TMEM176B

Summary

TMEM176B (transmembrane protein 176B, HGNC:29596) is a protein-coding gene on chromosome 7q36.1, encoding Transmembrane protein 176B (Q3YBM2). May play a role in the process of maturation of dendritic cells.

Predicted to be involved in negative regulation of dendritic cell differentiation. Predicted to be located in nuclear membrane.

Source: NCBI Gene 28959 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 58 total — 1 pathogenic
• MANE Select transcript: NM_001101312

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29596
Approved symbol	TMEM176B
Name	transmembrane protein 176B
Location	7q36.1
Locus type	gene with protein product
Status	Approved
Aliases	LR8, MS4B2
Ensembl gene	ENSG00000106565
Ensembl biotype	protein_coding
OMIM	610385
Entrez	28959

Gene structure

Transcript identifiers

Ensembl transcripts: 88 — 88 protein_coding

ENST00000326442, ENST00000429904, ENST00000447204, ENST00000450753, ENST00000492607, ENST00000854800, ENST00000854801, ENST00000854803, ENST00000854804, ENST00000854805, ENST00000854806, ENST00000854807, ENST00000854808, ENST00000854809, ENST00000854810, ENST00000854811, ENST00000854812, ENST00000854813, ENST00000854814, ENST00000854815, ENST00000854816, ENST00000854817, ENST00000854818, ENST00000854819, ENST00000854820, ENST00000854821, ENST00000854822, ENST00000854823, ENST00000854824, ENST00000854825, ENST00000854826, ENST00000854827, ENST00000854828, ENST00000854829, ENST00000854830, ENST00000854831, ENST00000854832, ENST00000854833, ENST00000854834, ENST00000854835, ENST00000854836, ENST00000854837, ENST00000854838, ENST00000854839, ENST00000854840, ENST00000854841, ENST00000854842, ENST00000854843, ENST00000854844, ENST00000854845, ENST00000854846, ENST00000854847, ENST00000854848, ENST00000854849, ENST00000854850, ENST00000854851, ENST00000854852, ENST00000854853, ENST00000854854, ENST00000854855, ENST00000854856, ENST00000854857, ENST00000854858, ENST00000854859, ENST00000854860, ENST00000854861, ENST00000854862, ENST00000854863, ENST00000854864, ENST00000854865, ENST00000854866, ENST00000854867, ENST00000854868, ENST00000854869, ENST00000854870, ENST00000854871, ENST00000854872, ENST00000854873, ENST00000854874, ENST00000854875, ENST00000854876, ENST00000854877, ENST00000854878, ENST00000854879, ENST00000854880, ENST00000956466, ENST00000956467, ENST00000956468

RefSeq mRNA: 6 — MANE Select: NM_001101312 NM_001101311, NM_001101312, NM_001101314, NM_001362691, NM_001362692, NM_014020

CCDS: CCDS47746, CCDS5908

Canonical transcript exons

ENST00000326442 — 7 exons

Exon	Start	End
ENSE00000729864	150793544	150793600
ENSE00000729866	150793961	150794071
ENSE00000872377	150796366	150796574
ENSE00001929051	150791301	150791623
ENSE00001956871	150800298	150800364
ENSE00002251909	150793088	150793315
ENSE00002305287	150792056	150792175

Expression profiles

Bgee: expression breadth ubiquitous, 264 present calls, max score 99.71.

FANTOM5 (CAGE): breadth broad, TPM avg 22.8806 / max 1156.1802, expressed in 607 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
86815	19.1947	594
86820	1.8134	303
86822	1.5670	288
86821	0.1320	61
86823	0.0643	42
86816	0.0564	22
86817	0.0529	30

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	99.71	gold quality
liver	UBERON:0002107	99.44	gold quality
granulocyte	CL:0000094	99.34	gold quality
mucosa of transverse colon	UBERON:0004991	99.21	gold quality
gall bladder	UBERON:0002110	99.08	gold quality
rectum	UBERON:0001052	98.95	gold quality
adult mammalian kidney	UBERON:0000082	98.77	gold quality
ileal mucosa	UBERON:0000331	98.76	gold quality
small intestine Peyer’s patch	UBERON:0003454	98.76	gold quality
caecum	UBERON:0001153	98.70	gold quality
vermiform appendix	UBERON:0001154	98.67	gold quality
transverse colon	UBERON:0001157	98.50	gold quality
metanephros cortex	UBERON:0010533	98.50	gold quality
decidua	UBERON:0002450	98.46	gold quality
small intestine	UBERON:0002108	98.32	gold quality
right atrium auricular region	UBERON:0006631	98.13	gold quality
mucosa of sigmoid colon	UBERON:0004993	98.05	gold quality
colonic mucosa	UBERON:0000317	98.01	gold quality
left ovary	UBERON:0002119	97.91	gold quality
cardiac atrium	UBERON:0002081	97.87	gold quality
dorsal root ganglion	UBERON:0000044	97.86	gold quality
renal medulla	UBERON:0000362	97.80	gold quality
islet of Langerhans	UBERON:0000006	97.77	gold quality
right ovary	UBERON:0002118	97.75	gold quality
large intestine	UBERON:0000059	97.65	gold quality
saphenous vein	UBERON:0007318	97.65	gold quality
intestine	UBERON:0000160	97.62	gold quality
colon	UBERON:0001155	97.62	gold quality
duodenum	UBERON:0002114	97.37	gold quality
tibial nerve	UBERON:0001323	97.35	gold quality

Single-cell (SCXA)

Detected in 26 experiment(s), a significant marker in 26.

Experiment	Marker?	Max mean expression
E-MTAB-9906	yes	1486.44
E-GEOD-81547	yes	1259.97
E-GEOD-81608	yes	925.59
E-CURD-55	yes	857.81
E-ENAD-27	yes	856.65
E-GEOD-149689	yes	831.50
E-MTAB-9154	yes	624.93
E-ANND-5	yes	516.37
E-MTAB-8221	yes	471.42
E-HCAD-38	yes	466.49
E-HCAD-56	yes	274.60
E-CURD-122	yes	67.87
E-HCAD-11	yes	58.72
E-HCAD-31	yes	57.15
E-HCAD-1	yes	43.01

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

31 targeting TMEM176B, 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-4481	100.00	66.42	1669
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-7157-5P	99.66	69.33	1829
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-4310	99.59	68.84	2527
HSA-MIR-6833-5P	99.50	68.93	1161
HSA-MIR-491-5P	99.13	65.98	1468
HSA-MIR-4434	99.10	67.01	1984
HSA-MIR-5703	99.10	67.09	2053
HSA-MIR-589-5P	98.72	66.96	927
HSA-MIR-3187-5P	98.36	65.74	1776
HSA-MIR-4782-5P	98.35	69.33	1474
HSA-MIR-5706	98.35	69.33	1463
HSA-MIR-1285-3P	97.72	67.02	1932
HSA-MIR-5189-5P	97.72	66.96	1814
HSA-MIR-612	97.26	65.95	1597
HSA-MIR-6860	97.21	66.31	1656
HSA-MIR-4445-5P	97.21	66.16	832
HSA-MIR-34A-3P	96.80	67.70	805
HSA-MIR-6839-5P	96.74	68.29	1088
HSA-MIR-378J	96.44	66.20	1020
HSA-MIR-6742-5P	96.32	64.01	869
HSA-MIR-6796-5P	95.37	66.08	1120
HSA-MIR-4466	92.97	63.23	39

Literature-anchored findings (GeneRIF, showing 5)

• human TMEM176A and 176B protein levels are significantly elevated in lymphoma, but not in normal tissues (PMID:22244448)
• Study characterized Tmem176a and b expression in RORgamma t+ lymphocytes at transcriptional and protein levels and present evidence that both genes exert a redundant ion channel function related to a colocalisation in close proximity to the Golgi apparatus. (PMID:27009467)
• TMEM176A and TMEM176B Are Candidate Regulators of Inhibition of Dendritic Cell Maturation and Function after Chronic Spinal Cord Injury. (PMID:31354034)
• TMEM176B Regulates AKT/mTOR Signaling and Tumor Growth in Triple-Negative Breast Cancer. (PMID:34943938)
• The Ala134Thr variant in TMEM176B exerts a beneficial role in colorectal cancer prognosis by increasing NLRP3 inflammasome activation. (PMID:35980484)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Tmem176b	ENSMUSG00000029810
rattus_norvegicus	Tmem176b	ENSRNOG00000008465

Paralogs (1): TMEM176A (ENSG00000002933)

Protein

Protein identifiers

Transmembrane protein 176B — Q3YBM2 (reviewed: Q3YBM2)

Alternative names: Protein LR8

All UniProt accessions (2): Q3YBM2, A0A090N7V7

UniProt curated annotations — full annotation on UniProt →

Function. May play a role in the process of maturation of dendritic cells. Required for the development of cerebellar granule cells.

Subcellular location. Nucleus membrane.

Tissue specificity. Expressed in lung and dermal fibroblasts.

Induction. Up-regulated in fibrotic lung. Down-regulated in activated dendritic cells.

Similarity. Belongs to the TMEM176 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q3YBM2-1	1	yes
Q3YBM2-2	2

RefSeq proteins (6): NP_001094781, NP_001094782, NP_001094784, NP_001349620, NP_001349621, NP_054739 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007237	CD20-like_TM	Domain
IPR009281	TMEM176A/TMEM176B	Family

Pfam: PF04103

UniProt features (20 total): sequence variant 6, transmembrane region 4, modified residue 4, sequence conflict 2, chain 1, splice variant 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q3YBM2-F1	69.72	0.16

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (4): 258, 236, 245, 254

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 281 (showing top): GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, GOBP_DENDRITIC_CELL_DIFFERENTIATION, GOBP_REGULATION_OF_DENDRITIC_CELL_DIFFERENTIATION, GNF2_GSTM1, GNF2_HPN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, JOHANSSON_GLIOMAGENESIS_BY_PDGFB_UP, FERREIRA_EWINGS_SARCOMA_UNSTABLE_VS_STABLE_DN, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_SUSTAINDED_IN_ERYTHROCYTE_UP, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_ERYTHROCYTE_UP, GOBP_REGULATION_OF_LEUKOCYTE_DIFFERENTIATION, PICCALUGA_ANGIOIMMUNOBLASTIC_LYMPHOMA_UP, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, GOBP_REGULATION_OF_HEMOPOIESIS, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS

GO Biological Process (4): animal organ morphogenesis (GO:0009887), dendritic cell differentiation (GO:0097028), negative regulation of dendritic cell differentiation (GO:2001199), cell differentiation (GO:0030154)

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

GO Cellular Component (3): nuclear membrane (GO:0031965), nucleus (GO:0005634), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
anatomical structure morphogenesis	1
animal organ development	1
mononuclear cell differentiation	1
dendritic cell differentiation	1
negative regulation of leukocyte differentiation	1
regulation of dendritic cell differentiation	1
cellular developmental process	1
binding	1
nucleus	1
nuclear envelope	1
organelle membrane	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1516 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMEM176B	SP9	P0CG40	542
TMEM176B	ZNF775	Q96BV0	482
TMEM176B	ACRV1	P26436	475
TMEM176B	APOE	P02649	474
TMEM176B	BCLAF1	Q9NYF8	453
TMEM176B	CPXM1	Q96SM3	433
TMEM176B	GDAP1L1	Q96MZ0	416
TMEM176B	TMEM47	Q9BQJ4	411
TMEM176B	GIMAP8	Q8ND71	409
TMEM176B	GIMAP6	Q6P9H5	409
TMEM176B	THBS4	P35443	405
TMEM176B	KLF9	Q13886	402
TMEM176B	MS4A18	Q3C1V0	397
TMEM176B	LGALS3	P17931	394
TMEM176B	IL17RC	Q8NAC3	388

IntAct

25 interactions, top by confidence:

A	B	Type	Score
TMEM176B	TMEM176A	psi-mi:“MI:0915”(physical association)	0.560
LAMP2	TMEM176B	psi-mi:“MI:0915”(physical association)	0.560
TMEM176B	PRKCA	psi-mi:“MI:0915”(physical association)	0.560
TMEM176B	YWHAG	psi-mi:“MI:0915”(physical association)	0.560
TMEM176B	SETDB1	psi-mi:“MI:0915”(physical association)	0.560
TMEM176B	KAT5	psi-mi:“MI:0915”(physical association)	0.560
LMO3	TMEM176B	psi-mi:“MI:0915”(physical association)	0.560
SHANK3	IGKV3D-15	psi-mi:“MI:0914”(association)	0.350
TMEM176B	IGLL5	psi-mi:“MI:0914”(association)	0.350
TMEM176B	TMEM176A	psi-mi:“MI:0915”(physical association)	0.000
TMEM176B	repS	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (26): TMEM176B (PCA), TMEM176B (Two-hybrid), TMEM176B (PCA), IGHM (Affinity Capture-MS), LACRT (Affinity Capture-MS), IGLL5 (Affinity Capture-MS), BPIFB1 (Affinity Capture-MS), RBM45 (Affinity Capture-MS), IGLC2 (Affinity Capture-MS), LTF (Affinity Capture-MS), PIGR (Affinity Capture-MS), SCGB2A1 (Affinity Capture-MS), IGJ (Affinity Capture-MS), IGHA1 (Affinity Capture-MS), SERPINA3 (Affinity Capture-MS)

ESM2 similar proteins: A0A087WTH1, A0A125YWU9, A0PK84, A6PVL3, C9JQL5, F1QHM7, F1QX91, O15503, O41933, O70418, O88728, P0DI73, P13164, P26376, Q01628, Q01629, Q08755, Q0II74, Q21642, Q32L65, Q3UNB8, Q3YBM2, Q5FVR1, Q5FWL7, Q5I0I2, Q5R8D6, Q5RF75, Q5Y5T3, Q6DHI1, Q76IC6, Q7M734, Q7TQJ1, Q8BGI3, Q8CES1, Q8CFA6, Q8IYP9, Q8N6L7, Q8WVZ1, Q91WU6, Q921C1

Diamond homologs: Q3YBM2, Q4G068, Q5R8D6, Q7YQI4, Q925D4, Q96HP8, Q9DCS1, Q9R1Q6

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	1
Likely pathogenic	0
Uncertain significance	36
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
2685275	GRCh37/hg19 7q36.1(chr7:148538593-150967829)x1	Pathogenic

SpliceAI

2306 predictions. Top by Δscore:

Variant	Effect	Δscore
7:150792050:ACT:A	donor_loss	1.0000
7:150792051:CTC:C	donor_loss	1.0000
7:150792053:CACC:C	donor_loss	1.0000
7:150792054:ACCA:A	donor_loss	1.0000
7:150792171:AACTT:A	acceptor_gain	1.0000
7:150792173:CTT:C	acceptor_gain	1.0000
7:150792174:TT:T	acceptor_gain	1.0000
7:150792175:TCTG:T	acceptor_loss	1.0000
7:150792176:C:CC	acceptor_gain	1.0000
7:150792176:CTG:C	acceptor_loss	1.0000
7:150792182:A:AC	acceptor_gain	1.0000
7:150792182:A:C	acceptor_gain	1.0000
7:150793033:C:CA	donor_gain	1.0000
7:150793078:T:TA	donor_gain	1.0000
7:150793086:AC:A	donor_gain	1.0000
7:150793087:CC:C	donor_gain	1.0000
7:150793119:T:TA	donor_gain	1.0000
7:150793311:TAGCC:T	acceptor_gain	1.0000
7:150793538:ACTC:A	donor_loss	1.0000
7:150793539:CTC:C	donor_loss	1.0000
7:150793540:TCA:T	donor_loss	1.0000
7:150793541:CA:C	donor_loss	1.0000
7:150793542:A:AC	donor_gain	1.0000
7:150793542:ACAG:A	donor_gain	1.0000
7:150793543:C:CG	donor_gain	1.0000
7:150793543:CA:C	donor_gain	1.0000
7:150793543:CAG:C	donor_gain	1.0000
7:150793543:CAGC:C	donor_gain	1.0000
7:150793543:CAGCA:C	donor_gain	1.0000
7:150793597:TCAC:T	acceptor_gain	1.0000

AlphaMissense

1723 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:150794042:A:C	S78R	0.966
7:150794042:A:T	S78R	0.966
7:150794044:T:G	S78R	0.966
7:150794053:C:G	G75R	0.929
7:150794053:C:T	G75R	0.929
7:150793241:G:C	S149R	0.927
7:150793241:G:T	S149R	0.927
7:150793243:T:G	S149R	0.927
7:150793975:A:G	W101R	0.925
7:150793975:A:T	W101R	0.925
7:150794041:A:G	C79R	0.898
7:150794052:C:T	G75E	0.889
7:150792136:A:G	C214R	0.878
7:150794032:C:G	G82R	0.877
7:150794032:C:T	G82R	0.877
7:150792167:G:C	F203L	0.875
7:150792167:G:T	F203L	0.875
7:150792169:A:G	F203L	0.875
7:150793197:C:G	C164S	0.872
7:150793198:A:T	C164S	0.872
7:150793976:G:C	F100L	0.870
7:150793976:G:T	F100L	0.870
7:150793978:A:G	F100L	0.870
7:150794026:A:G	C84R	0.858
7:150793969:C:A	G103W	0.857
7:150794053:C:A	G75W	0.856
7:150793969:C:G	G103R	0.855
7:150793969:C:T	G103R	0.855
7:150794031:C:T	G82E	0.855
7:150793973:C:A	W101C	0.852

dbSNP variants (sampled 300 via entrez): RS1000385570 (7:150801115 G>A,C,T), RS1000409615 (7:150798280 G>A), RS1000505564 (7:150791186 T>C), RS1000657366 (7:150792477 G>T), RS1000693691 (7:150800282 G>A,T), RS1000853523 (7:150801986 A>G,T), RS1001262339 (7:150791285 T>A,C), RS1001359282 (7:150796983 A>G), RS1001414967 (7:150796734 G>A), RS1001614821 (7:150794792 T>G), RS1001873796 (7:150802273 G>A,C,T), RS1002312715 (7:150796001 A>G), RS1002419102 (7:150795355 C>T), RS1002520192 (7:150803125 G>A,C), RS1002554835 (7:150802719 T>C)

Disease associations

OMIM: gene MIM:610385 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST010083_191	Hemoglobin levels	2.000000e-10
GCST90000025_316	Appendicular lean mass	2.000000e-15
GCST90002383_440	Hematocrit	7.000000e-14
GCST90002384_165	Hemoglobin	7.000000e-14

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004509	hemoglobin measurement
EFO:0004980	appendicular lean mass
EFO:0004348	hematocrit

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
sodium arsenite	affects methylation, decreases expression, increases expression	3
Acetaminophen	decreases expression, increases expression	2
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	2
Tobacco Smoke Pollution	decreases expression, decreases methylation	2
Cyclosporine	decreases expression	2
Aflatoxin B1	affects expression, decreases methylation	2
FR900359	decreases phosphorylation	1
triphenyl phosphate	affects expression	1
bisphenol S	increases expression	1
Sunitinib	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Amphotericin B	decreases expression	1
Calcitriol	decreases expression	1
Diazinon	increases methylation	1
Diethylhexyl Phthalate	decreases expression	1
Doxorubicin	increases expression	1
Methotrexate	decreases expression	1
Nickel	increases expression	1
Valproic Acid	decreases methylation	1
1-Methyl-4-phenylpyridinium	increases expression	1
Antirheumatic Agents	decreases expression	1
Okadaic Acid	decreases expression	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

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