TM6SF1

Summary

TM6SF1 (transmembrane 6 superfamily member 1, HGNC:11860) is a protein-coding gene on chromosome 15q25.2, encoding Transmembrane 6 superfamily member 1 (Q9BZW5). May function as sterol isomerase.

Predicted to be located in lysosome and membrane. Predicted to be active in lysosomal membrane.

Source: NCBI Gene 53346 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 6 total
• MANE Select transcript: NM_023003

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11860
Approved symbol	TM6SF1
Name	transmembrane 6 superfamily member 1
Location	15q25.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000136404
Ensembl biotype	protein_coding
OMIM	606562
Entrez	53346

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 8 protein_coding, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000258909, ENST00000322019, ENST00000379384, ENST00000379390, ENST00000561551, ENST00000564988, ENST00000565774, ENST00000565982, ENST00000880031, ENST00000948708, ENST00000948709

RefSeq mRNA: 10 — MANE Select: NM_023003 NM_001144903, NM_001330385, NM_001353878, NM_001353879, NM_001353880, NM_001353881, NM_001353882, NM_001353883, NM_001353884, NM_023003

CCDS: CCDS10323, CCDS45338, CCDS81915

Canonical transcript exons

ENST00000322019 — 10 exons

Exon	Start	End
ENSE00001763331	83136481	83137408
ENSE00001825113	83107645	83107772
ENSE00003467130	83122757	83122878
ENSE00003507090	83119578	83119681
ENSE00003548411	83115845	83115942
ENSE00003572950	83126755	83126847
ENSE00003579096	83127358	83127477
ENSE00003580199	83121921	83122003
ENSE00003655530	83112797	83112900
ENSE00003674810	83124672	83124776

Expression profiles

Bgee: expression breadth ubiquitous, 235 present calls, max score 92.31.

FANTOM5 (CAGE): breadth broad, TPM avg 5.7696 / max 110.5625, expressed in 868 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
148114	5.2655	845
148113	0.5041	271

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	92.31	gold quality
mononuclear cell	CL:0000842	91.86	gold quality
leukocyte	CL:0000738	91.41	gold quality
hindlimb stylopod muscle	UBERON:0004252	91.26	gold quality
diaphragm	UBERON:0001103	90.82	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	90.22	gold quality
muscle of leg	UBERON:0001383	88.95	gold quality
gastrocnemius	UBERON:0001388	88.53	gold quality
muscle organ	UBERON:0001630	88.44	gold quality
biceps brachii	UBERON:0001507	87.92	gold quality
blood	UBERON:0000178	87.59	gold quality
vastus lateralis	UBERON:0001379	87.56	gold quality
skeletal muscle tissue	UBERON:0001134	87.54	gold quality
prefrontal cortex	UBERON:0000451	86.99	gold quality
quadriceps femoris	UBERON:0001377	86.43	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	85.91	gold quality
muscle tissue	UBERON:0002385	85.78	gold quality
right lung	UBERON:0002167	85.64	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	85.61	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.51	gold quality
Brodmann (1909) area 9	UBERON:0013540	84.44	gold quality
frontal cortex	UBERON:0001870	84.12	gold quality
deltoid	UBERON:0001476	84.07	gold quality
anterior cingulate cortex	UBERON:0009835	84.04	gold quality
granulocyte	CL:0000094	83.99	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	83.93	gold quality
cingulate cortex	UBERON:0003027	83.92	gold quality
tibialis anterior	UBERON:0001385	83.46	gold quality
neocortex	UBERON:0001950	83.21	gold quality
right frontal lobe	UBERON:0002810	83.01	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.84

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

64 targeting TM6SF1, 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-3613-3P	100.00	76.36	7965
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-2052	99.79	69.37	2031
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548F-5P	99.78	71.02	3093
HSA-MIR-548G-5P	99.78	71.12	3085
HSA-MIR-548X-5P	99.78	71.12	3085

Literature-anchored findings (GeneRIF, showing 3)

• Data conclude that AKR1B1 and TM6SF1 may serve as candidate methylation biomarkers for early breast cancer detection. (PMID:25123395)
• TM6SF2 reduces lipid accumulation in vascular smooth muscle cells by inhibiting LOX-1 and CD36 expression. (PMID:37271250)
• TM6SF1 suppresses the progression of lung adenocarcinoma and M2 macrophage polarization by inactivating the PI3K/AKT/mtor pathway. (PMID:38718735)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Tm6sf1	ENSMUSG00000038623
rattus_norvegicus	Tm6sf1	ENSRNOG00000019662

Paralogs (1): TM6SF2 (ENSG00000213996)

Protein

Protein identifiers

Transmembrane 6 superfamily member 1 — Q9BZW5 (reviewed: Q9BZW5)

All UniProt accessions (6): E9PD04, Q9BZW5, H3BM84, H3BMK0, Q6P4D7, Q8N5N8

UniProt curated annotations — full annotation on UniProt →

Function. May function as sterol isomerase.

Subcellular location. Lysosome membrane.

Tissue specificity. Enhanced expression in spleen, testis and peripheral blood leukocytes.

Similarity. Belongs to the TM6SF family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9BZW5-1	1	yes
Q9BZW5-2	2

RefSeq proteins (10): NP_001138375, NP_001317314, NP_001340807, NP_001340808, NP_001340809, NP_001340810, NP_001340811, NP_001340812, NP_001340813, NP_075379* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR033118	EXPERA	Domain
IPR047195	TM6SF1-like	Family
IPR059044	TM_Tm6sf1/2	Domain

Pfam: PF26083

UniProt features (18 total): transmembrane region 9, sequence conflict 3, domain 2, sequence variant 2, chain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BZW5-F1	92.68	0.80

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 216 (showing top): VERHAAK_AML_WITH_NPM1_MUTATED_DN, GOCC_VACUOLAR_MEMBRANE, ZHAN_MULTIPLE_MYELOMA_CD1_UP, CEBP_Q2, MARTINEZ_RB1_TARGETS_DN, BILD_E2F3_ONCOGENIC_SIGNATURE, CASORELLI_APL_SECONDARY_VS_DE_NOVO_UP, DODD_NASOPHARYNGEAL_CARCINOMA_UP, SPIELMAN_LYMPHOBLAST_EUROPEAN_VS_ASIAN_UP, MARTINEZ_RB1_AND_TP53_TARGETS_UP, RIGGI_EWING_SARCOMA_PROGENITOR_UP, DEURIG_T_CELL_PROLYMPHOCYTIC_LEUKEMIA_UP, ZHAN_MULTIPLE_MYELOMA_CD1_VS_CD2_UP, GAVIN_FOXP3_TARGETS_CLUSTER_P2, SCHUETZ_BREAST_CANCER_DUCTAL_INVASIVE_UP

GO Biological Process (0):

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

GO Cellular Component (3): lysosomal membrane (GO:0005765), lysosome (GO:0005764), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1
lysosome	1
lytic vacuole membrane	1
lytic vacuole	1
cellular anatomical structure	1

Protein interactions and networks

STRING

542 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TM6SF1	HAPLN4	Q86UW8	946
TM6SF1	RASGRF2	O14827	574
TM6SF1	TMEFF2	Q9UIK5	571
TM6SF1	TRIM58	Q8NG06	560
TM6SF1	TMEM182	Q6ZP80	499
TM6SF1	TLX3	O43711	449
TM6SF1	TSPAN33	Q86UF1	447
TM6SF1	ARHGEF7	Q14155	445
TM6SF1	AKR1B1	P15121	444
TM6SF1	EBPL	Q9BY08	438
TM6SF1	A0A494C0F3	A0A494C0F3	431
TM6SF1	HOXB4	P17483	413
TM6SF1	COL6A2	P12110	393
TM6SF1	CDH15	P55291	382
TM6SF1	RASSF1	Q9NS23	373

IntAct

1 interactions, top by confidence:

BioGRID (4): TM6SF1 (Two-hybrid), MFF (Two-hybrid), TM6SF1 (Cross-Linking-MS (XL-MS)), TM6SF1 (Affinity Capture-RNA)

ESM2 similar proteins: A1A4P6, A1A5B4, A5PK40, A6NDV4, A6NFX1, A6NGC4, A6QL84, A6QLK4, B1AWJ5, B6ID01, E1BY51, P58749, Q2TA01, Q2YDG0, Q32PG7, Q3T9M1, Q4R7X9, Q5HZE5, Q5JZQ7, Q5R6H1, Q5RBY7, Q60HE8, Q6AY05, Q6AYM9, Q6PHN7, Q6TCG5, Q6UX01, Q6UXD7, Q7RTT9, Q7Z403, Q80ZE4, Q8CE47, Q8R139, Q8TBR7, Q96FZ5, Q96HE8, Q96S97, Q9BSA9, Q9BZW5, Q9CQC4

Diamond homologs: A6QL84, B0BNG2, P58749, Q0V982, Q5RBJ7, Q6DCP8, Q8R1J1, Q9BZW4, Q9BZW5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

2157 predictions. Top by Δscore:

Variant	Effect	Δscore
15:83107771:GA:G	donor_gain	1.0000
15:83107773:G:GG	donor_gain	1.0000
15:83115843:A:AG	acceptor_gain	1.0000
15:83115843:AGT:A	acceptor_gain	1.0000
15:83115844:G:GT	acceptor_gain	1.0000
15:83115844:GT:G	acceptor_gain	1.0000
15:83115844:GTG:G	acceptor_gain	1.0000
15:83115844:GTGT:G	acceptor_gain	1.0000
15:83119678:GGGA:G	donor_gain	1.0000
15:83119679:G:GT	donor_gain	1.0000
15:83119679:GGA:G	donor_gain	1.0000
15:83119680:GA:G	donor_gain	1.0000
15:83119680:GAG:G	donor_gain	1.0000
15:83119682:G:GG	donor_gain	1.0000
15:83139144:CAAA:C	donor_gain	1.0000
15:83107777:G:GG	donor_gain	0.9900
15:83115938:GAGAG:G	donor_gain	0.9900
15:83119574:TTA:T	acceptor_loss	0.9900
15:83119576:A:T	acceptor_loss	0.9900
15:83119576:AG:A	acceptor_gain	0.9900
15:83119577:GG:G	acceptor_gain	0.9900
15:83119659:A:AG	donor_gain	0.9900
15:83119677:TGGGA:T	donor_gain	0.9900
15:83119678:GGGAG:G	donor_gain	0.9900
15:83119679:G:T	donor_gain	0.9900
15:83119686:G:GG	donor_gain	0.9900
15:83121999:TGTAG:T	donor_loss	0.9900
15:83122001:TAG:T	donor_loss	0.9900
15:83122002:AGG:A	donor_loss	0.9900
15:83122003:GGTAA:G	donor_loss	0.9900

AlphaMissense

2376 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:83115868:A:C	S74R	0.998
15:83115870:C:A	S74R	0.998
15:83115870:C:G	S74R	0.998
15:83119668:G:C	A129P	0.998
15:83121949:T:A	W143R	0.998
15:83121949:T:C	W143R	0.998
15:83119623:T:A	W114R	0.997
15:83119623:T:C	W114R	0.997
15:83107727:C:A	A16D	0.995
15:83115881:T:C	L78P	0.995
15:83119654:T:C	L124P	0.995
15:83121940:G:C	G140R	0.995
15:83121941:G:A	G140D	0.995
15:83112894:T:C	F64L	0.994
15:83112896:C:A	F64L	0.994
15:83112896:C:G	F64L	0.994
15:83121955:G:A	G145R	0.994
15:83121955:G:C	G145R	0.994
15:83121956:G:A	G145E	0.994
15:83121958:T:C	S146P	0.994
15:83115893:T:C	L82P	0.993
15:83107697:C:A	A6D	0.992
15:83119629:G:C	G116R	0.992
15:83119630:G:A	G116D	0.992
15:83122003:G:A	G161R	0.992
15:83122003:G:C	G161R	0.992
15:83127460:G:C	A302P	0.992
15:83127464:G:A	G303E	0.992
15:83119625:G:C	W114C	0.991
15:83119625:G:T	W114C	0.991

dbSNP variants (sampled 300 via entrez): RS1000095506 (15:83132257 T>C), RS1000125578 (15:83135458 T>C), RS1000244087 (15:83107583 C>A,T), RS1000577851 (15:83106050 C>T), RS1000650951 (15:83130590 T>A,G), RS1000741978 (15:83116587 C>G), RS1001009868 (15:83105915 TAA>T), RS1001177121 (15:83125934 A>G), RS1001305727 (15:83111436 A>T), RS1001308657 (15:83122442 C>A,T), RS1001344691 (15:83118980 C>T), RS1001375744 (15:83119312 C>T), RS1001420648 (15:83112062 G>A), RS1001432039 (15:83106126 G>A), RS1001542965 (15:83137259 CT>C)

Disease associations

OMIM: gene MIM:606562 | 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
GCST007094_75	Diastolic blood pressure	2.000000e-11
GCST007098_89	Diastolic blood pressure	5.000000e-06
GCST90002388_157	Lymphocyte count	1.000000e-13

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0006336	diastolic blood pressure
EFO:0004587	lymphocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases methylation, affects cotreatment, decreases expression, increases expression	6
Arsenic Trioxide	increases expression	2
Air Pollutants	decreases expression, increases abundance, increases expression	2
Benzo(a)pyrene	decreases expression, increases methylation	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
triphenyl phosphate	affects expression	1
2,5,2’,5’-tetrachlorobiphenyl	increases expression	1
arsenite	affects expression	1
mono-(2-ethylhexyl)phthalate	increases expression	1
sulforaphane	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
racecadotril	increases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
ICG 001	increases expression	1
dorsomorphin	decreases expression, affects cotreatment	1
jinfukang	decreases expression	1
Dasatinib	increases expression	1
Resveratrol	decreases expression	1
Sunitinib	increases expression	1
Arsenic	affects methylation	1
Hexachlorocyclohexane	increases expression	1
Cisplatin	decreases expression	1
Coumestrol	decreases expression	1
Cyclophosphamide	decreases expression	1
Diazinon	increases expression	1
Diethylhexyl Phthalate	decreases expression	1
Progesterone	increases expression	1
Silicon Dioxide	increases expression	1
Tobacco Smoke Pollution	increases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TS55	HAP1 TM6SF1 (-) 1	Cancer cell line	Male
CVCL_XU30	HAP1 TM6SF1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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