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:0005515	Function	Protein binding	IPI	10551867, 11583995, 30126976
GO:0005829	Component	Cytosol	TAS
GO:0005886	Component	Plasma membrane	IDA
GO:0005886	Component	Plasma membrane	ISS
GO:0007610	Process	Behavior	IBA	21873635
GO:0007616	Process	Long-term memory	ISS
GO:0008022	Function	Protein C-terminus binding	ISS
GO:0008306	Process	Associative learning	ISS
GO:0008328	Component	Ionotropic glutamate receptor complex	IBA	21873635
GO:0008328	Component	Ionotropic glutamate receptor complex	ISS
GO:0014069	Component	Postsynaptic density	IBA	21873635
GO:0014069	Component	Postsynaptic density	ISS
GO:0016020	Component	Membrane	IDA	10551867
GO:0017124	Function	SH3 domain binding	ISS
GO:0017146	Component	NMDA selective glutamate receptor complex	ISS
GO:0030160	Function	Synaptic receptor adaptor activity	IBA	21873635
GO:0030160	Function	Synaptic receptor adaptor activity	ISS
GO:0030425	Component	Dendrite	NAS	10551867
GO:0030534	Process	Adult behavior	IMP	22503632
GO:0031877	Function	Somatostatin receptor binding	ISS
GO:0032232	Process	Negative regulation of actin filament bundle assembly	ISS
GO:0035176	Process	Social behavior	IMP	22503632
GO:0035255	Function	Ionotropic glutamate receptor binding	IBA	21873635
GO:0035255	Function	Ionotropic glutamate receptor binding	ISS
GO:0035418	Process	Protein localization to synapse	ISS
GO:0042802	Function	Identical protein binding	ISS
GO:0043005	Component	Neuron projection	ISS
GO:0043197	Component	Dendritic spine	IBA	21873635
GO:0043197	Component	Dendritic spine	ISS
GO:0044877	Function	Protein-containing complex binding	ISS
GO:0045211	Component	Postsynaptic membrane	IBA	21873635
GO:0045211	Component	Postsynaptic membrane	ISS
GO:0045211	Component	Postsynaptic membrane	ISS
GO:0048854	Process	Brain morphogenesis	IBA	21873635
GO:0050885	Process	Neuromuscular process controlling balance	ISS
GO:0050894	Process	Determination of affect	IMP	22503632
GO:0051124	Process	Synaptic growth at neuromuscular junction	IBA	21873635
GO:0051968	Process	Positive regulation of synaptic transmission, glutamatergic	IBA	21873635
GO:0060074	Process	Synapse maturation	ISS
GO:0060076	Component	Excitatory synapse	ISS
GO:0060291	Process	Long-term synaptic potentiation	IBA	21873635
GO:0060997	Process	Dendritic spine morphogenesis	IBA	21873635
GO:0060997	Process	Dendritic spine morphogenesis	ISS
GO:0060999	Process	Positive regulation of dendritic spine development	IBA	21873635
GO:0060999	Process	Positive regulation of dendritic spine development	ISS
GO:0065003	Process	Protein-containing complex assembly	ISS
GO:0071532	Function	Ankyrin repeat binding	ISS
GO:0071625	Process	Vocalization behavior	IMP	22503632
GO:0097107	Process	Postsynaptic density assembly	IBA	21873635
GO:0097110	Function	Scaffold protein binding	ISS
GO:2000311	Process	Regulation of AMPA receptor activity	IBA	21873635
GO:2000311	Process	Regulation of AMPA receptor activity	ISS
GO:2000463	Process	Positive regulation of excitatory postsynaptic potential	IBA	21873635
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

Causal
Disease term	Disease name	dbSNP ID	References
Autism	Autistic Disorder	rs121964908, rs62643608, rs181327458, rs797046134, rs869312704, rs1555013332, rs876657679, rs1057518999, rs1057518658, rs771827120, rs1555187899, rs773080572, rs753871454, rs1684130791, rs1684180699, rs1553510219, rs1684182454, rs1559060428, rs1553510677, rs1576352885, rs1574152522, rs1574152672, rs1696658542	18272690
Colorectal cancer	Colorectal Carcinoma	rs137854568, rs137854573, rs137854575, rs387906234, rs121908380, rs121908702, rs267606674, rs794729661, rs121909055, rs281865417, rs267606884, rs28934575, rs587776769, rs104893815, rs587776800, rs63750198, rs63751109, rs863223312, rs63750710, rs63751615, rs63750206, rs63750781, rs63750899, rs63750691, rs63750217, rs121912965, rs63749939, rs63751194, rs63750693, rs63750540, rs63751221, rs193922370, rs80359596, rs397514632, rs483352909, rs200495564, rs397514684, rs397516436, rs398122386, rs79512956, rs74953290, rs587779001, rs63750677, rs63749837, rs267607816, rs63751715, rs267607819, rs267607815, rs267607822, rs63749906, rs587778883, rs63750472, rs63751012, rs63750715, rs63750580, rs267607706, rs267607709, rs267607710, rs587778894, rs63750749, rs63750483, rs63751015, rs63751153, rs63751094, rs63751118, rs63750316, rs63749981, rs587778906, rs267607821, rs587778908, rs63750020, rs587778909, rs63750713, rs267607825, rs63751592, rs281864936, rs587778913, rs587778914, rs63749795, rs63750855, rs63749916, rs63749923, rs63751472, rs63751689, rs267607832, rs267607837, rs267607836, rs587778923, rs63750028, rs587778928, rs587778929, rs587778930, rs63751277, rs587778933, rs267607842, rs267607843, rs63750192, rs587778934, rs63750193, rs587778937, rs587778938, rs267607845, rs63751244, rs63751393, rs63751460, rs267607849, rs267607853, rs267607856, rs267607850, rs63751657, rs267607854, rs267607852, rs587778942, rs63750309, rs63750587, rs63749863, rs63751486, rs63750016, rs63749868, rs63750375, rs63750035, rs63750604, rs63750386, rs63750150, rs63750486, rs63751428, rs267607866, rs63749986, rs63751594, rs63750152, rs63750850, rs267607867, rs267607868, rs63751632, rs267607871, rs63751892, rs587778956, rs63750469, rs587778958, rs63749792, rs267607875, rs63751255, rs281864938, rs63751202, rs63750726, rs63751310, rs63749900, rs587778964, rs267607879, rs267607878, rs587778966, rs267607883, rs267607887, rs63750061, rs63750663, rs587778968, rs587778971, rs63750809, rs63749867, rs63750864, rs587778972, rs63751275, rs267607718, rs267607722, rs63750769, rs267607717, rs587778973, rs267607716, rs267607720, rs63749995, rs63750859, rs587778975, rs63750114, rs587778976, rs63750603, rs267607889, rs267607723, rs63750561, rs63750499, rs63751642, rs63751022, rs587778981, rs63750971, rs267607898, rs267607906, rs267607903, rs587778989, rs587778992, rs267607894, rs267607901, rs267607892, rs63750437, rs587778997, rs587778998, rs63750005, rs63750641, rs63751421, rs11541859, rs63750266, rs111052004, rs267607726, rs267607727, rs63750453, rs267607734, rs267607735, rs63751665, rs267607736, rs267607732, rs63749816, rs63750539, rs267607739, rs587779006, rs587779008, rs267607745, rs267607742, rs63751595, rs267607743, rs587779010, rs587779012, rs63750057, rs63749818, rs63751124, rs587779014, rs587779015, rs63749820, rs63751302, rs267607750, rs267607751, rs267607749, rs63750891, rs63749959, rs63749804, rs267607765, rs267607760, rs587779021, rs267607759, rs63750515, rs587779023, rs63751021, rs63751480, rs267607772, rs267607773, rs587779024, rs63751653, rs587779027, rs267607767, rs587779029, rs63750706, rs63750385, rs267607774, rs267607778, rs267607780, rs587779034, rs63751711, rs267607784, rs587779035, rs63750823, rs63750822, rs267607787, rs63750303, rs63749839, rs63749827, rs267607789, rs267607790, rs267607791, rs267607786, rs267607771, rs267607795, rs267607794, rs267607788, rs267607799, rs267607801, rs587779045, rs63750034, rs587779047, rs63750216, rs63751707, rs63751598, rs267607803, rs267607777, rs63750144, rs267607805, rs63750547, rs63750489, rs63750993, rs587779054, rs63751259, rs63749926, rs63750796, rs587779058, rs63750745, rs63750582, rs180177084, rs587779866, rs200389141, rs587779950, rs587780104, rs587780183, rs587778536, rs587780683, rs587781554, rs267607712, rs587777627, rs587783057, rs730881734, rs41542214, rs730881273, rs786203456, rs786201990, rs786202767, rs748005072, rs786204317, rs786204318, rs797045117, rs63750549, rs863225383, rs863225384, rs863225373, rs863225376, rs863225377, rs863225378, rs863225379, rs863225380, rs863225381, rs63750059, rs267607823, rs864622457, rs869312767, rs869312753, rs876661059, rs876658915, rs876658923, rs876660860, rs876660822, rs876660458, rs876660214, rs876658657, rs876658247, rs876659226, rs876658821, rs876660589, rs876659068, rs876659681, rs876659608, rs878853794, rs878853778, rs878853780, rs878853785, rs886039423, rs886039424, rs1057517543, rs1057517541, rs756843954, rs1057517617, rs1057517558, rs1057519256, rs1060500689, rs764085979, rs1060500707, rs1060500699, rs1060500706, rs1060500703, rs1064795341, rs1064793607, rs1064794348, rs1064795441, rs1064794373, rs1064793172, rs1064794122, rs1064795515, rs1064794331, rs63750978, rs1114167435, rs1553641362, rs63751448, rs1553648029, rs1553648058, rs587778903, rs1553653237, rs1553664353, rs267607744, rs1553647995, rs1553648047, rs1553653084, rs1553663750, rs1553664436, rs1553488015, rs1553637293, rs63750310, rs63750443, rs63751596, rs1553646681, rs550890395, rs1064796057, rs1553642079, rs1553648023, rs587782087, rs746536721, rs1553653037, rs1248251121, rs1553646602, rs1434898623, rs1553665683, rs1553648068, rs1553645331, rs1553644123, rs1553658246, rs1553651299, rs1553648149, rs1553663159, rs1302248679, rs1553664119, rs1553658009, rs1553665977, rs1416171624, rs1553663834, rs1553664617, rs1553664702, rs1553647969, rs1553648040, rs1437454428, rs1553641273, rs63751101, rs1553646764, rs1553648225, rs1554082118, rs1553648201, rs1553638868, rs1553665866, rs376736188, rs1553642707, rs1553645226, rs1553652883, rs63751435, rs1553653115, rs1553653195, rs63750300, rs1553662622, rs1553658104, rs1553648220, rs1559544064, rs63750584, rs267608083, rs1559551570, rs1559575107, rs1559553501, rs1565986506, rs1559524405, rs1559553492, rs1559554339, rs1559588540, rs1559558071, rs761329565, rs1559521039, rs1559574795, rs1567221417, rs1559578422, rs1481129490, rs1570714352, rs779783209, rs1575376830, rs1575469070, rs1575537843, rs1575620443, rs1575621506, rs587779022, rs1575414904, rs1575449093, rs1575469505, rs1575536254, rs1575537933, rs1575632112, rs1575639851, rs1575441094, rs1575449402, rs267607831, rs2081922847, rs2083403132, rs2085415927, rs2085469647, rs2043913790, rs147542208
Papillary renal carcinoma	Papillary Renal Cell Carcinoma	rs5030823, rs2137087134, rs121913668, rs121913669, rs121913670, rs121913671, rs121913673, rs121913243, rs786202724	22138691
Renal carcinoma	Renal Cell Carcinoma, Conventional (Clear Cell) Renal Cell Carcinoma, Sarcomatoid Renal Cell Carcinoma, Collecting Duct Carcinoma of the Kidney	rs121913668, rs121913670, rs121913243, rs786202724	22138691
Schizophrenia	Schizophrenia	rs13447324, rs387906932, rs387906933, rs863223354, rs863223355, rs776061422, rs863223349, rs748809996, rs759748655, rs863223353, rs863223350, rs863223356, rs781821239, rs863223348, rs863223346, rs863223347, rs863223351, rs863223352, rs61734270, rs797045205, rs869312829, rs869312830, rs770913157, rs869312832, rs869312831, rs781720548, rs1262969313	21901269

Unknown
Disease term	Disease name	Evidence	References	Source
Chromophobe carcinoma	Chromophobe Renal Cell Carcinoma		22138691	ClinVar
Breast cancer	Breast cancer	Importantly, breast cancer patients bearing PRC2 LOF mutations displayed significantly worse prognosis compared with PRC2 wild-type patients		GWAS, CBGDA
Insomnia	Insomnia			GWAS

Associations from Text Mining
Disease Name	Relationship Type	References
Autism Spectrum Disorder	Associate	22503632, 28720872, 37012247
Autistic Disorder	Associate	22503632, 27824329
Developmental Disabilities	Associate	24372385
Epilepsy	Associate	24372385
Epilepsy Rolandic	Associate	24372385
Epilepsy rolandic with paroxysmal exercise induced dystonia and writer's cramp	Associate	24372385
Fragile X Syndrome	Associate	25692235
Glioblastoma	Associate	38019838
Heredodegenerative Disorders Nervous System	Associate	28720872