TMEM178B

Summary

TMEM178B (transmembrane protein 178B, HGNC:44112) is a protein-coding gene on chromosome 7q34, encoding Transmembrane protein 178B (H3BS89).

Predicted to be active in membrane.

Source: NCBI Gene 100507421 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 36 total
• MANE Select transcript: NM_001195278

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:44112
Approved symbol	TMEM178B
Name	transmembrane protein 178B
Location	7q34
Locus type	gene with protein product
Status	Approved
Aliases	DKFZp547G036
Ensembl gene	ENSG00000261115
Ensembl biotype	protein_coding
Entrez	100507421

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 1 retained_intron, 1 protein_coding

ENST00000563442, ENST00000565468

RefSeq mRNA: 1 — MANE Select: NM_001195278 NM_001195278

CCDS: CCDS59086

Canonical transcript exons

ENST00000565468 — 4 exons

Exon	Start	End
ENSE00002593751	141437608	141437745
ENSE00002619141	141470536	141480380
ENSE00002625251	141212591	141212704
ENSE00003843986	141074064	141074692

Expression profiles

Bgee: expression breadth ubiquitous, 200 present calls, max score 96.80.

FANTOM5 (CAGE): breadth broad, TPM avg 0.4248 / max 30.2612, expressed in 249 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
81522	0.4248	249

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cardiac muscle of right atrium	UBERON:0003379	96.80	gold quality
left ventricle myocardium	UBERON:0006566	95.88	gold quality
lateral nuclear group of thalamus	UBERON:0002736	92.42	gold quality
endothelial cell	CL:0000115	92.10	gold quality
Brodmann (1909) area 46	UBERON:0006483	90.74	gold quality
substantia nigra pars compacta	UBERON:0001965	90.62	gold quality
parietal lobe	UBERON:0001872	89.70	gold quality
postcentral gyrus	UBERON:0002581	89.70	gold quality
cortical plate	UBERON:0005343	89.35	gold quality
superior frontal gyrus	UBERON:0002661	89.32	gold quality
myocardium	UBERON:0002349	89.13	gold quality
middle temporal gyrus	UBERON:0002771	88.95	gold quality
Brodmann (1909) area 23	UBERON:0013554	88.69	gold quality
substantia nigra pars reticulata	UBERON:0001966	88.15	gold quality
entorhinal cortex	UBERON:0002728	86.83	gold quality
superior vestibular nucleus	UBERON:0007227	86.35	gold quality
ganglionic eminence	UBERON:0004023	86.18	gold quality
occipital lobe	UBERON:0002021	86.10	gold quality
dorsal root ganglion	UBERON:0000044	85.51	gold quality
ventricular zone	UBERON:0003053	85.35	gold quality
lateral globus pallidus	UBERON:0002476	84.99	gold quality
cerebellar vermis	UBERON:0004720	84.60	gold quality
primary visual cortex	UBERON:0002436	84.43	gold quality
ventral tegmental area	UBERON:0002691	84.05	gold quality
prefrontal cortex	UBERON:0000451	83.79	gold quality
dorsal plus ventral thalamus	UBERON:0001897	83.53	gold quality
frontal cortex	UBERON:0001870	83.51	gold quality
medial globus pallidus	UBERON:0002477	83.43	gold quality
heart right ventricle	UBERON:0002080	83.26	gold quality
globus pallidus	UBERON:0001875	83.01	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-GEOD-131882	yes	1126.11
E-CURD-119	yes	1058.06
E-MTAB-11268	yes	895.14
E-HCAD-35	yes	93.69
E-ANND-3	no	5.48

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

486 targeting TMEM178B, 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-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-3134	100.00	66.43	777
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-4500	99.99	72.72	2367

Literature-anchored findings (GeneRIF, showing 2)

• Tmem178 modulates the rate-limiting step of STIM1 puncta formation and therefore controls SOCE in inflammatory conditions. (PMID:31018906)
• Tmem178 Negatively Regulates IL-1beta Production Through Inhibition of the NLRP3 Inflammasome. (PMID:37534578)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	tmem178ba	ENSDARG00000004577
danio_rerio	tmem178bb	ENSDARG00000006747
mus_musculus	Tmem178b	ENSMUSG00000057716
rattus_norvegicus	Tmem178b	ENSRNOG00000047635

Paralogs (1): TMEM178A (ENSG00000152154)

Protein

Protein identifiers

Transmembrane protein 178B — H3BS89 (reviewed: H3BS89)

All UniProt accessions (1): H3BS89

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

Similarity. Belongs to the TMEM178 family.

RefSeq proteins (1): NP_001182207* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004031	PMP22/EMP/MP20/Claudin	Family
IPR039625	T178A/B	Family

Pfam: PF13903

UniProt features (7 total): transmembrane region 3, glycosylation site 2, signal peptide 1, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-H3BS89-F1	74.82	0.26

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 (2): 148, 152

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 135 (showing top): GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_UP, GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_UP, WANG_LMO4_TARGETS_DN, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_5, NAKAMURA_TUMOR_ZONE_PERIPHERAL_VS_CENTRAL_DN, RIGGI_EWING_SARCOMA_PROGENITOR_UP, PANGAS_TUMOR_SUPPRESSION_BY_SMAD1_AND_SMAD5_UP, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_UP, NFKBIA_TARGET_GENES, PBXIP1_TARGET_GENES, RYBP_TARGET_GENES, ZNF618_TARGET_GENES, MIR8485, MIR335_3P, MIR3658

GO Biological Process (0):

GO Molecular Function (0):

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	1

Protein interactions and networks

STRING

452 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMEM178B	ZNF723	P0DPD5	608
TMEM178B	C19orf81	C9J6K1	507
TMEM178B	MROH7	Q68CQ1	416
TMEM178B	YIPF4	Q9BSR8	403
TMEM178B	AGK	Q53H12	398
TMEM178B	OR1Q1	Q15612	393
TMEM178B	NSUN3	Q9H649	389
TMEM178B	MEX3B	Q6ZN04	389
TMEM178B	B4GALNT4	Q76KP1	384
TMEM178B	LINC03041	A6NGG3	380
TMEM178B	SNCAIP	Q9Y6H5	378
TMEM178B	ZNF605	Q86T29	372
TMEM178B	BTBD17	A6NE02	357
TMEM178B	DGKI	O75912	351
TMEM178B	STX19	Q8N4C7	343

IntAct

119 interactions, top by confidence:

A	B	Type	Score
TMEM178B	HTRA3	psi-mi:“MI:0407”(direct interaction)	0.440
TMEM178B	LNX2	psi-mi:“MI:0407”(direct interaction)	0.440
TMEM178B	HTRA1	psi-mi:“MI:0407”(direct interaction)	0.440
TMEM178B	MAST2	psi-mi:“MI:0407”(direct interaction)	0.440
TMEM178B	ARHGAP21	psi-mi:“MI:0407”(direct interaction)	0.440
TMEM178B	LNX1	psi-mi:“MI:0407”(direct interaction)	0.440
TMEM178B	WHRN	psi-mi:“MI:0407”(direct interaction)	0.440
TMEM178B	SYNJ2BP	psi-mi:“MI:0407”(direct interaction)	0.440
APBA3	TMEM178B	psi-mi:“MI:0407”(direct interaction)	0.440
TMEM178B	PATJ	psi-mi:“MI:0407”(direct interaction)	0.440
TMEM178B	PCLO	psi-mi:“MI:0407”(direct interaction)	0.440
TMEM178B	NHERF4	psi-mi:“MI:0407”(direct interaction)	0.440
TMEM178B	PDZRN4	psi-mi:“MI:0407”(direct interaction)	0.440
TMEM178B	MPP2	psi-mi:“MI:0407”(direct interaction)	0.440
TMEM178B	HTRA4	psi-mi:“MI:0407”(direct interaction)	0.440
SIPA1L2	TMEM178B	psi-mi:“MI:0407”(direct interaction)	0.440
PALS2	TMEM178B	psi-mi:“MI:0407”(direct interaction)	0.440
TMEM178B	DLG1	psi-mi:“MI:0407”(direct interaction)	0.440
TMEM178B	TAX1BP3	psi-mi:“MI:0407”(direct interaction)	0.440
TMEM178B	FRMPD1	psi-mi:“MI:0407”(direct interaction)	0.440
TMEM178B	GRIP1	psi-mi:“MI:0407”(direct interaction)	0.440
TMEM178B	LIMK2	psi-mi:“MI:0407”(direct interaction)	0.440
TMEM178B	CARD11	psi-mi:“MI:0407”(direct interaction)	0.440
TMEM178B	HTRA2	psi-mi:“MI:0407”(direct interaction)	0.440
TMEM178B	TJP3	psi-mi:“MI:0407”(direct interaction)	0.440
TMEM178B	SNTG1	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (4): TMEM178B (Affinity Capture-MS), TMEM178B (Affinity Capture-MS), SPTBN1 (Cross-Linking-MS (XL-MS)), TMEM178B (Affinity Capture-RNA)

ESM2 similar proteins: B3SHH9, F6V1J6, H3BS89, M0RAS4, P54825, P55344, P56563, P62955, P62956, P62957, Q06432, Q13635, Q17R16, Q1L8F4, Q3KRC4, Q4R4I5, Q5BJS2, Q5H8A4, Q5U4E0, Q5ZML7, Q61115, Q68FV0, Q6GQW0, Q6PFT6, Q6QRN8, Q6ZVK1, Q7TNR6, Q7TSY2, Q7Z6J6, Q7Z7J7, Q86UP9, Q8BHH9, Q8BM86, Q8NBL3, Q8NBT3, Q8NCR0, Q8VHW2, Q8VHW4, Q8VHW5, Q8VHW8

Diamond homologs: F6V1J6, H3BS89, Q08CE6, Q1L8F4, Q5XGU1, Q68FV0, Q8NBL3, Q9CZ16

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 77 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Ras activation upon Ca2+ influx through NMDA receptor	5	56.0×	1e-06
Unblocking of NMDA receptors, glutamate binding and activation	5	53.3×	1e-06
Negative regulation of NMDA receptor-mediated neuronal transmission	5	53.3×	1e-06
Assembly and cell surface presentation of NMDA receptors	10	49.8×	4e-13
Dopamine Neurotransmitter Release Cycle	5	48.7×	2e-06
Long-term potentiation	5	46.6×	2e-06
Neurexins and neuroligins	11	42.5×	2e-13
Protein-protein interactions at synapses	7	36.5×	5e-08

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	11	86.4×	9e-17
protein localization to synapse	6	62.1×	7e-08
receptor clustering	7	59.0×	5e-09
regulation of postsynaptic membrane neurotransmitter receptor levels	6	40.2×	5e-07
protein-containing complex assembly	10	15.4×	1e-07
cell-cell adhesion	10	13.7×	2e-07
protein localization to plasma membrane	5	7.3×	9e-03
chemical synaptic transmission	7	7.3×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	33
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3923 predictions. Top by Δscore:

Variant	Effect	Δscore
7:141074688:GAAAG:G	donor_gain	1.0000
7:141074689:AAAGG:A	donor_loss	1.0000
7:141074690:AAGGT:A	donor_loss	1.0000
7:141074691:AGGTA:A	donor_loss	1.0000
7:141074692:GGTA:G	donor_loss	1.0000
7:141074693:G:GA	donor_loss	1.0000
7:141074693:G:GG	donor_gain	1.0000
7:141074694:T:A	donor_loss	1.0000
7:141212587:CTAG:C	acceptor_loss	1.0000
7:141212588:TA:T	acceptor_loss	1.0000
7:141212589:A:AG	acceptor_gain	1.0000
7:141212589:AG:A	acceptor_gain	1.0000
7:141212590:G:GA	acceptor_gain	1.0000
7:141212590:GG:G	acceptor_gain	1.0000
7:141212590:GGA:G	acceptor_gain	1.0000
7:141212590:GGAGA:G	acceptor_gain	1.0000
7:141212686:GA:G	donor_gain	1.0000
7:141212700:CCTAC:C	donor_gain	1.0000
7:141212701:CTAC:C	donor_gain	1.0000
7:141212702:TAC:T	donor_gain	1.0000
7:141212702:TACGT:T	donor_loss	1.0000
7:141212703:AC:A	donor_gain	1.0000
7:141212704:CG:C	donor_loss	1.0000
7:141212705:G:GA	donor_loss	1.0000
7:141212705:G:GG	donor_gain	1.0000
7:141212706:TAAGT:T	donor_loss	1.0000
7:141212707:AAGT:A	donor_loss	1.0000
7:141212708:AGTG:A	donor_loss	1.0000
7:141223220:GA:G	donor_gain	1.0000
7:141291388:G:GG	donor_gain	1.0000

AlphaMissense

1910 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:141212692:T:A	W162R	1.000
7:141212692:T:C	W162R	1.000
7:141212694:G:C	W162C	1.000
7:141212694:G:T	W162C	1.000
7:141437611:T:C	L167P	1.000
7:141437631:T:C	F174L	1.000
7:141437633:C:A	F174L	1.000
7:141437633:C:G	F174L	1.000
7:141437664:G:C	G185R	1.000
7:141437665:G:A	G185D	1.000
7:141437667:T:A	W186R	1.000
7:141437667:T:C	W186R	1.000
7:141437724:G:A	G205R	1.000
7:141437724:G:C	G205R	1.000
7:141437724:G:T	G205W	1.000
7:141437725:G:A	G205E	1.000
7:141437728:T:C	L206P	1.000
7:141437731:T:C	L207P	1.000
7:141437737:T:C	L209P	1.000
7:141437742:G:A	G211R	1.000
7:141437742:G:C	G211R	1.000
7:141437743:G:A	G211E	1.000
7:141437745:G:A	G212R	1.000
7:141437745:G:C	G212R	1.000
7:141470551:T:A	I217N	1.000
7:141470559:T:C	C220R	1.000
7:141470560:G:A	C220Y	1.000
7:141470583:T:C	F228L	1.000
7:141470584:T:G	F228C	1.000
7:141470585:T:A	F228L	1.000

dbSNP variants (sampled 300 via entrez): RS1000002701 (7:141179733 G>A), RS1000032254 (7:141401358 G>T), RS1000036374 (7:141480293 G>A,C), RS1000041331 (7:141310150 A>G), RS1000046686 (7:141370343 G>A), RS1000055125 (7:141149829 C>T), RS1000065295 (7:141263846 AG>A), RS1000066751 (7:141351059 T>C), RS1000068041 (7:141346037 C>T), RS1000072259 (7:141106703 C>T), RS1000075547 (7:141267967 C>A,G,T), RS1000082099 (7:141282862 AAAG>A), RS1000086761 (7:141113160 G>T), RS1000088662 (7:141479944 G>A,T), RS1000114929 (7:141396457 G>A)

Disease associations

OMIM: gene `` | 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
GCST008103_6	Bipolar disorder	6.000000e-10
GCST010819_4	Gut microbiota alpha diversity (Chao1 index)	8.000000e-06
GCST012490_247	Femur bone mineral density x serum urate levels interaction	7.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007874	gut microbiome measurement
EFO:0004531	urate measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Aflatoxin B1	decreases expression	2
aristolochic acid I	decreases expression	1
bisphenol F	affects cotreatment, increases methylation	1
methyleugenol	decreases expression	1
bisphenol A	affects cotreatment, increases methylation	1
sulforaphane	decreases expression	1
benzo(e)pyrene	decreases methylation	1
diallyl trisulfide	decreases expression	1
perfluorooctane sulfonic acid	increases expression	1
2-palmitoylglycerol	increases expression	1
abrine	decreases expression	1
licochalcone B	decreases expression	1
theaflavin-3,3’-digallate	affects expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Acetaminophen	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Doxorubicin	decreases expression	1
Estradiol	affects cotreatment, decreases expression	1
Methapyrilene	decreases methylation	1
Tobacco Smoke Pollution	increases expression	1
Cyclosporine	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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