TM9SF4

Summary

TM9SF4 (transmembrane 9 superfamily member 4, HGNC:30797) is a protein-coding gene on chromosome 20q11.21, encoding Transmembrane 9 superfamily member 4 (Q92544). Associates with proteins harboring glycine-rich transmembrane domains and ensures their efficient localization to the cell surface.

Involved in several processes, including positive regulation of protein localization; regulation of intracellular pH; and vacuolar proton-transporting V-type ATPase complex assembly. Located in Golgi apparatus and early endosome.

Source: NCBI Gene 9777 — RefSeq curated summary.

At a glance

• Gene–disease (curated): autism spectrum disorder (Limited, GenCC)
• GWAS associations: 5
• Clinical variants (ClinVar): 75 total
• Druggable target: yes
• MANE Select transcript: NM_014742

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30797
Approved symbol	TM9SF4
Name	transmembrane 9 superfamily member 4
Location	20q11.21
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0255, dJ836N17.2
Ensembl gene	ENSG00000101337
Ensembl biotype	protein_coding
OMIM	617727
Entrez	9777

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 22 protein_coding, 2 nonsense_mediated_decay, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000217315, ENST00000398022, ENST00000417389, ENST00000442842, ENST00000450829, ENST00000479591, ENST00000495749, ENST00000860212, ENST00000860213, ENST00000860214, ENST00000860215, ENST00000860216, ENST00000860217, ENST00000860218, ENST00000860219, ENST00000860220, ENST00000860221, ENST00000860222, ENST00000860223, ENST00000911757, ENST00000911758, ENST00000911759, ENST00000961363, ENST00000961364, ENST00000961365, ENST00000961366, ENST00000961367

RefSeq mRNA: 2 — MANE Select: NM_014742 NM_001363731, NM_014742

CCDS: CCDS13196, CCDS86943

Canonical transcript exons

ENST00000398022 — 18 exons

Exon	Start	End
ENSE00000661166	32141766	32141895
ENSE00000661167	32142982	32143105
ENSE00000661168	32145091	32145209
ENSE00000859899	32136074	32136173
ENSE00000859904	32145312	32145423
ENSE00001593990	32149634	32149766
ENSE00001602289	32155103	32155186
ENSE00001604138	32157794	32157969
ENSE00001730989	32159992	32160111
ENSE00001731768	32150800	32150875
ENSE00001734633	32158451	32158514
ENSE00001763078	32150622	32150703
ENSE00002285631	32146785	32146855
ENSE00002303835	32109714	32109755
ENSE00003563878	32161276	32161365
ENSE00003626818	32133013	32133126
ENSE00003661236	32141497	32141665
ENSE00003888753	32165295	32167256

Expression profiles

Bgee: expression breadth ubiquitous, 296 present calls, max score 94.78.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 51.1049 / max 333.3914, expressed in 1822 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
184027	47.3072	1822
184025	2.5470	1364
184024	0.8680	587
184026	0.1952	67
184028	0.1876	62

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	94.78	gold quality
monocyte	CL:0000576	94.55	gold quality
mononuclear cell	CL:0000842	94.49	gold quality
leukocyte	CL:0000738	94.44	gold quality
type B pancreatic cell	CL:0000169	94.43	silver quality
islet of Langerhans	UBERON:0000006	93.91	gold quality
granulocyte	CL:0000094	93.25	gold quality
olfactory bulb	UBERON:0002264	93.20	silver quality
frontal pole	UBERON:0002795	93.10	gold quality
rectum	UBERON:0001052	93.05	gold quality
lower esophagus mucosa	UBERON:0035834	92.99	gold quality
endometrium epithelium	UBERON:0004811	92.77	gold quality
smooth muscle tissue	UBERON:0001135	92.69	gold quality
diaphragm	UBERON:0001103	92.49	silver quality
paraflocculus	UBERON:0005351	92.45	gold quality
esophagus mucosa	UBERON:0002469	91.95	gold quality
middle frontal gyrus	UBERON:0002702	91.87	gold quality
adrenal tissue	UBERON:0018303	91.87	gold quality
skin of abdomen	UBERON:0001416	91.79	gold quality
skin of leg	UBERON:0001511	91.74	gold quality
right uterine tube	UBERON:0001302	91.73	gold quality
right hemisphere of cerebellum	UBERON:0014890	90.98	gold quality
vagina	UBERON:0000996	90.90	gold quality
cerebellar hemisphere	UBERON:0002245	90.89	gold quality
prefrontal cortex	UBERON:0000451	90.88	gold quality
cerebellar cortex	UBERON:0002129	90.86	gold quality
adenohypophysis	UBERON:0002196	90.85	gold quality
left ovary	UBERON:0002119	90.84	gold quality
transverse colon	UBERON:0001157	90.80	gold quality
pituitary gland	UBERON:0000007	90.79	gold quality

Single-cell (SCXA)

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

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

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HIF1A

miRNA regulators (miRDB)

105 targeting TM9SF4, 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-4262	100.00	73.26	3931
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-3613-3P	100.00	76.36	7965
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-548C-3P	99.99	74.01	7587
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-3151-5P	99.86	63.83	1069
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-4668-5P	99.79	70.58	3782

Literature-anchored findings (GeneRIF, showing 8)

• TM9SF4 is a new marker of malignancy, representing a potential new target for anti-tumour strategies with a specific role in tumour cannibalism and in the establishment of a metastatic phenotype. (PMID:19893578)
• Our study shows for the first time the important role of TM9SF4 in the aberrant constitutive activation of the V-ATPase, and the development of a malignant phenotype. (PMID:25659576)
• TM9SF4 is a direct target of HIF-1alpha, down-regulated in leukemic cells by hypoxia and involved in cell adhesion. (PMID:25961573)
• The TM9SF4 functions to facilitate mTOR inactivation, resulting in an enhanced autophagic flux, which serves to protect cells from apoptotic cell death. (PMID:29125601)
• Results show that TM9SF4 controls the sorting of TMDs at the ER-Golgi interface. Remarkably, sorting of T-R1 in HCT116 cells was different from that in HEK cells: in HCT116 cells, a substantial fraction of T-R1 was localized to the Golgi complex, and it was relocated to the ER by genetic ablation of TM9SF4. (PMID:30301779)
• results uncovered a novel role of TM9SF4 proteins in alleviating endoplasmic reticulum stress and protecting chemoresistant breast cancer cells from apoptotic/necrotic cell death (PMID:31249383)
• TM9SF4 Is a Crucial Regulator of Inflammation and ER Stress in Inflammatory Bowel Disease. (PMID:35398597)
• TM9SF4 is an F-actin disassembly factor that promotes tumor progression and metastasis. (PMID:36175399)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	tm9sf4	ENSDARG00000002536
mus_musculus	Tm9sf4	ENSMUSG00000068040
rattus_norvegicus	Tm9sf4	ENSRNOG00000009406
drosophila_melanogaster	TM9SF4	FBGN0028541
caenorhabditis_elegans	ZK858.6	WBGENE00014119

Paralogs (3): TM9SF3 (ENSG00000077147), TM9SF1 (ENSG00000100926), TM9SF2 (ENSG00000125304)

Protein

Protein identifiers

Transmembrane 9 superfamily member 4 — Q92544 (reviewed: Q92544)

Alternative names: Tumor cannibalism associated protein 1

All UniProt accessions (4): A0A024QYR3, A0A0C4DFM1, Q92544, F2Z2L1

UniProt curated annotations — full annotation on UniProt →

Function. Associates with proteins harboring glycine-rich transmembrane domains and ensures their efficient localization to the cell surface. Regulates the assembly and activity of V-ATPase in colon cancer cells via its interaction with V-type proton ATPase subunit H (ATP6V1H) and contributes to V-ATPase-mediated pH alterations in cancer cells which play an important role in drug resistance and invasiveness of colon cancer cells. Plays an important role in an atypical phagocytic activity of metastatic melanoma cells called cannibalism and is involved in the pH regulation of the intracellular vesicles in tumor cells.

Subunit / interactions. Interacts with ATP6V1H in colon cancer cells.

Subcellular location. Membrane. Golgi apparatus. Early endosome.

Tissue specificity. Highly expressed in metastatic melanoma cells whereas it is undetectable in primary melanoma cells, healthy skin tissues and peripheral blood lymphocytes. Expressed in CD34(+) hematopoietic progenitor cells and during monocyte and granulocyte differentiation. Overexpressed in acute myeloid leukemia, in particular in those displaying granulocytic differentiation (at protein level).

Induction. Transcriptionally repressed following hypoxia by HIF1A in leukemic cells.

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

RefSeq proteins (2): NP_001350660, NP_055557* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004240	EMP70	Family

Pfam: PF02990

UniProt features (22 total): topological domain 10, transmembrane region 9, signal peptide 1, chain 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q92544-F1	85.71	0.51

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 312

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 196 (showing top): AGGAAGC_MIR5163P, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, YAGI_AML_WITH_INV_16_TRANSLOCATION, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION_TO_CELL_SURFACE, MORF_HDAC2, GOBP_VESICLE_MEDIATED_TRANSPORT, ACTGCAG_MIR173P, PUJANA_CHEK2_PCC_NETWORK, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_TRANSPORT, SHAFFER_IRF4_TARGETS_IN_PLASMA_CELL_VS_MATURE_B_LYMPHOCYTE, GOBP_REGULATION_OF_PROTEIN_LOCALIZATION_TO_CELL_SURFACE, GOBP_RESPONSE_TO_OXYGEN_LEVELS

GO Biological Process (8): response to hypoxia (GO:0001666), phagocytosis (GO:0006909), cell adhesion (GO:0007155), regulation of intracellular pH (GO:0051453), vacuolar proton-transporting V-type ATPase complex assembly (GO:0070072), positive regulation of protein exit from endoplasmic reticulum (GO:0070863), protein localization to membrane (GO:0072657), positive regulation of protein localization to cell surface (GO:2000010)

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

GO Cellular Component (4): early endosome (GO:0005769), Golgi apparatus (GO:0005794), membrane (GO:0016020), endosome (GO:0005768)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
endomembrane system	2
response to stress	1
response to decreased oxygen levels	1
endocytosis	1
cellular process	1
regulation of pH	1
intracellular monoatomic cation homeostasis	1
regulation of biological quality	1
proton-transporting V-type ATPase complex assembly	1
protein exit from endoplasmic reticulum	1
regulation of protein exit from endoplasmic reticulum	1
positive regulation of intracellular protein transport	1
intracellular protein localization	1
localization within membrane	1
protein localization to cell surface	1
positive regulation of protein localization	1
regulation of protein localization to cell surface	1
binding	1
endosome	1
cytoplasm	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1
cytoplasmic vesicle	1

Protein interactions and networks

STRING

1328 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TM9SF4	RBBP8NL	Q8NC74	690
TM9SF4	POFUT1	Q9H488	651
TM9SF4	PLAGL2	Q9UPG8	645
TM9SF4	KIF3B	O15066	573
TM9SF4	SOX15	P35717	503
TM9SF4	C10orf71	Q711Q0	496
TM9SF4	RCHY1	Q96PM5	493
TM9SF4	HCK	P08631	492
TM9SF4	ENC1	O14682	473
TM9SF4	DDX27	Q96GQ7	447
TM9SF4	ANO8	Q9HCE9	440
TM9SF4	NOL4L	Q96MY1	430
TM9SF4	PDPN	Q86YL7	421
TM9SF4	IER5L	Q5T953	414
TM9SF4	GPR85	P60893	391

IntAct

88 interactions, top by confidence:

A	B	Type	Score
FAM3B	FUT3	psi-mi:“MI:0914”(association)	0.670
ASPH	STXBP3	psi-mi:“MI:0914”(association)	0.640
TACR1	ATP5PB	psi-mi:“MI:0914”(association)	0.640
SLC16A3	CASK	psi-mi:“MI:0914”(association)	0.590
F3	TM9SF4	psi-mi:“MI:0915”(physical association)	0.560
TSPAN11	IGLL5	psi-mi:“MI:0914”(association)	0.530
FAM3B	LRP5	psi-mi:“MI:0914”(association)	0.530
FAM174A	BLTP3B	psi-mi:“MI:0914”(association)	0.530
APLNR	SLC33A1	psi-mi:“MI:0914”(association)	0.530
CXCR4	FANCA	psi-mi:“MI:0914”(association)	0.530
TM9SF4	MTOR	psi-mi:“MI:0915”(physical association)	0.520
MTOR	TM9SF4	psi-mi:“MI:2364”(proximity)	0.520
MTOR	TM9SF4	psi-mi:“MI:0403”(colocalization)	0.520
	VAPB	psi-mi:“MI:0914”(association)	0.500
RAB5A	TM9SF4	psi-mi:“MI:0403”(colocalization)	0.430
TM9SF4	RAB5A	psi-mi:“MI:0403”(colocalization)	0.430
GPC1	SNAP23	psi-mi:“MI:0915”(physical association)	0.400
GPC1	GANAB	psi-mi:“MI:0915”(physical association)	0.400
Uso1	SLC30A6	psi-mi:“MI:0914”(association)	0.350
TM9SF4		psi-mi:“MI:0914”(association)	0.350
Mecom	ESYT2	psi-mi:“MI:0914”(association)	0.350
F3	DAD1	psi-mi:“MI:0914”(association)	0.350
	TMEM223	psi-mi:“MI:0914”(association)	0.350
RAB1A	SCAMP3	psi-mi:“MI:0914”(association)	0.350
SACM1L	VAPB	psi-mi:“MI:0914”(association)	0.350
PCDHGA9	TMEM223	psi-mi:“MI:0914”(association)	0.350

BioGRID (160): TM9SF4 (Affinity Capture-MS), TM9SF4 (Affinity Capture-MS), ERMP1 (Co-fractionation), LMAN2 (Co-fractionation), RAB1A (Co-fractionation), STX12 (Co-fractionation), STX7 (Co-fractionation), TM9SF4 (Co-fractionation), TM9SF4 (Co-fractionation), CALD1 (Affinity Capture-MS), HIST1H1B (Affinity Capture-MS), KDM5A (Affinity Capture-MS), RPN2 (Affinity Capture-MS), S100A6 (Affinity Capture-MS), SLC25A12 (Affinity Capture-MS)

ESM2 similar proteins: A0A067DFU5, A0A067E3D8, A0A1Y0BRF5, A0A9Y1LNE1, A0A9Y1LQX3, A5D7E2, A7S6Y0, A9UY97, B6HV37, B6JWP7, F4HW17, F4KIB2, O48962, O59802, O64761, O94673, P0DXH1, P25338, P38312, P70245, Q06537, Q09906, Q0V982, Q10255, Q12155, Q15125, Q28GF5, Q4KLL4, Q4V7N7, Q54ZW0, Q55E32, Q5R8F1, Q5R8Y6, Q5RDY2, Q5U3Y7, Q60490, Q641M3, Q66HF2, Q6DCP8, Q8BH24

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

4 interactions.

A	Effect	B	Mechanism
TM9SF4	“down-regulates activity”	MTOR	binding
TM9SF4	up-regulates	Autophagy
HIF1A	“down-regulates quantity by repression”	TM9SF4	“transcriptional regulation”
TM9SF4	“up-regulates activity”	ATP6V1H	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	47
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3035 predictions. Top by Δscore:

Variant	Effect	Δscore
20:32136060:T:A	acceptor_gain	1.0000
20:32141491:C:CA	acceptor_gain	1.0000
20:32141661:CACCT:C	donor_gain	1.0000
20:32141662:ACCT:A	donor_gain	1.0000
20:32141663:CCT:C	donor_gain	1.0000
20:32141664:CT:C	donor_gain	1.0000
20:32141664:CTGTA:C	donor_loss	1.0000
20:32141665:TGTAA:T	donor_loss	1.0000
20:32141666:G:GG	donor_gain	1.0000
20:32141667:TAA:T	donor_loss	1.0000
20:32141760:TTCCA:T	acceptor_loss	1.0000
20:32141761:TCCA:T	acceptor_loss	1.0000
20:32141762:CCAG:C	acceptor_loss	1.0000
20:32141763:CA:C	acceptor_loss	1.0000
20:32141764:A:AC	acceptor_loss	1.0000
20:32141764:A:AG	acceptor_gain	1.0000
20:32141765:G:GG	acceptor_gain	1.0000
20:32141765:GC:G	acceptor_gain	1.0000
20:32141765:GCA:G	acceptor_gain	1.0000
20:32141765:GCAT:G	acceptor_gain	1.0000
20:32141765:GCATT:G	acceptor_gain	1.0000
20:32141891:ACAAG:A	donor_loss	1.0000
20:32141892:CAAGG:C	donor_loss	1.0000
20:32141893:AAGG:A	donor_loss	1.0000
20:32141894:AGGTA:A	donor_loss	1.0000
20:32141895:GGTAG:G	donor_loss	1.0000
20:32141897:T:A	donor_loss	1.0000
20:32142966:T:A	acceptor_gain	1.0000
20:32142969:T:A	acceptor_gain	1.0000
20:32142972:T:A	acceptor_gain	1.0000

AlphaMissense

4245 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:32136173:G:A	G77R	1.000
20:32136173:G:C	G77R	1.000
20:32141497:G:A	G77E	1.000
20:32141665:T:C	L133P	1.000
20:32141780:T:C	L138P	1.000
20:32141864:G:A	G166D	1.000
20:32141875:G:C	G170R	1.000
20:32143001:T:C	L183P	1.000
20:32143061:G:C	R203P	1.000
20:32145204:T:A	W256R	1.000
20:32145204:T:C	W256R	1.000
20:32145206:G:C	W256C	1.000
20:32145206:G:T	W256C	1.000
20:32145327:T:A	W263R	1.000
20:32145327:T:C	W263R	1.000
20:32145329:G:C	W263C	1.000
20:32145329:G:T	W263C	1.000
20:32145336:C:A	R266S	1.000
20:32145336:C:G	R266G	1.000
20:32145337:G:C	R266P	1.000
20:32145339:T:A	W267R	1.000
20:32145339:T:C	W267R	1.000
20:32145341:G:C	W267C	1.000
20:32145341:G:T	W267C	1.000
20:32145352:T:C	L271P	1.000
20:32145375:C:G	H279D	1.000
20:32145395:C:A	N285K	1.000
20:32145395:C:G	N285K	1.000
20:32146815:T:C	L305P	1.000
20:32149658:T:A	W327R	1.000

dbSNP variants (sampled 300 via entrez): RS1000009335 (20:32163771 C>T), RS1000043001 (20:32133667 C>T), RS1000051545 (20:32109505 C>A,G), RS1000102415 (20:32116073 C>T), RS1000120765 (20:32129129 A>C,G), RS1000129153 (20:32132404 A>C,G), RS1000129207 (20:32125589 T>C), RS1000149470 (20:32163492 C>G,T), RS1000244183 (20:32125165 A>C,G), RS1000354883 (20:32156401 G>A,C), RS1000381598 (20:32165686 G>T), RS1000412923 (20:32165399 C>T), RS1000462648 (20:32124117 C>T), RS1000476652 (20:32120470 A>G), RS1000478621 (20:32131481 A>T)

Disease associations

OMIM: gene MIM:617727 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
autism spectrum disorder	Limited	Autosomal dominant

Mondo (1): autism spectrum disorder (MONDO:0005258)

Orphanet (1): NON RARE IN EUROPE: Autism (Orphanet:106)

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST004131_132	Inflammatory bowel disease	6.000000e-06
GCST004147_18	Chronic obstructive pulmonary disease	1.000000e-06
GCST007611_4	Chronic obstructive pulmonary disease or high blood pressure (pleiotropy)	4.000000e-08
GCST008790_59	Urinary albumin-to-creatinine ratio	2.000000e-08
GCST008791_27	Microalbuminuria	2.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007778	urinary albumin to creatinine ratio

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067183 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 4 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.01	Kd	9652	nM	CHEMBL3752910
5.01	ED50	9652	nM	CHEMBL3752910

PubChem BioAssay actives

1 with measured affinity, of 4 total; 1 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-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149598: Binding affinity to human TM9SF4 incubated for 45 mins by Kinobead based pull down assay	kd	9.6524	uM

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol F	increases expression, affects cotreatment, increases methylation	2
deoxynivalenol	decreases expression	1
beta-lapachone	increases expression	1
ochratoxin A	decreases expression	1
nivalenol	decreases expression	1
tamibarotene	decreases expression	1
CGP 52608	affects binding, increases reaction	1
Temozolomide	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Vehicle Emissions	decreases expression, increases abundance	1
Benzo(a)pyrene	increases methylation	1
Dexamethasone	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Indomethacin	affects cotreatment, increases expression	1
Ivermectin	decreases expression	1
Selenium	increases expression	1
Smoke	decreases expression	1
Thiram	decreases expression	1
Tretinoin	decreases expression	1
Valproic Acid	affects expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Cadmium Chloride	decreases expression	1
Particulate Matter	decreases expression, increases abundance	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
CHEMBL5652640	Binding	Binding affinity to human TM9SF4 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

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2IQ	Abcam HeLa TM9SF4 KO	Cancer cell line	Female
CVCL_TS62	HAP1 TM9SF4 (-) 1	Cancer cell line	Male
CVCL_TS63	HAP1 TM9SF4 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT01302964	PHASE3	COMPLETED	Mirtazapine Treatment of Anxiety in Children and Adolescents With Pervasive Developmental Disorders
NCT01706523	PHASE3	TERMINATED	Open Label Extension Study of STX209 (Arbaclofen) in Autism Spectrum Disorders
NCT01825798	PHASE3	COMPLETED	Treatment of Overweight Induced by Antipsychotic Medication in Young People With Autism Spectrum Disorders (ASD)
NCT01972074	PHASE3	COMPLETED	Behavioral and Neural Response to Memantine in Adolescents With Autism Spectrum Disorder
NCT02985749	PHASE3	COMPLETED	A Study of Oxytocin for the Treatment of Social Impairment in Individuals With High Functioning Autism Spectrum Disorder
NCT03197922	PHASE3	COMPLETED	Treatment of Encopresis in Children With Autism Spectrum Disorders
NCT03504917	PHASE3	TERMINATED	A Study of Balovaptan in Adults With Autism Spectrum Disorder With a 2-Year Open-Label Extension
NCT03553875	PHASE3	TERMINATED	Memantine for the Treatment of Social Deficits in Youth With Disorders of Impaired Social Interactions
NCT03640156	PHASE3	COMPLETED	Modulating Socially Adaptive Mirror System Functioning in Autism by Oxytocin
NCT03715153	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children Aged From 2 to Less Than 7 Years Old With Autism Spectrum Disorder.
NCT03715166	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children and Adolescents Aged From 7 to Less Than 18 Years Old With Autism Spectrum Disorder
NCT04233502	PHASE3	WITHDRAWN	Efficacy and Safety of Slenyto for Insomnia in Children With ASD
NCT04578756	PHASE3	COMPLETED	Open-Label, Flexible-dose Study to Evaluate the Long-Term Safety and Tolerability of Cariprazine in the Treatment of Pediatric Participants With Schizophrenia, Bipolar I Disorder, or Autism Spectrum Disorder
NCT04623398	PHASE3	COMPLETED	Effect of Lithium in Patients With Autism Spectrum Disorder and Phelan-McDermid Syndrome (SHANK3 Haploinsufficiency)
NCT04725383	PHASE3	TERMINATED	Amitriptyline for Repetitive Behaviors in Autism Spectrum Disorders
NCT05212493	PHASE3	COMPLETED	The Effects of Medical Cannabis in Children With Autistic Spectrum Disorder
NCT05361707	PHASE3	UNKNOWN	Evaluating the Effects of Tasimelteon in Individuals With Autism Spectrum Disorder (ASD) and Sleep Disturbances
NCT05439616	PHASE3	COMPLETED	Study of Cariprazine Oral Capsules or Solution to Assess Adverse Events and Change in Irritability Due to Autism Spectrum Disorder (ASD) in Participants Aged 5-17 Years With ASD
NCT06229210	PHASE3	RECRUITING	Safety and Tolerability Trial of Lumateperone in Pediatric Patients With Schizophrenia, Bipolar Disorder or Autism Spectrum Disorder