SHANK2 SH3 and multiple ankyrin repeat domains 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: SHANK2provided by HGNC
Official Full Name: SH3 and multiple ankyrin repeat domains 2provided by HGNC
Primary source: HGNC:HGNC:14295
See related: Ensembl:ENSG00000162105 MIM:603290; AllianceGenome:HGNC:14295
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: SHANK; AUTS17; CORTBP1; CTTNBP1; ProSAP1; SPANK-3
Summary: This gene encodes a protein that is a member of the Shank family of synaptic proteins that may function as molecular scaffolds in the postsynaptic density of excitatory synapses. Shank proteins contain multiple domains for protein-protein interaction, including ankyrin repeats, and an SH3 domain. This particular family member contains a PDZ domain, a consensus sequence for cortactin SH3 domain-binding peptides and a sterile alpha motif. The alternative splicing demonstrated in Shank genes has been suggested as a mechanism for regulating the molecular structure of Shank and the spectrum of Shank-interacting proteins in the postsynaptic densities of the adult and developing brain. Alterations in the encoded protein may be associated with susceptibility to autism spectrum disorder. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2014]
Expression: Broad expression in brain (RPKM 4.2), kidney (RPKM 2.6) and 18 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 11q13.3-q13.4

Exon count:: 34

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	11	NC_000011.10 (70467854..71253228, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	11	NC_060935.1 (70488279..71179617, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	11	NC_000011.9 (70313959..70963623, complement)

Chromosome 11 - NC_000011.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Structural deficits in key domains of Shank2 lead to alterations in postsynaptic nanoclusters and to a neurodevelopmental disorder in humans.
Title: Structural deficits in key domains of Shank2 lead to alterations in postsynaptic nanoclusters and to a neurodevelopmental disorder in humans.
Autism patient-derived SHANK2B[Y29X] mutation affects the development of ALDH1A1 negative dopamine neuron.
Title: Autism patient-derived SHANK2B(Y29X) mutation affects the development of ALDH1A1 negative dopamine neuron.
Expression profiles of the autism-related SHANK proteins in the human brain.
Title: Expression profiles of the autism-related SHANK proteins in the human brain.
Remote ischemic conditioning alleviates chronic cerebral hypoperfusion-induced cognitive decline and synaptic dysfunction via the miR-218a-5p/SHANK2 pathway.
Title: Remote ischemic conditioning alleviates chronic cerebral hypoperfusion-induced cognitive decline and synaptic dysfunction via the miR-218a-5p/SHANK2 pathway.
Genetic Analysis Implicates Dysregulation of SHANK2 in Renal Cell Carcinoma Progression.
Title: Genetic Analysis Implicates Dysregulation of SHANK2 in Renal Cell Carcinoma Progression.
Somatic structural variation targets neurodevelopmental genes and identifies SHANK2 as a tumor suppressor in neuroblastoma.
Title: Somatic structural variation targets neurodevelopmental genes and identifies SHANK2 as a tumor suppressor in neuroblastoma.
SHANK2 mutations impair apoptosis, proliferation and neurite outgrowth during early neuronal differentiation in SH-SY5Y cells.
Title: SHANK2 mutations impair apoptosis, proliferation and neurite outgrowth during early neuronal differentiation in SH-SY5Y cells.
Identification of SHANK2 Pathogenic Variants in a Chinese Uygur Population with Schizophrenia.
Title: Identification of SHANK2 Pathogenic Variants in a Chinese Uygur Population with Schizophrenia.
meQTL and ncRNA functional analyses of 102 GWAS-SNPs associated with depression implicate HACE1 and SHANK2 genes.
Title: meQTL and ncRNA functional analyses of 102 GWAS-SNPs associated with depression implicate HACE1 and SHANK2 genes.
Phenotypic spectrum of SHANK2-related neurodevelopmental disorder.
Title: Phenotypic spectrum of SHANK2-related neurodevelopmental disorder.

Submit: New GeneRIF Correction See all GeneRIFs (29)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Autism spectrum disorder MedGen: C1510586 GeneReviews: Not available	Compare labs
Autism, susceptibility to, 17 MedGen: C3150693 OMIM: 613436 GeneReviews: Not available	Compare labs

Copy number response

Description
Copy number response Haploinsufficency Sufficient evidence for dosage pathogenicity (Last evaluated 2023-10-26) ClinGen Genome Curation PagePubMed Triplosensitivity No evidence available (Last evaluated 2023-10-26) ClinGen Genome Curation Page

EBI GWAS Catalog

Description
A genome-wide association study of recipient genotype and medium-term kidney allograft function. EBI GWAS Catalog EBI GWAS CatalogPubMed
Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population. EBI GWAS Catalog EBI GWAS CatalogPubMed
Preliminary evidence of genetic determinants of adiponectin response to fenofibrate in the Genetics of Lipid Lowering Drugs and Diet Network. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

STS-T84114 (e-PCR)
- UniSTS:13075

D11S3627 (e-PCR)
- UniSTS:152864

G48072 (e-PCR)
- UniSTS:108836

RH76480 (e-PCR)
- UniSTS:89134

D11S1126 (e-PCR)
- UniSTS:67377

D11S971 (e-PCR), detects polymorphism
- UniSTS:91705

D11S4057 (e-PCR)
- UniSTS:34361

D1S2718 (e-PCR)
- UniSTS:42809

A008P15 (e-PCR)
- UniSTS:10811

WIAF-2195 (e-PCR)
- UniSTS:12356

WI-14325 (e-PCR)
- UniSTS:1380

RH36629 (e-PCR)
- UniSTS:9574

SHGC-141871 (e-PCR)
- UniSTS:171129

NoName (e-PCR)
- UniSTS:24206

SHGC-146094 (e-PCR)
- UniSTS:175000

D11S2288E (e-PCR)
- UniSTS:47770

SHGC-154075 (e-PCR)
- UniSTS:182433

G17560 (e-PCR)
- UniSTS:71335

RH124032 (e-PCR)
- UniSTS:134572

RH36039 (e-PCR)
- UniSTS:10416

D11S4139 (e-PCR)
- UniSTS:62908

NoName (e-PCR)
- UniSTS:485571

D11S1975 (e-PCR)
- UniSTS:14535

RH66696 (e-PCR)
- UniSTS:80855

G59906 (e-PCR)
- UniSTS:137188

SHGC-106206 (e-PCR)
- UniSTS:169701

RH48629 (e-PCR)
- UniSTS:41704

RH91142 (e-PCR)
- UniSTS:83693

D11S579 (e-PCR)
- UniSTS:90101

SHGC-78908 (e-PCR)
- UniSTS:95735

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables SH3 domain binding	IEA Inferred from Electronic Annotation more info
enables ionotropic glutamate receptor binding	IBA Inferred from Biological aspect of Ancestor more info
enables ionotropic glutamate receptor binding	ISS Inferred from Sequence or Structural Similarity more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables structural constituent of postsynaptic density	IEA Inferred from Electronic Annotation more info
enables synaptic receptor adaptor activity	IBA Inferred from Biological aspect of Ancestor more info
enables synaptic receptor adaptor activity	NAS Non-traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
involved_in adult behavior	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in adult locomotory behavior	IEA Inferred from Electronic Annotation more info
involved_in associative learning	IEA Inferred from Electronic Annotation more info
involved_in learning	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in long-term synaptic depression	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in long-term synaptic potentiation	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in maintenance of postsynaptic density structure	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of hippo signaling	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of cell population proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of postsynapse organization	IEA Inferred from Electronic Annotation more info
involved_in response to nutrient	IEA Inferred from Electronic Annotation more info
involved_in response to xenobiotic stimulus	IEA Inferred from Electronic Annotation more info
involved_in social behavior	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in synapse assembly	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in vocalization behavior	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
located_in apical plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in brush border membrane	ISS Inferred from Sequence or Structural Similarity more info
is_active_in cellular_component	ND No biological Data available more info
located_in ciliary membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in cytosol	TAS Traceable Author Statement more info
is_active_in dendritic spine	IBA Inferred from Biological aspect of Ancestor more info
located_in dendritic spine	ISS Inferred from Sequence or Structural Similarity more info
located_in glutamatergic synapse	IEA Inferred from Electronic Annotation more info
located_in growth cone	ISS Inferred from Sequence or Structural Similarity more info
located_in hippocampal mossy fiber to CA3 synapse	IEA Inferred from Electronic Annotation more info
colocalizes_with neurofilament	ISS Inferred from Sequence or Structural Similarity more info
located_in neuron projection	ISS Inferred from Sequence or Structural Similarity more info
located_in neuronal cell body	ISS Inferred from Sequence or Structural Similarity more info
located_in photoreceptor inner segment	ISS Inferred from Sequence or Structural Similarity more info
located_in photoreceptor outer segment	ISS Inferred from Sequence or Structural Similarity more info
located_in plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
is_active_in postsynaptic density	IBA Inferred from Biological aspect of Ancestor more info
located_in postsynaptic density	ISS Inferred from Sequence or Structural Similarity more info
colocalizes_with postsynaptic membrane	IBA Inferred from Biological aspect of Ancestor more info
colocalizes_with postsynaptic membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in presynaptic active zone	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: SH3 and multiple ankyrin repeat domains protein 2

Names: GKAP/SAPAP interacting protein; cortactin SH3 domain-binding protein; cortactin-binding protein 1; proline-rich synapse associated protein 1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_042866.2 RefSeqGene

Range

5651..690374

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001379226.1 → NP_001366155.1 SH3 and multiple ankyrin repeat domains protein 2 isoform 3

Status: REVIEWED

Source sequence(s)

AP000590, AP001271, AP003783

Consensus CDS

CCDS91527.1

UniProtKB/TrEMBL

A6NHU9, C0SPH0

Related

ENSP00000499561.1, ENST00000656230.1

Conserved Domains (4) summary

cd09506
Location:1403 → 1468

SAM_Shank1,2,3; SAM domain of Shank1,2,3 family proteins

cd11983
Location:150 → 201

SH3_Shank2; Src homology 3 domain of SH3 and multiple ankyrin repeat domains protein 2

cd00992
Location:245 → 338

PDZ_signaling; PDZ domain found in a variety of Eumetazoan signaling molecules, often in tandem arrangements. May be responsible for specific protein-protein interactions, as most PDZ domains bind C-terminal polypeptides, and binding to internal (non-C-terminal) ...

TIGR00600
Location:910 → 1122

rad2; DNA excision repair protein (rad2)
NM_012309.5 → NP_036441.2 SH3 and multiple ankyrin repeat domains protein 2 isoform 1

See identical proteins and their annotated locations for NP_036441.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longer isoform (1).

Source sequence(s)

AC234421, AP000590, AP001271, AP003783, AP004370, AP005401

UniProtKB/Swiss-Prot

C0SPG8, C0SPG9, Q3Y8G9, Q52LK2, Q9UKP1, Q9UPX8

Related

ENSP00000469689.2, ENST00000601538.6

Conserved Domains (8) summary

cd09506
Location:1782 → 1847

SAM_Shank1,2,3; SAM domain of Shank1,2,3 family proteins

cd11983
Location:529 → 580

SH3_Shank2; Src homology 3 domain of SH3 and multiple ankyrin repeat domains protein 2

COG0666
Location:201 → 365

ANKYR; Ankyrin repeat [Signal transduction mechanisms]

cd00992
Location:624 → 717

PDZ_signaling; PDZ domain found in a variety of Eumetazoan signaling molecules, often in tandem arrangements. May be responsible for specific protein-protein interactions, as most PDZ domains bind C-terminal polypeptides, and binding to internal (non-C-terminal) ...

TIGR00600
Location:1289 → 1501

rad2; DNA excision repair protein (rad2)

sd00045
Location:230 → 261

ANK; ANK repeat [structural motif]

cd17176
Location:55 → 142

FERM_F0_SHANK2; FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F0 sub-domain, found in SH3 and multiple ankyrin repeat domains protein 2 (SHANK2)

pfam12796
Location:335 → 398

Ank_2; Ankyrin repeats (3 copies)
NM_133266.5 → NP_573573.2 SH3 and multiple ankyrin repeat domains protein 2 isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in its 5' UTR, lacks a portion of the 5' coding region, and uses an alternate start codon, compared to variant 1. The encoded isoform (2) has a shorter and distinct N-terminus, compared to isoform 1.

Source sequence(s)

AP000590, AP001271

UniProtKB/TrEMBL

A6NHU9, C0SPH0

Related

ENSP00000345193.7, ENST00000338508.9

Conserved Domains (3) summary

cd09506
Location:1194 → 1259

SAM_Shank1,2,3; SAM domain of Shank1,2,3 family proteins

smart00454
Location:1195 → 1261

SAM; Sterile alpha motif

cd00992
Location:36 → 129

PDZ_signaling; PDZ domain found in a variety of Eumetazoan signaling molecules, often in tandem arrangements. May be responsible for specific protein-protein interactions, as most PDZ domains bind C-terminal polypeptides, and binding to internal (non-C-terminal) ...

RNA

NR_110766.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (3) uses an alternate splice site at an internal exon and lacks two internal exons, compared to variant 1. This variant is represented as non-coding because the predicted protein does not meet RefSeq quality criteria.

Source sequence(s)

AP000590, AP001271

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000011.10 Reference GRCh38.p14 Primary Assembly

Range

70467854..71253228 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047426616.1 → XP_047282572.1 SH3 and multiple ankyrin repeat domains protein 2 isoform X3
XM_047426618.1 → XP_047282574.1 SH3 and multiple ankyrin repeat domains protein 2 isoform X3
XM_047426614.1 → XP_047282570.1 SH3 and multiple ankyrin repeat domains protein 2 isoform X3
XM_047426619.1 → XP_047282575.1 SH3 and multiple ankyrin repeat domains protein 2 isoform X4
XM_047426611.1 → XP_047282567.1 SH3 and multiple ankyrin repeat domains protein 2 isoform X3
XM_017017389.2 → XP_016872878.1 SH3 and multiple ankyrin repeat domains protein 2 isoform X2
XM_047426620.1 → XP_047282576.1 SH3 and multiple ankyrin repeat domains protein 2 isoform X4
XM_047426612.1 → XP_047282568.1 SH3 and multiple ankyrin repeat domains protein 2 isoform X3
XM_047426615.1 → XP_047282571.1 SH3 and multiple ankyrin repeat domains protein 2 isoform X3
XM_047426613.1 → XP_047282569.1 SH3 and multiple ankyrin repeat domains protein 2 isoform X3
XM_047426617.1 → XP_047282573.1 SH3 and multiple ankyrin repeat domains protein 2 isoform X3
XM_017017388.2 → XP_016872877.1 SH3 and multiple ankyrin repeat domains protein 2 isoform X1

UniProtKB/Swiss-Prot

C0SPG8, C0SPG9, Q3Y8G9, Q52LK2, Q9UKP1, Q9UPX8

Conserved Domains (8) summary

cd09506
Location:1782 → 1847

SAM_Shank1,2,3; SAM domain of Shank1,2,3 family proteins

cd11983
Location:529 → 580

SH3_Shank2; Src homology 3 domain of SH3 and multiple ankyrin repeat domains protein 2

COG0666
Location:201 → 365

ANKYR; Ankyrin repeat [Signal transduction mechanisms]

cd00992
Location:624 → 717

PDZ_signaling; PDZ domain found in a variety of Eumetazoan signaling molecules, often in tandem arrangements. May be responsible for specific protein-protein interactions, as most PDZ domains bind C-terminal polypeptides, and binding to internal (non-C-terminal) ...

TIGR00600
Location:1289 → 1501

rad2; DNA excision repair protein (rad2)

sd00045
Location:230 → 261

ANK; ANK repeat [structural motif]

cd17176
Location:55 → 142

FERM_F0_SHANK2; FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F0 sub-domain, found in SH3 and multiple ankyrin repeat domains protein 2 (SHANK2)

pfam12796
Location:335 → 398

Ank_2; Ankyrin repeats (3 copies)
XM_047426622.1 → XP_047282578.1 SH3 and multiple ankyrin repeat domains protein 2 isoform X6
XM_047426621.1 → XP_047282577.1 SH3 and multiple ankyrin repeat domains protein 2 isoform X5
XM_017017390.2 → XP_016872879.1 SH3 and multiple ankyrin repeat domains protein 2 isoform X7

UniProtKB/TrEMBL

A0A590UJ45, A6NHU9, C0SPH0

Related

ENSP00000499270.1, ENST00000659264.1

Alternate T2T-CHM13v2.0

Genomic

NC_060935.1 Alternate T2T-CHM13v2.0

Range

70488279..71179617 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054368112.1 → XP_054224087.1 SH3 and multiple ankyrin repeat domains protein 2 isoform X3
XM_054368114.1 → XP_054224089.1 SH3 and multiple ankyrin repeat domains protein 2 isoform X3
XM_054368110.1 → XP_054224085.1 SH3 and multiple ankyrin repeat domains protein 2 isoform X3
XM_054368115.1 → XP_054224090.1 SH3 and multiple ankyrin repeat domains protein 2 isoform X4
XM_054368107.1 → XP_054224082.1 SH3 and multiple ankyrin repeat domains protein 2 isoform X3
XM_054368106.1 → XP_054224081.1 SH3 and multiple ankyrin repeat domains protein 2 isoform X2
XM_054368116.1 → XP_054224091.1 SH3 and multiple ankyrin repeat domains protein 2 isoform X4
XM_054368108.1 → XP_054224083.1 SH3 and multiple ankyrin repeat domains protein 2 isoform X3
XM_054368111.1 → XP_054224086.1 SH3 and multiple ankyrin repeat domains protein 2 isoform X3
XM_054368109.1 → XP_054224084.1 SH3 and multiple ankyrin repeat domains protein 2 isoform X3
XM_054368105.1 → XP_054224080.1 SH3 and multiple ankyrin repeat domains protein 2 isoform X1

UniProtKB/Swiss-Prot

C0SPG8, C0SPG9, Q3Y8G9, Q52LK2, Q9UKP1, Q9UPX8
XM_054368113.1 → XP_054224088.1 SH3 and multiple ankyrin repeat domains protein 2 isoform X3
XM_054368118.1 → XP_054224093.1 SH3 and multiple ankyrin repeat domains protein 2 isoform X6
XM_054368117.1 → XP_054224092.1 SH3 and multiple ankyrin repeat domains protein 2 isoform X5
XM_054368119.1 → XP_054224094.1 SH3 and multiple ankyrin repeat domains protein 2 isoform X7

UniProtKB/TrEMBL

A0A590UJ45