SHANK1
SH3 and multiple ankyrin repeat domains 1, the group of PDZ domain containing|Sterile alpha motif domain containing|Ankyrin repeat domain containing
Basic information
Region (hg38): 19:50659255-50719802
Links
Phenotypes
GenCC
Source:
- autism (Strong), mode of inheritance: AD
ClinVar
This is a list of variants' phenotypes submitted to
- Inborn_genetic_diseases (293 variants)
- not_provided (211 variants)
- SHANK1-related_disorder (47 variants)
- Intellectual_disability (7 variants)
- not_specified (7 variants)
- Complex_neurodevelopmental_disorder (3 variants)
- Neurodevelopmental_disorder (2 variants)
- SHANK1-related_Neurodevelopmental_Disorder (2 variants)
- See_cases (2 variants)
- SHANK1-related_autism (1 variants)
- SHANK1-associated_disorder (1 variants)
- Hearing_impairment (1 variants)
- EBV-positive_nodal_T-_and_NK-cell_lymphoma (1 variants)
- VATER_association (1 variants)
- SHANK1-associated_neurodevelopmental_disorder (1 variants)
- Multiple_congenital_anomalies/dysmorphic_syndrome (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the SHANK1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000016148.5. 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 | 61 | 15 | 77 | |||
| missense | 381 | 47 | 434 | |||
| nonsense | 9 | |||||
| start loss | 0 | |||||
| frameshift | 10 | |||||
| splice donor/acceptor (+/-2bp) | 1 | |||||
| Total | 7 | 10 | 386 | 108 | 20 |
Highest pathogenic variant AF is 0.00000273654
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| SHANK1 | protein_coding | protein_coding | ENST00000293441 | 23 | 57624 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.00 | 4.53e-7 | 125740 | 0 | 8 | 125748 | 0.0000318 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 3.64 | 738 | 1.07e+3 | 0.687 | 0.0000662 | 13397 |
| Missense in Polyphen | 63 | 163.29 | 0.38582 | 1768 | ||
| Synonymous | -0.580 | 512 | 496 | 1.03 | 0.0000336 | 4871 |
| Loss of Function | 7.07 | 7 | 71.5 | 0.0979 | 0.00000432 | 769 |
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) | 0.0000637 | 0.0000615 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.0000327 | 0.0000327 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Seems to be an adapter protein in the postsynaptic density (PSD) of excitatory synapses that interconnects receptors of the postsynaptic membrane including NMDA-type and metabotropic glutamate receptors via complexes with GKAP/PSD-95 and Homer, respectively, and the actin-based cytoskeleton. Plays a role in the structural and functional organization of the dendritic spine and synaptic junction.;
- Pathway
- Glutamatergic synapse - Homo sapiens (human);Neuronal System;Neurexins and neuroligins;Protein-protein interactions at synapses
(Consensus)
Recessive Scores
- pRec
- 0.103
Haploinsufficiency Scores
- pHI
- 0.150
- hipred
- Y
- hipred_score
- 0.700
- ghis
- 0.626
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- N
- gene_indispensability_score
- 0.309
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Shank1
- Phenotype
- behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); reproductive system phenotype;
Gene ontology
- Biological process
- cytoskeletal anchoring at plasma membrane;synapse assembly;long-term memory;associative learning;adult behavior;negative regulation of actin filament bundle assembly;social behavior;protein localization to synapse;olfactory behavior;habituation;brain morphogenesis;neuromuscular process controlling balance;determination of affect;synaptic growth at neuromuscular junction;positive regulation of synaptic transmission, glutamatergic;righting reflex;synapse maturation;long-term synaptic potentiation;dendritic spine morphogenesis;positive regulation of dendritic spine development;protein-containing complex assembly;vocalization behavior;postsynaptic density assembly;regulation of AMPA receptor activity;positive regulation of excitatory postsynaptic potential
- Cellular component
- cytosol;plasma membrane;ionotropic glutamate receptor complex;postsynaptic density;membrane;NMDA selective glutamate receptor complex;cell junction;dendrite;neuron projection;dendritic spine;neuron spine;postsynaptic membrane;excitatory synapse;Schaffer collateral - CA1 synapse;glutamatergic synapse
- Molecular function
- protein binding;protein C-terminus binding;SH3 domain binding;receptor signaling complex scaffold activity;GKAP/Homer scaffold activity;somatostatin receptor binding;ionotropic glutamate receptor binding;identical protein binding;protein-containing complex binding;ankyrin repeat binding;scaffold protein binding