SHOC2

SHOC2 leucine rich repeat scaffold protein, the group of MicroRNA protein coding host genes

Basic information

Region (hg38): 10:110919367-111017307

Links

ENSG00000108061 ∙ NCBI:8036 ∙ OMIM:602775 ∙ HGNC:15454 ∙ Uniprot:Q9UQ13 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Noonan syndrome-like disorder with loose anagen hair 1 (Strong), mode of inheritance: AD
• Noonan syndrome-like disorder with loose anagen hair 1 (Definitive), mode of inheritance: AD
• Noonan syndrome-like disorder with loose anagen hair 1 (Strong), mode of inheritance: AD
• Noonan syndrome-like disorder with loose anagen hair 1 (Strong), mode of inheritance: AD
• Noonan syndrome-like disorder with loose anagen hair (Supportive), mode of inheritance: AD
• Noonan syndrome-like disorder with loose anagen hair (Definitive), mode of inheritance: AD
• Noonan syndrome (Disputed Evidence), mode of inheritance: AD
• Costello syndrome (Disputed Evidence), mode of inheritance: AD
• cardiofaciocutaneous syndrome (Disputed Evidence), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Noonan-like syndrome with loose anagen hair 1	AD	Cardiovascular; Endocrine; Hematologic	Surveillance and treatment related to manifestations such as cardiac anomalies (which include pulmonic stenosis and hypertrophic cardiomyopathy) can be beneficial; Recognition of endocrine anomalies (eg, GH deficiency) may allow early diagnosis and treatment; Individuals with coagulopathy have been reported, and awareness may allow prompt recognition and management	Cardiovascular; Craniofacial; Dermatologic; Endocrine; Hematologic; Musculoskeletal; Neurologic	1884862; 9301585; 12673660; 19684605

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SHOC2 gene.

• RASopathy (2 variants)
• Noonan syndrome and Noonan-related syndrome (1 variants)
• Noonan syndrome (1 variants)
• not provided (1 variants)
• Noonan syndrome-like disorder with loose anagen hair 1 (1 variants)
• Pectus excavatum;Noonan syndrome-like disorder with loose anagen hair 1 (1 variants)
• Inborn genetic diseases (1 variants)
• Polycystic kidney disease 4 (1 variants)
• Noonan syndrome-like disorder with loose anagen hair (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SHOC2 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				117	5	122
missense	2	1	200	4	2	209
nonsense			3			3
start loss						0
frameshift			4			4
inframe indel						0
splice donor/acceptor (+/-2bp)			1			1
splice region			5	19	1	25
non coding			26	53	29	108
Total	2	1	234	174	36

Highest pathogenic variant AF is 0.00000657

Variants in SHOC2

This is a list of pathogenic ClinVar variants found in the SHOC2 region.

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

Position	Type	Phenotype	Significance	ClinVar
10-110919433-C-T			Benign (Aug 13, 2021)
10-110919546-T-G		Noonan syndrome-like disorder with loose anagen hair 1	Uncertain significance (Jan 13, 2018)
10-110919628-A-T		Noonan syndrome-like disorder with loose anagen hair 1	Uncertain significance (Jan 13, 2018)
10-110919633-G-A		Noonan syndrome-like disorder with loose anagen hair 1	Uncertain significance (Jan 12, 2018)
10-110919638-C-T		Noonan syndrome-like disorder with loose anagen hair 1	Uncertain significance (Jan 12, 2018)
10-110919648-G-T		not specified • Noonan syndrome-like disorder with loose anagen hair 1	Conflicting classifications of pathogenicity (Jan 12, 2018)
10-110919672-A-G		Noonan syndrome-like disorder with loose anagen hair 1	Uncertain significance (Jan 13, 2018)
10-110919872-G-C			Benign (May 16, 2021)
10-110964111-A-G		not specified	Likely benign (Sep 27, 2017)
10-110964131-T-G		not specified	Benign (May 13, 2014)
10-110964180-T-A		not specified • Noonan syndrome-like disorder with loose anagen hair 1	Benign/Likely benign (Jan 12, 2018)
10-110964200-T-C		not specified • Noonan syndrome-like disorder with loose anagen hair 1 • Noonan syndrome and Noonan-related syndrome	Conflicting classifications of pathogenicity (Jan 13, 2018)
10-110964234-C-T		not specified	Likely benign (Oct 25, 2010)
10-110964245-C-G		Noonan syndrome-like disorder with loose anagen hair 1	Conflicting classifications of pathogenicity (Jan 12, 2018)
10-110964293-A-G		not specified	Likely benign (May 18, 2011)
10-110964317-A-G			Likely benign (Jun 23, 2021)
10-110964358-C-T		RASopathy • Cardiovascular phenotype	Uncertain significance (Sep 17, 2024)
10-110964362-A-G		Noonan syndrome-like disorder with loose anagen hair 1 • RASopathy • Noonan syndrome • Noonan syndrome-like disorder with loose anagen hair • Noonan syndrome and Noonan-related syndrome • Polycystic kidney disease 4 • Noonan syndrome-like disorder with loose anagen hair 1;Pectus excavatum • SHOC2-related disorder • Inborn genetic diseases	Pathogenic (Apr 03, 2017)
10-110964363-G-C		Cardiovascular phenotype	Uncertain significance (Feb 04, 2022)
10-110964365-A-G			Uncertain significance (Jun 08, 2016)
10-110964368-A-C		not specified • RASopathy • Noonan syndrome-like disorder with loose anagen hair 1 • SHOC2-related disorder	Benign (Sep 17, 2024)
10-110964369-G-A			Uncertain significance (Feb 01, 2023)
10-110964374-G-A		SHOC2-related disorder	Uncertain significance (Feb 29, 2024)
10-110964374-G-C		RASopathy	Uncertain significance (Aug 21, 2022)
10-110964379-A-C		Cardiovascular phenotype	Uncertain significance (Jan 02, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SHOC2	protein_coding	protein_coding	ENST00000369452	8	94125

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.999	0.000541	125674	0	1	125675	0.00000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.97	153	297	0.515	0.0000148	3803
Missense in Polyphen		32	98.668	0.32432		1337
Synonymous	0.804	98	109	0.902	0.00000488	1139
Loss of Function	4.31	0	21.7	0.00	0.00000104	331

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00000880	0.00000880
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Regulatory subunit of protein phosphatase 1 (PP1c) that acts as a M-Ras/MRAS effector and participates in MAPK pathway activation. Upon M-Ras/MRAS activation, targets PP1c to specifically dephosphorylate the 'Ser-259' inhibitory site of RAF1 kinase and stimulate RAF1 activity at specialized signaling complexes. {ECO:0000269|PubMed:10783161, ECO:0000269|PubMed:16630891, ECO:0000269|PubMed:25137548}.
• Disease: DISEASE: Noonan syndrome-like disorder with loose anagen hair 1 (NSLH1) [MIM:607721]: A syndrome characterized by Noonan dysmorphic features such as macrocephaly, high forehead, hypertelorism, palpebral ptosis, low-set and posteriorly rotated ears, short and webbed neck, pectus anomalies, in association with pluckable, sparse, thin and slow-growing hair. {ECO:0000269|PubMed:19684605, ECO:0000269|PubMed:23918763, ECO:0000269|PubMed:25137548}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Ras signaling pathway - Homo sapiens (human);EGF-Ncore;miR-targeted genes in leukocytes - TarBase;miR-targeted genes in lymphocytes - TarBase;miR-targeted genes in muscle cell - TarBase;Ras Signaling (Consensus)

Recessive Scores

• pRec: 0.246

Intolerance Scores

• loftool: 0.0544
• rvis_EVS: -0.18
• rvis_percentile_EVS: 39.95

Haploinsufficiency Scores

• pHI: 0.464
• hipred: Y
• hipred_score: 0.825
• ghis: 0.600

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.984

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Shoc2
• Phenotype: growth/size/body region 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); homeostasis/metabolism phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); respiratory system phenotype; embryo phenotype

Gene ontology

• Biological process: protein dephosphorylation;Ras protein signal transduction;fibroblast growth factor receptor signaling pathway;regulation of phosphoprotein phosphatase activity;positive regulation of Ras protein signal transduction
• Cellular component: protein phosphatase type 1 complex;photoreceptor inner segment;nucleus;nucleoplasm;cytoplasm;cytosol;photoreceptor outer segment membrane
• Molecular function: protein serine/threonine phosphatase activity;protein binding;protein phosphatase 1 binding;protein phosphatase regulator activity;protein phosphatase binding