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TMEM176A

gene
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Also known as HCA112MS4B1

Summary

TMEM176A (transmembrane protein 176A, HGNC:24930) is a protein-coding gene on chromosome 7q36.1, encoding Transmembrane protein 176A (Q96HP8).

Predicted to act upstream of or within negative regulation of dendritic cell differentiation. Predicted to be located in membrane.

Source: NCBI Gene 55365 — RefSeq curated summary.

At a glance

  • GWAS associations: 9
  • Clinical variants (ClinVar): 47 total
  • MANE Select transcript: NM_018487

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:24930
Approved symbolTMEM176A
Nametransmembrane protein 176A
Location7q36.1
Locus typegene with protein product
StatusApproved
AliasesHCA112, MS4B1
Ensembl geneENSG00000002933
Ensembl biotypeprotein_coding
OMIM610334
Entrez55365

Gene structure

Transcript identifiers

Ensembl transcripts: 49 — 43 protein_coding, 6 retained_intron

ENST00000004103, ENST00000461345, ENST00000462826, ENST00000468689, ENST00000474166, ENST00000475007, ENST00000475536, ENST00000475710, ENST00000481305, ENST00000484928, ENST00000494349, ENST00000855157, ENST00000855158, ENST00000855159, ENST00000855160, ENST00000855161, ENST00000855162, ENST00000855163, ENST00000855164, ENST00000855165, ENST00000855166, ENST00000855167, ENST00000855168, ENST00000855169, ENST00000855170, ENST00000855171, ENST00000855172, ENST00000855173, ENST00000855174, ENST00000855175, ENST00000855176, ENST00000855177, ENST00000855178, ENST00000855179, ENST00000855180, ENST00000855181, ENST00000855182, ENST00000855183, ENST00000855184, ENST00000855185, ENST00000855186, ENST00000956676, ENST00000956677, ENST00000956678, ENST00000956679, ENST00000956680, ENST00000956681, ENST00000956682, ENST00000956683

RefSeq mRNA: 1 — MANE Select: NM_018487 NM_018487

CCDS: CCDS5909

Canonical transcript exons

ENST00000004103 — 7 exons

ExonStartEnd
ENSE00000729869150801536150801724
ENSE00001827596150800769150800828
ENSE00003493198150803620150803832
ENSE00003604647150804362150804472
ENSE00003656853150803400150803456
ENSE00003674137150802215150802325
ENSE00003832811150804827150805118

Expression profiles

Bgee: expression breadth ubiquitous, 259 present calls, max score 99.67.

FANTOM5 (CAGE): breadth broad, TPM avg 21.4836 / max 1351.2671, expressed in 641 samples.

FANTOM5 promoters (15 alternative TSS)

Promoter IDTPM avgSamples expressed
8197716.2701606
819741.3934326
819730.9277270
819800.7865166
819720.6019245
819790.2944108
819830.290522
819850.2645112
819780.217470
819750.151782

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
right lobe of liverUBERON:000111499.67gold quality
liverUBERON:000210799.42gold quality
ileal mucosaUBERON:000033198.98gold quality
dorsal root ganglionUBERON:000004498.90gold quality
mucosa of transverse colonUBERON:000499198.89gold quality
adult mammalian kidneyUBERON:000008298.88gold quality
renal medullaUBERON:000036298.80gold quality
gall bladderUBERON:000211098.67gold quality
rectumUBERON:000105298.53gold quality
pericardiumUBERON:000240798.48gold quality
caecumUBERON:000115398.44gold quality
granulocyteCL:000009498.33gold quality
small intestine Peyer’s patchUBERON:000345498.27gold quality
vermiform appendixUBERON:000115498.22gold quality
saphenous veinUBERON:000731898.20gold quality
vena cavaUBERON:000408798.03gold quality
nephron tubuleUBERON:000123197.97gold quality
small intestineUBERON:000210897.83gold quality
trigeminal ganglionUBERON:000167597.82gold quality
pylorusUBERON:000116697.77gold quality
metanephros cortexUBERON:001053397.76gold quality
transverse colonUBERON:000115797.70gold quality
left ovaryUBERON:000211997.70gold quality
cardia of stomachUBERON:000116297.69gold quality
type B pancreatic cellCL:000016997.53gold quality
islet of LangerhansUBERON:000000697.49gold quality
kidney epitheliumUBERON:000481997.45gold quality
right ovaryUBERON:000211897.36gold quality
lymph nodeUBERON:000002997.07gold quality
kidneyUBERON:000211396.70gold quality

Single-cell (SCXA)

Detected in 21 experiment(s), a significant marker in 21.

ExperimentMarker?Max mean expression
E-MTAB-9906yes1055.11
E-MTAB-9154yes976.46
E-GEOD-124472yes709.50
E-CURD-55yes502.90
E-HCAD-38yes471.42
E-HCAD-56yes298.87
E-HCAD-11yes59.41
E-HCAD-31yes42.25
E-HCAD-10yes34.90
E-GEOD-81547yes31.64
E-MTAB-5061yes30.38
E-MTAB-10553yes29.74
E-MTAB-8410yes24.22
E-CURD-46yes23.84
E-GEOD-135922yes23.14

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

14 targeting TMEM176A, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-4795-3P100.0074.624024
HSA-MIR-4725-3P99.9669.532520
HSA-MIR-6780B-5P99.9669.602562
HSA-MIR-185-3P99.9567.011743
HSA-MIR-4778-3P99.9370.401818
HSA-MIR-427199.8868.322244
HSA-MIR-453099.6966.471509
HSA-MIR-1227-5P98.6565.321549
HSA-MIR-3135B98.6165.331470
HSA-MIR-510-5P97.6665.82916
HSA-MIR-6762-5P96.5564.62972
HSA-MIR-6845-5P96.5564.65969
HSA-MIR-6782-5P96.4564.42612
HSA-MIR-6747-5P96.1764.99743

Literature-anchored findings (GeneRIF, showing 8)

  • 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)
  • Expression of TMEM176A in colorectal cancer cells is regulated by promoter region methylation. Methylation of TMEM176A was associated with tumor metastasis and was an independent prognostic factor for 5-year overall survival. (PMID:28678648)
  • Single nucleotide polymorphism in TMEM176A gene is associated with schizophrenia risk loci with potential implications for neurocognitive performance. (PMID:28902459)
  • The promoter region of TMEM176A is frequently methylated in human hepatocellular carcinoma (HCC), and the expression of TMEM176A is regulated by promoter region methylation. Methylation of the TMEM176A promoter may serve as a diagnostic and prognostic marker in HCC. TMEM176A suppresses HCC growth by inhibiting the ERK signaling pathway. (PMID:30400968)
  • TMEM176A and TMEM176B Are Candidate Regulators of Inhibition of Dendritic Cell Maturation and Function after Chronic Spinal Cord Injury. (PMID:31354034)
  • TMEM176A acts as a tumor suppressor gene in pancreatic cancer by inhibiting ERK signaling. (PMID:33593482)
  • Methylation of TMEM176A, a key ERK signaling regulator, is a novel synthetic lethality marker of ATM inhibitors in human lung cancer. (PMID:34558311)

Cross-species orthologs

2 orthologs

OrganismSymbolGene ID
mus_musculusTmem176aENSMUSG00000023367
rattus_norvegicusTmem176aENSRNOG00000023708

Paralogs (1): TMEM176B (ENSG00000106565)

Protein

Protein identifiers

Transmembrane protein 176A — Q96HP8 (reviewed: Q96HP8)

Alternative names: Hepatocellular carcinoma-associated antigen 112

All UniProt accessions (4): Q96HP8, A0A090N8H6, C9JJ63, H7C4P5

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Interacts with MCOLN2.

Subcellular location. Membrane.

Similarity. Belongs to the TMEM176 family.

RefSeq proteins (1): NP_060957* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR007237CD20-like_TMDomain
IPR009281TMEM176A/TMEM176BFamily

Pfam: PF04103

UniProt features (9 total): transmembrane region 4, sequence variant 3, chain 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-Q96HP8-F173.910.19

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 (1): 38

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 212 (showing top): GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_DN, 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, FERREIRA_EWINGS_SARCOMA_UNSTABLE_VS_STABLE_DN, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_ERYTHROCYTE_UP, GOBP_REGULATION_OF_LEUKOCYTE_DIFFERENTIATION, PICCALUGA_ANGIOIMMUNOBLASTIC_LYMPHOMA_UP, GOBP_REGULATION_OF_HEMOPOIESIS, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, CHIARADONNA_NEOPLASTIC_TRANSFORMATION_CDC25_UP, GOBP_NEGATIVE_REGULATION_OF_HEMOPOIESIS

GO Biological Process (1): negative regulation of dendritic cell differentiation (GO:2001199)

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:

CategoryTerms
dendritic cell differentiation1
negative regulation of leukocyte differentiation1
regulation of dendritic cell differentiation1
binding1
cellular anatomical structure1

Protein interactions and networks

STRING

724 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
TMEM176AMS4A18Q3C1V0600
TMEM176AMS4A5Q9H3V2597
TMEM176AMS4A15Q8N5U1568
TMEM176AMS4A6AQ9H2W1534
TMEM176ATMEM98Q9Y2Y6496
TMEM176AMS4A12Q9NXJ0487
TMEM176AMS4A8Q9BY19466
TMEM176ACPXM1Q96SM3438
TMEM176AMS4A4AQ96JQ5425
TMEM176AKLF9Q13886418
TMEM176AGDAP1L1Q96MZ0418
TMEM176ATMEM47Q9BQJ4412
TMEM176ATMEM252Q8N6L7391
TMEM176APLTPP55058387
TMEM176AGDAP1Q8TB36381

IntAct

46 interactions, top by confidence:

ABTypeScore
TMEM176BTMEM176Apsi-mi:“MI:0915”(physical association)0.560
TMEM176ASCD5psi-mi:“MI:0915”(physical association)0.560
RETREG3TMEM176Apsi-mi:“MI:0915”(physical association)0.560
SGPL1TMEM176Apsi-mi:“MI:0915”(physical association)0.560
CD79ATMEM176Apsi-mi:“MI:0915”(physical association)0.560
KCNK5TMEM176Apsi-mi:“MI:0915”(physical association)0.560
TMEM176ATMX2psi-mi:“MI:0915”(physical association)0.560
TMEM176AMTIF3psi-mi:“MI:0915”(physical association)0.560
TMEM176ATIMMDC1psi-mi:“MI:0915”(physical association)0.560
GOLM1TMEM176Apsi-mi:“MI:0915”(physical association)0.560
MFSD14BTMEM176Apsi-mi:“MI:0915”(physical association)0.560
TMEM176ACERS4psi-mi:“MI:0915”(physical association)0.560
TMEM176ALITAFpsi-mi:“MI:0915”(physical association)0.560
TMEM176AHIVEP1psi-mi:“MI:0915”(physical association)0.370
TGM2TMEM176Apsi-mi:“MI:0915”(physical association)0.370
RIDATMEM176Apsi-mi:“MI:0915”(physical association)0.370
VCPSHTN1psi-mi:“MI:0914”(association)0.350
VCPFAM171A2psi-mi:“MI:0914”(association)0.350
TMEM176BTMEM176Apsi-mi:“MI:0915”(physical association)0.000
TMEM176ASCD5psi-mi:“MI:0915”(physical association)0.000
TMEM176ACD79Apsi-mi:“MI:0915”(physical association)0.000
TMEM176AKCNK5psi-mi:“MI:0915”(physical association)0.000
TMEM176ATMX2psi-mi:“MI:0915”(physical association)0.000
TMEM176AMTIF3psi-mi:“MI:0915”(physical association)0.000
TMEM176AMFSD14Bpsi-mi:“MI:0915”(physical association)0.000
TMEM176ACERS4psi-mi:“MI:0915”(physical association)0.000
TMEM176ARETREG3psi-mi:“MI:0915”(physical association)0.000
TMEM176ASGPL1psi-mi:“MI:0915”(physical association)0.000

BioGRID (17): CERS4 (Two-hybrid), CD79A (Two-hybrid), TMEM176B (Two-hybrid), TIMMDC1 (Two-hybrid), MTIF3 (Two-hybrid), GOLM1 (Two-hybrid), FAM134C (Two-hybrid), SCD5 (Two-hybrid), HIATL1 (Two-hybrid), KCNK5 (Two-hybrid), SGPL1 (Two-hybrid), TMX2 (Two-hybrid), TMEM176A (Affinity Capture-MS), TMEM176A (Two-hybrid), TMEM176A (Two-hybrid)

ESM2 similar proteins: A4IIU3, A6NML5, D3YWQ9, O75204, P0DP42, P11836, P20490, P56749, Q01362, Q0IIL2, Q2KJ11, Q2YDM3, Q32KQ5, Q3T110, Q3YBM2, Q497B3, Q4G068, Q504G0, Q5EB63, Q5FWC3, Q5HYL7, Q5M962, Q5R8D6, Q5R9K1, Q5RCD5, Q5RFC1, Q6GV28, Q7T392, Q7TQI0, Q7YQI4, Q8BGP5, Q8BHH8, Q8C6V3, Q8K177, Q8NCR9, Q8VHW1, Q8WXS4, Q920C4, Q925D4, Q940P5

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

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance31
Likely benign4
Benign0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1348 predictions. Top by Δscore:

VariantEffectΔscore
7:150801202:G:GTdonor_gain1.0000
7:150801534:A:AGacceptor_gain1.0000
7:150801535:G:GGacceptor_gain1.0000
7:150801535:GACT:Gacceptor_gain1.0000
7:150801828:T:Gdonor_gain1.0000
7:150802213:A:AGacceptor_gain1.0000
7:150802214:G:GGacceptor_gain1.0000
7:150802323:GTG:Gdonor_gain1.0000
7:150802324:TG:Tdonor_gain1.0000
7:150802325:GG:Gdonor_gain1.0000
7:150802326:G:GGdonor_gain1.0000
7:150802326:GTGA:Gdonor_loss1.0000
7:150802327:T:Gdonor_loss1.0000
7:150803618:A:AGacceptor_gain1.0000
7:150803619:G:GGacceptor_gain1.0000
7:150803829:GAAG:Gdonor_gain1.0000
7:150803830:AAG:Adonor_gain1.0000
7:150803831:AG:Adonor_gain1.0000
7:150803831:AGG:Adonor_loss1.0000
7:150803832:GG:Gdonor_gain1.0000
7:150803833:G:GGdonor_gain1.0000
7:150804470:GGG:Gdonor_gain1.0000
7:150804471:GGG:Gdonor_gain1.0000
7:150804825:A:AGacceptor_gain1.0000
7:150804826:G:GAacceptor_gain1.0000
7:150804826:GAAAA:Gacceptor_gain1.0000
7:150800961:G:GTdonor_gain0.9900
7:150801531:CATA:Cacceptor_loss0.9900
7:150801533:T:Gacceptor_gain0.9900
7:150801533:TA:Tacceptor_loss0.9900

AlphaMissense

1504 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
7:150802242:A:CS68R0.984
7:150802244:T:AS68R0.984
7:150802244:T:GS68R0.984
7:150804401:T:AW199R0.963
7:150804401:T:CW199R0.963
7:150802233:G:AG65R0.961
7:150802233:G:CG65R0.961
7:150802311:T:AW91R0.958
7:150802311:T:CW91R0.958
7:150802234:G:AG65E0.949
7:150802233:G:TG65W0.931
7:150803806:T:AC177S0.927
7:150803807:G:CC177S0.927
7:150802317:G:TG93W0.916
7:150802254:G:AG72R0.915
7:150802254:G:CG72R0.915
7:150802257:G:AG73R0.914
7:150802257:G:CG73R0.914
7:150802318:G:AG93E0.914
7:150803424:T:CF104L0.911
7:150803426:C:AF104L0.911
7:150803426:C:GF104L0.911
7:150804395:G:CG197R0.911
7:150803412:G:AG100R0.906
7:150803412:G:CG100R0.906
7:150802255:G:AG72E0.904
7:150803806:T:CC177R0.904
7:150802317:G:AG93R0.902
7:150802317:G:CG93R0.902
7:150803413:G:AG100E0.902

dbSNP variants (sampled 300 via entrez): RS1000385570 (7:150801115 G>A,C,T), RS1000693691 (7:150800282 G>A,T), RS1000853523 (7:150801986 A>G,T), RS1001873796 (7:150802273 G>A,C,T), RS1002186835 (7:150804648 A>G), RS1002520192 (7:150803125 G>A,C), RS1002554835 (7:150802719 T>C), RS1002871316 (7:150799915 G>A), RS1002984757 (7:150805450 T>C), RS1004260764 (7:150804753 T>A), RS1004499859 (7:150798982 T>C), RS1004633590 (7:150805069 T>C), RS1004989859 (7:150802339 G>C), RS1006273896 (7:150801716 G>A,T), RS1006446041 (7:150801226 G>A,T)

Disease associations

OMIM: gene MIM:610334 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

9 associations (top):

StudyTraitp-value
GCST000817_88Height3.000000e-13
GCST001956_82Height4.000000e-09
GCST002223_57HDL cholesterol2.000000e-08
GCST002955_6Forced expiratory volume in 1 second (occupational environmental exposures interaction)4.000000e-07
GCST004232_74HDL cholesterol levels2.000000e-08
GCST005648_3Serum metabolite concentrations in chronic kidney disease2.000000e-12
GCST009391_185Metabolite levels5.000000e-09
GCST90011900_194Serum alkaline phosphatase levels3.000000e-10
GCST90020029_1137Waist circumference adjusted for body mass index1.000000e-08

EFO canonical traits (6, from GWAS)

EFO IDTrait name
EFO:0004612high density lipoprotein cholesterol measurement
EFO:0004314forced expiratory volume
EFO:0006994response to gases and fumes exposure
EFO:0010482gamma-aminoisobutyric acid measurement
EFO:0004533alkaline phosphatase measurement
EFO:0007789BMI-adjusted waist circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

ChemicalActions (top 5)PubMed papers
Tobacco Smoke Pollutiondecreases expression, decreases methylation3
Aflatoxin B1affects expression, decreases expression, decreases methylation3
Benzo(a)pyrenedecreases expression2
Cyclosporinedecreases expression2
methyleugenoldecreases expression1
triphenyl phosphateaffects expression1
terbufosincreases methylation1
beta-lapachonedecreases expression1
sodium arsenitedecreases expression1
S-(1,2-dichlorovinyl)cysteineaffects response to substance, increases expression, decreases expression1
perfluoro-n-nonanoic aciddecreases expression1
Acetaminophendecreases expression1
Atrazineincreases expression1
Calcitrioldecreases expression1
Fonofosincreases methylation1
Lipopolysaccharidesaffects response to substance, increases expression1
Nickelincreases expression1
Parathionincreases methylation1
Rotenoneincreases expression1
Triclosanincreases expression1
Valproic Aciddecreases expression, decreases methylation1
Vitamin Eincreases expression1
1-Methyl-4-phenylpyridiniumincreases expression1
Antirheumatic Agentsdecreases expression1
Okadaic Aciddecreases expression1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

CellosaurusNameCategorySex
CVCL_E0RCUbigene HeLa TMEM176A KOCancer cell lineFemale

Clinical trials (associated diseases)

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

No linked Atlas pages yet — the cross-entity mesh grows as the corpus expands.

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.4
BioBTree
v2.0.2

Sources 74

This page pulls from 74 datasets indexed by BioBTree:

alphafoldalphamissenseantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticsccdscellosauruschembl_activitychembl_targetciviccivic_evidenceclingen_dosageclingen_gene_validityclinical_trialsclinvarcollectrictd_gene_interactiondbsnpdepmapdiamond_similarityefoensemblentrezesm2_similarityexonfantom5_genefantom5_promotergenccgenerifgogoparentgtopdbgwasgwas_studyhgnchpointactinterprointogenjasparmeshmimmirdbmondomsigdborphanetorthologparalogpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assaypubmedreactomerefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorspliceaistring_interactiontranscriptufeatureuniprot