TM9SF3

Summary

TM9SF3 (transmembrane 9 superfamily member 3, HGNC:21529) is a protein-coding gene on chromosome 10q24.1, encoding Transmembrane 9 superfamily member 3 (Q9HD45).

Predicted to be involved in protein localization to membrane. Predicted to be active in membrane.

Source: NCBI Gene 56889 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 54 total
• Druggable target: yes
• MANE Select transcript: NM_020123

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21529
Approved symbol	TM9SF3
Name	transmembrane 9 superfamily member 3
Location	10q24.1
Locus type	gene with protein product
Status	Approved
Aliases	SMBP
Ensembl gene	ENSG00000077147
Ensembl biotype	protein_coding
OMIM	616872
Entrez	56889

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 14 protein_coding, 5 protein_coding_CDS_not_defined

ENST00000371142, ENST00000443638, ENST00000464654, ENST00000475401, ENST00000485093, ENST00000490192, ENST00000649367, ENST00000852770, ENST00000852771, ENST00000852772, ENST00000852773, ENST00000922471, ENST00000922472, ENST00000922473, ENST00000941889, ENST00000941890, ENST00000941891, ENST00000941892, ENST00000941893

RefSeq mRNA: 1 — MANE Select: NM_020123 NM_020123

CCDS: CCDS7450

Canonical transcript exons

ENST00000371142 — 15 exons

Exon	Start	End
ENSE00000503269	96530540	96530608
ENSE00000811066	96552928	96553059
ENSE00000811069	96544076	96544206
ENSE00000811075	96528031	96528177
ENSE00000811076	96527413	96527496
ENSE00001222091	96533051	96533190
ENSE00001454453	96518110	96522330
ENSE00001454476	96586734	96587012
ENSE00003484072	96551245	96551411
ENSE00003510732	96576634	96576829
ENSE00003525607	96565304	96565426
ENSE00003555214	96547895	96547989
ENSE00003580745	96527213	96527289
ENSE00003602891	96559659	96559736
ENSE00003650516	96561978	96562138

Expression profiles

Bgee: expression breadth ubiquitous, 287 present calls, max score 99.34.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 64.3853 / max 2037.8490, expressed in 1819 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
110874	60.1849	1819
110873	1.8217	1013
110875	1.3534	921
110876	0.5764	320
110868	0.4370	228
110872	0.0120	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	99.34	gold quality
tendon	UBERON:0000043	99.07	gold quality
mucosa of sigmoid colon	UBERON:0004993	98.97	gold quality
tendon of biceps brachii	UBERON:0008188	98.77	gold quality
pylorus	UBERON:0001166	98.72	gold quality
colonic mucosa	UBERON:0000317	98.69	gold quality
esophagus squamous epithelium	UBERON:0006920	98.65	gold quality
jejunal mucosa	UBERON:0000399	98.62	gold quality
palpebral conjunctiva	UBERON:0001812	98.50	gold quality
amniotic fluid	UBERON:0000173	98.47	gold quality
colonic epithelium	UBERON:0000397	98.47	gold quality
endothelial cell	CL:0000115	98.39	gold quality
corpus epididymis	UBERON:0004359	98.30	gold quality
endometrium	UBERON:0001295	98.25	gold quality
mucosa of paranasal sinus	UBERON:0005030	98.25	gold quality
gall bladder	UBERON:0002110	98.17	gold quality
islet of Langerhans	UBERON:0000006	98.08	gold quality
rectum	UBERON:0001052	98.08	gold quality
pancreatic ductal cell	CL:0002079	98.04	gold quality
stromal cell of endometrium	CL:0002255	98.03	gold quality
adrenal tissue	UBERON:0018303	98.03	gold quality
nasal cavity epithelium	UBERON:0005384	97.99	gold quality
pigmented layer of retina	UBERON:0001782	97.95	gold quality
medial globus pallidus	UBERON:0002477	97.93	gold quality
duodenum	UBERON:0002114	97.87	gold quality
parotid gland	UBERON:0001831	97.86	gold quality
epithelium of esophagus	UBERON:0001976	97.76	gold quality
caput epididymis	UBERON:0004358	97.69	gold quality
squamous epithelium	UBERON:0006914	97.69	gold quality
nasal cavity mucosa	UBERON:0001826	97.64	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-6075	no	2577.07
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

313 targeting TM9SF3, 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-8485	100.00	77.57	4731
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-432-3P	100.00	67.86	705
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-1193	100.00	65.93	529
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-340-5P	100.00	72.50	4437
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-7110-3P	100.00	73.18	2486
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-1184	99.99	68.19	1458
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-3662	99.99	73.82	5684

Literature-anchored findings (GeneRIF, showing 2)

• TM9SF3 participates in tumor invasion and serves as a prognostic factor. (PMID:24642718)
• Authors confirmed that TM9SF3 was a target gene of miR-1193 by luciferase reporter gene assay. Gene overexpression and knockdown experiments in Jurkat cells revealed that TM9SF3 positively regulated cell proliferation and invasion. (PMID:28390114)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	tm9sf3	ENSDARG00000028748
mus_musculus	Tm9sf3	ENSMUSG00000025016
rattus_norvegicus	Tm9sf3	ENSRNOG00000013443
drosophila_melanogaster	TM9SF3	FBGN0035622
caenorhabditis_elegans		WBGENE00021506

Paralogs (3): TM9SF1 (ENSG00000100926), TM9SF4 (ENSG00000101337), TM9SF2 (ENSG00000125304)

Protein

Protein identifiers

Transmembrane 9 superfamily member 3 — Q9HD45 (reviewed: Q9HD45)

Alternative names: EP70-P-iso, SM-11044-binding protein

All UniProt accessions (3): Q9HD45, A0A024QYS2, Q5TB53

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

Similarity. Belongs to the nonaspanin (TM9SF) (TC 8.A.68) family.

RefSeq proteins (1): NP_064508* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004240	EMP70	Family

Pfam: PF02990

UniProt features (19 total): transmembrane region 9, sequence conflict 6, glycosylation site 2, signal peptide 1, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9HD45-F1	86.47	0.54

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): 174, 419

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 205 (showing top): HORIUCHI_WTAP_TARGETS_DN, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_10, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, ATGCAGT_MIR217, FOXO4_01, AATGGAG_MIR136, CCATCCA_MIR432, SP1_Q2_01, TTGGGAG_MIR150, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, RYTTCCTG_ETS2_B, BASAKI_YBX1_TARGETS_DN, GCM_NF2, MCCLUNG_COCAINE_REWARD_5D, GOBP_LOCALIZATION_WITHIN_MEMBRANE

GO Biological Process (1): protein localization to membrane (GO:0072657)

GO Molecular Function (0):

GO Cellular Component (1): membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular protein localization	1
localization within membrane	1
cellular anatomical structure	1

Protein interactions and networks

STRING

930 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TM9SF3	SSMEM1	Q8WWF3	544
TM9SF3	TMED4	Q7Z7H5	481
TM9SF3	ZFPL1	O95159	469
TM9SF3	TMED7	Q9Y3B3	448
TM9SF3	SPATA46	Q5T0L3	440
TM9SF3	PGAP2	Q9UHJ9	420
TM9SF3	FBXO8	Q9NRD0	418
TM9SF3	GRAMD1C	Q8IYS0	416
TM9SF3	TMEM205	Q6UW68	402
TM9SF3	WDR17	Q8IZU2	391
TM9SF3	MSLNL	Q96KJ4	385
TM9SF3	HSPA13	P48723	383
TM9SF3	TTC9	Q92623	377
TM9SF3	IFT74	Q96LB3	376
TM9SF3	SPRING1	Q9H741	370

IntAct

120 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
RAF1	CALU	psi-mi:“MI:0914”(association)	0.640
HTR2C	KLRG2	psi-mi:“MI:0914”(association)	0.530
EFNB2	FAM171A2	psi-mi:“MI:0914”(association)	0.530
GDPD5	GOLIM4	psi-mi:“MI:0914”(association)	0.530
STOM	EI24	psi-mi:“MI:0914”(association)	0.510
FOXJ1	ACSL4	psi-mi:“MI:0914”(association)	0.350
		psi-mi:“MI:0914”(association)	0.350
	ESYT2	psi-mi:“MI:0914”(association)	0.350
E5	ESYT2	psi-mi:“MI:0914”(association)	0.350
	HAX1	psi-mi:“MI:0914”(association)	0.350
HSCB	RBP5	psi-mi:“MI:0914”(association)	0.350
CLN6	SCAMP3	psi-mi:“MI:0914”(association)	0.350
	TSPO	psi-mi:“MI:0914”(association)	0.350
APP	MGST3	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
LRRK2		psi-mi:“MI:0914”(association)	0.350
P2RY12	GPR89A	psi-mi:“MI:0914”(association)	0.350
	TMEM223	psi-mi:“MI:0914”(association)	0.350

BioGRID (217): TM9SF3 (Affinity Capture-MS), TM9SF3 (Proximity Label-MS), TM9SF3 (Proximity Label-MS), TM9SF3 (Affinity Capture-MS), TM9SF3 (Affinity Capture-MS), TM9SF3 (Affinity Capture-MS), TM9SF3 (Affinity Capture-MS), STOM (Affinity Capture-MS), TM9SF3 (Affinity Capture-RNA), TM9SF3 (Affinity Capture-MS), TM9SF3 (Affinity Capture-MS), TM9SF3 (Affinity Capture-MS), TM9SF3 (Affinity Capture-MS), TM9SF3 (Affinity Capture-MS), TM9SF3 (Affinity Capture-MS)

ESM2 similar proteins: A0A075TRL0, A0A125YSC7, A0A411KUP9, A1CFK8, A3LPS1, A5DEQ7, A5DSM9, A9UY97, B0YBR5, B3M9W1, B3NDM7, B4GRI8, B4HIJ8, B4J043, B4L0H1, B4LIH0, B4MXW6, B4PD01, B4QLP9, G4YM00, G4Z2L3, O14201, O59815, O74375, O74631, P25613, P25619, P32907, P38079, P38166, P41943, P50537, P94853, Q04767, Q10227, Q11080, Q12117, Q12359, Q24JP1, Q28614

Diamond homologs: A4IFE9, A5D7E2, F4HW17, F4KIB2, O15321, P58021, Q4KLL4, Q54ZW0, Q5R8F1, Q5R8Y6, Q5RDY2, Q66HF2, Q66HG5, Q8BH24, Q8RWW1, Q92544, Q940G0, Q940S0, Q99805, Q9C5N2, Q9C720, Q9DBU0, Q9ET30, Q9FHT4, Q9HD45, Q9LIC2, Q9Y819, Q9ZPS7, F4JRE0, P32802, Q04562, Q55FP0, Q9FYQ8, Q7YTA6

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 151 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.

Reactome pathways:

Pathway	Partners	Fold	FDR
Amino acid transport across the plasma membrane	6	17.9×	2e-04
R-HSA-425366	9	16.1×	1e-06
SLC transporter disorders	6	12.1×	1e-03
Disorders of transmembrane transporters	6	8.3×	7e-03
SLC-mediated transmembrane transport	14	8.2×	7e-07
Transport of small molecules	16	4.0×	3e-04

GO biological processes:

GO term	Partners	Fold	FDR
amino acid transport	9	21.0×	5e-07
phospholipase C-activating G protein-coupled receptor signaling pathway	10	9.8×	5e-05
transport across blood-brain barrier	7	9.4×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	33
Likely benign	0
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

2568 predictions. Top by Δscore:

Variant	Effect	Δscore
10:96527411:A:AC	donor_gain	1.0000
10:96527412:C:CC	donor_gain	1.0000
10:96528154:C:CT	acceptor_gain	1.0000
10:96528154:C:T	acceptor_gain	1.0000
10:96528155:A:T	acceptor_gain	1.0000
10:96530532:AAACT:A	donor_loss	1.0000
10:96530533:AACT:A	donor_loss	1.0000
10:96530534:ACT:A	donor_loss	1.0000
10:96530535:CTTAC:C	donor_loss	1.0000
10:96530536:TTACA:T	donor_loss	1.0000
10:96530537:TAC:T	donor_loss	1.0000
10:96530538:A:AC	donor_gain	1.0000
10:96530538:A:C	donor_loss	1.0000
10:96530539:C:CC	donor_gain	1.0000
10:96530539:C:G	donor_loss	1.0000
10:96530539:CA:C	donor_gain	1.0000
10:96530539:CAT:C	donor_gain	1.0000
10:96530539:CATTT:C	donor_gain	1.0000
10:96530608:CCTGG:C	acceptor_loss	1.0000
10:96530610:T:A	acceptor_loss	1.0000
10:96544068:CAACT:C	donor_loss	1.0000
10:96544069:AACTC:A	donor_loss	1.0000
10:96544070:ACTCA:A	donor_loss	1.0000
10:96544071:CTCA:C	donor_loss	1.0000
10:96544072:TCAC:T	donor_loss	1.0000
10:96544073:CACCA:C	donor_loss	1.0000
10:96544074:A:AC	donor_gain	1.0000
10:96544074:ACCAT:A	donor_loss	1.0000
10:96544075:C:CC	donor_gain	1.0000
10:96544075:CCA:C	donor_gain	1.0000

AlphaMissense

3876 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:96522299:A:C	F578L	1.000
10:96522299:A:T	F578L	1.000
10:96522301:A:G	F578L	1.000
10:96522321:C:T	G571D	1.000
10:96522322:C:G	G571R	1.000
10:96522330:C:T	G568E	1.000
10:96527213:C:G	G568R	1.000
10:96527213:C:T	G568R	1.000
10:96527484:A:C	S518R	1.000
10:96527484:A:T	S518R	1.000
10:96527486:T:G	S518R	1.000
10:96527492:A:G	W516R	1.000
10:96527492:A:T	W516R	1.000
10:96527496:C:A	W514C	1.000
10:96527496:C:G	W514C	1.000
10:96528032:A:G	W514R	1.000
10:96528032:A:T	W514R	1.000
10:96528034:C:G	R513P	1.000
10:96528041:C:G	D511H	1.000
10:96528042:T:A	E510D	1.000
10:96528042:T:G	E510D	1.000
10:96528043:T:A	E510V	1.000
10:96528047:C:G	A509P	1.000
10:96528052:A:G	L507P	1.000
10:96528052:A:T	L507Q	1.000
10:96528055:A:G	L506P	1.000
10:96528062:A:G	Y504H	1.000
10:96528083:A:G	C497R	1.000
10:96528100:A:G	L491P	1.000
10:96528123:G:C	F483L	1.000

dbSNP variants (sampled 300 via entrez): RS1000087737 (10:96571422 T>C), RS1000111854 (10:96564803 C>A), RS1000167062 (10:96577335 A>G), RS1000196670 (10:96577694 T>C), RS1000213294 (10:96587622 C>T), RS1000214141 (10:96586400 C>T), RS1000220178 (10:96545887 C>A,T), RS1000326487 (10:96531655 T>C), RS1000341625 (10:96556950 T>C), RS1000370538 (10:96583389 G>C), RS1000415936 (10:96538286 T>A,C), RS1000459969 (10:96571059 A>C), RS1000497701 (10:96576024 C>T), RS1000520324 (10:96532536 A>C), RS1000571552 (10:96576345 C>T)

Disease associations

OMIM: gene MIM:616872 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST010485_6	Platelet reactivity in response to clopidogrel treatment	4.000000e-35
GCST010485_7	Platelet reactivity in response to clopidogrel treatment	1.000000e-33
GCST012490_246	Femur bone mineral density x serum urate levels interaction	7.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004531	urate measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066479 (SINGLE PROTEIN)

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

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.66	Kd	21.79	nM	CHEMBL5653589
7.66	ED50	21.79	nM	CHEMBL5653589
5.38	Kd	4217	nM	CHEMBL3752910
5.38	ED50	4217	nM	CHEMBL3752910

PubChem BioAssay actives

2 with measured affinity, of 4 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149597: Binding affinity to human TM9SF3 incubated for 45 mins by Kinobead based pull down assay	kd	0.0218	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149597: Binding affinity to human TM9SF3 incubated for 45 mins by Kinobead based pull down assay	kd	4.2168	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases methylation, affects cotreatment, decreases expression, affects expression	5
Acetaminophen	decreases expression	2
Cadmium	decreases reaction, increases abundance, increases palmitoylation, increases expression	2
Cadmium Chloride	decreases reaction, increases abundance, increases palmitoylation, increases expression	2
aristolochic acid I	decreases expression	1
bisphenol F	affects cotreatment, increases expression	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
deoxynivalenol	decreases expression	1
2-bromopalmitate	decreases reaction, increases abundance, increases palmitoylation	1
beta-methylcholine	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	increases reaction, affects binding	1
deguelin	decreases expression	1
fenpyroximate	decreases expression	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
pyrimidifen	decreases expression	1
ICG 001	decreases expression	1
bisphenol B	increases expression	1
pyrachlostrobin	decreases expression	1
dorsomorphin	decreases expression, affects cotreatment	1
jinfukang	decreases expression	1
picoxystrobin	decreases expression	1
NSC 689534	affects binding, decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Antimycin A	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652639	Binding	Binding affinity to human TM9SF3 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TS60	HAP1 TM9SF3 (-) 1	Cancer cell line	Male
CVCL_TS61	HAP1 TM9SF3 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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