TM7SF3

Summary

TM7SF3 (transmembrane 7 superfamily member 3, HGNC:23049) is a protein-coding gene on chromosome 12p11.23, encoding Transmembrane 7 superfamily member 3 (Q9NS93). Involved in the inhibition of cytokine-induced death of pancreatic beta cells.

Involved in cellular response to unfolded protein; negative regulation of programmed cell death; and positive regulation of insulin secretion. Located in plasma membrane.

Source: NCBI Gene 51768 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 97 total
• MANE Select transcript: NM_016551

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23049
Approved symbol	TM7SF3
Name	transmembrane 7 superfamily member 3
Location	12p11.23
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000064115
Ensembl biotype	protein_coding
OMIM	605181
Entrez	51768

Gene structure

Transcript identifiers

Ensembl transcripts: 41 — 34 protein_coding, 3 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000343028, ENST00000512808, ENST00000535260, ENST00000535423, ENST00000535819, ENST00000537406, ENST00000539399, ENST00000539741, ENST00000541081, ENST00000542019, ENST00000542667, ENST00000543088, ENST00000543655, ENST00000543803, ENST00000543882, ENST00000544179, ENST00000545303, ENST00000545344, ENST00000545600, ENST00000867958, ENST00000867959, ENST00000867960, ENST00000867961, ENST00000867962, ENST00000867963, ENST00000867964, ENST00000867965, ENST00000867966, ENST00000867967, ENST00000867968, ENST00000867969, ENST00000867970, ENST00000867971, ENST00000867972, ENST00000867973, ENST00000867974, ENST00000867975, ENST00000867976, ENST00000913605, ENST00000913606, ENST00000949294

RefSeq mRNA: 1 — MANE Select: NM_016551 NM_016551

CCDS: CCDS8710

Canonical transcript exons

ENST00000343028 — 12 exons

Exon	Start	End
ENSE00000732913	26979784	26979936
ENSE00000835917	26990450	26990627
ENSE00001388310	26971579	26974227
ENSE00002232459	27014078	27014384
ENSE00003472171	26975496	26975658
ENSE00003473954	26996742	26996862
ENSE00003510136	26976260	26976357
ENSE00003513515	26995237	26995408
ENSE00003544261	26999526	26999676
ENSE00003546896	27003236	27003390
ENSE00003594858	26982773	26982859
ENSE00003790305	26980566	26980646

Expression profiles

Bgee: expression breadth ubiquitous, 278 present calls, max score 98.49.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 28.1055 / max 587.6823, expressed in 1810 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
130246	27.8435	1810
130245	0.2621	140

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
body of pancreas	UBERON:0001150	98.49	gold quality
sperm	CL:0000019	98.18	gold quality
gall bladder	UBERON:0002110	97.21	gold quality
rectum	UBERON:0001052	97.11	gold quality
right adrenal gland	UBERON:0001233	96.88	gold quality
right adrenal gland cortex	UBERON:0035827	96.85	gold quality
stromal cell of endometrium	CL:0002255	96.72	gold quality
descending thoracic aorta	UBERON:0002345	96.40	gold quality
mucosa of stomach	UBERON:0001199	96.21	gold quality
left adrenal gland	UBERON:0001234	96.20	gold quality
thoracic aorta	UBERON:0001515	96.16	gold quality
minor salivary gland	UBERON:0001830	96.16	gold quality
ascending aorta	UBERON:0001496	96.13	gold quality
male germ cell	CL:0000015	96.10	gold quality
pancreas	UBERON:0001264	96.09	gold quality
esophagus mucosa	UBERON:0002469	95.82	gold quality
metanephros cortex	UBERON:0010533	95.72	gold quality
right coronary artery	UBERON:0001625	95.67	gold quality
left adrenal gland cortex	UBERON:0035825	95.61	gold quality
adrenal gland	UBERON:0002369	95.54	gold quality
adrenal cortex	UBERON:0001235	95.45	gold quality
left coronary artery	UBERON:0001626	95.39	gold quality
saliva-secreting gland	UBERON:0001044	95.35	gold quality
mouth mucosa	UBERON:0003729	95.33	gold quality
islet of Langerhans	UBERON:0000006	95.31	gold quality
mucosa of transverse colon	UBERON:0004991	95.13	gold quality
skin of abdomen	UBERON:0001416	94.92	gold quality
aorta	UBERON:0000947	94.91	gold quality
right lobe of liver	UBERON:0001114	94.85	gold quality
skin of leg	UBERON:0001511	94.80	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-10553	yes	19.50
E-MTAB-9067	yes	13.63
E-ANND-3	yes	11.59
E-CURD-112	yes	10.30

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

115 targeting TM7SF3, 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-5692A	100.00	74.40	6850
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-497-5P	99.92	71.83	2674

Literature-anchored findings (GeneRIF, showing 3)

• Data indicate that TM7SF3 plays a role in inhibition of cytokine-induced cell death/apoptosis in pancreatic beta cells and in inhibition of insulin secretion from pancreatic beta cells. (PMID:21853325)
• Lack of TM7SF3 activates nitric oxide production and the PKR-like ER kinase arm of the unfolded protein response that involves inhibition of eIF2alpha activity, enhanced expression of ATF4 and ATF3, and induction of CHOP that culminates in apoptosis. (PMID:27740623)
• TM7SF3 controls TEAD1 splicing to prevent MASH-induced liver fibrosis. (PMID:38670107)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	tm7sf3	ENSDARG00000093658
mus_musculus	Tm7sf3	ENSMUSG00000040234
rattus_norvegicus	Tm7sf3	ENSRNOG00000001817

Protein

Protein identifiers

Transmembrane 7 superfamily member 3 — Q9NS93 (reviewed: Q9NS93)

Alternative names: Seven span transmembrane protein

All UniProt accessions (14): Q9NS93, F5GWC3, F5GXE1, F5GY35, F5GY59, F5H3K5, F5H4T1, F5H587, F5H7C5, H0YFM3, H0YFT0, H0YFW7, H0YGR1, H0YH23

UniProt curated annotations — full annotation on UniProt →

Function. Involved in the inhibition of cytokine-induced death of pancreatic beta cells. Involved in the promotion of insulin secretion from pancreatic beta cells. Is a downstream transcriptional target of p53/TP53, and acts as a pro-survival homeostatic factor that attenuates the development of cellular stress. Maintains protein homeostasis and promotes cell survival through attenuation of endoplasmic reticulum (ER) stress and the subsequent induction of unfolded protein response (UPR).

Subcellular location. Cell membrane.

Tissue specificity. Widely expressed. Highly expressed in kidney and pancreas.

RefSeq proteins (1): NP_057635* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR025256	TM7S3/TM198-like_dom	Domain
IPR042502	TM7SF3	Family

Pfam: PF13886, PF25992

UniProt features (17 total): transmembrane region 7, glycosylation site 5, sequence variant 2, signal peptide 1, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NS93-F1	88.66	0.74

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 (5): 61, 75, 87, 264, 27

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 217 (showing top): BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_INSULIN_SECRETION, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_HORMONE_TRANSPORT, GOBP_CELLULAR_RESPONSE_TO_TOPOLOGICALLY_INCORRECT_PROTEIN, GOBP_CELL_CELL_SIGNALING, chr12p11, GOBP_POSITIVE_REGULATION_OF_INSULIN_SECRETION, GOBP_REGULATION_OF_PROTEIN_SECRETION, BLALOCK_ALZHEIMERS_DISEASE_UP, GOBP_SECRETION, GOBP_POSITIVE_REGULATION_OF_HORMONE_SECRETION

GO Biological Process (3): positive regulation of insulin secretion (GO:0032024), cellular response to unfolded protein (GO:0034620), negative regulation of programmed cell death (GO:0043069)

GO Molecular Function (0):

GO Cellular Component (3): plasma membrane (GO:0005886), extracellular exosome (GO:0070062), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
insulin secretion	1
positive regulation of protein secretion	1
regulation of insulin secretion	1
positive regulation of peptide hormone secretion	1
response to unfolded protein	1
cellular response to topologically incorrect protein	1
programmed cell death	1
regulation of programmed cell death	1
negative regulation of cellular process	1
membrane	1
cell periphery	1
extracellular vesicle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

636 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TM7SF3	INTS13	Q9NVM9	566
TM7SF3	FAM89B	Q8N5H3	549
TM7SF3	FGFR1OP2	Q9NVK5	521
TM7SF3	MED21	Q13503	468
TM7SF3	RFX7	Q2KHR2	456
TM7SF3	KLHL42	Q9P2K6	442
TM7SF3	GPR137	Q96N19	436
TM7SF3	GPR137B	O60478	432
TM7SF3	LNPK	Q9C0E8	420
TM7SF3	LXN	Q9BS40	413
TM7SF3	DACH1	Q9UI36	402
TM7SF3	ITFG1	Q8TB96	394
TM7SF3	PRPSAP2	O60256	383
TM7SF3	MYBPC1	Q00872	379
TM7SF3	TXNDC16	Q9P2K2	378

IntAct

10 interactions, top by confidence:

A	B	Type	Score
NIPAL1	ESYT2	psi-mi:“MI:0914”(association)	0.640
TAFA4	NRP1	psi-mi:“MI:0914”(association)	0.530
Npc1	ESYT2	psi-mi:“MI:0914”(association)	0.350
CLGN	TMEM131L	psi-mi:“MI:0914”(association)	0.350
GPR12	MGST3	psi-mi:“MI:0914”(association)	0.350
PPT1	CLGN	psi-mi:“MI:0914”(association)	0.350
SLC37A2	WWP2	psi-mi:“MI:0914”(association)	0.350
TM7SF3	spoIIIAA	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (14): TM7SF3 (Affinity Capture-MS), TM7SF3 (Affinity Capture-RNA), TM7SF3 (Affinity Capture-RNA), TM7SF3 (Proximity Label-MS), TM7SF3 (Affinity Capture-MS), TM7SF3 (Proximity Label-MS), TM7SF3 (Affinity Capture-MS), TRAP1 (Co-fractionation), TM7SF3 (Affinity Capture-MS), TM7SF3 (Affinity Capture-RNA), TM7SF3 (Proximity Label-MS), TM7SF3 (Affinity Capture-RNA), TM7SF3 (Proximity Label-MS), TM7SF3 (Affinity Capture-RNA)

ESM2 similar proteins: A0A140LIJ0, A1L3G9, A4IFL1, B9X187, O18968, O70491, P08033, P08034, P28230, P35212, P36380, P51915, P60572, Q02738, Q059Y8, Q0V8E7, Q1LXZ7, Q28FG4, Q29559, Q4QR83, Q5E9Z5, Q5FVF4, Q5FWS4, Q5JW98, Q5R7B4, Q5T197, Q5T1A1, Q60HF7, Q640M6, Q6GMB1, Q6WGK6, Q7SY10, Q7TNJ0, Q8BXV2, Q8C2L6, Q8C9E8, Q8CE93, Q8CEG0, Q8N5C1, Q8NDZ6

Diamond homologs: Q5FVF4, Q9CRG1, Q9NS93

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	67
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2321 predictions. Top by Δscore:

Variant	Effect	Δscore
12:26975489:GTCTT:G	donor_loss	1.0000
12:26975490:TCTTA:T	donor_loss	1.0000
12:26975491:CTTAC:C	donor_loss	1.0000
12:26975492:TTACC:T	donor_loss	1.0000
12:26975493:TA:T	donor_loss	1.0000
12:26975494:A:AC	donor_gain	1.0000
12:26975494:A:C	donor_loss	1.0000
12:26975495:C:CC	donor_gain	1.0000
12:26975655:TCAG:T	acceptor_gain	1.0000
12:26975656:CAG:C	acceptor_gain	1.0000
12:26975656:CAGC:C	acceptor_gain	1.0000
12:26975659:C:CC	acceptor_gain	1.0000
12:26976258:A:AC	donor_gain	1.0000
12:26976259:C:CC	donor_gain	1.0000
12:26976259:CTATT:C	donor_gain	1.0000
12:26980660:C:CT	acceptor_gain	1.0000
12:26980663:C:CT	acceptor_gain	1.0000
12:26980664:A:T	acceptor_gain	1.0000
12:26995232:TTTA:T	donor_loss	1.0000
12:26995234:TACC:T	donor_loss	1.0000
12:26995235:A:AG	donor_loss	1.0000
12:26995236:C:A	donor_loss	1.0000
12:26995404:CGCCT:C	acceptor_gain	1.0000
12:26995407:CT:C	acceptor_gain	1.0000
12:26995409:C:CC	acceptor_gain	1.0000
12:26995416:C:CT	acceptor_gain	1.0000
12:26995417:A:T	acceptor_gain	1.0000
12:26995421:A:T	acceptor_gain	1.0000
12:26996737:CGTA:C	donor_loss	1.0000
12:26996738:GTACC:G	donor_loss	1.0000

AlphaMissense

3717 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:26974207:A:G	W491R	0.984
12:26974207:A:T	W491R	0.984
12:26990545:A:T	V258D	0.983
12:26996768:A:C	F164L	0.982
12:26996768:A:T	F164L	0.982
12:26996770:A:G	F164L	0.982
12:26990560:A:T	I253K	0.980
12:26996844:C:G	C139S	0.979
12:26996845:A:T	C139S	0.979
12:26974187:A:C	S497R	0.974
12:26974187:A:T	S497R	0.974
12:26974189:T:G	S497R	0.974
12:26990519:C:G	A267P	0.973
12:26996760:G:T	A167E	0.971
12:26995352:A:G	L192S	0.969
12:26996831:G:C	F143L	0.969
12:26996831:G:T	F143L	0.969
12:26996833:A:G	F143L	0.969
12:26982803:A:G	C309R	0.967
12:26982815:C:G	G305R	0.967
12:26999595:A:G	W110R	0.967
12:26999595:A:T	W110R	0.967
12:26979909:C:T	G355E	0.966
12:26980617:C:G	G329R	0.965
12:26980617:C:T	G329R	0.965
12:26990551:A:T	V256D	0.965
12:26996853:G:T	P136H	0.965
12:26996840:A:C	N140K	0.964
12:26996840:A:T	N140K	0.964
12:26996850:C:A	G137V	0.964

dbSNP variants (sampled 300 via entrez): RS1000030349 (12:26978378 T>C), RS1000061396 (12:26977989 G>A), RS1000081137 (12:27000668 C>T), RS1000164507 (12:26986841 G>T), RS1000278582 (12:26980071 A>G), RS1000278868 (12:26991435 A>C,G,T), RS1000316234 (12:27004445 C>T), RS1000354903 (12:27013587 C>T), RS1000521712 (12:26985234 C>T), RS1000533563 (12:26973093 A>C), RS1000535508 (12:27003108 T>C), RS1000650037 (12:27002796 G>A), RS1000660249 (12:26980530 T>C), RS1000808951 (12:27005861 C>T), RS1000850688 (12:26998756 G>A)

Disease associations

OMIM: gene MIM:605181 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST005759_6	Dimensional psychopathology (Social)	4.000000e-07
GCST012335_22	Hodgkin’s lymphoma	2.000000e-11

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009100	social domain measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, decreases expression	4
Aflatoxin B1	affects expression, increases expression, increases methylation	4
sodium arsenite	affects expression, decreases expression, affects cotreatment, increases abundance	3
Acetaminophen	decreases expression, increases expression	3
Benzo(a)pyrene	increases expression	3
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tobacco Smoke Pollution	decreases expression, increases expression	2
triphenyl phosphate	affects expression	1
bisphenol A	affects expression	1
potassium perchlorate	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
azoxystrobin	increases expression	1
K 7174	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
ICG 001	increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, increases expression	1
picoxystrobin	increases 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	increases expression	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Atrazine	increases expression	1
Cadmium	increases abundance, increases expression	1
Cisplatin	affects cotreatment, increases expression	1
Cycloheximide	affects cotreatment, increases expression	1
Diethylstilbestrol	decreases expression	1
Doxorubicin	affects expression	1

Clinical trials (associated diseases)

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