RUSC2

RUN and SH3 domain containing 2

Basic information

Region (hg38): 9:35490111-35561898

Links

ENSG00000198853 ∙ NCBI:9853 ∙ OMIM:611053 ∙ HGNC:23625 ∙ Uniprot:Q8N2Y8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intellectual disability, autosomal recessive 61 (Strong), mode of inheritance: AR
• intellectual disability, autosomal recessive 61 (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Mental retardation, autosomal recessive, 61	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	Craniofacial; Musculoskeletal; Neurologic	27612186

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RUSC2 gene.

• not provided (28 variants)
• Intellectual disability, autosomal recessive 61 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RUSC2 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	253	8	264
missense			439	7	7	453
nonsense	15	2	2			19
start loss						0
frameshift	13		1			14
inframe indel			10	2	1	13
splice donor/acceptor (+/-2bp)		4				4
splice region			5	17	1	23
non coding			1	45	4	50
Total	28	6	456	307	20

Highest pathogenic variant AF is 0.0000263

Variants in RUSC2

This is a list of pathogenic ClinVar variants found in the RUSC2 region.

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

Position	Type	Phenotype	Significance	ClinVar
9-35546535-C-A			Uncertain significance (Dec 27, 2021)
9-35546536-A-G			Likely benign (Jul 09, 2023)
9-35546545-T-G			Likely benign (Aug 24, 2022)
9-35546560-C-T			Likely benign (Aug 23, 2022)
9-35546576-C-T			Likely benign (Sep 25, 2023)
9-35546582-C-T		Intellectual disability, autosomal recessive 61	Uncertain significance (Dec 25, 2021)
9-35546583-A-T			Uncertain significance (May 16, 2022)
9-35546584-C-A			Uncertain significance (May 15, 2023)
9-35546591-G-A			Uncertain significance (Jul 30, 2023)
9-35546592-T-C		not specified	Uncertain significance (Jul 17, 2023)
9-35546605-G-T			Uncertain significance (Feb 01, 2022)
9-35546607-G-A			Uncertain significance (Apr 16, 2022)
9-35546609-T-C			Uncertain significance (May 14, 2022)
9-35546615-G-C		not specified	Uncertain significance (Aug 10, 2023)
9-35546616-G-A			Uncertain significance (Aug 23, 2022)
9-35546619-C-T			Uncertain significance (Feb 28, 2022)
9-35546627-G-A			Uncertain significance (Nov 27, 2021)
9-35546640-C-A		Intellectual disability, autosomal recessive 61 • not specified	Uncertain significance (Oct 31, 2022)
9-35546656-C-T			Likely benign (Mar 12, 2022)
9-35546663-C-T			Uncertain significance (Apr 28, 2021)
9-35546673-G-C			Uncertain significance (Aug 09, 2022)
9-35546675-A-C			Uncertain significance (Sep 24, 2021)
9-35546677-C-T			Likely benign (May 31, 2022)
9-35546686-C-T			Likely benign (Jan 24, 2024)
9-35546691-A-T			Uncertain significance (Jun 13, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RUSC2	protein_coding	protein_coding	ENST00000455600	11	71772

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.999	0.000510	125728	0	20	125748	0.0000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.951	794	873	0.909	0.0000521	9694
Missense in Polyphen		327	389.75	0.839		4382
Synonymous	0.0388	354	355	0.997	0.0000198	3318
Loss of Function	6.02	8	57.1	0.140	0.00000350	564

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000177	0.000177
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.000186	0.000185
European (Non-Finnish)	0.0000714	0.0000703
Middle Eastern	0.00	0.00
South Asian	0.000102	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Disease: DISEASE: Mental retardation, autosomal recessive 61 (MRT61) [MIM:617773]: A form of mental retardation, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRT61 patients manifest delayed psychomotor development, moderate to severe intellectual disability, and variable dysmorphic facial features. Refractory seizures and brain abnormalities are present in severely affected patients. {ECO:0000269|PubMed:27612186}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.0945

Intolerance Scores

• loftool: 0.191
• rvis_EVS: -2.09
• rvis_percentile_EVS: 1.56

Haploinsufficiency Scores

• pHI: 0.123
• hipred: Y
• hipred_score: 0.565
• ghis: 0.555

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.691

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Rusc2

Gene ontology

• Biological process: biological_process
• Cellular component: cytosol;cytoplasmic vesicle;extracellular exosome
• Molecular function: protein binding;Rab GTPase binding