SHISA8

Summary

SHISA8 (shisa family member 8, HGNC:18351) is a protein-coding gene on chromosome 22q13.2, encoding Protein shisa-8 (B8ZZ34). May regulate trafficking and current kinetics of AMPA-type glutamate receptor (AMPAR) at synapses.

Predicted to be involved in regulation of short-term neuronal synaptic plasticity. Predicted to be located in membrane. Predicted to be part of AMPA glutamate receptor complex. Predicted to be active in dendritic spine membrane; postsynaptic density; and postsynaptic membrane.

Source: NCBI Gene 440829 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 73 total
• MANE Select transcript: NM_001207020

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18351
Approved symbol	SHISA8
Name	shisa family member 8
Location	22q13.2
Locus type	gene with protein product
Status	Approved
Aliases	Orf26
Ensembl gene	ENSG00000234965
Ensembl biotype	protein_coding
OMIM	617329
Entrez	440829

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000457093, ENST00000621082

RefSeq mRNA: 3 — MANE Select: NM_001207020 NM_001207020, NM_001353438, NM_001353439

CCDS: CCDS74872

Canonical transcript exons

ENST00000621082 — 4 exons

Exon	Start	End
ENSE00003713747	41909543	41910147
ENSE00003717219	41914138	41915074
ENSE00003729754	41910408	41910554
ENSE00003740750	41911216	41911349

Expression profiles

Bgee: expression breadth ubiquitous, 115 present calls, max score 94.49.

FANTOM5 (CAGE): breadth broad, TPM avg 0.6381 / max 97.3608, expressed in 206 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
194387	0.5311	173
194388	0.1069	43

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	94.49	gold quality
cerebellar cortex	UBERON:0002129	93.87	gold quality
cerebellar hemisphere	UBERON:0002245	93.84	gold quality
cerebellum	UBERON:0002037	93.31	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	80.92	gold quality
left adrenal gland cortex	UBERON:0035825	80.87	gold quality
cerebellar vermis	UBERON:0004720	80.70	gold quality
left adrenal gland	UBERON:0001234	80.53	gold quality
right adrenal gland	UBERON:0001233	80.29	gold quality
right adrenal gland cortex	UBERON:0035827	80.03	gold quality
adrenal cortex	UBERON:0001235	79.94	gold quality
oocyte	CL:0000023	78.41	gold quality
secondary oocyte	CL:0000655	77.90	gold quality
adrenal gland	UBERON:0002369	75.73	gold quality
apex of heart	UBERON:0002098	68.23	gold quality
right frontal lobe	UBERON:0002810	67.82	gold quality
anterior cingulate cortex	UBERON:0009835	66.69	gold quality
ileal mucosa	UBERON:0000331	66.65	gold quality
Brodmann (1909) area 9	UBERON:0013540	65.49	gold quality
tibialis anterior	UBERON:0001385	65.29	silver quality
spleen	UBERON:0002106	64.95	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	62.22	gold quality
pancreatic ductal cell	CL:0002079	61.87	silver quality
endothelial cell	CL:0000115	61.07	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	60.48	gold quality
right atrium auricular region	UBERON:0006631	60.24	gold quality
cardiac atrium	UBERON:0002081	59.62	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	59.30	gold quality
heart left ventricle	UBERON:0002084	59.15	gold quality
cardiac ventricle	UBERON:0002082	58.51	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-10855	yes	555.97
E-HCAD-30	yes	286.42
E-GEOD-137537	yes	6.06
E-ANND-3	no	2.20

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

6 targeting SHISA8, 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-4699-3P	99.71	70.15	3142
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-3158-3P	98.45	64.25	560
HSA-MIR-4518	98.12	66.82	1030
HSA-MIR-1266-5P	97.71	66.92	1052
HSA-MIR-3914	94.91	65.77	643

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	shisa9a	ENSDARG00000045145
danio_rerio	shisa9b	ENSDARG00000052642
danio_rerio	shisa8b	ENSDARG00000088204
danio_rerio		ENSDARG00000105972
mus_musculus	Shisa8	ENSMUSG00000096883
rattus_norvegicus	Shisa8	ENSRNOG00000049407

Paralogs (3): SHISA7 (ENSG00000187902), SHISA6 (ENSG00000188803), SHISA9 (ENSG00000237515)

Protein

Protein identifiers

Protein shisa-8 — B8ZZ34 (reviewed: B8ZZ34)

Alternative names: Shisa family member 8

All UniProt accessions (2): B8ZZ34, A0A2Q2RX16

UniProt curated annotations — full annotation on UniProt →

Function. May regulate trafficking and current kinetics of AMPA-type glutamate receptor (AMPAR) at synapses.

Subunit / interactions. Interacts with AMPAR subunits GRIA1 and GRIA2.

Subcellular location. Membrane.

Similarity. Belongs to the shisa family.

Isoforms (2)

UniProt ID	Names	Canonical?
B8ZZ34-1	2	yes
B8ZZ34-3	1

RefSeq proteins (3): NP_001193949, NP_001340367, NP_001340368 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026910	Shisa	Family
IPR053891	Shisa_N	Domain

Pfam: PF13908

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

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-B8ZZ34-F1	57.18	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 (1): 75

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 48 (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, BILD_E2F3_ONCOGENIC_SIGNATURE, GOBP_SYNAPTIC_SIGNALING, GOCC_NEURON_PROJECTION, 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, GOCC_POSTSYNAPTIC_MEMBRANE

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

GO Molecular Function (0):

GO Cellular Component (5): postsynaptic density (GO:0014069), AMPA glutamate receptor complex (GO:0032281), dendritic spine membrane (GO:0032591), postsynaptic membrane (GO:0045211), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
synaptic membrane	2
regulation of neuronal synaptic plasticity	1
asymmetric synapse	1
postsynaptic specialization	1
ionotropic glutamate receptor complex	1
neuron projection membrane	1
dendrite membrane	1
dendritic spine	1
postsynapse	1
cellular anatomical structure	1

Protein interactions and networks

STRING

478 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SHISA8	LDLRAD1	Q5T700	580
SHISA8	SNTN	A6NMZ2	517
SHISA8	CDHR3	Q6ZTQ4	454
SHISA8	MCIDAS	D6RGH6	445
SHISA8	RBM3	P98179	444
SHISA8	CFAP53	Q96M91	441
SHISA8	PRR18	Q8N4B5	438
SHISA8	SHISA9	B4DS77	433
SHISA8	CRYAB	P02511	418
SHISA8	MN1	Q10571	416
SHISA8	TTLL8	A6PVC2	380
SHISA8	HSPH1	Q92598	377
SHISA8	SHISAL2A	Q6UWV7	376
SHISA8	SHISA5	Q8N114	372
SHISA8	PHETA2	Q6ICB4	370
SHISA8	MEOX1	P50221	370

IntAct

0 interactions, top by confidence:

BioGRID (4): SHISA8 (Proximity Label-MS), SHISA8 (Positive Genetic), SHISA8 (Proximity Label-MS), SHISA8 (Protein-peptide)

ESM2 similar proteins: A0A0U1RQ45, A0A0U1RQS6, A0A2R8YCJ5, A2A699, A2AEV7, A6NGB7, A6NJG2, A6NKF7, A6NKL6, A6NL88, A8MVW0, A9JSM3, B2RU40, B8ZZ34, C9JH25, D4A9R4, J3QNX5, P0CG09, P98077, Q0VD38, Q14761, Q17QH7, Q29RK8, Q2KJ18, Q2M3V2, Q3SX20, Q5BJT1, Q5HZJ5, Q5RKR3, Q5T442, Q64697, Q69YZ2, Q6PB97, Q6PCT2, Q6UXK2, Q6ZMQ8, Q6ZVH7, Q6ZW31, Q80XF7, Q8BLS7

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

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	70
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

727 predictions. Top by Δscore:

Variant	Effect	Δscore
22:41914133:CTCA:C	donor_loss	1.0000
22:41914134:TCACC:T	donor_loss	1.0000
22:41914135:CA:C	donor_loss	1.0000
22:41914137:C:CT	donor_loss	1.0000
22:41910403:CTCA:C	donor_loss	0.9900
22:41910404:TCA:T	donor_loss	0.9900
22:41910405:CACCT:C	donor_loss	0.9900
22:41910406:A:AT	donor_loss	0.9900
22:41910407:C:CG	donor_loss	0.9900
22:41910407:CCTG:C	donor_gain	0.9900
22:41914136:A:AC	donor_gain	0.9900
22:41914137:C:CC	donor_gain	0.9900
22:41910406:A:AC	donor_gain	0.9800
22:41910407:C:CC	donor_gain	0.9800
22:41911346:CGCC:C	acceptor_gain	0.9800
22:41911348:CC:C	acceptor_gain	0.9800
22:41911349:CC:C	acceptor_gain	0.9800
22:41911350:C:CG	acceptor_loss	0.9800
22:41910400:CCACT:C	donor_loss	0.9700
22:41910401:CACTC:C	donor_loss	0.9700
22:41910402:ACTCA:A	donor_loss	0.9700
22:41911211:CTCA:C	donor_loss	0.9700
22:41911212:TCA:T	donor_loss	0.9700
22:41911213:CAC:C	donor_loss	0.9700
22:41911214:ACC:A	donor_loss	0.9700
22:41911215:C:CT	donor_loss	0.9700
22:41914137:CCTGG:C	donor_gain	0.9700
22:41911210:ACT:A	donor_loss	0.9500
22:41911345:GCGCC:G	acceptor_gain	0.9500
22:41911346:CGCCC:C	acceptor_gain	0.9500

AlphaMissense

2486 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:41914326:C:A	W114C	1.000
22:41914326:C:G	W114C	1.000
22:41914392:G:C	F92L	1.000
22:41914392:G:T	F92L	1.000
22:41914393:A:C	F92C	1.000
22:41914394:A:G	F92L	1.000
22:41914412:C:A	G86C	1.000
22:41914446:G:C	F74L	1.000
22:41914446:G:T	F74L	1.000
22:41914447:A:C	F74C	1.000
22:41914448:A:G	F74L	1.000
22:41914458:C:A	W70C	1.000
22:41914458:C:G	W70C	1.000
22:41914344:G:C	N108K	0.999
22:41914344:G:T	N108K	0.999
22:41914351:C:G	C106S	0.999
22:41914352:A:T	C106S	0.999
22:41914411:C:A	G86V	0.999
22:41914447:A:G	F74S	0.999
22:41914466:C:A	G68C	0.999
22:41914474:T:A	D65V	0.999
22:41914480:T:C	Y63C	0.999
22:41914228:C:T	G147D	0.998
22:41914328:A:G	W114R	0.998
22:41914328:A:T	W114R	0.998
22:41914352:A:G	C106R	0.998
22:41914387:C:T	C94Y	0.998
22:41914390:C:T	C93Y	0.998
22:41914393:A:G	F92S	0.998
22:41914397:G:A	R91C	0.998

dbSNP variants (sampled 300 via entrez): RS1000023058 (22:41914238 C>A), RS1000544479 (22:41913979 G>T), RS1001144427 (22:41912937 G>A), RS1001357290 (22:41909175 C>T), RS1001369367 (22:41915260 G>C), RS1001370198 (22:41916523 G>A), RS1001549318 (22:41911094 C>T), RS1001609840 (22:41910819 C>A), RS1002422575 (22:41913598 G>A,C), RS1002435746 (22:41914878 C>G), RS1002488695 (22:41916327 G>T), RS1002539169 (22:41909874 C>G), RS1002614435 (22:41909574 C>T), RS1003044931 (22:41916573 A>G,T), RS1003143698 (22:41910086 G>A)

Disease associations

OMIM: gene MIM:617329 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST002539_95	Schizophrenia	2.000000e-09
GCST006803_13	Schizophrenia	2.000000e-14
GCST010132_1	Processed meat consumption	1.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008111	diet measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

9 total (human), top 9 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	decreases expression, increases abundance, increases expression	2
Allergens	increases expression	1
Demecolcine	decreases expression	1
Methyl Methanesulfonate	increases expression	1
Smoke	increases abundance, increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Triclosan	increases expression	1
Vincristine	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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