RUBCN

rubicon autophagy regulator, the group of MicroRNA protein coding host genes|PIK3C3 complex subunits

Basic information

Region (hg38): 3:197668867-197749727

Previous symbols: [ "KIAA0226" ]

Links

ENSG00000145016 ∙ NCBI:9711 ∙ OMIM:613516 ∙ HGNC:28991 ∙ Uniprot:Q92622 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal recessive spinocerebellar ataxia 15 (Supportive), mode of inheritance: AR
• autosomal recessive spinocerebellar ataxia 15 (Limited), mode of inheritance: AR
• autosomal recessive spinocerebellar ataxia 15 (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spinocerebellar ataxia, autosomal recessive 15	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	Neurologic	20826435; 23728897

ClinVar

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

• not_specified (127 variants)
• not_provided (70 variants)
• Autosomal_recessive_spinocerebellar_ataxia_15 (17 variants)
• RUBCN-related_disorder (11 variants)
• Cerebral_hypomyelination (2 variants)
• Hypotonia (2 variants)
• Nystagmus (2 variants)
• Elbow_flexion_contracture (2 variants)
• Knee_flexion_contracture (2 variants)
• Global_developmental_delay (2 variants)
• Intellectual_disability (2 variants)
• Spinocerebellar_ataxia_type_15/16 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RUBCN gene is commonly pathogenic or not. These statistics are base on transcript: NM_000014687.4. 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				22	4	26
missense			127	20	4	151
nonsense						0
start loss						0
frameshift	1	1	1			3
splice donor/acceptor (+/-2bp)	1	2	2			5
Total	2	3	130	42	8

Highest pathogenic variant AF is 0.0000105344

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RUBCN	protein_coding	protein_coding	ENST00000296343	20	78335

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.39e-13	0.996	124761	0	64	124825	0.000256

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.47	472	571	0.827	0.0000362	6383
Missense in Polyphen		160	231.2	0.69204		2589
Synonymous	0.979	213	232	0.918	0.0000148	1895
Loss of Function	2.78	29	50.3	0.577	0.00000264	568

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000332	0.000332
Ashkenazi Jewish	0.0000993	0.0000993
East Asian	0.0000556	0.0000556
Finnish	0.000282	0.000278
European (Non-Finnish)	0.000346	0.000344
Middle Eastern	0.0000556	0.0000556
South Asian	0.000229	0.000229
Other	0.000165	0.000165

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Inhibits PIK3C3 activity; under basal conditions negatively regulates PI3K complex II (PI3KC3-C2) function in autophagy. Negatively regulates endosome maturation and degradative endocytic trafficking and impairs autophagosome maturation process. Can sequester UVRAG from association with a class C Vps complex (possibly the HOPS complex) and negatively regulates Rab7 activation (PubMed:20974968, PubMed:21062745). {ECO:0000269|PubMed:20974968, ECO:0000269|PubMed:21062745}.
• Disease: DISEASE: Spinocerebellar ataxia, autosomal recessive, 15 (SCAR15) [MIM:615705]: Spinocerebellar ataxia defines a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAR15 patients manifest cerebellar ataxia in early childhood and delayed motor development with delayed walking. Additional features include dysarthria, upper limb involvement, abnormal eye movements, and hyporeflexia. {ECO:0000269|PubMed:20826435}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Autophagy - animal - Homo sapiens (human) (Consensus)

Recessive Scores

• pRec: 0.100

Intolerance Scores

• rvis_EVS: 0.43
• rvis_percentile_EVS: 77.33

Haploinsufficiency Scores

• pHI: 0.185
• hipred: Y
• hipred_score: 0.706
• ghis: 0.535

Essentials

• essential_gene_gene_trap: K

Mouse Genome Informatics

• Gene name: Rubcn
• Phenotype: immune system phenotype; hematopoietic system phenotype

Gene ontology

• Biological process: immune system process;phagocytosis;autophagy;negative regulation of autophagy;negative regulation of phosphatidylinositol 3-kinase activity;negative regulation of endocytosis;multivesicular body sorting pathway;negative regulation of autophagosome maturation
• Cellular component: nucleoplasm;lysosome;early endosome;late endosome;Golgi apparatus;cytosol;intracellular membrane-bounded organelle
• Molecular function: protein binding