SHISA9

Summary

SHISA9 (shisa family member 9, HGNC:37231) is a protein-coding gene on chromosome 16p13.12, encoding Protein shisa-9 (B4DS77). Regulator of short-term neuronal synaptic plasticity in the dentate gyrus.

Predicted to enable PDZ domain binding activity. Predicted to be involved in regulation of postsynaptic neurotransmitter receptor activity and regulation of short-term neuronal synaptic plasticity. Predicted to act upstream of or within regulation of AMPA receptor activity. Predicted to be located in synapse. Predicted to be part of AMPA glutamate receptor complex. Predicted to be active in dendritic spine membrane; glutamatergic synapse; and postsynaptic density membrane.

Source: NCBI Gene 729993 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 66 total
• MANE Select transcript: NM_001145204

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:37231
Approved symbol	SHISA9
Name	shisa family member 9
Location	16p13.12
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000237515
Ensembl biotype	protein_coding
OMIM	613346
Entrez	729993

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 2 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000423335, ENST00000482916, ENST00000558583, ENST00000566106

RefSeq mRNA: 2 — MANE Select: NM_001145204 NM_001145204, NM_001145205

CCDS: CCDS45417, CCDS45418

Canonical transcript exons

ENST00000558583 — 5 exons

Exon	Start	End
ENSE00001704250	13213253	13213300
ENSE00001716508	12916688	12916815
ENSE00002556335	13235030	13240416
ENSE00003638322	13203394	13203549
ENSE00003847034	12901598	12902627

Expression profiles

Bgee: expression breadth ubiquitous, 151 present calls, max score 92.72.

FANTOM5 (CAGE): breadth broad, TPM avg 5.1953 / max 172.9776, expressed in 535 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
152834	2.5856	463
152833	1.6022	394
152835	1.0076	382

Top tissues by expression

235 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	92.72	gold quality
lateral nuclear group of thalamus	UBERON:0002736	91.68	gold quality
prefrontal cortex	UBERON:0000451	82.13	gold quality
nucleus accumbens	UBERON:0001882	79.24	gold quality
entorhinal cortex	UBERON:0002728	78.97	gold quality
buccal mucosa cell	CL:0002336	78.74	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	78.50	gold quality
frontal cortex	UBERON:0001870	78.39	gold quality
dorsal plus ventral thalamus	UBERON:0001897	78.11	gold quality
neocortex	UBERON:0001950	78.11	gold quality
Brodmann (1909) area 9	UBERON:0013540	77.66	gold quality
anterior cingulate cortex	UBERON:0009835	77.65	gold quality
Brodmann (1909) area 46	UBERON:0006483	77.12	gold quality
cerebral cortex	UBERON:0000956	76.92	gold quality
superior frontal gyrus	UBERON:0002661	76.81	gold quality
caudate nucleus	UBERON:0001873	76.29	gold quality
temporal lobe	UBERON:0001871	75.37	gold quality
hypothalamus	UBERON:0001898	75.26	gold quality
putamen	UBERON:0001874	75.20	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	75.19	silver quality
postcentral gyrus	UBERON:0002581	74.95	gold quality
parietal lobe	UBERON:0001872	74.86	gold quality
forebrain	UBERON:0001890	74.39	gold quality
amygdala	UBERON:0001876	73.62	gold quality
substantia nigra pars compacta	UBERON:0001965	73.15	silver quality
right frontal lobe	UBERON:0002810	73.12	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	73.02	gold quality
superior vestibular nucleus	UBERON:0007227	72.30	gold quality
Ammon’s horn	UBERON:0001954	71.64	gold quality
subthalamic nucleus	UBERON:0001906	71.53	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.18
E-MTAB-6386	no	10.39
E-CURD-112	no	3.42
E-MTAB-9543	no	1.22

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

219 targeting SHISA9, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-6793-5P	99.97	65.95	758
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-6508-5P	99.92	70.67	2465

Literature-anchored findings (GeneRIF, showing 1)

• Functionally characterizes the homologous mouse gene. (PMID:20185686)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Shisa9	ENSMUSG00000022494
rattus_norvegicus	Shisa9	ENSRNOG00000063400

Paralogs (3): SHISA7 (ENSG00000187902), SHISA6 (ENSG00000188803), SHISA8 (ENSG00000234965)

Protein

Protein identifiers

Protein shisa-9 — B4DS77 (reviewed: B4DS77)

All UniProt accessions (1): B4DS77

UniProt curated annotations — full annotation on UniProt →

Function. Regulator of short-term neuronal synaptic plasticity in the dentate gyrus. Associates with AMPA receptors (ionotropic glutamate receptors) in synaptic spines and promotes AMPA receptor desensitization at excitatory synapses.

Subunit / interactions. Component of some AMPA receptors (ionotropic glutamate receptors) complex, at least composed of some AMPA receptor (GRIA1, GRIA2 and/or GRIA3), CACNG2 and SHISA9, as well as low level of DLG4.

Subcellular location. Cell projection. Dendritic spine membrane. Synapse.

Similarity. Belongs to the shisa family. SHISA9 subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
B4DS77-1	1	yes
B4DS77-2	2
B4DS77-3	3

RefSeq proteins (2): NP_001138676, NP_001138677 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026910	Shisa	Family
IPR053891	Shisa_N	Domain

Pfam: PF13908

UniProt features (13 total): splice variant 3, glycosylation site 3, topological domain 2, signal peptide 1, chain 1, transmembrane region 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-B4DS77-F1	57.01	0.14

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Glycosylation sites (3): 45, 89, 116

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 119 (showing top): GOBP_REGULATION_OF_NEURONAL_SYNAPTIC_PLASTICITY, GOBP_REGULATION_OF_SHORT_TERM_NEURONAL_SYNAPTIC_PLASTICITY, GOBP_CELL_CELL_SIGNALING, GOBP_REGULATION_OF_SYNAPTIC_PLASTICITY, GOBP_SYNAPTIC_SIGNALING, FONTAINE_PAPILLARY_THYROID_CARCINOMA_DN, GOCC_NEURON_PROJECTION, RIGGI_EWING_SARCOMA_PROGENITOR_UP, GOCC_PLASMA_MEMBRANE_SIGNALING_RECEPTOR_COMPLEX, GOCC_CELL_PROJECTION_MEMBRANE, GOCC_POSTSYNAPSE, GOCC_AMPA_GLUTAMATE_RECEPTOR_COMPLEX, GOCC_NEURON_SPINE, GOCC_LEADING_EDGE_MEMBRANE, GOCC_SYNAPSE

GO Biological Process (1): regulation of short-term neuronal synaptic plasticity (GO:0048172)

GO Molecular Function (1): PDZ domain binding (GO:0030165)

GO Cellular Component (11): ionotropic glutamate receptor complex (GO:0008328), postsynaptic density (GO:0014069), AMPA glutamate receptor complex (GO:0032281), dendritic spine membrane (GO:0032591), synapse (GO:0045202), postsynaptic membrane (GO:0045211), postsynaptic density membrane (GO:0098839), glutamatergic synapse (GO:0098978), plasma membrane (GO:0005886), membrane (GO:0016020), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
synaptic membrane	2
cellular anatomical structure	2
regulation of neuronal synaptic plasticity	1
protein domain specific binding	1
monoatomic ion channel complex	1
neurotransmitter receptor complex	1
asymmetric synapse	1
postsynaptic specialization	1
ionotropic glutamate receptor complex	1
neuron projection membrane	1
dendrite membrane	1
dendritic spine	1
cell junction	1
postsynapse	1
postsynaptic density	1
postsynaptic membrane	1
postsynaptic specialization membrane	1
synapse	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

628 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SHISA9	GRIA1	P42261	946
SHISA9	CACNG2	Q9Y698	906
SHISA9	GSG1L	Q6UXU4	860
SHISA9	CNIH2	Q6PI25	826
SHISA9	CNIH4	Q9P003	813
SHISA9	CACNG8	Q8WXS5	812
SHISA9	CNIH1	O95406	734
SHISA9	GRIA4	P48058	717
SHISA9	DLG4	P78352	706
SHISA9	SYNDIG1	Q9H7V2	705
SHISA9	GRIA2	P42262	506
SHISA9	NETO1	Q8TDF5	485
SHISA9	GSG1L2	A8MUP6	474
SHISA9	CNIH3	Q8TBE1	454
SHISA9	SHISA8	B8ZZ34	433

IntAct

2 interactions, top by confidence:

A	B	Type	Score
SHISA9	SPTAN1	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (3): SHISA9 (Affinity Capture-RNA), SPTAN1 (Proximity Label-MS), SHISA9 (Protein-RNA)

ESM2 similar proteins: A0JPB5, A2A699, A5PLA0, A6QPA0, A8MVW0, B0BN44, B4DS77, D3ZZP4, O35451, P04921, P28906, Q06186, Q08DP3, Q08EA8, Q13113, Q1LVN1, Q28270, Q5F3A4, Q5FVQ7, Q5HZE8, Q5R5B8, Q60846, Q640B5, Q64314, Q7TNI2, Q810F0, Q86VZ4, Q8C4Q9, Q8CB67, Q8IUW5, Q8K064, Q8K201, Q8K2J7, Q8NC54, Q8NEA5, Q8R138, Q8TBP5, Q8WWG9, Q96L08, Q99941

Diamond homologs: A0PJX4, A2RV66, A6QPA0, A7MC48, B3DHW5, B4DS77, J3QNX5, Q2WFL8, Q3UPR0, Q5BLC7, Q6UWI4, Q7T0Z7, Q8QZV2, Q9CZN4, Q9D7I0, A6NL88, B8ZZ34, Q3UH99, Q6ZSJ9, Q8C3Q5, Q8CA71, Q96DD7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

66 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	62
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2717 predictions. Top by Δscore:

Variant	Effect	Δscore
16:12916682:TTTCA:T	acceptor_loss	1.0000
16:12916683:TTCA:T	acceptor_loss	1.0000
16:12916684:TCAG:T	acceptor_loss	1.0000
16:12916685:CAG:C	acceptor_loss	1.0000
16:12916686:A:AG	acceptor_gain	1.0000
16:12916686:A:AT	acceptor_loss	1.0000
16:12916686:AG:A	acceptor_gain	1.0000
16:12916686:AGG:A	acceptor_gain	1.0000
16:12916687:G:GT	acceptor_gain	1.0000
16:12916687:GG:G	acceptor_gain	1.0000
16:12916687:GGG:G	acceptor_gain	1.0000
16:12916687:GGGCC:G	acceptor_gain	1.0000
16:12916811:TCTTC:T	donor_gain	1.0000
16:12916812:CTTC:C	donor_gain	1.0000
16:12916812:CTTCG:C	donor_loss	1.0000
16:12916813:TTC:T	donor_gain	1.0000
16:12916814:TC:T	donor_gain	1.0000
16:12916815:CG:C	donor_loss	1.0000
16:12916816:G:GG	donor_gain	1.0000
16:12916816:GTA:G	donor_loss	1.0000
16:12916817:TA:T	donor_loss	1.0000
16:12916818:A:AC	donor_loss	1.0000
16:12916819:A:AC	donor_loss	1.0000
16:13203386:A:AG	acceptor_gain	1.0000
16:13203387:C:G	acceptor_gain	1.0000
16:13203389:TCCA:T	acceptor_loss	1.0000
16:13203391:CA:C	acceptor_loss	1.0000
16:13203392:A:AG	acceptor_gain	1.0000
16:13203392:A:C	acceptor_loss	1.0000
16:13203392:AGAT:A	acceptor_gain	1.0000

AlphaMissense

2774 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:12902284:T:A	C74S	1.000
16:12902284:T:C	C74R	1.000
16:12902285:G:A	C74Y	1.000
16:12902285:G:C	C74S	1.000
16:12902285:G:T	C74F	1.000
16:12902286:C:G	C74W	1.000
16:12902290:G:C	G76R	1.000
16:12902290:G:T	G76C	1.000
16:12902291:G:A	G76D	1.000
16:12902291:G:T	G76V	1.000
16:12902293:T:C	Y77H	1.000
16:12902294:A:G	Y77C	1.000
16:12902296:T:C	F78L	1.000
16:12902297:T:G	F78C	1.000
16:12902298:C:A	F78L	1.000
16:12902298:C:G	F78L	1.000
16:12902299:G:A	D79N	1.000
16:12902299:G:C	D79H	1.000
16:12902299:G:T	D79Y	1.000
16:12902300:A:C	D79A	1.000
16:12902300:A:G	D79G	1.000
16:12902300:A:T	D79V	1.000
16:12902301:T:A	D79E	1.000
16:12902301:T:G	D79E	1.000
16:12902307:G:A	M81I	1.000
16:12902307:G:C	M81I	1.000
16:12902307:G:T	M81I	1.000
16:12902308:G:C	G82R	1.000
16:12902308:G:T	G82C	1.000
16:12902309:G:T	G82V	1.000

dbSNP variants (sampled 300 via entrez): RS1000002012 (16:13514252 C>A,T), RS1000005778 (16:13115777 T>A,C), RS1000014117 (16:12945835 C>T), RS1000015305 (16:13346367 G>T), RS1000016337 (16:13202924 A>G), RS1000016949 (16:13274315 C>T), RS1000020622 (16:13344099 A>G), RS1000022184 (16:13080337 C>A,T), RS1000022477 (16:12959312 T>G), RS1000027539 (16:13104097 G>A), RS1000029889 (16:13241585 G>T), RS1000033954 (16:13040252 A>G), RS1000038457 (16:13115943 A>T), RS1000042555 (16:12945065 C>A), RS1000042599 (16:13048799 G>T)

Disease associations

OMIM: gene MIM:613346 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST002936_5	Cadmium levels	6.000000e-06
GCST002938_25	Copper levels	4.000000e-06
GCST005839_17	Depression	2.000000e-08
GCST006143_5	Bone mineral density (total hip)	1.000000e-06
GCST006620_11	Self-rated health	5.000000e-08
GCST006665_12	Social science traits (pleiotropy) (HIPO component 1)	4.000000e-08
GCST008150_8	Triglyceride levels	9.000000e-06
GCST008839_112	Height	7.000000e-10
GCST009600_47	Anorexia nervosa, attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, or Tourette syndrome (pleiotropy)	1.000000e-08
GCST012796_9	Sjögren’s syndrome	1.000000e-06

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0007702	hip bone mineral density
EFO:0004778	self rated health
EFO:0007006	depressive symptom measurement
EFO:0007660	neuroticism measurement
EFO:0007869	wellbeing measurement
EFO:0004530	triglyceride measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases methylation, increases expression	5
Benzo(a)pyrene	affects methylation, increases methylation	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tobacco Smoke Pollution	decreases expression	2
methylmercuric chloride	increases expression	1
sodium arsenite	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases reaction, increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	affects cotreatment, decreases methylation	1
jinfukang	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	affects methylation	1
Cisplatin	decreases expression	1
Fluorouracil	increases expression	1
Lipopolysaccharides	increases expression, decreases reaction	1
Malathion	increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Smoke	increases expression	1
Aflatoxin M1	decreases expression	1
Cadmium Chloride	increases expression	1
Okadaic Acid	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.