TM2D2

Summary

TM2D2 (TM2 domain containing 2, HGNC:24127) is a protein-coding gene on chromosome 8p11.22, encoding TM2 domain-containing protein 2 (Q9BX73). It is a selective cancer dependency (DepMap: 13.5% of cell lines).

The protein encoded by this gene contains a structural module related to that of the seven transmembrane domain G protein-coupled receptor superfamily. This protein has sequence and structural similarities to the beta-amyloid binding protein (BBP), but, unlike BBP, it does not regulate a response to beta-amyloid peptide. This protein may have regulatory roles in cell death or proliferation signal cascades. This gene has multiple alternatively spliced transcript variants which encode two different isoforms.

Source: NCBI Gene 83877 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 36 total
• Cancer dependency (DepMap): dependent in 13.5% of screened cell lines
• MANE Select transcript: NM_078473

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24127
Approved symbol	TM2D2
Name	TM2 domain containing 2
Location	8p11.22
Locus type	gene with protein product
Status	Approved
Aliases	BLP1
Ensembl gene	ENSG00000169490
Ensembl biotype	protein_coding
OMIM	610081
Entrez	83877

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 8 protein_coding, 2 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000397070, ENST00000456397, ENST00000456845, ENST00000517872, ENST00000519186, ENST00000520152, ENST00000521060, ENST00000522142, ENST00000522434, ENST00000524331, ENST00000912343, ENST00000912344

RefSeq mRNA: 4 — MANE Select: NM_078473 NM_001024380, NM_001024381, NM_031940, NM_078473

CCDS: CCDS43733, CCDS6111

Canonical transcript exons

ENST00000456397 — 4 exons

Exon	Start	End
ENSE00001275041	38988808	38991545
ENSE00002103558	38996213	38996509
ENSE00003519832	38993545	38993660
ENSE00003591975	38995318	38995405

Expression profiles

Bgee: expression breadth ubiquitous, 256 present calls, max score 94.66.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 28.3298 / max 177.2784, expressed in 1817 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
92773	28.3249	1817
92774	0.0049	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
kidney epithelium	UBERON:0004819	94.66	gold quality
stromal cell of endometrium	CL:0002255	94.37	gold quality
ileal mucosa	UBERON:0000331	94.27	gold quality
islet of Langerhans	UBERON:0000006	94.19	gold quality
amniotic fluid	UBERON:0000173	94.15	gold quality
decidua	UBERON:0002450	93.79	gold quality
pancreatic ductal cell	CL:0002079	93.78	gold quality
placenta	UBERON:0001987	93.61	gold quality
germinal epithelium of ovary	UBERON:0001304	93.34	gold quality
palpebral conjunctiva	UBERON:0001812	93.33	gold quality
sperm	CL:0000019	93.22	gold quality
gall bladder	UBERON:0002110	92.95	gold quality
visceral pleura	UBERON:0002401	92.76	gold quality
corpus epididymis	UBERON:0004359	92.76	gold quality
parietal pleura	UBERON:0002400	92.69	gold quality
endothelial cell	CL:0000115	92.68	gold quality
monocyte	CL:0000576	92.40	gold quality
epithelial cell of pancreas	CL:0000083	92.30	gold quality
leukocyte	CL:0000738	92.22	gold quality
tibialis anterior	UBERON:0001385	91.84	gold quality
oviduct epithelium	UBERON:0004804	91.63	gold quality
calcaneal tendon	UBERON:0003701	91.62	gold quality
adult organism	UBERON:0007023	91.29	gold quality
lower lobe of lung	UBERON:0008949	91.24	gold quality
left adrenal gland	UBERON:0001234	91.15	gold quality
right adrenal gland cortex	UBERON:0035827	91.11	gold quality
smooth muscle tissue	UBERON:0001135	91.09	gold quality
skin of hip	UBERON:0001554	91.06	gold quality
adult mammalian kidney	UBERON:0000082	90.98	gold quality
seminal vesicle	UBERON:0000998	90.96	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-6701	yes	43.26
E-MTAB-2983	no	1211.29
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

96 targeting TM2D2, 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-4795-3P	100.00	74.62	4024
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-4715-3P	99.98	66.03	670
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-4302	99.89	67.94	1187
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-LET-7A-2-3P	99.87	70.53	1921
HSA-MIR-4492	99.87	68.25	3611
HSA-LET-7G-3P	99.85	70.43	1929
HSA-MIR-544A	99.84	68.66	1965

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 13.5% of screened cell lines.

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	tm2d2	ENSDARG00000035515
mus_musculus	Tm2d2	ENSMUSG00000031556
rattus_norvegicus	Tm2d2	ENSRNOG00000016559
drosophila_melanogaster	amrt	FBGN0030522
caenorhabditis_elegans		WBGENE00015353

Paralogs (2): TM2D1 (ENSG00000162604), TM2D3 (ENSG00000184277)

Protein

Protein identifiers

TM2 domain-containing protein 2 — Q9BX73 (reviewed: Q9BX73)

Alternative names: Beta-amyloid-binding protein-like protein 1

All UniProt accessions (4): E5RIQ5, E5RIT0, E5RJK9, Q9BX73

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

Tissue specificity. Widely expressed.

Similarity. Belongs to the TM2 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9BX73-1	1	yes
Q9BX73-2	2

RefSeq proteins (4): NP_001019551, NP_001019552, NP_114146, NP_510882* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007829	TM2	Domain
IPR050932	TM2D1-3-like	Family

Pfam: PF05154

UniProt features (12 total): topological domain 3, glycosylation site 2, transmembrane region 2, signal peptide 1, chain 1, splice variant 1, domain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BX73-F1	81.63	0.55

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 (2): 92, 37

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 132 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_DN, AHRARNT_01, CHIARADONNA_NEOPLASTIC_TRANSFORMATION_KRAS_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, CREBP1_Q2, TGACCTY_ERR1_Q2, BRUECKNER_TARGETS_OF_MIRLET7A3_DN, WEI_MYCN_TARGETS_WITH_E_BOX, TCF4_Q5, GARY_CD5_TARGETS_DN, DODD_NASOPHARYNGEAL_CARCINOMA_UP, AACTTT_UNKNOWN, CHIARADONNA_NEOPLASTIC_TRANSFORMATION_CDC25_DN, TGGAAA_NFAT_Q4_01, TAATTA_CHX10_01

GO Biological Process (0):

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
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

416 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TM2D2	TM2D1	Q9BX74	978
TM2D2	PLEKHA2	Q9HB19	620
TM2D2	DDHD2	O94830	582
TM2D2	PLPP5	Q8NEB5	570
TM2D2	NHLRC2	Q8NBF2	566
TM2D2	FAM110A	Q9BQ89	511
TM2D2	NSD3	Q9BZ95	507
TM2D2	ERLIN2	O94905	507
TM2D2	ZMAT4	Q9H898	489
TM2D2	PLPBP	O94903	489
TM2D2	HTRA4	P83105	483
TM2D2	LSM1	O15116	459
TM2D2	NPRL2	Q8WTW4	431
TM2D2	TM2D3	Q9BRN9	429
TM2D2	BAG4	O95429	428

IntAct

9 interactions, top by confidence:

A	B	Type	Score
GJB2	TM2D2	psi-mi:“MI:0915”(physical association)	0.560
TM2D2	TMEM97	psi-mi:“MI:0914”(association)	0.530
PARP2	TM2D2	psi-mi:“MI:0557”(adp ribosylation reaction)	0.440
TM2D3	SPINT1	psi-mi:“MI:0914”(association)	0.350
MFSD10	NDUFS8	psi-mi:“MI:0914”(association)	0.350
GJB2	TM2D2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (33): TM2D3 (Affinity Capture-MS), SIDT2 (Affinity Capture-MS), UQCC1 (Affinity Capture-MS), TMEM97 (Affinity Capture-MS), PCNXL3 (Affinity Capture-MS), UQCC2 (Affinity Capture-MS), SLC47A1 (Affinity Capture-MS), MBOAT7 (Affinity Capture-MS), PIGM (Affinity Capture-MS), ALG8 (Affinity Capture-MS), TMEM39A (Affinity Capture-MS), ERGIC2 (Affinity Capture-MS), SGPP1 (Affinity Capture-MS), TM2D2 (Affinity Capture-MS), TM2D2 (Positive Genetic)

ESM2 similar proteins: A0A1B0GRQ0, A0A1B0GVT2, A2RRL7, A3KN25, A4IFL1, G1TZA0, O18968, O54851, O70610, P08033, P0DKX4, P28230, P28234, P28235, P29414, P33725, P35212, P36382, P41987, P56513, Q01231, Q03190, Q08755, Q08EA8, Q0VCR2, Q2TA35, Q3MHM8, Q58CU5, Q5HZE8, Q5M8E3, Q5RCC0, Q60HF7, Q64448, Q6WGK6, Q7TNI2, Q866T7, Q8BSD4, Q8CFA6, Q8N6S5, Q8R0I4

Diamond homologs: A5PLF5, A5PLH4, P61228, Q07FZ2, Q2TA35, Q566R2, Q5M8E3, Q5RCC0, Q5XGR4, Q6DE06, Q6DHN3, Q8BJ83, Q8R0I4, Q95PJ8, Q95QZ5, Q99MB3, Q9BRN9, Q9BX73, Q9BX74, Q9U4H5, Q9VY86, Q9W2H1, Q9GPR3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	27
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

664 predictions. Top by Δscore:

Variant	Effect	Δscore
8:38993543:A:AC	donor_gain	1.0000
8:38993544:C:CC	donor_gain	1.0000
8:38995472:G:C	acceptor_gain	1.0000
8:38995477:C:CT	acceptor_gain	1.0000
8:38996211:A:AC	donor_gain	1.0000
8:38996212:C:CC	donor_gain	1.0000
8:38993537:ACACT:A	donor_loss	0.9900
8:38993538:CACTT:C	donor_loss	0.9900
8:38993539:ACTT:A	donor_loss	0.9900
8:38993540:CTTAC:C	donor_loss	0.9900
8:38993541:TT:T	donor_loss	0.9900
8:38993542:TACT:T	donor_loss	0.9900
8:38993543:ACTT:A	donor_loss	0.9900
8:38993544:C:T	donor_loss	0.9900
8:38993544:CT:C	donor_gain	0.9900
8:38993544:CTTTA:C	donor_gain	0.9900
8:38993656:CCGAA:C	acceptor_gain	0.9900
8:38993657:CGAAC:C	acceptor_gain	0.9900
8:38993658:GAAC:G	acceptor_loss	0.9900
8:38993659:AAC:A	acceptor_loss	0.9900
8:38993660:AC:A	acceptor_loss	0.9900
8:38993661:C:CC	acceptor_gain	0.9900
8:38993661:C:CG	acceptor_loss	0.9900
8:38993662:T:A	acceptor_loss	0.9900
8:38995313:CTCA:C	donor_loss	0.9900
8:38995314:TCAC:T	donor_loss	0.9900
8:38995315:CAC:C	donor_loss	0.9900
8:38995316:A:AT	donor_loss	0.9900
8:38995317:C:A	donor_loss	0.9900
8:38995471:C:CT	acceptor_gain	0.9900

AlphaMissense

1371 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:38991347:C:A	W210C	1.000
8:38991347:C:G	W210C	1.000
8:38991349:A:G	W210R	1.000
8:38991349:A:T	W210R	1.000
8:38991387:A:T	L197Q	1.000
8:38991396:A:G	L194P	1.000
8:38991398:G:C	D193E	1.000
8:38991398:G:T	D193E	1.000
8:38991399:T:A	D193V	1.000
8:38991399:T:C	D193G	1.000
8:38991399:T:G	D193A	1.000
8:38991400:C:G	D193H	1.000
8:38991400:C:T	D193N	1.000
8:38991409:A:G	W190R	1.000
8:38991409:A:T	W190R	1.000
8:38991412:A:G	W189R	1.000
8:38991412:A:T	W189R	1.000
8:38991417:C:T	G187E	1.000
8:38991423:C:T	G185E	1.000
8:38991424:C:G	G185R	1.000
8:38991424:C:T	G185R	1.000
8:38991426:C:A	G184V	1.000
8:38991426:C:T	G184E	1.000
8:38991427:C:G	G184R	1.000
8:38991427:C:T	G184R	1.000
8:38991438:A:G	L180P	1.000
8:38991440:C:A	K179N	1.000
8:38991440:C:G	K179N	1.000
8:38991444:C:T	G178E	1.000
8:38991473:G:C	F168L	1.000

dbSNP variants (sampled 300 via entrez): RS1000030858 (8:38993967 GCTTTACTTAT>G), RS1000331919 (8:38996639 C>T), RS1000716955 (8:38996653 T>C), RS1000754451 (8:38992499 AT>A), RS1000984841 (8:38992010 G>C), RS1000987417 (8:38990512 T>C,G), RS1001206948 (8:38996141 T>C), RS1001244347 (8:38993271 T>C), RS1001375936 (8:38998942 T>A,C), RS1001451867 (8:38997419 TC>T,TCC), RS1001654635 (8:38993581 G>A), RS1002331117 (8:38996809 G>A,T), RS1002388535 (8:38997597 G>A,T), RS1002654268 (8:38991776 G>A), RS1002700944 (8:38989285 T>C)

Disease associations

OMIM: gene MIM:610081 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cisplatin	increases expression	2
Valproic Acid	increases expression	2
aristolochic acid I	decreases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
sodium arsenite	increases abundance, increases expression	1
ferrous chloride	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
deguelin	decreases expression	1
2-palmitoylglycerol	increases expression	1
Bortezomib	increases expression	1
Sunitinib	decreases expression	1
Acetaminophen	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Antimycin A	decreases expression	1
Arsenic	increases abundance, increases expression	1
Benzene	increases expression	1
Benzo(a)pyrene	increases methylation	1
Dimethyl Sulfoxide	increases expression	1
Drugs, Chinese Herbal	increases expression	1
Naphthoquinones	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Urethane	increases expression	1
Cyclosporine	decreases expression	1
Aflatoxin B1	decreases methylation	1
Copper Sulfate	affects expression	1
Acrylamide	increases expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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