SHOC2
SHOC2 leucine rich repeat scaffold protein, the group of MicroRNA protein coding host genes
Basic information
Region (hg38): 10:110919367-111017307
Links
Phenotypes
GenCC
Source:
- 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:
| 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
- RASopathy (417 variants)
- Cardiovascular_phenotype (206 variants)
- not_provided (98 variants)
- not_specified (55 variants)
- Noonan_syndrome-like_disorder_with_loose_anagen_hair_1 (48 variants)
- SHOC2-related_disorder (24 variants)
- Noonan_syndrome_and_Noonan-related_syndrome (21 variants)
- Noonan_syndrome (11 variants)
- Noonan_syndrome-like_disorder_with_loose_anagen_hair (4 variants)
- Noonan_syndrome_3 (2 variants)
- Polycystic_kidney_disease_4 (1 variants)
- Non-immune_hydrops_fetalis (1 variants)
- Inborn_genetic_diseases (1 variants)
- Intellectual_disability (1 variants)
- See_cases (1 variants)
- Primary_familial_hypertrophic_cardiomyopathy (1 variants)
- Pectus_excavatum (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. These statistics are base on transcript: NM_000007373.4. 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 | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 180 | 188 | ||||
| missense | 269 | 15 | 296 | |||
| nonsense | 3 | |||||
| start loss | 0 | |||||
| frameshift | 6 | |||||
| splice donor/acceptor (+/-2bp) | 1 | |||||
| Total | 4 | 6 | 282 | 195 | 7 |
Highest pathogenic variant AF is 0.00000657289
Loading clinvar variants...
GnomAD
Source:
| 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:
- 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