TM9SF1

Summary

TM9SF1 (transmembrane 9 superfamily member 1, HGNC:11864) is a protein-coding gene on chromosome 14q12, encoding Transmembrane 9 superfamily member 1 (O15321). Plays an essential role in autophagy.

Predicted to be involved in protein localization to membrane. Predicted to be located in autophagosome membrane; cytoplasmic vesicle; and lysosomal membrane. Predicted to be active in membrane.

Source: NCBI Gene 10548 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 93 total
• MANE Select transcript: NM_006405

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11864
Approved symbol	TM9SF1
Name	transmembrane 9 superfamily member 1
Location	14q12
Locus type	gene with protein product
Status	Approved
Aliases	MP70, HMP70
Ensembl gene	ENSG00000100926
Ensembl biotype	protein_coding
OMIM	618965
Entrez	10548

Gene structure

Transcript identifiers

Ensembl transcripts: 26 — 24 protein_coding, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000261789, ENST00000396854, ENST00000524835, ENST00000525592, ENST00000528010, ENST00000528669, ENST00000528895, ENST00000529332, ENST00000530468, ENST00000530563, ENST00000531406, ENST00000532632, ENST00000903983, ENST00000903984, ENST00000903985, ENST00000903986, ENST00000903987, ENST00000903988, ENST00000903989, ENST00000933740, ENST00000933741, ENST00000933742, ENST00000933743, ENST00000933744, ENST00000967639, ENST00000967640

RefSeq mRNA: 3 — MANE Select: NM_006405 NM_001014842, NM_001289006, NM_006405

CCDS: CCDS41934, CCDS73623, CCDS9617

Canonical transcript exons

ENST00000261789 — 6 exons

Exon	Start	End
ENSE00001419735	24195346	24195441
ENSE00002152967	24189149	24189808
ENSE00003467995	24192648	24193269
ENSE00003479928	24192171	24192356
ENSE00003563865	24190380	24190653
ENSE00003628784	24194675	24195036

Expression profiles

Bgee: expression breadth ubiquitous, 180 present calls, max score 95.93.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 31.7704 / max 132.5334, expressed in 1816 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
142546	18.9874	1807
142547	12.4982	1796
142545	0.2848	121

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	95.93	gold quality
islet of Langerhans	UBERON:0000006	95.89	gold quality
body of pancreas	UBERON:0001150	95.02	gold quality
gall bladder	UBERON:0002110	94.20	gold quality
right uterine tube	UBERON:0001302	94.08	gold quality
smooth muscle tissue	UBERON:0001135	94.06	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	93.97	gold quality
right adrenal gland	UBERON:0001233	93.90	gold quality
left adrenal gland	UBERON:0001234	93.68	gold quality
right adrenal gland cortex	UBERON:0035827	93.62	gold quality
pancreas	UBERON:0001264	93.55	gold quality
left adrenal gland cortex	UBERON:0035825	93.23	gold quality
minor salivary gland	UBERON:0001830	93.06	gold quality
endocervix	UBERON:0000458	92.85	gold quality
right lobe of thyroid gland	UBERON:0001119	92.74	gold quality
left lobe of thyroid gland	UBERON:0001120	92.62	gold quality
body of stomach	UBERON:0001161	92.53	gold quality
left uterine tube	UBERON:0001303	92.32	gold quality
rectum	UBERON:0001052	92.18	gold quality
mucosa of transverse colon	UBERON:0004991	91.88	gold quality
upper lobe of left lung	UBERON:0008952	91.69	gold quality
right coronary artery	UBERON:0001625	91.67	gold quality
metanephros cortex	UBERON:0010533	91.66	gold quality
body of uterus	UBERON:0009853	91.64	gold quality
right lung	UBERON:0002167	91.60	gold quality
right ovary	UBERON:0002118	91.56	gold quality
ectocervix	UBERON:0012249	91.39	gold quality
adrenal gland	UBERON:0002369	91.27	gold quality
thoracic aorta	UBERON:0001515	91.19	gold quality
left coronary artery	UBERON:0001626	91.13	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	11.62
E-MTAB-6142	no	254.55

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

45 targeting TM9SF1, 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-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-891B	99.59	69.81	1083
HSA-MIR-3120-3P	99.54	70.28	2669
HSA-MIR-365A-3P	99.43	70.02	836
HSA-MIR-365B-3P	99.43	70.02	836
HSA-MIR-513A-3P	99.39	70.63	3620
HSA-MIR-513C-3P	99.39	70.63	3620
HSA-MIR-377-3P	99.37	70.18	1905
HSA-MIR-6731-5P	99.28	67.42	2375
HSA-MIR-8085	99.28	67.56	2362
HSA-MIR-3606-3P	99.11	69.84	3254
HSA-MIR-3168	99.08	67.75	1384
HSA-MIR-5000-3P	98.79	65.63	1251
HSA-MIR-500A-5P	98.76	69.13	1241
HSA-MIR-330-5P	98.73	67.63	1788
HSA-MIR-4501	98.72	67.19	921
HSA-MIR-5197-3P	98.71	67.05	1905
HSA-MIR-4700-5P	98.63	67.43	1915
HSA-MIR-8060	98.61	66.93	1187
HSA-MIR-3689A-5P	98.35	70.12	1049
HSA-MIR-3689B-5P	98.35	70.12	1049

Literature-anchored findings (GeneRIF, showing 1)

• The results of transmission electron microscopy and immunoblotting to examine LC3-II levels further confirmed the ability of TM9SF1 to induce autophagy. (PMID:19029833)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	tm9sf1	ENSDARG00000022970
mus_musculus	Tm9sf1	ENSMUSG00000002320
rattus_norvegicus	Tm9sf1	ENSRNOG00000019710

Paralogs (3): TM9SF3 (ENSG00000077147), TM9SF4 (ENSG00000101337), TM9SF2 (ENSG00000125304)

Protein

Protein identifiers

Transmembrane 9 superfamily member 1 — O15321 (reviewed: O15321)

Alternative names: MP70 protein family member

All UniProt accessions (10): O15321, E9PJC4, E9PJM1, E9PL78, E9PMQ9, E9PNW2, E9PP24, E9PQY7, E9PS99, G3V1B9

UniProt curated annotations — full annotation on UniProt →

Function. Plays an essential role in autophagy.

Subcellular location. Lysosome membrane. Cytoplasmic vesicle. Autophagosome membrane.

Tissue specificity. Expressed in lung, pancreas, kidney, liver, placenta, skeletal muscle, heart and brain. The amount in skeletal muscle, heart and brain were considerably lower than in the other tissues.

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

Isoforms (2)

UniProt ID	Names	Canonical?
O15321-1	1	yes
O15321-2	2

RefSeq proteins (3): NP_001014842, NP_001275935, NP_006396* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004240	EMP70	Family

Pfam: PF02990

UniProt features (20 total): transmembrane region 9, glycosylation site 3, sequence conflict 3, sequence variant 2, signal peptide 1, chain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O15321-F1	84.47	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 (3): 178, 401, 559

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 148 (showing top): MORF_RAB5A, KAAB_FAILED_HEART_ATRIUM_DN, GOCC_VACUOLAR_MEMBRANE, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, CHANDRAN_METASTASIS_DN, EFC_Q6, chr14q12, TGTGTGA_MIR377, SCHAEFFER_PROSTATE_DEVELOPMENT_6HR_DN, MORF_PPP6C, MORF_PPP2R4, RFX1_02, GOBP_LOCALIZATION_WITHIN_MEMBRANE, GRADE_COLON_AND_RECTAL_CANCER_DN, MILI_PSEUDOPODIA_CHEMOTAXIS_DN

GO Biological Process (2): autophagy (GO:0006914), protein localization to membrane (GO:0072657)

GO Molecular Function (0):

GO Cellular Component (5): autophagosome membrane (GO:0000421), lysosomal membrane (GO:0005765), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410), lysosome (GO:0005764)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
catabolic process	1
transmembrane transport	1
process utilizing autophagic mechanism	1
intracellular protein localization	1
localization within membrane	1
vacuolar membrane	1
autophagosome	1
lysosome	1
lytic vacuole membrane	1
cellular anatomical structure	1
cytoplasm	1
intracellular vesicle	1
lytic vacuole	1

Protein interactions and networks

STRING

698 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TM9SF1	EBAG9	O00559	615
TM9SF1	NSA2	O95478	529
TM9SF1	TMEM74	Q96NL1	482
TM9SF1	TMEM174	Q8WUU8	479
TM9SF1	EVA1A	Q9H8M9	479
TM9SF1	SNAPC2	Q13487	452
TM9SF1	SZRD1	Q7Z422	434
TM9SF1	TMEM165	Q9HC07	394
TM9SF1	CERT1	Q9Y5P4	382
TM9SF1	HGS	O14964	380
TM9SF1	WDR45B	Q5MNZ6	356
TM9SF1	CHMP2A	O43633	350
TM9SF1	SNF8	Q96H20	350
TM9SF1	SNX15	Q9NRS6	349
TM9SF1	RUBCN	Q92622	338

IntAct

68 interactions, top by confidence:

A	B	Type	Score
TM9SF1	MTNR1A	psi-mi:“MI:0915”(physical association)	0.370
P2RX7	TM9SF1	psi-mi:“MI:0915”(physical association)	0.370
TCOF1	TM9SF1	psi-mi:“MI:0915”(physical association)	0.370
TM9SF1	RNASEH1	psi-mi:“MI:0915”(physical association)	0.370
		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
MME		psi-mi:“MI:0914”(association)	0.350
CLEC2D	TMEM120B	psi-mi:“MI:0914”(association)	0.350
	TMEM223	psi-mi:“MI:0914”(association)	0.350
M	TM9SF1	psi-mi:“MI:0914”(association)	0.350
POMK	ESYT2	psi-mi:“MI:0914”(association)	0.350
ATP6V1A		psi-mi:“MI:0914”(association)	0.350
	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
	HLA-C	psi-mi:“MI:0914”(association)	0.350
C5AR1	TCAF2	psi-mi:“MI:0914”(association)	0.350
OPRL1	METTL15	psi-mi:“MI:0914”(association)	0.350
ATP1B1	TM9SF1	psi-mi:“MI:0914”(association)	0.350
C5AR1	SLC12A8	psi-mi:“MI:0914”(association)	0.350
GPR182	SLC12A8	psi-mi:“MI:0914”(association)	0.350
CLEC2D	ESYT2	psi-mi:“MI:0914”(association)	0.350
RTN3	ESYT2	psi-mi:“MI:0914”(association)	0.350
TSPAN15	TMEM223	psi-mi:“MI:0914”(association)	0.350
DUOXA2	TMEM131L	psi-mi:“MI:0914”(association)	0.350
UPK2	TMEM131L	psi-mi:“MI:0914”(association)	0.350

BioGRID (91): TM9SF1 (Affinity Capture-MS), TM9SF1 (Affinity Capture-MS), TM9SF1 (Affinity Capture-MS), TM9SF1 (Affinity Capture-MS), TM9SF1 (Two-hybrid), TM9SF1 (Affinity Capture-MS), TM9SF1 (Affinity Capture-MS), TM9SF1 (Affinity Capture-MS), TM9SF1 (Affinity Capture-MS), TM9SF1 (Affinity Capture-MS), TM9SF1 (Proximity Label-MS), TM9SF1 (Proximity Label-MS), TM9SF1 (Proximity Label-MS), TM9SF1 (Proximity Label-MS), TM9SF1 (Proximity Label-MS)

ESM2 similar proteins: A0A060LAL9, A0A097ZPE6, A0A1I9R3Y5, A2VEI2, A2XVG1, A2YGP6, A4IFE9, A8B479, A8WQT4, B3H7A9, F4I1L3, G1JSL4, O15321, O22585, O22788, O45228, O64407, O65015, O81270, P10538, P31252, P58021, P80363, Q28C60, Q43727, Q5R8F1, Q5R8Y6, Q5Z8Y4, Q623S8, Q66HF2, Q66HG5, Q6DCK1, Q7FAX1, Q7JW12, Q8CD10, Q8IYU8, Q95PZ2, Q99805, Q99P63, Q9CAB7

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 85 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	5	26.8×	1e-04
R-HSA-425366	5	16.2×	5e-04
SLC-mediated transmembrane transport	11	11.6×	4e-07
R-HSA-425393	5	11.6×	2e-03
Class A/1 (Rhodopsin-like receptors)	7	9.3×	5e-04
GPCR ligand binding	6	6.9×	5e-03
Transport of small molecules	12	5.4×	1e-04

GO biological processes:

GO term	Partners	Fold	FDR
amino acid transport	8	33.3×	6e-08
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	5	14.6×	4e-03
transport across blood-brain barrier	5	11.9×	5e-03
phospholipase C-activating G protein-coupled receptor signaling pathway	6	10.5×	4e-03
response to xenobiotic stimulus	7	6.5×	7e-03
G protein-coupled receptor signaling pathway	10	4.8×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	82
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1245 predictions. Top by Δscore:

Variant	Effect	Δscore
14:24189804:TGGCA:T	acceptor_gain	1.0000
14:24189805:GGCA:G	acceptor_gain	1.0000
14:24189806:GCA:G	acceptor_gain	1.0000
14:24189807:CA:C	acceptor_gain	1.0000
14:24189807:CAC:C	acceptor_gain	1.0000
14:24189808:AC:A	acceptor_loss	1.0000
14:24189809:C:CC	acceptor_gain	1.0000
14:24189809:CTGTG:C	acceptor_loss	1.0000
14:24189811:G:C	acceptor_gain	1.0000
14:24190377:TACCT:T	donor_loss	1.0000
14:24190378:ACCTG:A	donor_loss	1.0000
14:24190556:C:CT	acceptor_gain	1.0000
14:24192166:CTCAC:C	donor_loss	1.0000
14:24192167:TCA:T	donor_loss	1.0000
14:24192168:CA:C	donor_loss	1.0000
14:24192169:A:AC	donor_gain	1.0000
14:24192169:A:C	donor_loss	1.0000
14:24192170:C:CC	donor_gain	1.0000
14:24192170:C:CT	donor_loss	1.0000
14:24194689:G:C	donor_gain	1.0000
14:24189811:G:GC	acceptor_gain	0.9900
14:24190654:C:CC	acceptor_gain	0.9900
14:24192217:G:A	donor_gain	0.9900
14:24192277:A:C	acceptor_gain	0.9900
14:24192357:C:CC	acceptor_gain	0.9900
14:24192938:C:CT	donor_gain	0.9900
14:24192939:C:CT	donor_gain	0.9900
14:24193266:CCAC:C	acceptor_gain	0.9900
14:24193267:CAC:C	acceptor_gain	0.9900
14:24193267:CACC:C	acceptor_gain	0.9900

AlphaMissense

3948 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:24189665:A:G	L524S	1.000
14:24190396:C:G	G471R	1.000
14:24192681:C:G	G312R	1.000
14:24192723:A:T	F298I	1.000
14:24192745:C:A	W290C	1.000
14:24192745:C:G	W290C	1.000
14:24192747:A:G	W290R	1.000
14:24192747:A:T	W290R	1.000
14:24192881:A:T	L245H	1.000
14:24192892:G:C	N241K	1.000
14:24192892:G:T	N241K	1.000
14:24193188:C:G	G143R	1.000
14:24194766:C:A	G85V	1.000
14:24194766:C:T	G85E	1.000
14:24194767:C:A	G85W	1.000
14:24189451:G:C	F595L	0.999
14:24189451:G:T	F595L	0.999
14:24189452:A:G	F595S	0.999
14:24189453:A:G	F595L	0.999
14:24189483:C:G	G585R	0.999
14:24189529:G:C	F569L	0.999
14:24189529:G:T	F569L	0.999
14:24189531:A:G	F569L	0.999
14:24189609:C:G	G543R	0.999
14:24189617:C:T	G540D	0.999
14:24189618:C:G	G540R	0.999
14:24189639:A:G	W533R	0.999
14:24189639:A:T	W533R	0.999
14:24189645:A:G	W531R	0.999
14:24189645:A:T	W531R	0.999

dbSNP variants (sampled 300 via entrez): RS1000071113 (14:24188974 A>C), RS1000173037 (14:24191135 G>A), RS1001921706 (14:24190900 C>T), RS1002039918 (14:24192105 A>C), RS1002389168 (14:24195623 G>A,T), RS1002429260 (14:24196808 T>C), RS1002585790 (14:24193525 C>T), RS1002616662 (14:24196546 T>G), RS1002928805 (14:24196308 G>A), RS1003225198 (14:24189891 C>A,T), RS1003409217 (14:24191888 G>C), RS1004725545 (14:24190219 G>A), RS1004817567 (14:24195625 C>T), RS1004945285 (14:24195338 G>A,C), RS1005321411 (14:24191991 T>A)

Disease associations

OMIM: gene MIM:618965 | 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

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, affects cotreatment, increases methylation	2
Nickel	increases expression	2
Valproic Acid	affects expression, increases methylation	2
sodium arsenite	decreases expression	1
cobaltous chloride	decreases expression	1
avobenzone	increases expression	1
perfluorooctane sulfonic acid	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Acetaminophen	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Atrazine	increases expression	1
Vehicle Emissions	decreases expression, increases abundance	1
Caffeine	decreases expression	1
Carbamazepine	affects expression	1
Diazinon	increases methylation	1
Ivermectin	decreases expression	1
Phenobarbital	affects expression	1
Selenium	affects cotreatment, increases expression	1
Smoke	increases abundance, increases expression	1
Thioacetamide	decreases expression	1
Tunicamycin	increases expression	1
Vitamin E	affects cotreatment, increases expression	1
Aflatoxin B1	decreases methylation	1
Copper Sulfate	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E0R4	Ubigene HeLa TM9SF1 KO	Cancer cell line	Female
CVCL_TS56	HAP1 TM9SF1 (-) 1	Cancer cell line	Male
CVCL_TS57	HAP1 TM9SF1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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