SHANK2

SH3 and multiple ankyrin repeat domains 2, the group of PDZ domain containing|Sterile alpha motif domain containing|Ankyrin repeat domain containing|MicroRNA protein coding host genes

Basic information

Region (hg38): 11:70467853-71252577

Previous symbols: [ "CORTBP1" ]

Links

ENSG00000162105 ∙ NCBI:22941 ∙ OMIM:603290 ∙ HGNC:14295 ∙ Uniprot:Q9UPX8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autism, susceptibility to, 17 (Strong), mode of inheritance: AD
• autism, susceptibility to, 17 (Strong), mode of inheritance: AD
• complex neurodevelopmental disorder (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Autism, susceptibility to 17	AD	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	20473310

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SHANK2 gene.

• not provided (141 variants)
• Autism spectrum disorder (56 variants)
• not specified (46 variants)
• Inborn genetic diseases (41 variants)
• Autism, susceptibility to, 17 (31 variants)
• SHANK2-related condition (4 variants)
• See cases (4 variants)
• Autism (3 variants)
• Intellectual disability (3 variants)
• Rare disease with autism (2 variants)
• Global developmental delay (1 variants)
• Neurodevelopmental disorder (1 variants)
• Autism spectrum disorder;Schizophrenia;Intellectual disability (1 variants)
• SHANK2-related disorder (1 variants)
• SHANK2-related Complex neurodevelopmental disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SHANK2 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			15	41	6	62
missense			101	25	3	129
nonsense	5	2	5			12
start loss						0
frameshift	9	9	8			26
inframe indel			2	1		3
splice donor/acceptor (+/-2bp)		1	1			2
splice region			4	1	1	6
non coding			19	10	1	30
Total	14	12	151	77	10

Highest pathogenic variant AF is 0.00000657

Variants in SHANK2

This is a list of pathogenic ClinVar variants found in the SHANK2 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-70468492-T-A		Autism spectrum disorder	Likely benign (Jun 14, 2016)
11-70468767-G-C		Autism spectrum disorder	Likely benign (Jun 14, 2016)
11-70468840-T-G		Autism spectrum disorder	Uncertain significance (Jun 14, 2016)
11-70468922-G-C		Autism spectrum disorder	Uncertain significance (Jun 14, 2016)
11-70469394-G-C		Autism spectrum disorder	Uncertain significance (Jun 14, 2016)
11-70469623-C-T		Autism spectrum disorder	Uncertain significance (Jun 14, 2016)
11-70469624-A-G		Autism spectrum disorder	Uncertain significance (Jun 14, 2016)
11-70469802-T-C		Autism spectrum disorder	Uncertain significance (Jun 14, 2016)
11-70470286-A-G		Autism spectrum disorder	Likely benign (Jun 14, 2016)
11-70471272-A-C		Autism spectrum disorder	Likely benign (Jun 14, 2016)
11-70471324-A-C		Autism spectrum disorder	Uncertain significance (Jun 14, 2016)
11-70471335-C-CA		Autism spectrum disorder	Conflicting classifications of pathogenicity (Jan 01, 2023)
11-70471847-A-G		Autism spectrum disorder	Uncertain significance (Jun 14, 2016)
11-70472278-G-T		Autism spectrum disorder	Uncertain significance (Jun 14, 2016)
11-70472284-G-A		Autism spectrum disorder	Uncertain significance (Jun 14, 2016)
11-70472925-G-A			Uncertain significance (Mar 17, 2014)
11-70472944-G-A		not specified	Uncertain significance (Jun 01, 2015)
11-70472947-G-GT		Inborn genetic diseases	Uncertain significance (Jan 25, 2022)
11-70472966-GGTAA-G		not specified	Uncertain significance (Sep 13, 2017)
11-70472983-G-A			Benign (Sep 01, 2022)
11-70473043-G-A		not specified	Likely benign (Aug 03, 2017)
11-70473102-T-C		not specified	Uncertain significance (Jan 31, 2018)
11-70473145-C-T			Likely benign (Jan 01, 2024)
11-70473146-G-A			Likely benign (Jun 01, 2022)
11-70473171-C-T			Uncertain significance (Apr 19, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SHANK2	protein_coding	protein_coding	ENST00000338508	33	649663

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
8.43e-7	1.00	125731	0	2	125733	0.00000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.32	923	1.14e+3	0.807	0.0000800	12010
Missense in Polyphen		186	266.31	0.69843		2734
Synonymous	-0.224	523	517	1.01	0.0000427	3812
Loss of Function	5.51	26	78.8	0.330	0.00000459	884

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)	0.0000176	0.0000176
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• 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, and the actin-based cytoskeleton. May play a role in the structural and functional organization of the dendritic spine and synaptic junction.
• Disease: DISEASE: Autism 17 (AUTS17) [MIM:613436]: A complex multifactorial, pervasive developmental disorder characterized by impairments in reciprocal social interaction and communication, restricted and stereotyped patterns of interests and activities, and the presence of developmental abnormalities by 3 years of age. Most individuals with autism also manifest moderate mental retardation. {ECO:0000269|PubMed:20473310}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.
• Pathway: Glutamatergic synapse - Homo sapiens (human);Neuronal System;Neurexins and neuroligins;Protein-protein interactions at synapses (Consensus)

Haploinsufficiency Scores

• pHI: 0.350
• hipred: Y
• hipred_score: 0.682
• ghis: 0.630

Essentials

• essential_gene_CRISPR2: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.788

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Shank2
• Phenotype: 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); 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); growth/size/body region phenotype

Gene ontology

• Biological process: synapse assembly;learning;adult behavior;social behavior;brain morphogenesis;synaptic growth at neuromuscular junction;positive regulation of synaptic transmission, glutamatergic;long-term synaptic potentiation;long-term synaptic depression;dendritic spine morphogenesis;positive regulation of dendritic spine development;vocalization behavior;postsynaptic density assembly;regulation of AMPA receptor activity;positive regulation of excitatory postsynaptic potential
• Cellular component: photoreceptor outer segment;photoreceptor inner segment;cellular_component;cytosol;neurofilament;plasma membrane;ionotropic glutamate receptor complex;postsynaptic density;apical plasma membrane;cell junction;dendrite;growth cone;brush border membrane;neuron projection;neuronal cell body;dendritic spine;neuron spine;postsynaptic membrane;ciliary membrane
• Molecular function: protein binding;SH3 domain binding;receptor signaling complex scaffold activity;GKAP/Homer scaffold activity;ionotropic glutamate receptor binding