VIPAS39

VPS33B interacting protein, apical-basolateral polarity regulator, spe-39 homolog

Basic information

Region (hg38): 14:77426675-77457952

Previous symbols: [ "C14orf133" ]

Links

ENSG00000151445 ∙ NCBI:63894 ∙ OMIM:613401 ∙ HGNC:20347 ∙ Uniprot:Q9H9C1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• arthrogryposis, renal dysfunction, and cholestasis 2 (Definitive), mode of inheritance: AR
• arthrogryposis, renal dysfunction, and cholestasis 2 (Strong), mode of inheritance: AR
• arthrogryposis-renal dysfunction-cholestasis syndrome (Supportive), mode of inheritance: AR
• arthrogryposis, renal dysfunction, and cholestasis 2 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Arthrogryposis, renal dysfunction, and cholestasis 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	Gastrointestinal; Musculoskeletal; Renal	20190753; 23636179

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the VIPAS39 gene.

• not provided (6 variants)
• Arthrogryposis, renal dysfunction, and cholestasis 1 (2 variants)
• Arthrogryposis, renal dysfunction, and cholestasis 2 (1 variants)
• Arthrogryposis with renal dysfunction and cholestasis syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the VIPAS39 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			4	21	3	28
missense			69	2	1	72
nonsense	5	1				6
start loss						0
frameshift	2	1				3
inframe indel		1	1			2
splice donor/acceptor (+/-2bp)	1	1	1			3
splice region			5	10		15
non coding			2	42	46	90
Total	8	4	77	65	50

Highest pathogenic variant AF is 0.0000394

Variants in VIPAS39

This is a list of pathogenic ClinVar variants found in the VIPAS39 region.

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

Position	Type	Phenotype	Significance	ClinVar
14-77427635-T-C		Inborn genetic diseases	Uncertain significance (Feb 06, 2024)
14-77427642-G-GA			Likely benign (Apr 01, 2022)
14-77428231-T-C			Likely benign (Jul 19, 2020)
14-77428255-T-C			Likely benign (Oct 28, 2019)
14-77428362-C-A			Uncertain significance (Dec 28, 2017)
14-77428370-C-T			Uncertain significance (Aug 22, 2022)
14-77428371-G-A		not specified • VIPAS39-related disorder	Conflicting classifications of pathogenicity (Dec 21, 2023)
14-77428376-G-T		Arthrogryposis, renal dysfunction, and cholestasis 2 • VIPAS39-related disorder	Conflicting classifications of pathogenicity (Jan 29, 2024)
14-77428381-G-A			Benign (Jan 24, 2024)
14-77428396-TCTC-T		not specified	Uncertain significance (Mar 06, 2024)
14-77428438-C-T			Uncertain significance (Jun 28, 2018)
14-77428452-C-T		Inborn genetic diseases	Conflicting classifications of pathogenicity (Feb 06, 2024)
14-77428465-C-T		Arthrogryposis, renal dysfunction, and cholestasis 2	Uncertain significance (Nov 18, 2019)
14-77428466-C-G			Uncertain significance (Jul 24, 2017)
14-77428468-G-A		not specified • Inborn genetic diseases	Uncertain significance (Oct 26, 2023)
14-77428474-T-A			Uncertain significance (Aug 22, 2022)
14-77428509-C-G		not specified	Likely benign (Nov 23, 2019)
14-77428776-T-C			Benign (Nov 12, 2018)
14-77428794-G-A			Benign (Oct 30, 2019)
14-77428907-G-A			Likely benign (Oct 28, 2019)
14-77428998-G-A		VIPAS39-related disorder	Conflicting classifications of pathogenicity (Dec 31, 2019)
14-77429014-C-T			Uncertain significance (Oct 11, 2017)
14-77429027-C-T		VIPAS39-related disorder	Likely benign (May 27, 2023)
14-77429030-G-T			Uncertain significance (Jun 24, 2022)
14-77429038-T-C		Inborn genetic diseases	Uncertain significance (Jul 25, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
VIPAS39	protein_coding	protein_coding	ENST00000553888	19	31278

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
7.26e-10	0.993	125686	0	62	125748	0.000247

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.858	229	269	0.853	0.0000164	3235
Missense in Polyphen		58	82.516	0.70289		1052
Synonymous	0.857	87	97.8	0.890	0.00000535	908
Loss of Function	2.54	21	37.9	0.554	0.00000244	408

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000242	0.000242
Ashkenazi Jewish	0.000595	0.000595
East Asian	0.000272	0.000272
Finnish	0.000739	0.000739
European (Non-Finnish)	0.000176	0.000176
Middle Eastern	0.000272	0.000272
South Asian	0.000327	0.000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Proposed to be involved in endosomal maturation implicating in part VPS33B. In epithelial cells, the VPS33B:VIPAS39 complex may play a role in the apical RAB11A- dependent recycling pathway and in the maintenance of the apical- basolateral polarity (PubMed:20190753). May play a role in lysosomal trafficking, probably via association with the core HOPS complex in a discrete population of endosomes; the functions seems to be indepenedent of VPS33B (PubMed:19109425). May play a role in vesicular trafficking during spermatogenesis (By similarity). May be involved in direct or indirect transcriptional regulation of E- cadherin (By similarity). {ECO:0000250|UniProtKB:Q23288, ECO:0000269|PubMed:19109425, ECO:0000269|PubMed:20190753}.
• Disease: DISEASE: Arthrogryposis, renal dysfunction and cholestasis syndrome 2 (ARCS2) [MIM:613404]: A multisystem disorder, characterized by neurogenic arthrogryposis multiplex congenita, renal tubular dysfunction and neonatal cholestasis with bile duct hypoplasia and low gamma glutamyl transpeptidase activity. Platelet dysfunction is common. Note=The disease is caused by mutations affecting the gene represented in this entry. In liver, CEACAM5 and ABCB11 are mislocalized and E-cadherin expression is decreased.

Recessive Scores

• pRec: 0.119

Intolerance Scores

• rvis_EVS: -0.4
• rvis_percentile_EVS: 26.73

Haploinsufficiency Scores

• pHI: 0.214
• hipred: N
• hipred_score: 0.492
• ghis: 0.618

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Vipas39
• Phenotype: integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); muscle phenotype; skeleton phenotype

Zebrafish Information Network

• Gene name: vipas39
• Affected structure: intrahepatic bile duct
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: intracellular protein transport;spermatogenesis;endosome to lysosome transport;peptidyl-lysine hydroxylation;cell differentiation;collagen fibril organization;collagen metabolic process;post-translational protein modification;autophagosome maturation
• Cellular component: cytoplasm;early endosome;late endosome;Golgi apparatus;HOPS complex;recycling endosome
• Molecular function: protein binding;protein-containing complex binding