TMUB2

Summary

TMUB2 (transmembrane and ubiquitin like domain containing 2, HGNC:28459) is a protein-coding gene on chromosome 17q21.31, encoding Transmembrane and ubiquitin-like domain-containing protein 2 (Q71RG4).

Predicted to be involved in ERAD pathway. Predicted to be located in membrane.

Source: NCBI Gene 79089 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 60 total
• MANE Select transcript: NM_001076674

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28459
Approved symbol	TMUB2
Name	transmembrane and ubiquitin like domain containing 2
Location	17q21.31
Locus type	gene with protein product
Status	Approved
Aliases	MGC3123
Ensembl gene	ENSG00000168591
Ensembl biotype	protein_coding
Entrez	79089

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 15 protein_coding, 3 nonsense_mediated_decay

ENST00000319511, ENST00000357984, ENST00000446571, ENST00000538716, ENST00000587172, ENST00000587326, ENST00000587630, ENST00000587775, ENST00000587989, ENST00000588413, ENST00000589184, ENST00000589785, ENST00000589856, ENST00000590235, ENST00000592825, ENST00000890098, ENST00000890099, ENST00000890100

RefSeq mRNA: 22 — MANE Select: NM_001076674 NM_001076674, NM_001330235, NM_001353173, NM_001353174, NM_001353175, NM_001353176, NM_001353177, NM_001353178, NM_001353180, NM_001353181, NM_001353182, NM_001353183, NM_001353184, NM_001353185, NM_001353186, NM_001353187, NM_001353188, NM_001353189, NM_001353190, NM_001353191, NM_024107, NM_177441

CCDS: CCDS11479, CCDS54134, CCDS82137

Canonical transcript exons

ENST00000538716 — 4 exons

Exon	Start	End
ENSE00002243157	44186972	44187109
ENSE00002770866	44190501	44191929
ENSE00003495800	44189022	44189588
ENSE00003640746	44187676	44187743

Expression profiles

Bgee: expression breadth ubiquitous, 282 present calls, max score 95.09.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 27.1029 / max 201.3321, expressed in 1821 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
161119	18.0210	1813
161117	8.3429	1773
161118	0.7390	477

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	95.09	gold quality
right testis	UBERON:0004534	94.46	gold quality
left testis	UBERON:0004533	94.40	gold quality
right lobe of thyroid gland	UBERON:0001119	94.25	gold quality
left lobe of thyroid gland	UBERON:0001120	93.94	gold quality
lower esophagus mucosa	UBERON:0035834	93.91	gold quality
transverse colon	UBERON:0001157	93.70	gold quality
mucosa of transverse colon	UBERON:0004991	93.56	gold quality
spleen	UBERON:0002106	93.36	gold quality
body of stomach	UBERON:0001161	93.33	gold quality
thyroid gland	UBERON:0002046	93.21	gold quality
mucosa of stomach	UBERON:0001199	93.17	gold quality
small intestine Peyer’s patch	UBERON:0003454	93.11	gold quality
right uterine tube	UBERON:0001302	93.03	gold quality
metanephros cortex	UBERON:0010533	92.98	gold quality
right adrenal gland	UBERON:0001233	92.92	gold quality
testis	UBERON:0000473	92.91	gold quality
right coronary artery	UBERON:0001625	92.88	gold quality
descending thoracic aorta	UBERON:0002345	92.84	gold quality
lower esophagus	UBERON:0013473	92.84	gold quality
right hemisphere of cerebellum	UBERON:0014890	92.84	gold quality
right adrenal gland cortex	UBERON:0035827	92.83	gold quality
lower esophagus muscularis layer	UBERON:0035833	92.83	gold quality
popliteal artery	UBERON:0002250	92.81	gold quality
endocervix	UBERON:0000458	92.80	gold quality
tibial artery	UBERON:0007610	92.80	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	92.78	gold quality
minor salivary gland	UBERON:0001830	92.72	gold quality
cerebellar hemisphere	UBERON:0002245	92.66	gold quality
apex of heart	UBERON:0002098	92.65	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.96

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

82 targeting TMUB2, 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-371B-5P	99.99	75.34	4759
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777
HSA-MIR-302C-3P	99.89	71.20	1778
HSA-MIR-302D-3P	99.89	71.25	1777
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-373-3P	99.84	70.68	1668
HSA-MIR-520E-3P	99.84	70.55	1698
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-372-3P	99.83	70.58	1691
HSA-MIR-520A-3P	99.83	70.59	1687
HSA-MIR-520B-3P	99.83	70.56	1699
HSA-MIR-520C-3P	99.83	70.56	1699
HSA-MIR-520D-3P	99.83	70.78	1676

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	tmub2	ENSDARG00000056467
mus_musculus	Tmub2	ENSMUSG00000034757
rattus_norvegicus	Tmub2	ENSRNOG00000020916
caenorhabditis_elegans		WBGENE00015126

Paralogs (1): TMUB1 (ENSG00000164897)

Protein

Protein identifiers

Transmembrane and ubiquitin-like domain-containing protein 2 — Q71RG4 (reviewed: Q71RG4)

All UniProt accessions (6): Q71RG4, E7ESS3, K7EJF7, K7EKW3, K7EPS1, K7ESL5

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

Isoforms (4)

UniProt ID	Names	Canonical?
Q71RG4-1	1	yes
Q71RG4-2	2
Q71RG4-3	3
Q71RG4-4	4

RefSeq proteins (22): NP_001070142, NP_001317164, NP_001340102, NP_001340103, NP_001340104, NP_001340105, NP_001340106, NP_001340107, NP_001340109, NP_001340110, NP_001340111, NP_001340112, NP_001340113, NP_001340114, NP_001340115, NP_001340116, NP_001340117, NP_001340118, NP_001340119, NP_001340120, NP_077012, NP_803190 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000626	Ubiquitin-like_dom	Domain
IPR029071	Ubiquitin-like_domsf	Homologous_superfamily
IPR040352	TMUB1/2	Family

Pfam: PF00240

UniProt features (15 total): splice variant 5, transmembrane region 3, region of interest 2, chain 1, sequence variant 1, sequence conflict 1, domain 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q71RG4-F1	63.39	0.16

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 152 (showing top): TGGTGCT_MIR29A_MIR29B_MIR29C, SHEPARD_BMYB_MORPHOLINO_UP, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, CREBP1_Q2, CAGCTG_AP4_Q5, CREB_Q4, TGACATY_UNKNOWN, TSENG_IRS1_TARGETS_DN, CCCNNNNNNAAGWT_UNKNOWN, NAKAMURA_TUMOR_ZONE_PERIPHERAL_VS_CENTRAL_DN, RYTTCCTG_ETS2_B, ELK1_01, LEF1_Q6

GO Biological Process (1): ERAD pathway (GO:0036503)

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:

Category	Terms
proteasomal protein catabolic process	1
response to endoplasmic reticulum stress	1
response to chemical	1
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

958 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMUB2	RNF185	Q96GF1	694
TMUB2	TMEM259	Q4ZIN3	663
TMUB2	AMMECR1L	Q6DCA0	584
TMUB2	DNAJC14	Q6Y2X3	580
TMUB2	ARMH3	Q5T2E6	540
TMUB2	TLK2	Q86UE8	535
TMUB2	EIF2B4	Q9UI10	519
TMUB2	TBC1D10B	Q4KMP7	511
TMUB2	C6orf120	Q7Z4R8	495
TMUB2	FAM8A1	Q9UBU6	491
TMUB2	GPATCH3	Q96I76	485
TMUB2	ZKSCAN5	Q9Y2L8	463
TMUB2	CNOT10	Q9H9A5	462
TMUB2	DDX50	Q9BQ39	456
TMUB2	TMUB1	Q9BVT8	456

IntAct

81 interactions, top by confidence:

A	B	Type	Score
SGTA	TMUB2	psi-mi:“MI:0915”(physical association)	0.560
TMUB2	BCL2L13	psi-mi:“MI:0915”(physical association)	0.560
TMUB2	UBQLN1	psi-mi:“MI:0915”(physical association)	0.560
BCL2L13	TMUB2	psi-mi:“MI:0915”(physical association)	0.560
UBQLN1	TMUB2	psi-mi:“MI:0915”(physical association)	0.560
TMUB2	SGTA	psi-mi:“MI:0915”(physical association)	0.560
TMUB2	MS4A4A	psi-mi:“MI:0915”(physical association)	0.560
GJB3	TMUB2	psi-mi:“MI:0915”(physical association)	0.560
AQP6	TMUB2	psi-mi:“MI:0915”(physical association)	0.560
TMUB2	ERGIC3	psi-mi:“MI:0915”(physical association)	0.560
IL10RA	TMUB2	psi-mi:“MI:0915”(physical association)	0.560
TMUB2	GOLM1	psi-mi:“MI:0915”(physical association)	0.560
ARL13B	TMUB2	psi-mi:“MI:0915”(physical association)	0.560
UPK1B	TMUB2	psi-mi:“MI:0915”(physical association)	0.560
FAM209A	TMUB2	psi-mi:“MI:0915”(physical association)	0.560
TMUB2	THSD7A	psi-mi:“MI:0915”(physical association)	0.560
TMUB2	GPX8	psi-mi:“MI:0915”(physical association)	0.560
TMEM52B	TMUB2	psi-mi:“MI:0915”(physical association)	0.560
NEMP1	TMUB2	psi-mi:“MI:0915”(physical association)	0.560
SLC10A1	TMUB2	psi-mi:“MI:0915”(physical association)	0.560
DPEP1	ILVBL	psi-mi:“MI:0914”(association)	0.530
SLC15A1	METTL15	psi-mi:“MI:0914”(association)	0.530
REEP5	SCAMP1	psi-mi:“MI:0914”(association)	0.530
DUSP3	ERLIN1	psi-mi:“MI:0914”(association)	0.530
REEP5	PLSCR1	psi-mi:“MI:0914”(association)	0.530

BioGRID (63): TMUB2 (Two-hybrid), TMUB2 (Two-hybrid), TMUB2 (Two-hybrid), TMUB2 (Two-hybrid), TMUB2 (Affinity Capture-MS), TMUB2 (Affinity Capture-MS), TMUB2 (Affinity Capture-MS), TMUB2 (Affinity Capture-MS), TMEM259 (Affinity Capture-MS), ERLIN1 (Affinity Capture-MS), TMUB1 (Affinity Capture-MS), ERLIN2 (Affinity Capture-MS), TMUB2 (Affinity Capture-MS), TMUB2 (Two-hybrid), TMUB2 (Two-hybrid)

ESM2 similar proteins: O70622, Q14154, Q29RU0, Q2HJA8, Q3KPV4, Q3T1H8, Q3UHI4, Q3V209, Q3ZBI9, Q4FZV7, Q4V9Y1, Q4ZIN3, Q53AQ4, Q566M8, Q58DS4, Q5DTZ6, Q5F479, Q5JV73, Q5R9S0, Q5RF74, Q5RF77, Q6P135, Q6P1H6, Q6P4T1, Q6PL24, Q6WN19, Q6ZQM0, Q71RG4, Q76N89, Q7TP65, Q7TSG2, Q7ZUK0, Q810L3, Q86XL3, Q86XS8, Q8BYU6, Q8CIK8, Q8CIN9, Q8CIV2, Q8R2K4

Diamond homologs: P34256, Q2HJA8, Q3KPV4, Q3V209, Q3ZBI9, Q4FZV7, Q4V9Y1, Q53AQ4, Q6P135, Q71RG4, Q9BVT8, Q9JMG3

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 60 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.

GO biological processes:

GO term	Partners	Fold	FDR
ERAD pathway	7	25.9×	3e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	49
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1103 predictions. Top by Δscore:

Variant	Effect	Δscore
17:44187674:A:AG	acceptor_gain	1.0000
17:44187675:G:GG	acceptor_gain	1.0000
17:44187675:GT:G	acceptor_gain	1.0000
17:44190482:A:AG	acceptor_gain	1.0000
17:44190483:T:G	acceptor_gain	1.0000
17:44190491:A:AG	acceptor_gain	1.0000
17:44190492:T:G	acceptor_gain	1.0000
17:44190496:TACAG:T	acceptor_loss	1.0000
17:44190498:C:G	acceptor_gain	1.0000
17:44190498:CAGCA:C	acceptor_loss	1.0000
17:44190499:A:AG	acceptor_gain	1.0000
17:44190500:G:GG	acceptor_gain	1.0000
17:44190500:GC:G	acceptor_gain	1.0000
17:44190500:GCA:G	acceptor_gain	1.0000
17:44190500:GCAA:G	acceptor_gain	1.0000
17:44190500:GCAAA:G	acceptor_gain	1.0000
17:44187108:AG:A	donor_loss	0.9900
17:44187109:GGTG:G	donor_loss	0.9900
17:44187110:G:A	donor_loss	0.9900
17:44187111:T:A	donor_loss	0.9900
17:44189586:GAG:G	donor_gain	0.9900
17:44190482:AT:A	acceptor_gain	0.9900
17:44190483:T:TA	acceptor_gain	0.9900
17:44190497:A:AG	acceptor_gain	0.9900
17:44189589:G:A	donor_loss	0.9800
17:44189590:T:A	donor_loss	0.9800
17:44189591:GAGTG:G	donor_loss	0.9800
17:44187052:A:T	donor_gain	0.9700
17:44187745:T:G	donor_loss	0.9700
17:44189021:GC:G	acceptor_gain	0.9700

AlphaMissense

2065 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:44190832:A:C	S312R	1.000
17:44190834:C:A	S312R	1.000
17:44190834:C:G	S312R	1.000
17:44190754:T:A	W286R	0.999
17:44190754:T:C	W286R	0.999
17:44190809:T:C	L304P	0.999
17:44190824:T:A	V309D	0.999
17:44189519:T:C	L178P	0.998
17:44190611:T:A	I238N	0.998
17:44190797:C:A	A300D	0.998
17:44190803:T:A	V302D	0.998
17:44190809:T:A	L304Q	0.998
17:44190814:G:A	G306R	0.998
17:44190814:G:C	G306R	0.998
17:44190815:G:A	G306E	0.998
17:44190784:T:C	F296L	0.997
17:44190786:C:A	F296L	0.997
17:44190786:C:G	F296L	0.997
17:44189519:T:A	L178H	0.996
17:44190611:T:G	I238S	0.996
17:44190613:C:G	H239D	0.996
17:44190745:G:C	G283R	0.996
17:44190757:T:G	Y287D	0.996
17:44190785:T:C	F296S	0.996
17:44190785:T:G	F296C	0.996
17:44190809:T:G	L304R	0.996
17:44190821:C:T	T308I	0.996
17:44189141:C:A	A52D	0.995
17:44189524:T:C	F180L	0.995
17:44189526:C:A	F180L	0.995

dbSNP variants (sampled 300 via entrez): RS1000341675 (17:44187027 C>G,T), RS1000545036 (17:44186787 G>T), RS1000945378 (17:44186035 T>C), RS1001002248 (17:44187043 C>T), RS1001481539 (17:44192351 G>C), RS1001614406 (17:44188239 T>C), RS1001674168 (17:44189962 G>A), RS1002045447 (17:44187950 A>G), RS1002268755 (17:44188476 T>G), RS1002453280 (17:44191822 G>A), RS1003300090 (17:44191073 A>G), RS1004162407 (17:44185386 G>A,T), RS1004667273 (17:44189738 C>T), RS1004917881 (17:44187642 A>G), RS1005264767 (17:44192330 G>A,C)

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

2 associations (top):

Study	Trait	p-value
GCST008103_24	Bipolar disorder	2.000000e-08
GCST90002396_620	Mean reticulocyte volume	2.000000e-14

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010701	mean reticulocyte volume

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.

Chemical	Actions (top 5)	PubMed papers
Particulate Matter	increases abundance, increases expression, affects cotreatment, decreases expression	2
triphenyl phosphate	affects expression	1
cobaltous chloride	decreases expression	1
isobutyl alcohol	affects cotreatment, decreases expression, increases abundance	1
beta-methylcholine	affects expression	1
abrine	increases expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	increases expression	1
(+)-JQ1 compound	decreases expression	1
Air Pollutants	increases abundance, affects expression	1
Amiodarone	increases expression	1
Vehicle Emissions	increases abundance, increases expression	1
Caffeine	decreases phosphorylation	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Estradiol	decreases expression	1
Gasoline	increases abundance, affects cotreatment, decreases expression	1
Methyl Methanesulfonate	increases expression	1
Ozone	affects expression, increases abundance	1
Polycyclic Aromatic Hydrocarbons	decreases expression, increases abundance, affects cotreatment	1
Smoke	decreases expression	1
Testosterone	decreases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Vanadates	decreases expression	1
Aflatoxin B1	increases methylation	1
Cadmium Chloride	increases expression	1

Clinical trials (associated diseases)

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