TMEM26

Summary

TMEM26 (transmembrane protein 26, HGNC:28550) is a protein-coding gene on chromosome 10q21.2, encoding Transmembrane protein 26 (Q6ZUK4).

This gene encodes a protein containing multiple transmembrane helices. It is a selective surface protein marker of brite/beige adipocytes, which may coexist with classical brown adipocytes in brown adipose tissue. Alternative splicing of this gene results in multiple transcript variants.

Source: NCBI Gene 219623 — RefSeq curated summary.

At a glance

• GWAS associations: 16
• Clinical variants (ClinVar): 44 total
• MANE Select transcript: NM_178505

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28550
Approved symbol	TMEM26
Name	transmembrane protein 26
Location	10q21.2
Locus type	gene with protein product
Status	Approved
Aliases	MGC35010, Em:AC068892.1
Ensembl gene	ENSG00000196932
Ensembl biotype	protein_coding
OMIM	617803
Entrez	219623

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 2 protein_coding, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000277749, ENST00000399298, ENST00000488505, ENST00000503886, ENST00000507507

RefSeq mRNA: 1 — MANE Select: NM_178505 NM_178505

CCDS: CCDS41530

Canonical transcript exons

ENST00000399298 — 6 exons

Exon	Start	End
ENSE00001537392	61406642	61410746
ENSE00001537402	61452891	61453381
ENSE00001597424	61428926	61429146
ENSE00001655795	61431219	61431332
ENSE00001694783	61413459	61413535
ENSE00001796327	61436170	61436248

Expression profiles

Bgee: expression breadth ubiquitous, 144 present calls, max score 91.75.

FANTOM5 (CAGE): breadth broad, TPM avg 0.8965 / max 311.9907, expressed in 379 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
109570	0.2338	106
109571	0.1892	91
109573	0.1770	50
109574	0.1695	65
109572	0.0530	8
109569	0.0399	13
109575	0.0341	8

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adrenal tissue	UBERON:0018303	91.75	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.68	silver quality
stromal cell of endometrium	CL:0002255	86.47	gold quality
spleen	UBERON:0002106	75.00	gold quality
smooth muscle tissue	UBERON:0001135	67.71	gold quality
metanephros cortex	UBERON:0010533	66.98	gold quality
rectum	UBERON:0001052	63.49	gold quality
gall bladder	UBERON:0002110	63.34	gold quality
colonic epithelium	UBERON:0000397	63.01	silver quality
vermiform appendix	UBERON:0001154	62.16	gold quality
adult mammalian kidney	UBERON:0000082	61.82	gold quality
endocervix	UBERON:0000458	61.82	gold quality
body of uterus	UBERON:0009853	61.75	gold quality
right lung	UBERON:0002167	61.74	gold quality
islet of Langerhans	UBERON:0000006	60.81	gold quality
endometrium	UBERON:0001295	59.56	gold quality
ectocervix	UBERON:0012249	59.50	gold quality
right testis	UBERON:0004534	59.23	gold quality
left testis	UBERON:0004533	59.12	gold quality
metanephros	UBERON:0000081	59.11	gold quality
adrenal gland	UBERON:0002369	58.76	gold quality
right adrenal gland cortex	UBERON:0035827	58.68	gold quality
testis	UBERON:0000473	58.49	gold quality
prostate gland	UBERON:0002367	58.43	gold quality
uterus	UBERON:0000995	58.07	gold quality
cortex of kidney	UBERON:0001225	57.79	gold quality
right lobe of liver	UBERON:0001114	57.49	gold quality
caecum	UBERON:0001153	57.37	gold quality
uterine cervix	UBERON:0000002	57.29	gold quality
left adrenal gland	UBERON:0001234	57.23	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.36

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

159 targeting TMEM26, 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-3163	100.00	77.23	8605
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3134	100.00	66.43	777
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-5688	99.96	73.23	4504

Literature-anchored findings (GeneRIF, showing 3)

• show novel expression of genes near regions of significantly associated SNPS, including TMEM26 and FOXA1 in airway epithelium and lung parenchyma, and ANK3 in alveolar macrophages in COPD (PMID:22986903)
• High TMEM26 expression was found to be associated with a higher risk of recurrence. (PMID:27224909)
• The role of TMEM26 in disrupting tight junctions and activating NF-kappaB signaling to promote epithelial-mesenchymal transition in esophageal squamous cell carcinoma. (PMID:37611445)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	tmem26b	ENSDARG00000014682
danio_rerio	tmem26a	ENSDARG00000077979
mus_musculus	Tmem26	ENSMUSG00000060044
rattus_norvegicus	Tmem26	ENSRNOG00000027859
drosophila_melanogaster	CG14238	FBGN0039429
caenorhabditis_elegans	Y119C1B.3	WBGENE00022469

Protein

Protein identifiers

Transmembrane protein 26 — Q6ZUK4 (reviewed: Q6ZUK4)

All UniProt accessions (2): H7BXI3, Q6ZUK4

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Isoforms (2)

UniProt ID	Names	Canonical?
Q6ZUK4-1	1	yes
Q6ZUK4-2	2

RefSeq proteins (1): NP_848600* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR019169	Transmembrane_26	Family

Pfam: PF09772

UniProt features (14 total): transmembrane region 8, splice variant 2, chain 1, compositionally biased region 1, glycosylation site 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6ZUK4-F1	78.08	0.45

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 (1): 110

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 121 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_DN, GSE45365_NK_CELL_VS_CD11B_DC_UP, chr10q21, MORF_RAD51L3, MARTORIATI_MDM4_TARGETS_NEUROEPITHELIUM_DN, CUI_TCF21_TARGETS_2_DN, MORF_ATF2, MORF_BCL2L11, MORF_PPP2R5B, MORF_KDR, MORF_PTPRR, MORF_PAX7, MORF_MYL3, MORF_MAP2K7, MORF_IL16

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

392 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMEM26	UCP1	P25874	817
TMEM26	CIDEA	O60543	803
TMEM26	PRDM16	Q9HAZ2	795
TMEM26	TBX1	O43435	786
TMEM26	TNFRSF9	Q07011	724
TMEM26	HOXC9	P31274	716
TMEM26	PPARGC1A	Q9UBK2	685
TMEM26	ZIC1	Q15915	669
TMEM26	CITED1	Q99966	658
TMEM26	DIO2	Q92813	644
TMEM26	LHX8	Q68G74	629
TMEM26	ADRB3	P13945	617
TMEM26	ELOVL3	Q9HB03	598
TMEM26	SLC27A1	Q6PCB7	588
TMEM26	SLC36A2	Q495M3	575

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A0A0R4IDX9, A0A2C9VBV6, A2ARJ3, A7T1N0, A7Y2X0, A8Y2U2, O12977, O17386, O35119, O70131, O76689, O80739, P31662, P52166, P70617, P79100, Q05005, Q08469, Q0WMJ8, Q3UP23, Q57UM0, Q5JK32, Q5R9C2, Q5W0B7, Q69RI8, Q6H4R6, Q6NPT7, Q6ZUK4, Q75G84, Q84MS3, Q84MS4, Q8BG16, Q8BJI1, Q8MPP0, Q90X07, Q92982, Q94KB1, Q94KB9, Q9FI00, Q9FY75

Diamond homologs: Q3UP23, Q6ZUK4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	38
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1276 predictions. Top by Δscore:

Variant	Effect	Δscore
10:61410747:C:CC	acceptor_gain	1.0000
10:61413454:CTTA:C	donor_loss	1.0000
10:61413455:TTAC:T	donor_loss	1.0000
10:61413456:TA:T	donor_loss	1.0000
10:61413457:A:AC	donor_gain	1.0000
10:61413457:ACCTG:A	donor_gain	1.0000
10:61413458:C:CA	donor_gain	1.0000
10:61413458:CCT:C	donor_gain	1.0000
10:61413458:CCTG:C	donor_gain	1.0000
10:61413458:CCTGC:C	donor_gain	1.0000
10:61413531:TATTC:T	acceptor_gain	1.0000
10:61413533:TTC:T	acceptor_gain	1.0000
10:61413534:TCC:T	acceptor_loss	1.0000
10:61413535:CCTAG:C	acceptor_loss	1.0000
10:61413536:C:CC	acceptor_gain	1.0000
10:61413536:CTAGA:C	acceptor_loss	1.0000
10:61413541:A:AC	acceptor_gain	1.0000
10:61414953:T:TA	donor_gain	1.0000
10:61417545:AT:A	donor_gain	1.0000
10:61410742:CTGTA:C	acceptor_gain	0.9900
10:61412881:T:TA	donor_gain	0.9900
10:61413453:ACTT:A	donor_loss	0.9900
10:61413457:AC:A	donor_gain	0.9900
10:61413458:CC:C	donor_gain	0.9900
10:61413534:TC:T	acceptor_gain	0.9900
10:61413535:CC:C	acceptor_gain	0.9900
10:61414939:A:AC	donor_gain	0.9900
10:61414940:C:CC	donor_gain	0.9900
10:61414985:T:A	donor_gain	0.9900
10:61415028:TC:T	donor_gain	0.9900

AlphaMissense

2378 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:61410553:C:A	K292N	0.998
10:61410553:C:G	K292N	0.998
10:61410562:A:C	F289L	0.998
10:61410562:A:T	F289L	0.998
10:61410564:A:G	F289L	0.998
10:61413475:A:C	F222L	0.998
10:61413475:A:T	F222L	0.998
10:61413477:A:G	F222L	0.998
10:61410550:G:C	N293K	0.997
10:61410550:G:T	N293K	0.997
10:61413476:A:C	F222C	0.997
10:61413492:A:G	W217R	0.997
10:61413492:A:T	W217R	0.997
10:61413498:A:G	W215R	0.997
10:61413498:A:T	W215R	0.997
10:61428958:G:C	F191L	0.997
10:61428958:G:T	F191L	0.997
10:61428959:A:G	F191S	0.997
10:61428960:A:G	F191L	0.997
10:61428972:C:G	D187H	0.997
10:61428978:C:G	A185P	0.997
10:61410565:G:C	F288L	0.996
10:61410565:G:T	F288L	0.996
10:61410567:A:G	F288L	0.996
10:61410625:G:C	F268L	0.996
10:61410625:G:T	F268L	0.996
10:61410627:A:G	F268L	0.996
10:61413476:A:G	F222S	0.996
10:61428965:A:G	L189P	0.996
10:61428971:T:C	D187G	0.996

dbSNP variants (sampled 300 via entrez): RS1000030406 (10:61446586 C>A,G), RS1000111906 (10:61450500 T>C), RS1000141502 (10:61441269 T>C,G), RS1000142677 (10:61450801 G>A), RS1000155284 (10:61421802 C>G,T), RS1000186845 (10:61426649 G>T), RS1000328281 (10:61432709 T>C,G), RS1000356477 (10:61444920 C>G), RS1000450884 (10:61430133 A>G), RS1000537721 (10:61416120 G>A,C,T), RS1000583225 (10:61416334 C>T), RS1000612024 (10:61454946 T>C), RS1000768446 (10:61420682 T>A,G), RS1000784150 (10:61433051 C>T), RS1000861387 (10:61414958 T>C)

Disease associations

OMIM: gene MIM:617803 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

16 associations (top):

Study	Trait	p-value
GCST000394_2	Diastolic blood pressure	1.000000e-09
GCST001694_4	Response to taxane treatment (paclitaxel)	9.000000e-06
GCST002788_4	Milk allergy	5.000000e-06
GCST003542_49	Night sleep phenotypes	4.000000e-06
GCST003628_5	Clozapine-induced agranulocytosis/granulocytopenia in treatment-resistant schizophrenia	2.000000e-06
GCST005580_153	Intraocular pressure	7.000000e-09
GCST005580_312	Intraocular pressure	5.000000e-09
GCST006479_69	Diverticular disease	7.000000e-07
GCST006607_1	Response to TNF inhibitor in rheumatoid arthritis (erythrocyte sedimentation rate)	6.000000e-08
GCST006979_588	Heel bone mineral density	9.000000e-10
GCST008595_140	Cognitive ability, years of educational attainment or schizophrenia (pleiotropy)	1.000000e-09
GCST010320_16	PR interval	2.000000e-10
GCST010321_22	PR interval	3.000000e-10
GCST010988_441	Adult body size	3.000000e-08
GCST011962_4	HIgh-sensitivity cardiac troponin T levels (high vs low)	2.000000e-06
GCST90000047_207	Age at first sexual intercourse	4.000000e-09

EFO canonical traits (11, from GWAS)

EFO ID	Trait name
EFO:0006336	diastolic blood pressure
EFO:0007019	milk allergy measurement
EFO:0004695	intraocular pressure measurement
EFO:0009959	diverticular disease
EFO:0004653	response to TNF antagonist
EFO:0009270	heel bone mineral density
EFO:0004337	intelligence
EFO:0004784	self reported educational attainment
EFO:0004462	PR interval
EFO:0005043	cardiac troponin T measurement
EFO:0009749	age at first sexual intercourse measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, increases expression, increases methylation	3
propionaldehyde	increases expression	1
bisphenol A	increases expression	1
arsenite	increases methylation	1
sodium arsenite	increases expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
abrine	decreases expression	1
incobotulinumtoxinA	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Melphalan	decreases expression	1
Plant Extracts	decreases expression, affects cotreatment	1
Aflatoxin B1	increases methylation	1
Okadaic Acid	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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