB39B, member RAS oncogene family, the group of RAB, member RAS oncogene GTPases

Basic information

Region (hg38): X:155258235-155264491

Previous symbols: [ "MRX72", "WSN" ]

Links

ENSG00000155961 ∙ NCBI:116442 ∙ OMIM:300774 ∙ HGNC:16499 ∙ Uniprot:Q96DA2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intellectual disability, X-linked 72 (Definitive), mode of inheritance: XLR
• early-onset parkinsonism-intellectual disability syndrome (Strong), mode of inheritance: XL
• early-onset parkinsonism-intellectual disability syndrome (Strong), mode of inheritance: XL
• early-onset parkinsonism-intellectual disability syndrome (Supportive), mode of inheritance: XL
• non-syndromic X-linked intellectual disability (Supportive), mode of inheritance: XL
• intellectual disability, X-linked 72 (Moderate), mode of inheritance: XL
• early-onset parkinsonism-intellectual disability syndrome (Moderate), mode of inheritance: XL
• intellectual disability, X-linked 72 (Definitive), mode of inheritance: XL
• early-onset parkinsonism-intellectual disability syndrome (Definitive), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Waisman syndrome	XL	Neurologic	Waisman syndrome has been reported as being responsive to levodopa	Craniofacial; Neurologic	4025396; 11050621; 20159109; 25434005

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RAB39B gene.

• Early-onset parkinsonism-intellectual disability syndrome (3 variants)
• not provided (3 variants)
• Intellectual disability, X-linked 72 (1 variants)
• Parkinson disease, X-linked dominant (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RAB39B 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			2	9		11
missense	2	1	19			22
nonsense	2					2
start loss	2					2
frameshift		2	1			3
inframe indel			2			2
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			17	4	10	31
Total	6	3	41	13	10

Variants in RAB39B

This is a list of pathogenic ClinVar variants found in the RAB39B region.

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

Position	Type	Phenotype	Significance	ClinVar
X-155258252-A-G		Intellectual disability, X-linked 72	Uncertain significance (Jan 13, 2018)
X-155258437-C-T		Intellectual disability, X-linked 72	Uncertain significance (Jan 13, 2018)
X-155258703-G-A		Intellectual disability, X-linked 72	Uncertain significance (Jan 12, 2018)
X-155258846-TTTTG-T		Non-syndromic X-linked intellectual disability	Uncertain significance (Jun 14, 2016)
X-155258858-T-A		Intellectual disability, X-linked 72	Benign (Jan 13, 2018)
X-155258868-C-T		Intellectual disability, X-linked 72	Uncertain significance (Jan 13, 2018)
X-155258990-G-T		Intellectual disability, X-linked 72	Benign (Jan 13, 2018)
X-155259075-T-C		Intellectual disability, X-linked 72	Uncertain significance (Jan 12, 2018)
X-155259147-A-A		Intellectual disability, X-linked 72	Benign (Jan 13, 2018)
X-155259181-GT-G		Non-syndromic X-linked intellectual disability	Uncertain significance (Jun 14, 2016)
X-155259223-G-C		Intellectual disability, X-linked 72	Benign (Jan 13, 2018)
X-155259351-A-G		Intellectual disability, X-linked 72	Conflicting classifications of pathogenicity (Jun 01, 2023)
X-155259375-A-C		Intellectual disability, X-linked 72	Uncertain significance (Jan 13, 2018)
X-155259456-G-A		Intellectual disability, X-linked 72	Benign (Jan 12, 2018)
X-155259724-T-G		Intellectual disability, X-linked 72	Benign (Jan 12, 2018)
X-155259763-G-A		Intellectual disability, X-linked 72	Benign (Jan 13, 2018)
X-155259797-T-C		Intellectual disability, X-linked 72	Benign (Jan 12, 2018)
X-155260143-C-CTAT		Non-syndromic X-linked intellectual disability	Uncertain significance (Jun 14, 2016)
X-155260215-T-C		Intellectual disability, X-linked 72	Uncertain significance (Jan 13, 2018)
X-155260318-A-C		Intellectual disability, X-linked 72	Uncertain significance (Jan 12, 2018)
X-155260375-G-A		Intellectual disability, X-linked 72	Uncertain significance (Jan 12, 2018)
X-155260464-A-G		Intellectual disability, X-linked 72	Conflicting classifications of pathogenicity (Mar 01, 2023)
X-155260521-C-A		Intellectual disability, X-linked 72	Benign (Jan 12, 2018)
X-155260660-AGTCT-A		Non-syndromic X-linked intellectual disability	Uncertain significance (Jun 14, 2016)
X-155260738-T-C		Intellectual disability, X-linked 72	Uncertain significance (Jan 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RAB39B	protein_coding	protein_coding	ENST00000369454	2	6349

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.825	0.171	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.94	36	87.0	0.414	0.00000642	1383
Missense in Polyphen		7	40.003	0.17499		604
Synonymous	0.686	30	35.2	0.853	0.00000274	431
Loss of Function	2.22	0	5.76	0.00	4.38e-7	86

LoF frequencies by population

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

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Small GTPases Rab involved in autophagy (PubMed:27103069). 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 sets of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion (PubMed:27103069). May regulate the homeostasis of SNCA/alpha-synuclein. Together with PICK1 proposed to ensure selectively GRIA2 exit from the endoplasmic reticulum to the Golgi and to regulate AMPAR compostion at the post-synapses and thus synaptic transmission (By similarity). {ECO:0000250|UniProtKB:Q8BHC1, ECO:0000269|PubMed:27103069}.
• Disease: DISEASE: Waisman syndrome (WSMN) [MIM:311510]: A neurologic disorder characterized by delayed psychomotor development, intellectual disability, and early-onset Parkinson disease. {ECO:0000269|PubMed:25434005, ECO:0000269|PubMed:26399558, ECO:0000269|PubMed:27066548}. Note=The disease is caused by mutations affecting the gene represented in this entry. Its association with Parkinson disease is however unclear (PubMed:26739247, PubMed:27459931). According to a number of studies, variations affecting this gene are not a frequent cause of Parkinson disease, suggesting that RAB39B does not play a major role in Parkinson disease etiology (PubMed:26739247, PubMed:27459931). {ECO:0000269|PubMed:26739247, ECO:0000269|PubMed:27459931}.
• Pathway: Vesicle-mediated transport;Membrane Trafficking;Post-translational protein modification;Metabolism of proteins;Rab regulation of trafficking;RAB GEFs exchange GTP for GDP on RABs;RAB geranylgeranylation (Consensus)

Recessive Scores

• pRec: 0.113

Intolerance Scores

• rvis_EVS: 0.01
• rvis_percentile_EVS: 54.63

Haploinsufficiency Scores

• pHI: 0.516
• hipred: Y
• hipred_score: 0.579
• ghis: 0.569

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0314

Mouse Genome Informatics

• Gene name: Rab39b

Gene ontology

• Biological process: intracellular protein transport;autophagy;regulation of autophagy;vesicle-mediated transport;Rab protein signal transduction;synapse organization
• Cellular component: Golgi apparatus;plasma membrane;cytoplasmic vesicle membrane;vesicle;neuron projection
• Molecular function: GTPase activity;protein binding;GTP binding;myosin V binding