SHISAL2A

Summary

SHISAL2A (shisa like 2A, HGNC:28757) is a protein-coding gene on chromosome 1p32.3, encoding Protein shisa-like-2A (Q6UWV7).

Predicted to be located in membrane.

Source: NCBI Gene 348378 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 37 total
• MANE Select transcript: NM_001042693

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28757
Approved symbol	SHISAL2A
Name	shisa like 2A
Location	1p32.3
Locus type	gene with protein product
Status	Approved
Aliases	MGC52498
Ensembl gene	ENSG00000182183
Ensembl biotype	protein_coding
OMIM	620218
Entrez	348378

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding_CDS_not_defined, 1 protein_coding

ENST00000401050, ENST00000424164, ENST00000440303, ENST00000517870

RefSeq mRNA: 1 — MANE Select: NM_001042693 NM_001042693

CCDS: CCDS41336

Canonical transcript exons

ENST00000517870 — 3 exons

Exon	Start	End
ENSE00002122573	52656790	52657065
ENSE00003544169	52642863	52643002
ENSE00003544623	52633168	52633675

Expression profiles

Bgee: expression breadth ubiquitous, 153 present calls, max score 90.12.

FANTOM5 (CAGE): breadth broad, TPM avg 2.3780 / max 168.2881, expressed in 226 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
2880	1.7437	191
2881	0.6343	115

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	90.12	gold quality
granulocyte	CL:0000094	83.93	gold quality
blood	UBERON:0000178	81.28	gold quality
lymph node	UBERON:0000029	78.30	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	76.03	gold quality
vermiform appendix	UBERON:0001154	75.60	gold quality
spleen	UBERON:0002106	74.75	gold quality
bone marrow cell	CL:0002092	73.00	silver quality
caecum	UBERON:0001153	72.19	gold quality
sural nerve	UBERON:0015488	69.83	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	69.04	gold quality
bone marrow	UBERON:0002371	68.24	gold quality
hypothalamus	UBERON:0001898	66.63	gold quality
small intestine Peyer’s patch	UBERON:0003454	64.99	gold quality
tonsil	UBERON:0002372	64.96	gold quality
secondary oocyte	CL:0000655	64.92	silver quality
adenohypophysis	UBERON:0002196	64.06	gold quality
mucosa of transverse colon	UBERON:0004991	63.51	gold quality
cerebellar vermis	UBERON:0004720	62.85	gold quality
small intestine	UBERON:0002108	62.52	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	62.22	gold quality
vena cava	UBERON:0004087	61.95	gold quality
pituitary gland	UBERON:0000007	61.76	gold quality
lateral globus pallidus	UBERON:0002476	61.74	gold quality
nasal cavity epithelium	UBERON:0005384	60.60	gold quality
amniotic fluid	UBERON:0000173	60.43	silver quality
C1 segment of cervical spinal cord	UBERON:0006469	60.43	gold quality
oocyte	CL:0000023	60.21	gold quality
spinal cord	UBERON:0002240	60.13	gold quality
superficial temporal artery	UBERON:0001614	59.03	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.72

Regulation

Is transcription factor: no

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	SHISAL2A	ENSDARG00000112217
mus_musculus	Shisal2a	ENSMUSG00000059816
rattus_norvegicus	Shisal2a	ENSRNOG00000030641

Paralogs (5): SHISAL1 (ENSG00000138944), SHISAL2B (ENSG00000145642), SHISA3 (ENSG00000178343), SHISA2 (ENSG00000180730), SHISA4 (ENSG00000198892)

Protein

Protein identifiers

Protein shisa-like-2A — Q6UWV7 (reviewed: Q6UWV7)

All UniProt accessions (1): Q6UWV7

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Similarity. Belongs to the shisa family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q6UWV7-1	1	yes
Q6UWV7-2	2

RefSeq proteins (1): NP_001036158* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026910	Shisa	Family
IPR053891	Shisa_N	Domain

Pfam: PF13908

UniProt features (4 total): transmembrane region 2, chain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6UWV7-F1	65.51	0.24

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 45 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_DN, BENPORATH_ES_WITH_H3K27ME3, LEE_NAIVE_T_LYMPHOCYTE, GSE13762_CTRL_VS_125_VITAMIND_DAY12_DC_UP, DODD_NASOPHARYNGEAL_CARCINOMA_DN, MARTENS_BOUND_BY_PML_RARA_FUSION, KUMAR_PATHOGEN_LOAD_BY_MACROPHAGES, NFKBIA_TARGET_GENES, GSE12366_GC_VS_NAIVE_BCELL_DN, GSE12366_PLASMA_CELL_VS_NAIVE_BCELL_DN, GSE12366_PLASMA_CELL_VS_MEMORY_BCELL_DN, HAY_BONE_MARROW_NAIVE_T_CELL, DESCARTES_MAIN_FETAL_LYMPHOID_CELLS, DESCARTES_FETAL_CEREBRUM_MICROGLIA, DESCARTES_FETAL_HEART_LYMPHOID_CELLS

GO Biological Process (0):

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

GO Cellular Component (1): membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

180 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SHISAL2A	SHISAL1	Q3SXP7	579
SHISAL2A	VCF1	Q969W3	520
SHISAL2A	SEZ6	Q53EL9	448
SHISAL2A	TOGARAM2	Q6ZUX3	403
SHISAL2A	PRXL2B	Q8TBF2	389
SHISAL2A	SHISA8	B8ZZ34	376
SHISAL2A	CIBAR2	Q6ZTR7	370
SHISAL2A	KNDC1	Q76NI1	365
SHISAL2A	RETREG2	Q8NC44	359
SHISAL2A	ADAMTS15	Q8TE58	354
SHISAL2A	TMEM176A	Q96HP8	354
SHISAL2A	LBX2	Q6XYB7	348
SHISAL2A	FAM162A	Q96A26	331
SHISAL2A	EEPD1	Q7L9B9	323
SHISAL2A	MCOLN3	Q8TDD5	323

IntAct

7 interactions, top by confidence:

A	B	Type	Score
SHISAL2A	GOLT1B	psi-mi:“MI:0915”(physical association)	0.560
SHISAL2A	YIPF2	psi-mi:“MI:0915”(physical association)	0.560
YIPF2	SHISAL2A	psi-mi:“MI:0915”(physical association)	0.000
GOLT1B	SHISAL2A	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (3): FAM159A (Two-hybrid), FAM159A (Two-hybrid), FAM159A (Affinity Capture-RNA)

ESM2 similar proteins: A0A1B0GU29, A6NLX4, A6QNY1, A9CBA0, B7ZWI3, O14669, O88472, P14784, P16297, P25918, P26896, Q0VFL4, Q13651, Q32M26, Q38J84, Q38J85, Q3SYS8, Q58CT8, Q5BK39, Q5EAA5, Q5HZE8, Q5NCP0, Q5RCL0, Q64322, Q68DV7, Q6AXS2, Q6AXU5, Q6NUJ2, Q6UWV7, Q86UW2, Q8BHB3, Q8BLR5, Q8BSU2, Q8C353, Q8C708, Q8K1T1, Q8MII8, Q8N6P7, Q8NET5, Q8R182

Diamond homologs: A2A9G7, A6NKW6, A6QQ93, Q6UWV7, Q9D1Y9, Q2WFL8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	33
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

572 predictions. Top by Δscore:

Variant	Effect	Δscore
1:52633658:C:G	donor_gain	0.9900
1:52633666:G:GA	donor_gain	0.9900
1:52633671:CTCAG:C	donor_loss	0.9900
1:52633672:TCAG:T	donor_loss	0.9900
1:52633673:CAGG:C	donor_loss	0.9900
1:52633674:AGGTA:A	donor_loss	0.9900
1:52633676:GTA:G	donor_loss	0.9900
1:52633677:T:A	donor_loss	0.9900
1:52642862:GCATT:G	acceptor_gain	0.9600
1:52633669:GGCTC:G	donor_gain	0.9500
1:52642861:A:AG	acceptor_gain	0.9500
1:52642862:G:GG	acceptor_gain	0.9500
1:52642862:GC:G	acceptor_gain	0.9500
1:52633665:T:TA	donor_gain	0.9400
1:52643008:G:GT	donor_gain	0.9300
1:52642998:AGCAG:A	donor_loss	0.9100
1:52643000:CAG:C	donor_loss	0.9100
1:52643002:GGTAA:G	donor_loss	0.9100
1:52643003:G:GT	donor_loss	0.9100
1:52643004:TAA:T	donor_loss	0.9100
1:52633671:C:G	donor_gain	0.9000
1:52656788:A:AG	acceptor_gain	0.9000
1:52656789:G:GG	acceptor_gain	0.9000
1:52633533:G:GT	donor_gain	0.8900
1:52656589:A:AG	acceptor_gain	0.8900
1:52656590:A:G	acceptor_gain	0.8900
1:52656784:TTCCA:T	acceptor_loss	0.8900
1:52656785:TCCAG:T	acceptor_loss	0.8900
1:52656786:CCA:C	acceptor_loss	0.8900
1:52656787:CA:C	acceptor_loss	0.8900

AlphaMissense

1257 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:52633599:T:C	F36L	0.996
1:52633601:C:A	F36L	0.996
1:52633601:C:G	F36L	0.996
1:52633548:T:C	F19L	0.995
1:52633550:C:A	F19L	0.995
1:52633550:C:G	F19L	0.995
1:52633600:T:G	F36C	0.995
1:52633642:T:G	F50C	0.991
1:52633621:G:A	C43Y	0.989
1:52633591:G:A	C33Y	0.988
1:52633592:C:G	C33W	0.988
1:52633549:T:G	F19C	0.987
1:52633554:T:C	C21R	0.986
1:52633587:T:C	F32L	0.986
1:52633589:C:A	F32L	0.986
1:52633589:C:G	F32L	0.986
1:52633590:T:A	C33S	0.986
1:52633590:T:C	C33R	0.986
1:52633591:G:C	C33S	0.986
1:52633594:G:A	C34Y	0.986
1:52633619:C:G	C42W	0.986
1:52633554:T:A	C21S	0.985
1:52633555:G:C	C21S	0.985
1:52633600:T:C	F36S	0.985
1:52633613:G:C	K40N	0.985
1:52633613:G:T	K40N	0.985
1:52633641:T:C	F50L	0.985
1:52633643:C:A	F50L	0.985
1:52633643:C:G	F50L	0.985
1:52633593:T:A	C34S	0.984

dbSNP variants (sampled 300 via entrez): RS1000069463 (1:52643831 C>A,T), RS1000082835 (1:52642199 A>T), RS1000085896 (1:52650226 G>C), RS1000283563 (1:52631461 G>T), RS1000311991 (1:52667521 T>C), RS1000333874 (1:52631712 T>C), RS1000512993 (1:52639613 C>T), RS1000538118 (1:52642494 C>T), RS1000543443 (1:52653785 C>G), RS1000670269 (1:52661189 C>T), RS1000683009 (1:52633121 C>A,G,T), RS1000986525 (1:52669970 C>T), RS1001083151 (1:52632849 G>C), RS1001143025 (1:52641006 G>A), RS1001231308 (1:52636832 C>G)

Disease associations

OMIM: gene MIM:620218 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

11 total (human), top 11 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation	2
aflatoxin B2	increases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression	1
(+)-JQ1 compound	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Lead	decreases expression	1
Lipopolysaccharides	affects cotreatment, decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	increases expression	1
Aflatoxin B1	increases methylation	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

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