RAB33B

RAB33B, member RAS oncogene family, the group of RAB, member RAS oncogene GTPases

Basic information

Region (hg38): 4:139453232-139476609

Links

ENSG00000172007 ∙ NCBI:83452 ∙ OMIM:605950 ∙ HGNC:16075 ∙ Uniprot:Q9H082 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Smith-McCort dysplasia (Supportive), mode of inheritance: AR
• Smith-McCort dysplasia 2 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Dyggve-Melchior-Clausen syndrome; Smith-McCort dysplasia 2	AR	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	Musculoskeletal; Neurologic	22652534; 23042644

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RAB33B gene.

• not provided (2 variants)
• Smith-McCort dysplasia 2 (2 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RAB33B 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			3	13	2	18
missense		1	29	1		31
nonsense	2		2			4
start loss						0
frameshift	1	1				2
inframe indel	1					1
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			45	14	6	65
Total	4	2	79	28	8

Variants in RAB33B

This is a list of pathogenic ClinVar variants found in the RAB33B region.

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

Position	Type	Phenotype	Significance	ClinVar
4-139453828-C-T		Smith-McCort dysplasia	Uncertain significance (Jun 14, 2016)
4-139453833-G-A		Smith-McCort dysplasia	Uncertain significance (Jun 14, 2016)
4-139453848-G-C		Smith-McCort dysplasia	Uncertain significance (Jun 14, 2016)
4-139453854-T-C		Smith-McCort dysplasia	Uncertain significance (Jun 14, 2016)
4-139453941-C-T		Smith-McCort dysplasia	Uncertain significance (Jun 14, 2016)
4-139453991-G-C		Smith-McCort dysplasia	Benign (Nov 12, 2018)
4-139454003-G-T		Smith-McCort dysplasia	Uncertain significance (Jun 14, 2016)
4-139454029-A-C		Smith-McCort dysplasia	Uncertain significance (Jun 14, 2016)
4-139454032-G-A		Smith-McCort dysplasia	Likely benign (Jun 14, 2016)
4-139454033-C-T		Smith-McCort dysplasia	Uncertain significance (Jun 14, 2016)
4-139454036-G-A		Smith-McCort dysplasia	Uncertain significance (Jun 14, 2016)
4-139454142-C-G		Smith-McCort dysplasia 2	Benign (Nov 12, 2018)
4-139454148-C-T		Smith-McCort dysplasia 2	Uncertain significance (Jan 12, 2018)
4-139454160-C-T		Smith-McCort dysplasia 2	Benign (Jan 12, 2018)
4-139454209-T-C		Inborn genetic diseases	Uncertain significance (May 31, 2022)
4-139454237-G-T			Likely benign (Jul 09, 2022)
4-139454239-CCAGCGGGG-C		Smith-McCort dysplasia 2	Pathogenic (May 10, 2017)
4-139454261-C-T			Likely benign (Sep 05, 2023)
4-139454273-G-C			Uncertain significance (Dec 21, 2021)
4-139454278-C-T			Uncertain significance (Feb 11, 2022)
4-139454289-C-T		Inborn genetic diseases	Uncertain significance (Jan 11, 2023)
4-139454291-C-G			Likely benign (Jun 18, 2018)
4-139454292-A-C			Uncertain significance (Sep 27, 2022)
4-139454313-G-T		Smith-McCort dysplasia 2	Uncertain significance (Mar 25, 2024)
4-139454322-A-C			Uncertain significance (Mar 12, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RAB33B	protein_coding	protein_coding	ENST00000305626	2	23378

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.675	0.321	125551	0	3	125554	0.0000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.629	112	132	0.846	0.00000622	1523
Missense in Polyphen		37	58.833	0.6289		684
Synonymous	-1.02	59	49.9	1.18	0.00000250	440
Loss of Function	2.28	1	7.95	0.126	4.51e-7	82

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000580	0.0000580
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	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Protein transport. Acts, in coordination with RAB6A, to regulate intra-Golgi retrograde trafficking. It is involved in autophagy, acting as a modulator of autophagosome formation. {ECO:0000269|PubMed:20163571}.
• Disease: DISEASE: Smith-McCort dysplasia 2 (SMC2) [MIM:615222]: A rare autosomal recessive osteochondrodysplasia with skeletal features identical to those of Dyggve-Melchior-Clausen syndrome, but with normal intelligence and no microcephaly. It is characterized by short limbs and trunk with barrel-shaped chest. The radiographic phenotype includes platyspondyly, generalized abnormalities of the epiphyses and metaphyses, and a distinctive lacy appearance of the iliac crest. {ECO:0000269|PubMed:22652534, ECO:0000269|PubMed:23042644}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Autophagy - animal - Homo sapiens (human);Vesicle-mediated transport;TBC/RABGAPs;Membrane Trafficking;Post-translational protein modification;Metabolism of proteins;Rab regulation of trafficking;Intra-Golgi traffic;RAB geranylgeranylation;Intra-Golgi and retrograde Golgi-to-ER traffic (Consensus)

Recessive Scores

• pRec: 0.108

Intolerance Scores

• loftool: 0.0900
• rvis_EVS: 0.08
• rvis_percentile_EVS: 60.09

Haploinsufficiency Scores

• pHI: 0.153
• hipred: Y
• hipred_score: 0.728
• ghis: 0.505

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.781

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Rab33b

Gene ontology

• Biological process: autophagosome assembly;regulation of cell growth;intracellular protein transport;endoplasmic reticulum to Golgi vesicle-mediated transport;intra-Golgi vesicle-mediated transport;Rab protein signal transduction;protein localization to Golgi apparatus;skeletal system morphogenesis;regulation of epithelial cell proliferation;regulation of Golgi organization;negative regulation of constitutive secretory pathway;regulation of retrograde vesicle-mediated transport, Golgi to ER
• Cellular component: Golgi membrane;endoplasmic reticulum membrane;Golgi apparatus;Golgi lumen;presynapse
• Molecular function: GTPase activity;protein binding;GTP binding