SHISA4

Summary

SHISA4 (shisa family member 4, HGNC:27139) is a protein-coding gene on chromosome 1q32.1, encoding Protein shisa-4 (Q96DD7).

Predicted to be located in membrane.

Source: NCBI Gene 149345 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 33 total
• MANE Select transcript: NM_198149

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:27139
Approved symbol	SHISA4
Name	shisa family member 4
Location	1q32.1
Locus type	gene with protein product
Status	Approved
Aliases	hShisa4
Ensembl gene	ENSG00000198892
Ensembl biotype	protein_coding
OMIM	617326
Entrez	149345

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 2 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000362011, ENST00000464117, ENST00000481699, ENST00000868020

RefSeq mRNA: 1 — MANE Select: NM_198149 NM_198149

CCDS: CCDS1416

Canonical transcript exons

ENST00000362011 — 5 exons

Exon	Start	End
ENSE00001444076	201891800	201892587
ENSE00001444079	201888898	201889067
ENSE00003584354	201891401	201891568
ENSE00003629231	201889445	201889616
ENSE00003653964	201890454	201890587

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 98.67.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 24.6554 / max 349.0452, expressed in 1552 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
7764	17.1457	1536
7761	6.5889	1185
7763	0.6566	347
7762	0.2642	115

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
temporal lobe	UBERON:0001871	98.67	gold quality
amygdala	UBERON:0001876	98.67	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.63	gold quality
substantia nigra	UBERON:0002038	98.47	gold quality
prefrontal cortex	UBERON:0000451	98.46	gold quality
putamen	UBERON:0001874	98.33	gold quality
gastrocnemius	UBERON:0001388	98.31	gold quality
Ammon’s horn	UBERON:0001954	98.26	gold quality
caudate nucleus	UBERON:0001873	98.23	gold quality
frontal cortex	UBERON:0001870	98.22	gold quality
nucleus accumbens	UBERON:0001882	98.19	gold quality
apex of heart	UBERON:0002098	98.17	gold quality
right frontal lobe	UBERON:0002810	98.16	gold quality
hypothalamus	UBERON:0001898	97.99	gold quality
anterior cingulate cortex	UBERON:0009835	97.95	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	97.88	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	97.85	gold quality
cerebral cortex	UBERON:0000956	97.84	gold quality
primary visual cortex	UBERON:0002436	97.75	gold quality
Brodmann (1909) area 9	UBERON:0013540	97.72	gold quality
muscle of leg	UBERON:0001383	97.61	gold quality
heart left ventricle	UBERON:0002084	97.36	gold quality
superior frontal gyrus	UBERON:0002661	97.28	gold quality
right adrenal gland cortex	UBERON:0035827	97.15	gold quality
descending thoracic aorta	UBERON:0002345	96.88	gold quality
brain	UBERON:0000955	96.77	gold quality
thoracic aorta	UBERON:0001515	96.59	gold quality
ascending aorta	UBERON:0001496	96.54	gold quality
right adrenal gland	UBERON:0001233	96.42	gold quality
skeletal muscle tissue	UBERON:0001134	96.40	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

26 targeting SHISA4, 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-4283	100.00	66.42	2097
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-6515-3P	99.82	68.19	1933
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-6505-5P	99.73	69.25	1595
HSA-MIR-4527	99.66	67.43	714
HSA-MIR-4690-5P	99.65	66.24	813
HSA-MIR-6503-5P	99.62	66.96	597
HSA-MIR-6751-5P	99.56	64.99	1145
HSA-MIR-671-5P	99.52	67.11	1277
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-6510-5P	99.14	66.59	1081
HSA-MIR-6814-5P	99.03	66.68	1273
HSA-MIR-511-5P	98.97	70.94	2268
HSA-MIR-3691-5P	98.62	65.88	552
HSA-MIR-4642	97.52	67.60	916
HSA-MIR-6736-3P	96.98	65.22	1342
HSA-MIR-7160-3P	96.40	64.15	462
HSA-MIR-1266-3P	96.23	66.36	778
HSA-MIR-3651	95.62	64.67	287
HSA-MIR-4732-5P	90.07	64.77	412

Literature-anchored findings (GeneRIF, showing 1)

• New Transcriptomic Biomarkers of 5-Fluorouracil Resistance. (PMID:36675023)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	shisa4	ENSDARG00000006307
mus_musculus	Shisa4	ENSMUSG00000041889
rattus_norvegicus	Shisa4	ENSRNOG00000007369

Paralogs (5): SHISAL1 (ENSG00000138944), SHISAL2B (ENSG00000145642), SHISA3 (ENSG00000178343), SHISA2 (ENSG00000180730), SHISAL2A (ENSG00000182183)

Protein

Protein identifiers

Protein shisa-4 — Q96DD7 (reviewed: Q96DD7)

Alternative names: Transmembrane protein 58

All UniProt accessions (1): Q96DD7

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

Similarity. Belongs to the shisa family.

RefSeq proteins (1): NP_937792* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026910	Shisa	Family
IPR053891	Shisa_N	Domain

Pfam: PF13908

UniProt features (6 total): topological domain 2, signal peptide 1, chain 1, transmembrane region 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96DD7-F1	69.78	0.14

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 40 (showing top): GCANCTGNY_MYOD_Q6, CAGCTG_AP4_Q5, PATIL_LIVER_CANCER, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_DN, GSE13762_CTRL_VS_125_VITAMIND_DAY12_DC_UP, GOBERT_OLIGODENDROCYTE_DIFFERENTIATION_DN, YAP1_UP, LBP1_Q6, ZSCAN30_TARGET_GENES, GSE13306_RA_VS_UNTREATED_TCONV_DN, MANNE_COVID19_ICU_VS_HEALTHY_DONOR_PLATELETS_UP, MANNE_COVID19_COMBINED_COHORT_VS_HEALTHY_DONOR_PLATELETS_UP, FAN_EMBRYONIC_CTX_BIG_GROUPS_GLIAL, FAN_EMBRYONIC_CTX_OLIG, ZHONG_PFC_MAJOR_TYPES_ASTROCYTES

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

836 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SHISA4	SMIM12	Q96EX1	650
SHISA4	PTPRO	Q16827	556
SHISA4	MIA2	Q96PC5	551
SHISA4	BEND7	Q8N7W2	530
SHISA4	LRRC40	Q9H9A6	512
SHISA4	MNMIP1	A4FU49	511
SHISA4	PPP1R27	Q86WC6	506
SHISA4	NAIF1	Q69YI7	484
SHISA4	KLHL15	Q96M94	458
SHISA4	MOCS1	Q9NZB8	456
SHISA4	NABP2	Q9BQ15	453
SHISA4	PSKH1	P11801	449
SHISA4	SNAPC3	Q92966	448
SHISA4	SARAF	Q96BY9	447
SHISA4	LEPROTL1	O95214	447
SHISA4	OR6J1	Q8NGC5	447

IntAct

27 interactions, top by confidence:

A	B	Type	Score
SGTA	SHISA4	psi-mi:“MI:0915”(physical association)	0.560
MAL	SHISA4	psi-mi:“MI:0915”(physical association)	0.560
CYBC1	SHISA4	psi-mi:“MI:0915”(physical association)	0.560
DESI1	SHISA4	psi-mi:“MI:0915”(physical association)	0.560
UPK1B	SHISA4	psi-mi:“MI:0915”(physical association)	0.560
SHISA4	CYBC1	psi-mi:“MI:0915”(physical association)	0.560
UBE2V1	SHISA4	psi-mi:“MI:0915”(physical association)	0.560
TSPAN33	SHISA4	psi-mi:“MI:0915”(physical association)	0.560
CNIH1	SHISA4	psi-mi:“MI:0915”(physical association)	0.560
YAP1	SHISA4	psi-mi:“MI:0407”(direct interaction)	0.440
SHISA4	CHRM2	psi-mi:“MI:0915”(physical association)	0.370
UBE2V1	SHISA4	psi-mi:“MI:0915”(physical association)	0.000
TSPAN33	SHISA4	psi-mi:“MI:0915”(physical association)	0.000
CNIH1	SHISA4	psi-mi:“MI:0915”(physical association)	0.000
SHISA4	CNIH1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (13): SHISA4 (Two-hybrid), SHISA4 (Two-hybrid), SHISA4 (Two-hybrid), SHISA4 (Two-hybrid), SHISA4 (Two-hybrid), SHISA4 (Two-hybrid), SHISA4 (Two-hybrid), UBE2V1 (Two-hybrid), SHISA4 (Two-hybrid), PDCD6 (Far Western), SHISA4 (Reconstituted Complex), SHISA4 (Protein-peptide), SHISA4 (Affinity Capture-MS)

ESM2 similar proteins: A0PJX4, A2A8U2, A4D2P6, A6QM06, D4A6L0, E1BBQ2, O15079, O60320, P12755, P49797, P97260, Q0D2I5, Q12770, Q15884, Q1RMB5, Q3TS39, Q3UPR0, Q4FZH1, Q5MNU5, Q5SNT2, Q5T848, Q5XKK7, Q60698, Q6A044, Q7T0Z7, Q7TMB0, Q7TPB0, Q810F0, Q86XR5, Q8BX43, Q8BXL9, Q8C419, Q8CA71, Q8K064, Q8K2Y3, Q8N114, Q8NDY8, Q8WV15, Q91WM6, Q92537

Diamond homologs: A6NL88, A7MC48, B3DHW5, B4DS77, B8ZZ34, J3QNX5, Q3UH99, Q5BLC7, Q6ZSJ9, Q8C3Q5, Q8CA71, Q96DD7, Q9CZN4, Q3UPR0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	26
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

803 predictions. Top by Δscore:

Variant	Effect	Δscore
1:201889616:GGT:G	donor_loss	1.0000
1:201890502:T:A	acceptor_gain	1.0000
1:201890504:T:TA	acceptor_gain	1.0000
1:201889440:CGCA:C	acceptor_loss	0.9900
1:201889441:GCA:G	acceptor_loss	0.9900
1:201889442:CAG:C	acceptor_loss	0.9900
1:201889443:A:AG	acceptor_gain	0.9900
1:201889443:A:AT	acceptor_loss	0.9900
1:201889444:G:GG	acceptor_gain	0.9900
1:201889444:GT:G	acceptor_gain	0.9900
1:201889533:C:CA	acceptor_gain	0.9900
1:201889534:G:A	acceptor_gain	0.9900
1:201889617:G:GG	donor_gain	0.9900
1:201891399:A:AG	acceptor_gain	0.9900
1:201891400:G:GG	acceptor_gain	0.9900
1:201889439:CCGCA:C	acceptor_loss	0.9800
1:201889443:AGT:A	acceptor_gain	0.9800
1:201889444:GTG:G	acceptor_gain	0.9800
1:201889444:GTGCT:G	acceptor_gain	0.9800
1:201890505:G:A	acceptor_gain	0.9800
1:201891396:TCTA:T	acceptor_loss	0.9800
1:201891397:CTA:C	acceptor_loss	0.9800
1:201891398:TA:T	acceptor_loss	0.9800
1:201891399:A:AC	acceptor_loss	0.9800
1:201891400:G:C	acceptor_loss	0.9800
1:201891400:GGCCA:G	acceptor_gain	0.9800
1:201891798:A:AG	acceptor_gain	0.9800
1:201891799:G:GG	acceptor_gain	0.9800
1:201889052:C:CG	donor_gain	0.9700
1:201889066:GG:G	donor_gain	0.9700

AlphaMissense

1255 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:201889596:G:C	Q75H	0.998
1:201889596:G:T	Q75H	0.998
1:201889534:G:T	G55W	0.997
1:201889535:G:T	G55V	0.997
1:201889535:G:A	G55E	0.996
1:201890477:C:A	A90D	0.996
1:201889529:G:A	C53Y	0.995
1:201889603:T:A	C78S	0.995
1:201889604:G:C	C78S	0.995
1:201889511:G:A	C47Y	0.994
1:201889528:T:A	C53S	0.994
1:201889529:G:C	C53S	0.994
1:201889530:C:G	C53W	0.994
1:201889531:T:A	C54S	0.994
1:201889532:G:A	C54Y	0.994
1:201889532:G:C	C54S	0.994
1:201889595:A:C	Q75P	0.994
1:201889603:T:C	C78R	0.994
1:201889605:C:G	C78W	0.994
1:201890524:T:C	C106R	0.994
1:201889494:G:C	W41C	0.993
1:201889494:G:T	W41C	0.993
1:201889511:G:T	C47F	0.993
1:201889528:T:C	C53R	0.993
1:201889533:C:G	C54W	0.993
1:201889559:G:A	C63Y	0.993
1:201889604:G:A	C78Y	0.993
1:201889464:C:G	C31W	0.992
1:201889510:T:A	C47S	0.992
1:201889511:G:C	C47S	0.992

dbSNP variants (sampled 300 via entrez): RS1000199619 (1:201889121 A>G,T), RS1000470261 (1:201889712 G>A,T), RS1001366521 (1:201889842 C>T), RS1001802782 (1:201890744 C>T), RS1002705073 (1:201889778 G>A), RS1002797126 (1:201889391 G>A,C,T), RS1003800695 (1:201888144 T>G), RS1003823512 (1:201887271 T>G), RS1003939849 (1:201891975 C>T), RS1004708882 (1:201889771 G>C), RS1005346553 (1:201890661 T>C), RS1005939862 (1:201889374 G>A,T), RS1005948919 (1:201888832 G>A), RS1006314037 (1:201888600 A>T), RS1006465673 (1:201888975 G>C,T)

Disease associations

OMIM: gene MIM:617326 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST007559_12	Sleep duration (short sleep)	2.000000e-09
GCST008129_37	Body mass index	5.000000e-36
GCST008848_1	Depressive symptoms (sum-score)	6.000000e-11
GCST008849_1	Depressive symptoms (binary sum-score)	9.000000e-09
GCST008851_1	Depressive symptom (fatigue) (ordinal trait)	2.000000e-09
GCST008853_1	Depressive symptom (low self-esteem) (ordinal trait)	4.000000e-08
GCST011494_90	Daytime nap	7.000000e-40
GCST012355_23	Depression	1.000000e-13

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0007006	depressive symptom measurement
EFO:0007828	daytime rest measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tetrachlorodibenzodioxin	increases expression, affects expression	2
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
lead acetate	increases expression	1
decabromobiphenyl ether	affects expression	1
sodium arsenite	increases expression	1
aflatoxin B2	increases methylation	1
cupric chloride	increases expression	1
eprenetapopt	affects expression, affects reaction	1
Sunitinib	decreases expression	1
Atrazine	increases expression	1
Benzo(a)pyrene	affects methylation	1
Calcitriol	increases expression, affects cotreatment	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Doxorubicin	decreases expression	1
Lead	affects expression	1
Niclosamide	increases expression	1
Smoke	decreases expression	1
Testosterone	affects cotreatment, increases expression	1
Thiram	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Aflatoxin B1	increases methylation	1
Lactic Acid	decreases expression	1
Particulate Matter	decreases expression	1

Clinical trials (associated diseases)

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