VPS13B

vacuolar protein sorting 13 homolog B, the group of bridge-like lipid transfer protein family

Basic information

Region (hg38): 8:99013266-99877580

Previous symbols: [ "CHS1", "COH1" ]

Links

ENSG00000132549 ∙ NCBI:157680 ∙ OMIM:607817 ∙ HGNC:2183 ∙ Uniprot:Q7Z7G8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Cohen syndrome (Definitive), mode of inheritance: AR
• Cohen syndrome (Definitive), mode of inheritance: AR
• Cohen syndrome (Strong), mode of inheritance: AR
• Cohen syndrome (Strong), mode of inheritance: AR
• Cohen syndrome (Definitive), mode of inheritance: AR
• Cohen syndrome (Supportive), mode of inheritance: AR
• Cohen syndrome (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cohen syndrome	AR	Allergy/Immunology/Infectious	Though the condition may be frequently recognizable, individuals can have recurrent infections, and antiinfectious prophlyaxis and treatment (including G-CSF for neutropenia), as well as early and aggressive treatment of infections may be beneficial	Allergy/Immunology/Infectious; Craniofacial; Dental; Musculoskeletal; Neurologic; Ophthalmologic	4717588; 671157; 7438489; 7246618; 7166592; 6705238; 3989828; 3656371; 3223494; 9266925; 10466416; 10964838; 12676892; 12730828; 15211651; 15025727; 15141358; 20683995; 20301655; 20921020; 24311531
The condition may be frequently recognizable due to characteristic features, including dysmorphisms

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the VPS13B gene.

• Cohen_syndrome (5565 variants)
• VPS13B-related_disorder (955 variants)
• Inborn_genetic_diseases (730 variants)
• not_provided (653 variants)
• not_specified (202 variants)
• Intellectual_disability (15 variants)
• Microcephaly (6 variants)
• Retinitis_pigmentosa (4 variants)
• Retinal_dystrophy (4 variants)
• Global_developmental_delay (3 variants)
• Abnormality_of_the_nervous_system (3 variants)
• Abnormality_of_the_eye (3 variants)
• High_myopia (2 variants)
• Myopia (2 variants)
• Progressive_visual_loss (2 variants)
• Short_foot (2 variants)
• Small_hand (2 variants)
• Decreased_total_neutrophil_count (2 variants)
• Abnormal_brain_morphology (2 variants)
• Short_stature (2 variants)
• Optic_disc_pallor (2 variants)
• Mild_hearing_impairment (2 variants)
• Joint_laxity (2 variants)
• Recurrent_aphthous_stomatitis (2 variants)
• Neutropenia,_severe_congenital,_1,_autosomal_dominant (1 variants)
• Carious_teeth (1 variants)
• Pituitary_stalk_interruption_syndrome (1 variants)
• Attention_deficit_hyperactivity_disorder (1 variants)
• Congenital_long_QT_syndrome (1 variants)
• Hypotonia (1 variants)
• Generalized_joint_hypermobility (1 variants)
• See_cases (1 variants)
• Autism (1 variants)
• Susceptibility_to_severe_COVID-19 (1 variants)
• Unsteady_gait (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the VPS13B gene is commonly pathogenic or not. These statistics are base on transcript: NM_000152564.5. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous	2	3	53	1696	7	1761
missense	5	22	2125	116	4	2272
nonsense	172	108	5			285
start loss		1	1			2
frameshift	293	166	14		1	474
splice donor/acceptor (+/-2bp)	33	143	6	13	1	196
Total	505	443	2204	1825	13

Highest pathogenic variant AF is 0.0008433705

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
VPS13B	protein_coding	protein_coding	ENST00000358544	61	864315

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.50e-45	1.00	125352	0	396	125748	0.00158

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.982	1947	2.07e+3	0.939	0.000107	26435
Missense in Polyphen		340	406.8	0.83579		4958
Synonymous	-0.626	772	750	1.03	0.0000396	7801
Loss of Function	5.71	105	190	0.553	0.00000994	2298

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00261	0.00259
Ashkenazi Jewish	0.00179	0.00179
East Asian	0.00164	0.00163
Finnish	0.00353	0.00352
European (Non-Finnish)	0.00148	0.00146
Middle Eastern	0.00164	0.00163
South Asian	0.00145	0.00144
Other	0.000653	0.000652

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May be involved in protein sorting in post Golgi membrane traffic. {ECO:0000250}.

Recessive Scores

• pRec: 0.176

Intolerance Scores

• loftool: 0.933
• rvis_EVS: -0.61
• rvis_percentile_EVS: 17.5

Haploinsufficiency Scores

• pHI: 0.284
• hipred: Y
• hipred_score: 0.544
• ghis: 0.600

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.349

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High

Mouse Genome Informatics

• Gene name: Vps13b

Gene ontology

• Biological process: protein transport