SHISA2

Summary

SHISA2 (shisa family member 2, HGNC:20366) is a protein-coding gene on chromosome 13q12.13, encoding Protein shisa-2 homolog (Q6UWI4). Plays an essential role in the maturation of presomitic mesoderm cells by individual attenuation of both FGF and WNT signaling.

Predicted to be involved in negative regulation of Wnt signaling pathway and negative regulation of fibroblast growth factor receptor signaling pathway. Predicted to be located in endoplasmic reticulum membrane. Predicted to be active in endoplasmic reticulum.

Source: NCBI Gene 387914 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 58 total
• MANE Select transcript: NM_001007538

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20366
Approved symbol	SHISA2
Name	shisa family member 2
Location	13q12.13
Locus type	gene with protein product
Status	Approved
Aliases	bA398O19.2, PRO28631, WGAR9166, hShisa
Ensembl gene	ENSG00000180730
Ensembl biotype	protein_coding
OMIM	617324
Entrez	387914

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000319420

RefSeq mRNA: 1 — MANE Select: NM_001007538 NM_001007538

CCDS: CCDS31951

Canonical transcript exons

ENST00000319420 — 2 exons

Exon	Start	End
ENSE00001259752	26044597	26047066
ENSE00001259759	26050642	26052016

Expression profiles

Bgee: expression breadth ubiquitous, 175 present calls, max score 89.20.

FANTOM5 (CAGE): breadth broad, TPM avg 2.8564 / max 242.6022, expressed in 537 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
136472	2.8564	537

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	89.20	gold quality
vastus lateralis	UBERON:0001379	88.56	gold quality
quadriceps femoris	UBERON:0001377	87.87	gold quality
tibia	UBERON:0000979	86.51	gold quality
cortical plate	UBERON:0005343	86.13	gold quality
mucosa of paranasal sinus	UBERON:0005030	86.10	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.19	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	84.13	gold quality
nasal cavity epithelium	UBERON:0005384	84.00	silver quality
palpebral conjunctiva	UBERON:0001812	83.87	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	83.74	gold quality
epithelial cell of pancreas	CL:0000083	83.42	silver quality
biceps brachii	UBERON:0001507	83.17	gold quality
ganglionic eminence	UBERON:0004023	83.16	gold quality
skeletal muscle tissue	UBERON:0001134	83.08	gold quality
lower lobe of lung	UBERON:0008949	82.64	gold quality
deltoid	UBERON:0001476	82.56	silver quality
cartilage tissue	UBERON:0002418	81.13	gold quality
epithelium of nasopharynx	UBERON:0001951	79.20	gold quality
tibialis anterior	UBERON:0001385	78.75	silver quality
hindlimb stylopod muscle	UBERON:0004252	78.02	gold quality
muscle tissue	UBERON:0002385	77.33	gold quality
corpus epididymis	UBERON:0004359	77.15	gold quality
epithelium of mammary gland	UBERON:0003244	76.53	gold quality
mammary duct	UBERON:0001765	76.44	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	76.43	gold quality
pigmented layer of retina	UBERON:0001782	75.90	gold quality
thyroid gland	UBERON:0002046	75.52	gold quality
nasal cavity mucosa	UBERON:0001826	74.81	gold quality
left lobe of thyroid gland	UBERON:0001120	74.79	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	21.74
E-MTAB-6108	no	187.82

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

128 targeting SHISA2, 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-3163	100.00	77.23	8605
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	shisa2b	ENSDARG00000088232
mus_musculus	Shisa2	ENSMUSG00000044461
rattus_norvegicus	Shisa2	ENSRNOG00000012521

Paralogs (5): SHISAL1 (ENSG00000138944), SHISAL2B (ENSG00000145642), SHISA3 (ENSG00000178343), SHISAL2A (ENSG00000182183), SHISA4 (ENSG00000198892)

Protein

Protein identifiers

Protein shisa-2 homolog — Q6UWI4 (reviewed: Q6UWI4)

Alternative names: Transmembrane protein 46

All UniProt accessions (1): Q6UWI4

UniProt curated annotations — full annotation on UniProt →

Function. Plays an essential role in the maturation of presomitic mesoderm cells by individual attenuation of both FGF and WNT signaling.

Subcellular location. Endoplasmic reticulum membrane.

Similarity. Belongs to the shisa family.

RefSeq proteins (1): NP_001007539* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026910	Shisa	Family
IPR053891	Shisa_N	Domain

Pfam: PF13908

UniProt features (8 total): topological domain 2, region of interest 2, signal peptide 1, chain 1, transmembrane region 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6UWI4-F1	63.29	0.26

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 144 (showing top): GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_REGULATION_OF_WNT_SIGNALING_PATHWAY, GOBP_NEGATIVE_REGULATION_OF_FIBROBLAST_GROWTH_FACTOR_RECEPTOR_SIGNALING_PATHWAY, MARTINEZ_RB1_TARGETS_UP, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, MARTINEZ_RB1_TARGETS_DN, GOBP_RESPONSE_TO_FIBROBLAST_GROWTH_FACTOR, GOBP_REGULATION_OF_FIBROBLAST_GROWTH_FACTOR_RECEPTOR_SIGNALING_PATHWAY, KINSEY_TARGETS_OF_EWSR1_FLII_FUSION_DN, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_DN, TURASHVILI_BREAST_DUCTAL_CARCINOMA_VS_DUCTAL_NORMAL_DN, RICKMAN_HEAD_AND_NECK_CANCER_A, GOBP_RESPONSE_TO_GROWTH_FACTOR

GO Biological Process (2): negative regulation of Wnt signaling pathway (GO:0030178), negative regulation of fibroblast growth factor receptor signaling pathway (GO:0040037)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (3): endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
negative regulation of signal transduction	2
Wnt signaling pathway	1
regulation of Wnt signaling pathway	1
fibroblast growth factor receptor signaling pathway	1
regulation of fibroblast growth factor receptor signaling pathway	1
negative regulation of cellular response to growth factor stimulus	1
binding	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cellular anatomical structure	1

Protein interactions and networks

STRING

562 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SHISA2	ZNF646	O15015	505
SHISA2	H7BZ11	H7BZ11	471
SHISA2	CDC42EP5	Q6NZY7	449
SHISA2	PTGR3	Q8N4Q0	412
SHISA2	INO80E	Q8NBZ0	400
SHISA2	ANKUB1	A6NFN9	381
SHISA2	MEX3C	Q5U5Q3	379
SHISA2	SLITRK6	Q9H5Y7	374
SHISA2	ALKBH4	Q9NXW9	373
SHISA2	FKBP9	O95302	367
SHISA2	EXOC6B	Q9Y2D4	357
SHISA2	TMEM94	Q12767	351
SHISA2	MTIF3	Q9H2K0	348
SHISA2	SMIM31	A0A1B0GVY4	339
SHISA2	LRRC71	Q8N4P6	336

IntAct

14 interactions, top by confidence:

A	B	Type	Score
ATXN1L	SHISA2	psi-mi:“MI:0915”(physical association)	0.560
SHISA2	CEP170P1	psi-mi:“MI:0914”(association)	0.530
NRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.480
SHISA2	EPHX1	psi-mi:“MI:0914”(association)	0.350
TMEM17	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
TGOLN2	BLTP3B	psi-mi:“MI:2364”(proximity)	0.270
KRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
HRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
ATXN1L	SHISA2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (24): PTGES2 (Affinity Capture-MS), CEP170P1 (Affinity Capture-MS), SHISA2 (Proximity Label-MS), PTGES2 (Affinity Capture-MS), CEP170P1 (Affinity Capture-MS), SHISA2 (Proximity Label-MS), SHISA2 (Proximity Label-MS), SHISA2 (Proximity Label-MS), ATXN1L (Two-hybrid), SHISA2 (Proximity Label-MS), SHISA2 (Proximity Label-MS), SHISA2 (Proximity Label-MS), SHISA2 (Proximity Label-MS), SHISA2 (Proximity Label-MS), SHISA2 (Proximity Label-MS)

ESM2 similar proteins: A2A9G7, A2CEX1, A2RV66, A6NKW6, A6QQ93, A7MC48, B3DHW5, B4DS77, B7ZWI3, E9QCD3, P20293, P86045, P98153, P98154, Q02223, Q14CH0, Q28HY0, Q2WFL8, Q56A20, Q5BLC7, Q5HYM0, Q5RCS3, Q5RD34, Q5RGQ8, Q5RJX2, Q5VUB5, Q68F67, Q6INH1, Q6P995, Q6UWI4, Q6UWV7, Q6UWW9, Q6ZUJ8, Q7SXB3, Q7TMJ8, Q7ZUL9, Q7ZXH3, Q80ZA7, Q8BGN6, Q8K3Y6

Diamond homologs: A0PJX4, A2RV66, A6QPA0, A7MC48, Q2WFL8, Q3UPR0, Q5BLC7, Q6UWI4, Q7T0Z7, Q8QZV2, B3DHW5, B4DS77, J3QNX5, Q9CZN4, Q9D7I0, A6NL88, B8ZZ34, Q3UH99, Q6ZSJ9, Q8C3Q5, Q9D1Y9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	53
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

174 predictions. Top by Δscore:

Variant	Effect	Δscore
13:26047067:C:CC	acceptor_gain	1.0000
13:26047073:C:CT	acceptor_gain	1.0000
13:26050640:A:T	donor_loss	1.0000
13:26050641:C:G	donor_loss	1.0000
13:26050644:G:A	donor_gain	1.0000
13:26047062:GGGCA:G	acceptor_gain	0.9900
13:26047063:GGCA:G	acceptor_gain	0.9900
13:26047063:GGCAC:G	acceptor_loss	0.9900
13:26047064:GCA:G	acceptor_gain	0.9900
13:26047064:GCACT:G	acceptor_loss	0.9900
13:26047065:CA:C	acceptor_gain	0.9900
13:26047065:CAC:C	acceptor_gain	0.9900
13:26047065:CACTG:C	acceptor_loss	0.9900
13:26047066:ACTG:A	acceptor_loss	0.9900
13:26047067:C:CA	acceptor_loss	0.9900
13:26047068:T:G	acceptor_loss	0.9900
13:26047694:T:TA	donor_gain	0.9900
13:26050640:A:AC	donor_gain	0.9900
13:26050640:ACCTG:A	donor_gain	0.9900
13:26050641:C:CC	donor_gain	0.9900
13:26050641:CCTG:C	donor_gain	0.9900
13:26050641:CCTGC:C	donor_gain	0.9900
13:26047074:A:T	acceptor_gain	0.9800
13:26050014:T:C	acceptor_gain	0.9600
13:26047700:G:C	donor_gain	0.9500
13:26050575:C:CA	donor_gain	0.9400
13:26047612:C:CT	donor_gain	0.9200
13:26047613:T:TT	donor_gain	0.9200
13:26050612:C:CA	donor_gain	0.9200
13:26047009:A:T	acceptor_gain	0.9100

AlphaMissense

1912 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
13:26047006:C:T	G132E	1.000
13:26047007:C:G	G132R	1.000
13:26047007:C:T	G132R	1.000
13:26047017:A:C	F128L	1.000
13:26047017:A:T	F128L	1.000
13:26047019:A:G	F128L	1.000
13:26047036:C:T	G122D	1.000
13:26047037:C:G	G122R	1.000
13:26050751:G:C	C75W	1.000
13:26050755:T:C	Y74C	1.000
13:26050773:C:A	G68V	1.000
13:26050774:C:A	G68C	1.000
13:26050776:C:T	C67Y	1.000
13:26050778:G:C	C66W	1.000
13:26050779:C:T	C66Y	1.000
13:26050821:A:C	F52C	1.000
13:26050853:C:A	W41C	1.000
13:26050853:C:G	W41C	1.000
13:26047021:G:T	A127D	0.999
13:26047024:A:T	V126D	0.999
13:26047026:A:C	F125L	0.999
13:26047026:A:T	F125L	0.999
13:26047028:A:G	F125L	0.999
13:26047039:A:T	V121D	0.999
13:26047042:A:T	I120N	0.999
13:26047045:A:G	L119P	0.999
13:26047045:A:T	L119H	0.999
13:26047047:G:C	F118L	0.999
13:26047047:G:T	F118L	0.999
13:26047048:A:C	F118C	0.999

dbSNP variants (sampled 300 via entrez): RS1000058430 (13:26049530 G>A,C), RS1000211055 (13:26046284 TCA>T), RS1000333273 (13:26051143 A>G), RS1000450572 (13:26045791 A>C), RS1000818328 (13:26052470 T>G), RS1001018290 (13:26049898 A>ACG), RS1001295225 (13:26046091 A>T), RS1001323962 (13:26049024 A>G), RS1001389064 (13:26051416 G>A), RS1001441538 (13:26051251 A>C), RS1002869482 (13:26052759 C>G,T), RS1002994487 (13:26047740 T>C,G), RS1003009181 (13:26047509 C>T), RS1003115147 (13:26052047 A>G,T), RS1003309769 (13:26052535 T>G)

Disease associations

OMIM: gene MIM:617324 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST009391_1225	Metabolite levels	6.000000e-06
GCST009391_1230	Metabolite levels	2.000000e-07

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0010421	triacylglycerol 54:3 measurement
EFO:0010422	triacylglycerol 54:4 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

69 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases methylation, affects cotreatment, increases expression, decreases expression, affects expression	8
Particulate Matter	affects expression, increases abundance, increases expression, affects cotreatment	5
trichostatin A	affects cotreatment, decreases expression	3
bisphenol A	decreases expression	2
sodium arsenite	affects methylation, increases expression	2
Benzo(a)pyrene	increases expression, increases methylation, affects methylation	2
Estradiol	decreases expression, affects cotreatment, increases expression	2
Phenylmercuric Acetate	decreases expression, affects cotreatment	2
Smoke	increases expression	2
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
aristolochic acid I	increases expression	1
methylmercuric chloride	decreases expression	1
bis(tri-n-butyltin)oxide	decreases expression	1
sodium arsenate	decreases expression, increases abundance	1
thallium sulfate	increases expression	1
arsenite	increases methylation	1
16 alpha-ethyl-21-hydroxy-19-nor-4-pregnene-3,20-dione	decreases expression	1
tetrabromobisphenol A	increases expression	1
zinc chromate	decreases expression, increases abundance	1
ochratoxin A	decreases expression	1
potassium chromate(VI)	decreases expression	1
ferrous chloride	increases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, decreases expression	1
glycidamide	decreases expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
perfluorooctane sulfonic acid	increases expression	1
2-palmitoylglycerol	increases expression	1
entinostat	decreases expression	1
monomethylarsonous acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1

Clinical trials (associated diseases)

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