TMEM120B

Summary

TMEM120B (transmembrane protein 120B, HGNC:32008) is a protein-coding gene on chromosome 12q24.31, encoding Transmembrane protein 120B (A0PK00). Necessary for efficient adipogenesis.

Predicted to be involved in fat cell differentiation and protein heterooligomerization. Predicted to be located in membrane and nucleus. Predicted to be active in nuclear inner membrane.

Source: NCBI Gene 144404 — RefSeq curated summary.

At a glance

• GWAS associations: 23
• Clinical variants (ClinVar): 66 total
• MANE Select transcript: NM_001080825

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:32008
Approved symbol	TMEM120B
Name	transmembrane protein 120B
Location	12q24.31
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000188735
Ensembl biotype	protein_coding
OMIM	616551
Entrez	144404

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 3 protein_coding_CDS_not_defined, 3 protein_coding, 1 nonsense_mediated_decay

ENST00000342607, ENST00000411958, ENST00000416147, ENST00000449592, ENST00000538055, ENST00000540377, ENST00000541467

RefSeq mRNA: 1 — MANE Select: NM_001080825 NM_001080825

CCDS: CCDS41852

Canonical transcript exons

ENST00000449592 — 12 exons

Exon	Start	End
ENSE00001368632	121752128	121752223
ENSE00001369336	121712752	121712964
ENSE00001371117	121750380	121750439
ENSE00001379205	121748326	121748442
ENSE00001384413	121770907	121770972
ENSE00001387170	121743629	121743747
ENSE00001390940	121771488	121771549
ENSE00001723437	121775609	121782068
ENSE00003481022	121761649	121761738
ENSE00003615722	121773421	121773513
ENSE00003670065	121774658	121774722
ENSE00003687882	121775062	121775130

Expression profiles

Bgee: expression breadth ubiquitous, 208 present calls, max score 95.01.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.3467 / max 201.6748, expressed in 1749 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
128445	12.1297	1749
128446	0.1536	59
128447	0.0634	22

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	95.01	gold quality
cerebellar hemisphere	UBERON:0002245	94.88	gold quality
cerebellar cortex	UBERON:0002129	94.72	gold quality
right uterine tube	UBERON:0001302	94.22	gold quality
cerebellum	UBERON:0002037	93.28	gold quality
endocervix	UBERON:0000458	89.15	gold quality
hindlimb stylopod muscle	UBERON:0004252	88.31	gold quality
nucleus accumbens	UBERON:0001882	86.44	gold quality
ectocervix	UBERON:0012249	85.76	gold quality
adenohypophysis	UBERON:0002196	84.96	gold quality
pituitary gland	UBERON:0000007	84.78	gold quality
body of pancreas	UBERON:0001150	84.76	gold quality
putamen	UBERON:0001874	84.47	gold quality
left lobe of thyroid gland	UBERON:0001120	84.30	gold quality
stromal cell of endometrium	CL:0002255	84.14	gold quality
right lobe of thyroid gland	UBERON:0001119	84.05	gold quality
gastrocnemius	UBERON:0001388	84.00	gold quality
muscle of leg	UBERON:0001383	83.69	gold quality
caudate nucleus	UBERON:0001873	83.63	gold quality
body of uterus	UBERON:0009853	83.57	gold quality
sural nerve	UBERON:0015488	83.34	gold quality
thyroid gland	UBERON:0002046	83.19	gold quality
left uterine tube	UBERON:0001303	83.16	gold quality
muscle organ	UBERON:0001630	81.89	gold quality
metanephros cortex	UBERON:0010533	81.58	gold quality
cortical plate	UBERON:0005343	81.27	gold quality
apex of heart	UBERON:0002098	81.25	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	81.17	silver quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.78	gold quality
body of stomach	UBERON:0001161	80.78	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-112	yes	14.41
E-ANND-3	yes	7.51
E-GEOD-86618	no	139.31

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

213 targeting TMEM120B, 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-3613-3P	100.00	76.36	7965
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-6798-5P	100.00	65.77	699
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-7153-5P	99.94	68.89	1006
HSA-MIR-1-3P	99.93	72.35	1914

Literature-anchored findings (GeneRIF, showing 1)

• TMEM120B strengthens breast cancer cell stemness and accelerates chemotherapy resistance via beta1-integrin/FAK-TAZ-mTOR signaling axis by binding to MYH9. (PMID:38504374)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	tmem120b	ENSDARG00000042929
mus_musculus	Tmem120b	ENSMUSG00000054434
rattus_norvegicus	Tmem120b	ENSRNOG00000048050
drosophila_melanogaster	CG32795	FBGN0040384
caenorhabditis_elegans		WBGENE00019716

Paralogs (1): TMEM120A (ENSG00000189077)

Protein

Protein identifiers

Transmembrane protein 120B — A0PK00 (reviewed: A0PK00)

All UniProt accessions (3): A0PK00, F5H465, H0YG77

UniProt curated annotations — full annotation on UniProt →

Function. Necessary for efficient adipogenesis. Does not show ion channel activity.

Subunit / interactions. Heterooligomer with TMEM120A.

Subcellular location. Nucleus inner membrane.

Similarity. Belongs to the TMEM120 family.

RefSeq proteins (1): NP_001074294* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR012926	TMEM120A/B	Family

Pfam: PF07851

UniProt features (9 total): transmembrane region 6, chain 1, coiled-coil region 1, sequence conflict 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
7F73	ELECTRON MICROSCOPY	4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A0PK00-F1	91.77	0.69

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 137 (showing top): GOBP_FAT_CELL_DIFFERENTIATION, SENESE_HDAC3_TARGETS_DN, GOBP_PROTEIN_HETEROOLIGOMERIZATION, GOCC_NUCLEAR_ENVELOPE, GOCC_ORGANELLE_INNER_MEMBRANE, GOCC_NUCLEAR_INNER_MEMBRANE, GOCC_NUCLEAR_MEMBRANE, KIM_WT1_TARGETS_DN, chr12q24, GOMF_PASSIVE_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GAZDA_DIAMOND_BLACKFAN_ANEMIA_ERYTHROID_DN, GOMF_TRANSPORTER_ACTIVITY, KRIGE_RESPONSE_TO_TOSEDOSTAT_6HR_DN, GOCC_ORGANELLE_ENVELOPE, DAVICIONI_MOLECULAR_ARMS_VS_ERMS_UP

GO Biological Process (2): fat cell differentiation (GO:0045444), protein heterooligomerization (GO:0051291)

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

GO Cellular Component (3): nuclear inner membrane (GO:0005637), nucleus (GO:0005634), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell differentiation	1
protein complex oligomerization	1
binding	1
organelle inner membrane	1
nuclear membrane	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

656 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMEM120B	RHOF	Q9HBH0	563
TMEM120B	TMEM60	Q9H2L4	495
TMEM120B	NIBAN2	Q96TA1	475
TMEM120B	MORN3	Q6PF18	433
TMEM120B	TMEM81	Q6P7N7	433
TMEM120B	ZNF654	Q8IZM8	430
TMEM120B	FAM86B1	Q8N7N1	419
TMEM120B	RLIG1	Q8N999	409
TMEM120B	CCDC144A	A2RUR9	407
TMEM120B	KLHDC8B	Q8IXV7	372
TMEM120B	TMEM52	Q8NDY8	370
TMEM120B	PRELID3A	Q96N28	368
TMEM120B	ZNF440	Q8IYI8	365
TMEM120B	SUZ12	Q15022	365
TMEM120B	TMEM236	Q5W0B7	362

IntAct

236 interactions, top by confidence:

A	B	Type	Score
TMEM120B	CCNDBP1	psi-mi:“MI:0915”(physical association)	0.560
CCNDBP1	TMEM120B	psi-mi:“MI:0915”(physical association)	0.560
TMEM120B	REEP2	psi-mi:“MI:0915”(physical association)	0.560
TMEM120B	ANKS6	psi-mi:“MI:0915”(physical association)	0.560
TMEM120B	CPLX4	psi-mi:“MI:0915”(physical association)	0.560
TMEM120B	RETREG3	psi-mi:“MI:0915”(physical association)	0.560
TMEM120B	NCAPH2	psi-mi:“MI:0915”(physical association)	0.560
TMEM120B	BNIP3L	psi-mi:“MI:0915”(physical association)	0.560
TMEM120B	STX2	psi-mi:“MI:0915”(physical association)	0.560
TMEM120B	CD74	psi-mi:“MI:0915”(physical association)	0.560
TMEM120B	JPH1	psi-mi:“MI:0915”(physical association)	0.560
TMEM120B	CREB3L1	psi-mi:“MI:0915”(physical association)	0.560
TMEM120B	TMPRSS2	psi-mi:“MI:0915”(physical association)	0.560
TMEM120B	RNF5	psi-mi:“MI:0915”(physical association)	0.560
TMEM120B	SLC1A3	psi-mi:“MI:0915”(physical association)	0.560
TMEM120B	SLC18A1	psi-mi:“MI:0915”(physical association)	0.560
TMEM120B	IL7R	psi-mi:“MI:0915”(physical association)	0.560
TMEM120B	KCNJ6	psi-mi:“MI:0915”(physical association)	0.560
TMEM120B	MRPS18B	psi-mi:“MI:0915”(physical association)	0.560
TMEM120B	TLCD4	psi-mi:“MI:0915”(physical association)	0.560
TMEM120B	APOA5	psi-mi:“MI:0915”(physical association)	0.560
TMEM120B	EBP	psi-mi:“MI:0915”(physical association)	0.560
TMEM120B	STOM	psi-mi:“MI:0915”(physical association)	0.560
TMEM120B	FFAR2	psi-mi:“MI:0915”(physical association)	0.560
TMEM120B	HSD17B11	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (139): TMEM120B (Two-hybrid), TMEM120B (Affinity Capture-MS), TMEM120B (Affinity Capture-MS), TMEM120B (Affinity Capture-MS), TMEM120B (Proximity Label-MS), TMEM120B (Proximity Label-MS), TMEM120B (Affinity Capture-MS), TMEM120B (Affinity Capture-MS), TMEM120B (Affinity Capture-MS), TMEM120B (Affinity Capture-MS), TMEM120B (Affinity Capture-MS), TMEM120B (Affinity Capture-MS), TMEM120B (Affinity Capture-MS), TMEM120B (Affinity Capture-MS), TMEM120B (Affinity Capture-MS)

ESM2 similar proteins: A0PK00, A1L2R7, A2BIE7, A2VE61, A3KNK1, A6QPF8, A7XZ53, A8DZH4, B1AZA5, D3ZEH5, D3ZXD8, E1BD52, O35052, P58749, P98191, Q05B45, Q0VFK3, Q15035, Q17QL9, Q1LY80, Q3TA38, Q3UMR5, Q5EAX9, Q5EAY8, Q5FWV6, Q5HZE2, Q5R7B1, Q5U239, Q5ZMP3, Q63ZG0, Q68EY2, Q6DE21, Q6ZMG9, Q8BXA5, Q8C172, Q8C1E7, Q8CIF6, Q8N5B7, Q8NBJ9, Q8WVP7

Diamond homologs: A0PK00, A1L2R7, A3KNK1, A6QPF8, Q05B45, Q1LY80, Q3TA38, Q54IK2, Q5EAX9, Q5FWV6, Q5HZE2, Q63ZG0, Q6DE21, Q8C1E7, Q9BXJ8, Q9U1M2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	53
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2797 predictions. Top by Δscore:

Variant	Effect	Δscore
12:121712960:TGCAG:T	donor_loss	1.0000
12:121712961:GCAGG:G	donor_loss	1.0000
12:121712962:CAGGT:C	donor_loss	1.0000
12:121712963:AG:A	donor_loss	1.0000
12:121712964:GG:G	donor_loss	1.0000
12:121712965:G:GA	donor_loss	1.0000
12:121712966:T:A	donor_loss	1.0000
12:121743745:GAG:G	donor_gain	1.0000
12:121748317:T:TA	acceptor_gain	1.0000
12:121748324:A:AG	acceptor_gain	1.0000
12:121748324:AG:A	acceptor_gain	1.0000
12:121748325:G:GT	acceptor_gain	1.0000
12:121748325:GG:G	acceptor_gain	1.0000
12:121748325:GGTGC:G	acceptor_gain	1.0000
12:121748434:G:GT	donor_gain	1.0000
12:121748441:GG:G	donor_gain	1.0000
12:121748441:GGGT:G	donor_loss	1.0000
12:121748442:GG:G	donor_gain	1.0000
12:121748443:G:GG	donor_gain	1.0000
12:121748443:G:T	donor_gain	1.0000
12:121748444:T:G	donor_loss	1.0000
12:121750435:GCCAA:G	donor_gain	1.0000
12:121750436:CCAAG:C	donor_loss	1.0000
12:121750437:CAAG:C	donor_loss	1.0000
12:121750438:AAGTA:A	donor_loss	1.0000
12:121750439:AGTA:A	donor_loss	1.0000
12:121750440:G:GG	donor_gain	1.0000
12:121750440:GTA:G	donor_loss	1.0000
12:121761734:TCAAG:T	donor_loss	1.0000
12:121761735:CAAGG:C	donor_loss	1.0000

AlphaMissense

2235 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:121752140:G:C	K126N	1.000
12:121752140:G:T	K126N	1.000
12:121761683:T:A	W166R	0.999
12:121761683:T:C	W166R	0.999
12:121761720:T:A	L178H	0.999
12:121761720:T:C	L178P	0.999
12:121770917:T:A	W188R	0.999
12:121770917:T:C	W188R	0.999
12:121770920:T:A	W189R	0.999
12:121770920:T:C	W189R	0.999
12:121752138:A:G	K126E	0.998
12:121752147:T:C	Y129H	0.998
12:121752161:G:C	K133N	0.998
12:121752161:G:T	K133N	0.998
12:121761708:G:C	R174P	0.998
12:121761711:A:T	E175V	0.998
12:121761712:G:C	E175D	0.998
12:121761712:G:T	E175D	0.998
12:121761730:C:A	N181K	0.998
12:121761730:C:G	N181K	0.998
12:121770919:G:C	W188C	0.998
12:121770919:G:T	W188C	0.998
12:121770922:G:C	W189C	0.998
12:121770922:G:T	W189C	0.998
12:121770971:T:A	W206R	0.998
12:121770971:T:C	W206R	0.998
12:121773452:G:C	Q237H	0.998
12:121773452:G:T	Q237H	0.998
12:121773472:T:C	L244P	0.998
12:121774663:T:C	F260L	0.998

dbSNP variants (sampled 300 via entrez): RS1000104748 (12:121729691 C>T), RS1000135326 (12:121754530 C>T), RS1000233999 (12:121782059 C>T), RS1000239909 (12:121745331 C>T), RS1000284728 (12:121781892 T>C,G), RS1000294405 (12:121757749 C>T), RS1000336452 (12:121711537 G>A), RS1000382325 (12:121737532 C>T), RS1000399433 (12:121751851 G>A,C), RS1000408805 (12:121723432 C>G), RS1000620836 (12:121753271 C>G,T), RS1000622514 (12:121713031 C>A,G,T), RS1000675387 (12:121745111 C>G), RS1000736849 (12:121712615 G>C), RS1000762663 (12:121733212 G>A)

Disease associations

OMIM: gene MIM:616551 | disease phenotypes: MIM:258040

GenCC curated gene-disease

Mondo (1): exstrophy-epispadias complex (MONDO:0017919)

Orphanet (2): Exstrophy-epispadias complex (Orphanet:322), Cloacal exstrophy (Orphanet:93929)

HPO phenotypes

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

GWAS associations

23 associations (top):

Study	Trait	p-value
GCST002184_10	Mean platelet volume	6.000000e-38
GCST002937_12	Molybdenum levels	6.000000e-06
GCST004599_196	Mean platelet volume	0.000000e+00
GCST004603_124	Platelet count	1.000000e-45
GCST004607_85	Plateletcrit	6.000000e-81
GCST004607_86	Plateletcrit	2.000000e-26
GCST004616_97	Platelet distribution width	1.000000e-184
GCST004619_216	Reticulocyte fraction of red cells	3.000000e-09
GCST010242_192	HDL cholesterol levels	5.000000e-08
GCST90002385_7	High light scatter reticulocyte count	3.000000e-10
GCST90002386_340	High light scatter reticulocyte percentage of red cells	4.000000e-13
GCST90002387_130	Immature fraction of reticulocytes	8.000000e-11
GCST90002395_144	Mean platelet volume	1.000000e-10
GCST90002395_145	Mean platelet volume	0.000000e+00
GCST90002396_539	Mean reticulocyte volume	4.000000e-44
GCST90002398_153	Neutrophil count	1.000000e-13
GCST90002400_735	Plateletcrit	9.000000e-196
GCST90002400_736	Plateletcrit	7.000000e-17
GCST90002401_51	Platelet distribution width	2.000000e-212
GCST90002402_206	Platelet count	4.000000e-127
GCST90002405_246	Reticulocyte count	7.000000e-17
GCST90002406_351	Reticulocyte fraction of red cells	3.000000e-22
GCST90002407_298	White blood cell count	9.000000e-15

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0004309	platelet count
EFO:0007985	platelet crit
EFO:0007984	platelet component distribution width
EFO:0007986	reticulocyte count
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0010701	mean reticulocyte volume
EFO:0004833	neutrophil count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Estradiol	increases expression, affects cotreatment, decreases expression	2
bisphenol A	decreases expression	1
sodium arsenite	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
abrine	decreases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, increases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	affects cotreatment, decreases expression	1
bisphenol S	affects cotreatment, decreases methylation	1
jinfukang	affects cotreatment, increases expression	1
NSC 689534	affects binding, decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Leflunomide	increases expression	1
Catechin	affects cotreatment, increases expression	1
Cisplatin	affects cotreatment, increases expression	1
Copper	affects binding, decreases expression	1
Doxorubicin	decreases expression	1
Methotrexate	decreases expression	1
Plant Extracts	increases expression, affects cotreatment	1
Progesterone	affects cotreatment, decreases expression	1
Rifampin	decreases expression	1
Smoke	decreases expression	1
Tetrachlorodibenzodioxin	affects cotreatment, decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	decreases expression	1
Antirheumatic Agents	increases expression	1
Cadmium Chloride	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04760028	PHASE4	COMPLETED	Study on the Influencing Factors of Electroencephalogram Parameters Under Anesthesia
NCT06106425	Not specified	UNKNOWN	Diagnostic and Prognostic Criteria of EEG in Neonatal Convulsions at Assiut University Children Hospital