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

ENSG00000161681 ∙ NCBI:50944 ∙ OMIM:604999 ∙ HGNC:15474 ∙ Uniprot:Q9Y566 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autism (Strong), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SHANK1 gene.

• not provided (5 variants)
• Global developmental delay;Motor delay;Abnormal facial shape;Delayed speech and language development;Cleft palate (1 variants)
• Intellectual disability (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.

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				37	14	51
missense		1	263	33	3	300
nonsense	5		2			7
start loss						0
frameshift	1	2	2			5
inframe indel			4			4
splice donor/acceptor (+/-2bp)			1			1
splice region			1	3	4	8
non coding					1	1
Total	6	3	272	70	18

Highest pathogenic variant AF is 0.00000658

Variants in SHANK1

This is a list of pathogenic ClinVar variants found in the SHANK1 region.

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

Position	Type	Phenotype	Significance	ClinVar
19-50661970-T-C		Inborn genetic diseases	Uncertain significance (Dec 29, 2024)
19-50661993-C-T		Inborn genetic diseases	Uncertain significance (Sep 26, 2024)
19-50662013-G-A			Likely benign (May 31, 2018)
19-50662023-G-T			Uncertain significance (May 19, 2022)
19-50662031-T-C		SHANK1-related disorder	Likely benign (May 28, 2019)
19-50662040-G-A		SHANK1-related disorder	Likely benign (Jun 05, 2018)
19-50662060-C-T		Inborn genetic diseases	Uncertain significance (Apr 07, 2022)
19-50662078-C-T		Inborn genetic diseases	Uncertain significance (Oct 20, 2021)
19-50662090-C-T			Uncertain significance (Aug 01, 2019)
19-50662163-C-T			Benign (Dec 05, 2018)
19-50662171-G-T			Uncertain significance (Jun 17, 2024)
19-50662180-C-A		SHANK1-related disorder	Benign (Nov 15, 2018)
19-50662184-C-T		SHANK1-related disorder	Likely benign (Oct 28, 2019)
19-50662183-A-ACGGCTTGTC		SHANK1-related disorder	Uncertain significance (Jul 06, 2024)
19-50662196-G-A			Likely benign (Apr 16, 2018)
19-50662202-C-T		SHANK1-related disorder	Likely benign (Aug 16, 2019)
19-50662207-G-C		Inborn genetic diseases	Uncertain significance (Jul 13, 2021)
19-50662217-C-T			Likely benign (Sep 19, 2018)
19-50662222-A-G		SHANK1-related disorder • Inborn genetic diseases	Uncertain significance (Aug 27, 2024)
19-50662223-G-A			Likely benign (Feb 04, 2019)
19-50662230-C-T		Inborn genetic diseases	Uncertain significance (Mar 31, 2024)
19-50662236-G-A		Inborn genetic diseases	Uncertain significance (Jun 11, 2021)
19-50662237-C-A		Inborn genetic diseases	Uncertain significance (Jun 26, 2024)
19-50662237-C-T		Inborn genetic diseases	Uncertain significance (Feb 23, 2023)
19-50662243-A-C			Uncertain significance (Apr 25, 2024)

GnomAD

Source: gnomAD

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: 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 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