SHANK1 (SH3 and multiple ankyrin repeat domains 1)

Gene

• Entrez ID: 50944
• Gene name: SH3 and multiple ankyrin repeat domains 1
• Gene symbol: SHANK1
• Synonyms (NCBI Gene): SPANK-1, SSTRIP, synamon
• Chromosome: 19
• Chromosome location: 19q13.33
• Summary: This gene encodes a member of the SHANK (SH3 domain and ankyrin repeat containing) family of proteins. Members of this family act as scaffold proteins that are required for the development and function of neuronal synapses. Deletions in this gene may be a

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT019080	hsa-miR-335-5p	Microarray	18185580
MIRT051440	hsa-let-7e-5p	CLASH	23622248

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001664	Function	G protein-coupled receptor binding	IEA
GO:0005515	Function	Protein binding	IPI	10551867, 11583995, 30126976, 33436498, 34835087
GO:0005515	Function	Protein binding	ISS
GO:0005737	Component	Cytoplasm	IEA
GO:0005829	Component	Cytosol	TAS
GO:0005886	Component	Plasma membrane	IDA
GO:0005886	Component	Plasma membrane	IEA
GO:0005886	Component	Plasma membrane	ISS
GO:0007399	Process	Nervous system development	IEA
GO:0007616	Process	Long-term memory	IEA
GO:0007616	Process	Long-term memory	ISS
GO:0008306	Process	Associative learning	IBA
GO:0008306	Process	Associative learning	IEA
GO:0008306	Process	Associative learning	ISS
GO:0014069	Component	Postsynaptic density	IBA
GO:0014069	Component	Postsynaptic density	IEA
GO:0014069	Component	Postsynaptic density	ISS
GO:0016020	Component	Membrane	IDA	10551867
GO:0017124	Function	SH3 domain binding	IEA
GO:0017124	Function	SH3 domain binding	ISS
GO:0030154	Process	Cell differentiation	IEA
GO:0030159	Function	Signaling receptor complex adaptor activity	IEA
GO:0030160	Function	Synaptic receptor adaptor activity	IBA
GO:0030160	Function	Synaptic receptor adaptor activity	IEA
GO:0030160	Function	Synaptic receptor adaptor activity	ISS
GO:0030425	Component	Dendrite	IEA
GO:0030425	Component	Dendrite	NAS	10551867
GO:0030534	Process	Adult behavior	IEA
GO:0030534	Process	Adult behavior	IMP	22503632
GO:0031877	Function	Somatostatin receptor binding	IEA
GO:0031877	Function	Somatostatin receptor binding	ISS
GO:0032232	Process	Negative regulation of actin filament bundle assembly	IEA
GO:0032232	Process	Negative regulation of actin filament bundle assembly	ISS
GO:0035176	Process	Social behavior	IEA
GO:0035176	Process	Social behavior	IMP	22503632
GO:0035255	Function	Ionotropic glutamate receptor binding	IBA
GO:0035255	Function	Ionotropic glutamate receptor binding	IEA
GO:0035255	Function	Ionotropic glutamate receptor binding	ISS
GO:0035418	Process	Protein localization to synapse	IEA
GO:0035418	Process	Protein localization to synapse	ISS
GO:0042048	Process	Olfactory behavior	IEA
GO:0042802	Function	Identical protein binding	IEA
GO:0042802	Function	Identical protein binding	ISS
GO:0043005	Component	Neuron projection	IEA
GO:0043005	Component	Neuron projection	ISS
GO:0043197	Component	Dendritic spine	IBA
GO:0043197	Component	Dendritic spine	IEA
GO:0043197	Component	Dendritic spine	ISS
GO:0044877	Function	Protein-containing complex binding	IEA
GO:0044877	Function	Protein-containing complex binding	ISS
GO:0045202	Component	Synapse	IEA
GO:0045211	Component	Postsynaptic membrane	IBA
GO:0045211	Component	Postsynaptic membrane	IEA
GO:0045211	Component	Postsynaptic membrane	ISS
GO:0045211	Component	Postsynaptic membrane	ISS
GO:0046959	Process	Habituation	IEA
GO:0050804	Process	Modulation of chemical synaptic transmission	IEA
GO:0050808	Process	Synapse organization	IBA
GO:0050885	Process	Neuromuscular process controlling balance	IEA
GO:0050885	Process	Neuromuscular process controlling balance	ISS
GO:0050890	Process	Cognition	IEA
GO:0050894	Process	Determination of affect	IMP	22503632
GO:0060013	Process	Righting reflex	IEA
GO:0060074	Process	Synapse maturation	IEA
GO:0060074	Process	Synapse maturation	ISS
GO:0060076	Component	Excitatory synapse	IEA
GO:0060076	Component	Excitatory synapse	ISS
GO:0060997	Process	Dendritic spine morphogenesis	IEA
GO:0060997	Process	Dendritic spine morphogenesis	ISS
GO:0060999	Process	Positive regulation of dendritic spine development	IEA
GO:0060999	Process	Positive regulation of dendritic spine development	ISS
GO:0065003	Process	Protein-containing complex assembly	IEA
GO:0065003	Process	Protein-containing complex assembly	ISS
GO:0071532	Function	Ankyrin repeat binding	IEA
GO:0071532	Function	Ankyrin repeat binding	ISS
GO:0071625	Process	Vocalization behavior	IEA
GO:0071625	Process	Vocalization behavior	IMP	22503632
GO:0097110	Function	Scaffold protein binding	IEA
GO:0097110	Function	Scaffold protein binding	ISS
GO:0098685	Component	Schaffer collateral - CA1 synapse	IEA
GO:0098919	Function	Structural constituent of postsynaptic density	IEA
GO:0098978	Component	Glutamatergic synapse	IEA
GO:0098990	Process	AMPA selective glutamate receptor signaling pathway	IEA
GO:0098990	Process	AMPA selective glutamate receptor signaling pathway	ISS
GO:0099562	Process	Maintenance of postsynaptic density structure	IEA
GO:2000463	Process	Positive regulation of excitatory postsynaptic potential	IEA
GO:2000463	Process	Positive regulation of excitatory postsynaptic potential	ISS

Other IDs

• MIM: 604999
• HGNC: 15474
• e!Ensembl: ENSG00000161681

Protein

• UniProt ID: Q9Y566
• Protein name: SH3 and multiple ankyrin repeat domains protein 1 (Shank1) (Somatostatin receptor-interacting protein) (SSTR-interacting protein) (SSTRIP)
• Protein 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,
• PDB: 6CPI, 6YWZ, 6YX0, 6YX1, 6YX2, 7A00, 8S1R
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF12796	Ank_2	184 → 277	Ankyrin repeats (3 copies)	Repeat
  PF12796	Ank_2	318 → 409	Ankyrin repeats (3 copies)	Repeat
  PF07653	SH3_2	559 → 611	Variant SH3 domain	Domain
  PF17820	PDZ_6	701 → 754	PDZ domain	Domain
  PF00536	SAM_1	2096 → 2159	SAM domain (Sterile alpha motif)	Domain

• Tissue specificity: TISSUE SPECIFICITY: Expressed in brain particularly in the amygdala, hippocampus, substantia nigra and thalamus. Isoform 2 seems to be expressed ubiquitously.
• Sequence:

  MTHSPATSEDEERHSASECPEGGSESDSSPDGPGRGPRGTRGQGSGAPGSLASVRGLQGR
  SMSVPDDAHFSMMVFRIGIPDLHQTKCLRFNPDATIWTAKQQVLCALSESLQDVLNYGLF
  QPATSGRDANFLEEERLLREYPQSFEKGVPYLEFRYKTRVYKQTNLDEKQLAKLHTKTGL
  KKFLEYVQLGTSDKVARLLDKGLDPNYHDSDSGETPLTLAAQTEGSVEVIRTLCLGGAHI
  DFRARDGMTALHKAACARHCLALTALLDLGGSPNYKDRRGLTPLFHTAMVGGDPRCCELL
  LFNRAQLGIADENGWQEIHQACQRGHSQHLEHLLFYGAEPGAQNASGNTALHICALYNKE
  TCARILLYRGADKDVKNNNGQTPFQVAVIAGNFELGELIRNHREQDVVPFQESPKYAARR
  RGPPGTGLTVPPALLRANSDTSMALPDWMVFSAPGAASSGAPGPTSGSQGQSQPSAPTTK
  LSSGTLRSASSPRGARARSPSRGRHPEDAKRQPRGRPSSSGTPREGPAGGTGGSGGPGGS
  LGSRGRRRKLYSAVPGRSFMAVKSYQAQAEGEISLSKGEKIKVLSIGEGGFWEGQVKGRV
  GWFPSDCLEEVANRSQESKQESRSDKAKRLFRHYTVGSYDSFDAPSLMDGIGPGSDYIIK
  EKTVLLQKKDSEGFGFVLRGAKAQTPIEEFTPTPAFPALQYLESVDEGGVAWRAGLRMGD
  FLIEVNGQNVVKVGHRQVVNMIRQGGNTLMVKVVMVTRHPDMDEAVHKKAPQQAKRLPPP
  TISLRSKSMTSELEEMEYEQQPAPVPSMEKKRTVYQMALNKLDEILAAAQQTISASESPG
  PGGLASLGKHRPKGFFATESSFDPHHRAQPSYERPSFLPPGPGLMLRQKSIGAAEDDRPY
  LAPPAMKFSRSLSVPGSEDIPPPPTTSPPEPPYSTPPVPSSSGRLTPSPRGGPFNPGSGG
  PLPASSPASFDGPSPPDTRVGSREKSLYHSGPLPPAHHHPPHHHHHHAPPPQPHHHHAHP
  PHPPEMETGGSPDDPPPRLALGPQPSLRGWRGGGPSPTPGAPSPSHHGSAGGGGGSSQGP
  ALRYFQLPPRAASAAMYVPARSGRGRKGPLVKQTKVEGEPQKGGGLPPAPSPTSPASPQP
  PPAVAAPSEKNSIPIPTIIIKAPSTSSSGRSSQGSSTEAEPPTQPEPTGGGGGGGSSPSP
  APAMSPVPPSPSPVPTPASPSGPATLDFTSQFGAALVGAARREGGWQNEARRRSTLFLST
  DAGDEDGGDGGLGTGAAPGPRLRHSKSIDEGMFSAEPYLRLESAGSGAGYGGYGAGSRAY
  GGGGGSSAFTSFLPPRPLVHPLTGKALDPASPLGLALAARERALKESSEGGGAPQPPPRP
  PSPRYEAPPPTPHHHSPHAHHEPVLRLWGASPPDPARRELGYRAGLGSQEKSLPASPPAA
  RRSLLHRLPPTAPGVGPLLLQLGTEPPAPHPGVSKPWRSAAPEEPERLPLHVRFLENCQP
  RAPVTSGRGPPSEDGPGVPPPSPRRSVPPSPTSPRASEENGLPLLVLPPPAPSVDVEDGE
  FLFVEPLPPPLEFSNSFEKPESPLTPGPPHPLPDTPAPATPLPPVPPPAVAAAPPTLDST
  ASSLTSYDSEVATLTQGASAAPGDPHPPGPPAPAAPAPAAPQPGPDPPPGTDSGIEEVDS
  RSSSDHPLETISSASTLSSLSAEGGGSAGGGGGAGAGVASGPELLDTYVAYLDGQAFGGS
  STPGPPYPPQLMTPSKLRGRALGASGGLRPGPSGGLRDPVTPTSPTVSVTGAGTDGLLAL
  RACSGPPTAGVAGGPVAVEPEVPPVPLPTASSLPRKLLPWEEGPGPPPPPLPGPLAQPQA
  SALATVKASIISELSSKLQQFGGSSAAGGALPWARGGSGGGGDSHHGGASYVPERTSSLQ
  RQRLSDDSQSSLLSKPVSSLFQNWPKPPLPPLPTGTGVSPTAAAAPGATSPSASSSSTST
  RHLQGVEFEMRPPLLRRAPSPSLLPASEHKVSPAPRPSSLPILPSGPLYPGLFDIRGSPT
  GGAGGSADPFAPVFVPPHPGISGGLGGALSGASRSLSPTRLLSLPPDKPFGAKPLGFWTK
  FDVADWLEWLGLAEHRAQFLDHEIDGSHLPALTKEDYVDLGVTRVGHRMNIDRALKFFLE
  R

• Sequence length: 2161

Pathways

KEGG:

Glutamatergic synapse

Reactome:

Neurexins and neuroligins

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Intellectual disability	Pathogenic; Likely pathogenic	rs138273094, rs2513940332	RCV002287506 RCV002287592	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
SHANK1-associated disorder	Likely pathogenic; Pathogenic	rs1210431144	RCV005622164	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
SHANK1-related autism	Likely pathogenic	rs770588422	RCV003233357	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
SHANK1-related disorder	Likely pathogenic	rs2513919782	RCV003914151	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
SHANK1-related Neurodevelopmental Disorder	Likely pathogenic; Pathogenic	rs2123136215	RCV005401953	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
ANXIETY DISORDERS	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AUTISM	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AUTISTIC DISORDER	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BREAST CANCER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BREAST CARCINOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CARCINOMA, RENAL CELL	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
COMPLEX NEURODEVELOPMENTAL DISORDER	—	ClinGen, GenCC	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DEVELOPMENTAL COORDINATION DISORDER	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
EBV-positive nodal T- and NK-cell lymphoma	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
INSOMNIA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MOTOR SKILLS DISORDERS	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NEURODEVELOPMENTAL DISORDER	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NEURODEVELOPMENTAL DISORDERS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NON-SPECIFIC SYNDROMIC INTELLECTUAL DISABILITY	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NONORGANIC PSYCHOSIS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PSYCHOTIC DISORDERS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SCHIZOPHRENIA	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SHANK1-associated neurodevelopmental disorder	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
22q13.3 Deletion Syndrome	22q13.3 deletion syndrome	BEFREE	30405356		★☆☆☆☆ Found in Text Mining only
Anxiety	Anxiety Disorder	BEFREE	24124131		★☆☆☆☆ Found in Text Mining only
Anxiety Disorders	Anxiety Disorder	CTD_human_DG	18272690		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Anxiety Disorders	Anxiety Disorder	BEFREE	24124131		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Anxiety States, Neurotic	Anxiety Disorder	CTD_human_DG	18272690		★☆☆☆☆ Found in Text Mining only
Autism Spectrum Disorder	Autism	Pubtator	22503632, 28720872, 37012247	Associate	★☆☆☆☆ Found in Text Mining only
Autism Spectrum Disorders	Autism Spectrum Disorder	BEFREE	22503632, 25188300, 26335738, 26781567, 28179641, 28500650, 28720872, 28963042, 29074576, 29507711, 30405356, 30505269, 30629339		★☆☆☆☆ Found in Text Mining only
Autistic Disorder	Autism	CTD_human_DG	18272690		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Autistic Disorder	Autism	BEFREE	22503632, 25188300, 30405356		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Autistic Disorder	Autism	Pubtator	22503632, 27824329	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Autistic Disorder	Autism	GENOMICS_ENGLAND_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Borderline Personality Disorder	Borderline personality disorder	BEFREE	30505269		★☆☆☆☆ Found in Text Mining only
Bronchopulmonary Dysplasia	Bronchopulmonary Dysplasia	BEFREE	30505269		★☆☆☆☆ Found in Text Mining only
Chromophobe Renal Cell Carcinoma	Chromophobe Carcinoma	CTD_human_DG	22138691		★☆☆☆☆ Found in Text Mining only
Collecting Duct Carcinoma of the Kidney	Renal Carcinoma	CTD_human_DG	22138691		★☆☆☆☆ Found in Text Mining only
Colorectal Carcinoma	Colorectal Cancer	UNIPROT_DG			★☆☆☆☆ Found in Text Mining only
Conventional (Clear Cell) Renal Cell Carcinoma	Renal Carcinoma	CTD_human_DG	22138691		★☆☆☆☆ Found in Text Mining only
Developmental Coordination Disorder	Developmental dyspraxia	CTD_human_DG	20868654		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Developmental Disabilities	Developmental disability	Pubtator	24372385	Associate	★☆☆☆☆ Found in Text Mining only
Epilepsy	Epilepsy	Pubtator	24372385	Associate	★☆☆☆☆ Found in Text Mining only
Epilepsy Rolandic	Rolandic epilepsy	Pubtator	24372385	Associate	★☆☆☆☆ Found in Text Mining only
Fragile X Syndrome	Fragile X Syndrome	BEFREE	25692235, 27730449		★☆☆☆☆ Found in Text Mining only
Glioblastoma	Glioblastoma	Pubtator	38019838	Associate	★☆☆☆☆ Found in Text Mining only
Impaired cognition	Impaired Cognition	BEFREE	30053575		★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Mental retardation	BEFREE	22503632		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Mild Mental Retardation	Mental retardation	BEFREE	25188300		★☆☆☆☆ Found in Text Mining only
Motor Skills Disorders	Motor Skills Disorders	CTD_human_DG	20868654		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
nervous system disorder	Nervous System Disorder	BEFREE	30053575		★☆☆☆☆ Found in Text Mining only
Nonorganic psychosis	Nonorganic Psychosis	BEFREE	21901269		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Nonorganic psychosis	Nonorganic Psychosis	PSYGENET_DG	21901269		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Papillary Renal Cell Carcinoma	Papillary Renal Carcinoma	CTD_human_DG	22138691		★☆☆☆☆ Found in Text Mining only
Pervasive Development Disorder	Autism spectrum disorder	BEFREE	22503632, 28179641, 28500650, 28720872, 28963042, 29074576, 30629339		★☆☆☆☆ Found in Text Mining only
Post-Traumatic Stress Disorder	Stress Disorder	BEFREE	28716937		★☆☆☆☆ Found in Text Mining only
Profound Mental Retardation	Mental retardation	BEFREE	25188300		★☆☆☆☆ Found in Text Mining only
Psychotic Disorders	Psychosis	BEFREE	21901269		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Psychotic Disorders	Psychosis	PSYGENET_DG	21901269		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Renal Cell Carcinoma	Renal Carcinoma	CTD_human_DG	22138691		★☆☆☆☆ Found in Text Mining only
Sarcomatoid Renal Cell Carcinoma	Renal Carcinoma	CTD_human_DG	22138691		★☆☆☆☆ Found in Text Mining only
Schizophrenia	Schizophrenia	BEFREE	21901269, 30505269		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Schizophrenia	Schizophrenia	PSYGENET_DG	21901269		★★☆☆☆ Found in Text Mining + Unknown/Other Associations