TMEM88

Summary

TMEM88 (transmembrane protein 88, HGNC:32371) is a protein-coding gene on chromosome 17p13.1, encoding Transmembrane protein 88 (Q6PEY1). Inhibits the Wnt/beta-catenin signaling pathway.

Predicted to enable PDZ domain binding activity. Involved in negative regulation of canonical Wnt signaling pathway; protein localization to plasma membrane; and protein stabilization. Located in cytosol and plasma membrane.

Source: NCBI Gene 92162 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 37 total
• MANE Select transcript: NM_203411

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:32371
Approved symbol	TMEM88
Name	transmembrane protein 88
Location	17p13.1
Locus type	gene with protein product
Status	Approved
Aliases	MGC71744, FLJ20025
Ensembl gene	ENSG00000167874
Ensembl biotype	protein_coding
OMIM	617813
Entrez	92162

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000301599, ENST00000574668, ENST00000856543

RefSeq mRNA: 2 — MANE Select: NM_203411 NM_001319941, NM_203411

CCDS: CCDS11121, CCDS82058

Canonical transcript exons

ENST00000301599 — 2 exons

Exon	Start	End
ENSE00001117874	7855066	7855284
ENSE00001310136	7855445	7856099

Expression profiles

Bgee: expression breadth ubiquitous, 135 present calls, max score 97.29.

FANTOM5 (CAGE): breadth broad, TPM avg 15.3777 / max 1078.3980, expressed in 518 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
159420	15.3777	518

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	97.29	gold quality
heart left ventricle	UBERON:0002084	94.29	gold quality
omental fat pad	UBERON:0010414	93.07	gold quality
right lobe of thyroid gland	UBERON:0001119	92.04	gold quality
metanephros cortex	UBERON:0010533	91.23	gold quality
heart	UBERON:0000948	91.17	gold quality
left uterine tube	UBERON:0001303	90.54	gold quality
left lobe of thyroid gland	UBERON:0001120	90.35	gold quality
right atrium auricular region	UBERON:0006631	89.61	gold quality
thyroid gland	UBERON:0002046	89.46	gold quality
placenta	UBERON:0001987	89.40	gold quality
mucosa of stomach	UBERON:0001199	88.90	gold quality
lower esophagus muscularis layer	UBERON:0035833	88.13	gold quality
lower esophagus	UBERON:0013473	88.04	gold quality
adipose tissue	UBERON:0001013	87.77	gold quality
hindlimb stylopod muscle	UBERON:0004252	87.62	gold quality
adult mammalian kidney	UBERON:0000082	87.03	gold quality
adenohypophysis	UBERON:0002196	86.83	gold quality
gastrocnemius	UBERON:0001388	86.61	gold quality
myometrium	UBERON:0001296	86.56	gold quality
body of uterus	UBERON:0009853	86.48	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	86.34	gold quality
muscle of leg	UBERON:0001383	86.33	gold quality
pituitary gland	UBERON:0000007	86.22	gold quality
cortex of kidney	UBERON:0001225	85.74	gold quality
left coronary artery	UBERON:0001626	85.06	gold quality
left adrenal gland cortex	UBERON:0035825	84.81	gold quality
right adrenal gland	UBERON:0001233	84.70	gold quality
left adrenal gland	UBERON:0001234	84.63	gold quality
kidney	UBERON:0002113	84.46	gold quality

Single-cell (SCXA)

Detected in 10 experiment(s), a significant marker in 9.

Experiment	Marker?	Max mean expression
E-MTAB-9388	yes	2372.51
E-MTAB-10287	yes	69.07
E-HCAD-10	yes	46.95
E-GEOD-135922	yes	34.03
E-MTAB-8410	yes	26.03
E-MTAB-6701	yes	14.91
E-HCAD-9	yes	12.93
E-MTAB-8271	yes	8.60
E-MTAB-6678	no	2.43
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

18 targeting TMEM88, 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-6793-5P	99.97	65.95	758
HSA-MIR-767-5P	99.95	70.85	993
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-6512-3P	99.65	66.07	1468
HSA-MIR-6720-5P	99.65	66.22	1459
HSA-MIR-4472	99.56	66.08	1478
HSA-MIR-2116-5P	99.32	69.34	1273
HSA-MIR-6846-5P	98.81	65.86	1121
HSA-MIR-6848-5P	98.81	65.49	1126
HSA-MIR-22-5P	97.67	68.92	1355
HSA-MIR-6849-3P	97.25	64.57	1371
HSA-MIR-6823-5P	96.26	65.69	919
HSA-MIR-576-3P	96.14	65.63	773
HSA-MIR-1180-3P	95.98	66.88	65
HSA-MIR-3130-3P	94.98	66.97	574
HSA-MIR-6781-5P	94.61	59.49	155
HSA-MIR-6877-5P	93.84	61.41	74
HSA-MIR-4497	92.25	64.06	134

Literature-anchored findings (GeneRIF, showing 13)

• TMEM88 associates with Dvl proteins and regulates Wnt signaling in a context-dependent manner (PMID:21044957)
• miRNA-708 acts as an oncogene contributing to tumor growth and disease progression by directly downregulating TMEM88 (PMID:22573352)
• TMEM88 is crucial for heart development and acts downstream of GATA factors in the pre-cardiac mesoderm to specify lineage commitment of cardiomyocyte. (PMID:23924634)
• TMEM88 stimulated triple negative breast cancer cell invasion by interacting with DVL1. (PMID:26325443)
• mislocalization of TMEM88 to the cytosol in non-small cell lung cancer cells ablates its Wnt pathway regulatory properties, thereby promoting invasion and metastasis by activating the p38-GSK3beta-Snail signaling pathway. (PMID:26359454)
• Results support that OC platinum resistance was correlated with TMEM88 overexpression regulated through decreased promoter methylation. Data suggest that TMEM88 functions as an inhibitor of Wnt signaling, contributing to the development of platinum resistance. (PMID:27374141)
• TMEM88, CCL14, and CLEC3B genes were stable and available in predicting the survival and palindromia time of hepatocellular carcinoma. These genes could function as potential prognostic genes contributing to improve patients’ outcomes and survival (PMID:28718365)
• TMEM88 inhibits the TGF-beta1-stimulated cell proliferation, migration and extracellular matrix expression in keloid fibroblasts. (PMID:28946191)
• TMEM88 plays a significant role in TNF-alpha-enhanced cytokine (IL-6 and IL-1beta) secretion of LX-2 cells via regulating JNK/P38 and canonical Wnt/beta-catenin signaling pathway. (PMID:29159713)
• MicroRNA-708 modulates Hepatic Stellate Cells activation and enhances extracellular matrix accumulation via direct targeting TMEM88. (PMID:32463570)
• Transmembrane protein 88 exerts a tumor-inhibitory role in thyroid cancer through restriction of Wnt/beta-catenin signaling. (PMID:32710906)
• Transmembrane protein 88 inhibits transforming growth factor-beta1-induced-extracellular matrix accumulation and epithelial-mesenchymal transition program in human pleural mesothelial cells through modulating TGF-beta1/Smad pathway. (PMID:33167758)
• TMEM88 exhibits an antiproliferative and anti-invasive effect in bladder cancer by downregulating Wnt/beta-catenin signaling. (PMID:34057764)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Tmem88	ENSMUSG00000045377
rattus_norvegicus	Tmem88	ENSRNOG00000009870

Protein

Protein identifiers

Transmembrane protein 88 — Q6PEY1 (reviewed: Q6PEY1)

All UniProt accessions (2): Q6PEY1, I3L2J3

UniProt curated annotations — full annotation on UniProt →

Function. Inhibits the Wnt/beta-catenin signaling pathway. Crucial for heart development and acts downstream of GATA factors in the pre-cardiac mesoderm to specify lineage commitment of cardiomyocyte development.

Subunit / interactions. Interacts (via C-terminus) with DVL1.

Subcellular location. Cell membrane.

Similarity. Belongs to the TMEM88 family.

RefSeq proteins (2): NP_001306870, NP_981956* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR033355	TMEM88	Family

UniProt features (5 total): transmembrane region 2, chain 1, region of interest 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6PEY1-F1	69.73	0.25

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 148 (showing top): RNGTGGGC_UNKNOWN, CREL_01, BENPORATH_ES_WITH_H3K27ME3, LFA1_Q6, GOBP_REGULATION_OF_WNT_SIGNALING_PATHWAY, HNF1_Q6, FOXO1_01, GGGTGGRR_PAX4_03, GOBP_PROTEIN_LOCALIZATION_TO_CELL_PERIPHERY, FOXD3_01, NKX61_01, NFKB_C, SOX9_B1, GATA3_01, FREAC3_01

GO Biological Process (4): Wnt signaling pathway (GO:0016055), protein stabilization (GO:0050821), protein localization to plasma membrane (GO:0072659), negative regulation of canonical Wnt signaling pathway (GO:0090090)

GO Molecular Function (2): PDZ domain binding (GO:0030165), protein binding (GO:0005515)

GO Cellular Component (3): cytosol (GO:0005829), plasma membrane (GO:0005886), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
cell surface receptor signaling pathway	1
regulation of protein stability	1
protein localization to membrane	1
protein localization to cell periphery	1
negative regulation of Wnt signaling pathway	1
canonical Wnt signaling pathway	1
regulation of canonical Wnt signaling pathway	1
protein domain specific binding	1
binding	1
cytoplasm	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

460 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMEM88	DVL1	O14640	886
TMEM88	TMEM45A	Q9NWC5	541
TMEM88	TMEM94	Q12767	528
TMEM88	TMEM25	Q86YD3	468
TMEM88	TMEM178A	Q8NBL3	450
TMEM88	NDC1	Q9BTX1	446
TMEM88	TMEM207	Q6UWW9	438
TMEM88	VWC2	Q2TAL6	436
TMEM88	TMEM97	Q5BJF2	432
TMEM88	TMEM158	Q8WZ71	419
TMEM88	TMEM98	Q9Y2Y6	413
TMEM88	TMEM205	Q6UW68	396
TMEM88	NKX2-5	P52952	390
TMEM88	TMEM47	Q9BQJ4	387
TMEM88	TMEM14A	Q9Y6G1	378

IntAct

37 interactions, top by confidence:

A	B	Type	Score
C2CD2L	TMEM88	psi-mi:“MI:0915”(physical association)	0.560
TMEM120A	TMEM88	psi-mi:“MI:0915”(physical association)	0.560
VRK2	TMEM88	psi-mi:“MI:0915”(physical association)	0.560
TIMM23	TMEM88	psi-mi:“MI:0915”(physical association)	0.560
TMEM88	MFF	psi-mi:“MI:0915”(physical association)	0.560
TMEM50B	TMEM88	psi-mi:“MI:0915”(physical association)	0.560
TMEM218	TMEM88	psi-mi:“MI:0915”(physical association)	0.560
TMEM88	VRK2	psi-mi:“MI:0915”(physical association)	0.560
GYPC	TMEM88	psi-mi:“MI:0915”(physical association)	0.560
TMEM11	TMEM88	psi-mi:“MI:0915”(physical association)	0.560
NKG7	TMEM88	psi-mi:“MI:0915”(physical association)	0.560
TMEM88	ZDHHC22	psi-mi:“MI:0915”(physical association)	0.560
TMEM88	MLYCD	psi-mi:“MI:0914”(association)	0.530
CFAP107	KDM6A	psi-mi:“MI:0914”(association)	0.350
TMEM88	COX7A2L	psi-mi:“MI:0914”(association)	0.350
MFF	TMEM88	psi-mi:“MI:0915”(physical association)	0.000
TMEM50B	TMEM88	psi-mi:“MI:0915”(physical association)	0.000
TMEM218	TMEM88	psi-mi:“MI:0915”(physical association)	0.000
GYPC	TMEM88	psi-mi:“MI:0915”(physical association)	0.000
TMEM11	TMEM88	psi-mi:“MI:0915”(physical association)	0.000
NKG7	TMEM88	psi-mi:“MI:0915”(physical association)	0.000
TIMM23	TMEM88	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (16): TMEM88 (Two-hybrid), TMEM88 (Two-hybrid), TMEM88 (Two-hybrid), TMEM88 (Two-hybrid), TMEM88 (Two-hybrid), MFF (Two-hybrid), ZDHHC22 (Two-hybrid), TMEM11 (Two-hybrid), TIMM23 (Two-hybrid), RTN4 (Affinity Capture-MS), MLYCD (Affinity Capture-MS), GLMN (Affinity Capture-MS), MICAL1 (Affinity Capture-MS), TMEM88 (Affinity Capture-MS), CCDC115 (Affinity Capture-MS)

ESM2 similar proteins: A3KN95, A4IFG4, A7E2I7, E2RDP2, J3QMI4, O94810, O95382, P0C5W1, P23677, P82350, Q15628, Q16586, Q1RMX3, Q24JP5, Q28686, Q29RH2, Q3T904, Q3U0S6, Q45T69, Q49LS1, Q5FWU3, Q5RCS0, Q5U651, Q64255, Q674R7, Q684M2, Q68FE2, Q68FE7, Q6EBV9, Q6GQT5, Q6NY19, Q6P9Q4, Q6PEY1, Q7Z3C6, Q80WF4, Q80XF7, Q86TL0, Q86XJ0, Q8C052, Q8C152

Diamond homologs: A5D7M7, A6NKF7, Q0VD38, Q3TYP4, Q6PEY1, Q9D0N8

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	36
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

228 predictions. Top by Δscore:

Variant	Effect	Δscore
17:7855285:G:A	donor_loss	1.0000
17:7855286:T:G	donor_loss	1.0000
17:7855285:G:GG	donor_gain	0.9900
17:7855443:A:AG	acceptor_gain	0.9800
17:7855444:G:GG	acceptor_gain	0.9800
17:7855444:GTTC:G	acceptor_gain	0.9400
17:7855444:GTTCC:G	acceptor_gain	0.9400
17:7855440:CACA:C	acceptor_loss	0.9300
17:7855442:CA:C	acceptor_loss	0.9300
17:7855444:G:GT	acceptor_loss	0.9300
17:7855440:CACAG:C	acceptor_gain	0.9200
17:7855441:ACAG:A	acceptor_gain	0.9000
17:7855282:CAGGT:C	donor_gain	0.8900
17:7855285:G:GA	donor_gain	0.8900
17:7855286:T:A	donor_gain	0.8900
17:7855401:A:AG	acceptor_gain	0.8900
17:7855402:G:GG	acceptor_gain	0.8900
17:7855439:CCACA:C	acceptor_gain	0.8900
17:7855442:CAG:C	acceptor_gain	0.8900
17:7855444:G:T	acceptor_gain	0.8800
17:7855444:GTT:G	acceptor_gain	0.8800
17:7855281:TCAG:T	donor_gain	0.8700
17:7855284:GGT:G	donor_gain	0.8700
17:7855283:AGGTG:A	donor_gain	0.8600
17:7855443:A:T	acceptor_gain	0.8600
17:7855280:CTCAG:C	donor_gain	0.8500
17:7855283:AG:A	donor_gain	0.8500
17:7855284:GG:G	donor_gain	0.8500
17:7855444:GT:G	acceptor_gain	0.8400
17:7855282:CAG:C	donor_gain	0.8200

AlphaMissense

972 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:7855179:T:A	N35K	0.998
17:7855179:T:G	N35K	0.998
17:7855517:G:A	G95R	0.998
17:7855517:G:C	G95R	0.998
17:7855518:G:A	G95E	0.998
17:7855536:C:G	P101R	0.998
17:7855265:G:A	G64D	0.997
17:7855241:C:A	P56H	0.996
17:7855241:C:G	P56R	0.996
17:7855446:T:G	F71C	0.996
17:7855536:C:A	P101Q	0.996
17:7855200:T:A	N42K	0.995
17:7855200:T:G	N42K	0.995
17:7855264:G:C	G64R	0.995
17:7855273:T:A	C67S	0.995
17:7855273:T:C	C67R	0.995
17:7855274:G:A	C67Y	0.995
17:7855274:G:C	C67S	0.995
17:7855169:C:A	T32K	0.994
17:7855268:T:C	F65S	0.994
17:7855445:T:C	F71L	0.993
17:7855447:C:A	F71L	0.993
17:7855447:C:G	F71L	0.993
17:7855163:T:A	L30H	0.992
17:7855469:T:A	C79S	0.992
17:7855470:G:C	C79S	0.992
17:7855169:C:G	T32R	0.991
17:7855172:C:A	A33D	0.991
17:7855225:G:A	G51R	0.991
17:7855225:G:C	G51R	0.991

dbSNP variants (sampled 300 via entrez): RS1000018764 (17:7854003 G>A), RS1000378794 (17:7856253 C>G,T), RS1000749924 (17:7856110 G>A,C), RS1001850162 (17:7856143 G>T), RS1002218829 (17:7855989 C>A,G), RS1002377042 (17:7854232 A>C,G), RS1004239909 (17:7854052 GTTCTT>G), RS1004491881 (17:7855521 T>C), RS1004591300 (17:7855829 C>G,T), RS1005235452 (17:7854341 G>A,T), RS1005646319 (17:7856405 A>G), RS1005902986 (17:7856496 C>T), RS1006679825 (17:7855648 G>C), RS1007046154 (17:7854256 G>A,C), RS1008144152 (17:7854739 T>C)

Disease associations

OMIM: gene MIM:617813 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST010703_158	Brain morphology (MOSTest)	3.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004346	neuroimaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases methylation, affects cotreatment, decreases expression	7
trichostatin A	decreases expression, affects cotreatment	3
entinostat	decreases expression, affects cotreatment	2
Panobinostat	affects cotreatment, decreases expression	2
aristolochic acid I	increases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	decreases expression	1
tobacco tar	decreases reaction, increases expression	1
diallyl disulfide	increases expression, decreases reaction	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment	1
15-acetyldeoxynivalenol	increases expression	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	increases expression	1
dorsomorphin	decreases expression, affects cotreatment	1
jinfukang	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Cisplatin	affects cotreatment, decreases expression	1
Cytarabine	decreases expression	1
Doxorubicin	decreases expression	1
Estradiol	decreases expression	1
Lipopolysaccharides	increases expression, affects response to substance, affects cotreatment	1
Melphalan	increases expression	1
Ozone	affects expression, increases abundance	1
Plant Oils	increases expression	1

Clinical trials (associated diseases)

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