STARD3

Summary

STARD3 (StAR related lipid transfer domain containing 3, HGNC:17579) is a protein-coding gene on chromosome 17q12, encoding StAR-related lipid transfer protein 3 (Q14849). Sterol-binding protein that mediates cholesterol transport from the endoplasmic reticulum to endosomes.

This gene encodes a member of a subfamily of lipid trafficking proteins that are characterized by a C-terminal steroidogenic acute regulatory domain and an N-terminal metastatic lymph node 64 domain. The encoded protein localizes to the membranes of late endosomes and may be involved in exporting cholesterol. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 10948 — RefSeq curated summary.

At a glance

• GWAS associations: 28
• Clinical variants (ClinVar): 95 total
• Druggable target: yes
• MANE Select transcript: NM_006804

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17579
Approved symbol	STARD3
Name	StAR related lipid transfer domain containing 3
Location	17q12
Locus type	gene with protein product
Status	Approved
Aliases	es64, MLN64
Ensembl gene	ENSG00000131748
Ensembl biotype	protein_coding
OMIM	607048
Entrez	10948

Gene structure

Transcript identifiers

Ensembl transcripts: 60 — 42 protein_coding, 10 retained_intron, 6 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000336308, ENST00000394250, ENST00000443521, ENST00000460894, ENST00000471896, ENST00000481171, ENST00000484773, ENST00000488876, ENST00000544210, ENST00000577248, ENST00000578232, ENST00000578254, ENST00000578384, ENST00000578577, ENST00000578686, ENST00000579479, ENST00000580331, ENST00000580551, ENST00000580611, ENST00000581894, ENST00000582874, ENST00000583419, ENST00000583582, ENST00000583639, ENST00000583718, ENST00000583884, ENST00000584850, ENST00000585214, ENST00000585269, ENST00000908874, ENST00000908875, ENST00000908876, ENST00000908877, ENST00000908878, ENST00000908879, ENST00000908880, ENST00000908881, ENST00000908882, ENST00000908883, ENST00000908884, ENST00000908885, ENST00000908886, ENST00000908887, ENST00000908888, ENST00000908889, ENST00000908890, ENST00000908891, ENST00000936726, ENST00000936727, ENST00000936728, ENST00000936729, ENST00000936730, ENST00000936731, ENST00000936732, ENST00000936733, ENST00000964918, ENST00000964919, ENST00000964920, ENST00000964921, ENST00000964922

RefSeq mRNA: 3 — MANE Select: NM_006804 NM_001165937, NM_001165938, NM_006804

CCDS: CCDS11341, CCDS54117, CCDS54118

Canonical transcript exons

ENST00000336308 — 15 exons

Exon	Start	End
ENSE00002714142	39637144	39637231
ENSE00003464897	39657775	39657852
ENSE00003472523	39657008	39657085
ENSE00003476545	39657973	39658026
ENSE00003493315	39653481	39653750
ENSE00003521825	39660810	39660889
ENSE00003527074	39660211	39660273
ENSE00003543747	39659051	39659106
ENSE00003572659	39660981	39661085
ENSE00003580635	39662251	39662344
ENSE00003595153	39662804	39664201
ENSE00003616833	39660431	39660526
ENSE00003664300	39658722	39658820
ENSE00003668666	39659461	39659553
ENSE00003677600	39658405	39658522

Expression profiles

Bgee: expression breadth ubiquitous, 252 present calls, max score 97.26.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 58.2041 / max 331.2388, expressed in 1823 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
160586	53.8681	1822
160585	2.9508	1559
160589	1.0999	236
160588	0.1148	57
160591	0.0983	14
160590	0.0492	31
160587	0.0231	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lung	UBERON:0002167	97.26	gold quality
granulocyte	CL:0000094	97.20	gold quality
tibial nerve	UBERON:0001323	96.95	gold quality
right adrenal gland cortex	UBERON:0035827	96.34	gold quality
right adrenal gland	UBERON:0001233	96.22	gold quality
left adrenal gland cortex	UBERON:0035825	96.13	gold quality
left adrenal gland	UBERON:0001234	96.01	gold quality
upper lobe of left lung	UBERON:0008952	95.96	gold quality
right uterine tube	UBERON:0001302	95.76	gold quality
endocervix	UBERON:0000458	95.57	gold quality
stromal cell of endometrium	CL:0002255	95.46	gold quality
lower esophagus mucosa	UBERON:0035834	95.45	gold quality
adenohypophysis	UBERON:0002196	95.42	gold quality
skin of leg	UBERON:0001511	95.40	gold quality
body of stomach	UBERON:0001161	95.35	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	95.35	gold quality
left testis	UBERON:0004533	95.34	gold quality
adrenal cortex	UBERON:0001235	95.28	gold quality
body of uterus	UBERON:0009853	95.26	gold quality
right testis	UBERON:0004534	95.25	gold quality
right ovary	UBERON:0002118	95.17	gold quality
left ovary	UBERON:0002119	95.05	gold quality
small intestine Peyer’s patch	UBERON:0003454	95.04	gold quality
ectocervix	UBERON:0012249	95.03	gold quality
right lobe of thyroid gland	UBERON:0001119	95.02	gold quality
skin of abdomen	UBERON:0001416	94.99	gold quality
gall bladder	UBERON:0002110	94.88	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	94.78	gold quality
adrenal gland	UBERON:0002369	94.76	gold quality
left lobe of thyroid gland	UBERON:0001120	94.73	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.86
E-CURD-53	no	1304.20

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): SP1

miRNA regulators (miRDB)

38 targeting STARD3, 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-4692	100.00	67.32	2066
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-4708-3P	99.51	67.99	870
HSA-MIR-216A-5P	99.50	68.02	1288
HSA-MIR-940	99.37	66.14	2064
HSA-MIR-6808-5P	99.31	66.23	2150
HSA-MIR-6893-5P	99.31	66.25	2119
HSA-MIR-149-5P	99.25	67.16	1315
HSA-MIR-6809-5P	99.13	68.45	1223
HSA-MIR-328-5P	99.08	64.65	1000
HSA-MIR-4796-3P	99.08	68.38	1681
HSA-MIR-760	98.81	66.65	1392
HSA-MIR-6885-5P	98.71	64.33	902
HSA-MIR-1227-5P	98.65	65.32	1549
HSA-MIR-767-3P	98.61	67.69	1192
HSA-MIR-6887-5P	98.56	68.49	1295
HSA-MIR-6795-5P	98.52	68.51	1277
HSA-MIR-146B-3P	97.83	65.29	782
HSA-MIR-1972	97.67	67.38	1172
HSA-MIR-6793-3P	97.66	65.78	1084
HSA-MIR-8057	97.64	66.54	897
HSA-MIR-665	97.60	65.64	1781

Literature-anchored findings (GeneRIF, showing 27)

• role of MLN64 in cholesterol transport from lysosomes to steroidogenic mitochondria (PMID:12070139)
• NPC2, NPC1 and MLN64 may act in an ordered sequence to sense cholesterol, effect sterol movement, and consequently, influence the process of vesicular trafficking. (PMID:12398991)
• With saturating MLN64, steroidogenesis by placental mitochondria proceeds at near-maximal rate. (PMID:14715710)
• Oncogenomic recombination hotspot around the PPP1R1B-STARD3-TCAP-PNMT-PERLD1-ERBB2-C17orf37-GRB7 amplicon at human chromosome 17q12 is closely linked to evolutionary recombination hotspot around the GSDML-GSDM locus. (PMID:15010812)
• The MENTAL (MLN64 amino-terminal shared with MENTHO) domain might serve to maintain cholesterol at the membrane of late endosomes prior to its shuttle to cytoplasmic acceptor(s). (PMID:15718238)
• local sterol enrichment by MLN64 in the late endosomal membranes facilitates their association with actin, thereby governing actin-dependent fusion and degradative activity of late endocytic organelles (PMID:15930133)
• In this review, MLN64 defines discrete cholesterol-containing subdomains within the membrane of late endosomes where they may function in cholesterol transport. (PMID:16709157)
• three-dimensional atomic models of the StART domains of metastatic lymph node 64 (MLN64) and steroidogenic acute regulatory protein (StAR) proteins in complex with cholesterol (PMID:16990645)
• provide evidence for differential cholesterol binding of the two most closely related START domain proteins STARD1 and STARD3 (PMID:18331352)
• Differential regulation of STARD1 and D3 reflects their distinct roles in macrophage cholesterol metabolism, and may inform anti-atherogenic strategies. (PMID:19272380)
• a transport pathway for endosomal cholesterol to mitochondria that requires MLN64, but not NPC1 (PMID:19965586)
• FAK contributed to the increased adhesion in MDA-MB-231DeltaMLN64 cells. (PMID:20198306)
• data indicate that StARD3 is the primary lutein-binding protein in macula lutea; recombinant StARD3 selectively binds lutein with high affinity (PMID:21322544)
• STARD3 or STARD3NL and VAP form a novel molecular tether between late endosomes and the endoplasmic reticulum. (PMID:24105263)
• Findings show that PPP1R1B-STARD3 fusion transcript has a key role in subsets of gastric cancers through the activation of PI3K/AKT signaling. (PMID:24276243)
• Haplotype analysis indicated that combined effect of STARD3 variants (rs9972882, rs881844, rs11869286 and rs1877031) might affect the risk of GC. (PMID:24291029)
• Data indicate that mitochondrial proteolytic activation of START domain-containing protein 3 (STARD3) enhances steroidogenesis. (PMID:25459514)
• Elevated StARD3 expression may contribute to breast cancer aggressiveness by increasing membrane cholesterol and enhancing oncogenic signaling. (PMID:25681734)
• Study present a rare case of a 46,XY patient with CHD associated with ambiguous genitalia consisting of a clitoris-like phallus and a bifid scrotum. Exome sequencing revealed novel homozygous mutations in the FGFR1 and STARD3 genes that may be associated with the phenotype. (PMID:27055092)
• STARD3 or STARD3NL-mediated ER-endosome contacts, which affect endosome dynamics, are believed to be involved in cholesterol transport (PMID:27068960)
• Structure of the lutein-binding domain of human StARD3 at 1.74 A resolution and model of a complex with lutein has been presented. (PMID:27487925)
• Findings suggest that MLN64 overexpression induces an increase in mitochondrial cholesterol content and consequently a decrease in mitochondrial GSH content leading to mitochondrial dysfunction. In addition, MLN64 expression is increased in Niemann-Pick C1 deficient cells and plays a key role in cholesterol transport into the mitochondria. (PMID:28282615)
• Thus, STARD3 is a cholesterol transporter scaffolding endoplasmic reticulum-endosome contacts and modulating cellular cholesterol repartition by delivering cholesterol to endosomes. (PMID:28377464)
• Annexin A6 and NPC1 regulate LDL-inducible cell migration and distribution of focal adhesions. (PMID:35022465)
• The ultrastructural function of MLN64 in the late endosome-mitochondria membrane contact sites in placental cells. (PMID:37245582)
• Methionine sulfoxide reductases and cholesterol transporter STARD3 constitute an efficient system for detoxification of cholesterol hydroperoxides. (PMID:37507014)
• Metastatic Lymph Node 64 (MLN64) Expression in Gastric Cancer: The Clinical and Molecular Implications in Drug Resistance. (PMID:38151289)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	stard3	ENSDARG00000017809
mus_musculus	Stard3	ENSMUSG00000018167
rattus_norvegicus	Stard3	ENSRNOG00000042044
drosophila_melanogaster	Start1	FBGN0035028
caenorhabditis_elegans		WBGENE00017826

Paralogs (5): STARD3NL (ENSG00000010270), STAR (ENSG00000147465), STARD4 (ENSG00000164211), STARD5 (ENSG00000172345), STARD6 (ENSG00000174448)

Protein

Protein identifiers

StAR-related lipid transfer protein 3 — Q14849 (reviewed: Q14849)

Alternative names: Metastatic lymph node gene 64 protein, Protein CAB1, START domain-containing protein 3

All UniProt accessions (11): C9J555, Q14849, J3KSH0, J3KSL3, J3KT87, J3QLA7, J3QLM1, J3QLS1, J3QRG8, J3QRM3, J3QS10

UniProt curated annotations — full annotation on UniProt →

Function. Sterol-binding protein that mediates cholesterol transport from the endoplasmic reticulum to endosomes. The sterol transport mechanism is triggered by phosphorylation of FFAT motif that leads to membrane tethering between the endoplasmic reticulum and late endosomes via interaction with VAPA and VAPB. Acts as a lipid transfer protein that redirects sterol to the endosome at the expense of the cell membrane and favors membrane formation inside endosomes. May also mediate cholesterol transport between other membranes, such as mitochondria membrane or cell membrane. However, such results need additional experimental evidences; probably mainly mediates cholesterol transport from the endoplasmic reticulum to endosomes. Does not activate transcriptional cholesterol sensing. Able to bind other lipids, such as lutein, a xanthophyll carotenoids that form the macular pigment of the retina.

Subunit / interactions. Homodimer. Interacts (via the MENTAL domain) with STARD3NL. Interacts (via phosphorylated FFAT motif) with VAPA (via MSP domain). Interacts (via phosphorylated FFAT motif) with VAPB (via MSP domain). Interacts (via phosphorylated FFAT motif) with MOSPD2 (via MSP domain); this interaction allows enrichment of MOSPD2 around endosomes.

Subcellular location. Late endosome membrane.

Tissue specificity. Expressed in retina.

Post-translational modifications. Phosphorylation at Ser-209 is necessary and sufficient for the direct interaction of the phosphorylated FFAT motif with the MSP domain of MOSPD2, VAPA and VAPB and allows the tethering of two membranes that participates in the formation of ER-endosome contacts. Phosphorylation of the FFAT motif leads to conformation changes. Additional phosphorylations around the core FFAT motif (QFYSPPE) are not essential but strengthen the interaction with MOSPD2, VAPA and VAPB. Phosphorylation at Ser-209 of FFAT motif drives membrane tethering between the endoplasmic reticulum and late endosomes via interaction with VAPA and VAPB that in turn allows the efficient transport of sterol mediated by the START domain.

Domain organisation. The FFAT motif mediates interaction with VAPA, VAPB and MOSPD2. The START domain mediates lipid-transfer between membranes. It contains a hydrophobic cavity able to accommodate one lipid molecule, thereby serving as a ‘hydrophobic bridge’ across the aqueous gap between donor and acceptor organelle membranes. The MENTAL domain anchors the protein in endosome membranes and exposes the START domain in the cytosol. It binds cholesterol and mediates homotypic as well as heterotypic interactions between STARD3 and STARD3NL.

Induction. Not regulated by increases in total cholesterol content, or by marked alterations in cholesterol flux.

Similarity. Belongs to the STARD3 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q14849-1	1	yes
Q14849-2	2
Q14849-3	3

RefSeq proteins (3): NP_001159409, NP_001159410, NP_006795* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000799	StAR-like	Family
IPR002913	START_lipid-bd_dom	Domain
IPR019498	MENTAL	Domain
IPR023393	START-like_dom_sf	Homologous_superfamily
IPR029867	STARD3_MLN64_C	Domain
IPR051869	STARD3	Family

Pfam: PF01852, PF10457

Catalyzed reactions (Rhea), 1 shown:

• cholesterol(in) = cholesterol(out) (RHEA:39747)

UniProt features (48 total): strand 12, mutagenesis site 11, topological domain 5, helix 5, transmembrane region 4, domain 2, splice variant 2, sequence variant 2, turn 2, chain 1, short sequence motif 1, modified residue 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
5I9J	X-RAY DIFFRACTION	1.74
6TQR	X-RAY DIFFRACTION	1.85
1EM2	X-RAY DIFFRACTION	2.2
6TQU	X-RAY DIFFRACTION	2.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14849-F1	82.09	0.55

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): 209

Mutagenesis-validated functional residues (11):

Position	Phenotype
66–67	abolishes localization to late endosomes and leads to mislocalization to the endoplasmic reticulum.
89	abolishes localization to late endosomes and leads to mislocalization to the endoplasmic reticulum.
113	does not affect localization to late endosomes.
206–212	abolishes interaction with vapa and vapb, thereby preventing contact with the endoplasmic reticulum membrane.
207–208	abolishes interaction with vapa, vapb and mospd2, thereby preventing contact with the endoplasmic reticulum membrane. ab
209	impairs vapa and vapb interaction. does not affect endoplasmic reticulum membrane location of vapa, vapb and mospd2. is
209	does not affect vapa and vapb interactions; when associated with a-210. does not interact with vapa and vapb. recruits v
210	does not affect vapa and vapb interactions; when associated with d-209. improve vapa interaction. does not interact with
219	does not affect localization to late endosomes.
307–311	abolishes ability to transfer cholesterol between membranes.
311	does not affect localization to late endosomes.

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-196108	Pregnenolone biosynthesis
R-HSA-1430728	Metabolism
R-HSA-196071	Metabolism of steroid hormones
R-HSA-556833	Metabolism of lipids
R-HSA-8957322	Metabolism of steroids

MSigDB gene sets: 216 (showing top): SHEPARD_BMYB_MORPHOLINO_UP, GOBP_VESICLE_LOCALIZATION, GOCC_VACUOLAR_MEMBRANE, GOBP_C21_STEROID_HORMONE_METABOLIC_PROCESS, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_VESICLE_TARGETING, BROWNE_HCMV_INFECTION_16HR_UP, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_KETONE_METABOLIC_PROCESS, GOBP_MITOCHONDRIAL_TRANSPORT, GOBP_ORGANIC_HYDROXY_COMPOUND_TRANSPORT, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, NF1_Q6_01, BLALOCK_ALZHEIMERS_DISEASE_UP, GOBP_HORMONE_BIOSYNTHETIC_PROCESS

GO Biological Process (9): lipid metabolic process (GO:0006629), progesterone biosynthetic process (GO:0006701), mitochondrial transport (GO:0006839), steroid metabolic process (GO:0008202), cholesterol metabolic process (GO:0008203), cholesterol transport (GO:0030301), obsolete vesicle tethering to endoplasmic reticulum (GO:0099044), lipid transport (GO:0006869), small molecule metabolic process (GO:0044281)

GO Molecular Function (5): cholesterol binding (GO:0015485), protein homodimerization activity (GO:0042803), cholesterol transfer activity (GO:0120020), protein binding (GO:0005515), lipid binding (GO:0008289)

GO Cellular Component (12): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), mitochondrion (GO:0005739), lysosomal membrane (GO:0005765), endosome (GO:0005768), cytosol (GO:0005829), late endosome membrane (GO:0031902), organelle membrane contact site (GO:0044232), endoplasmic reticulum-endosome membrane contact site (GO:0140284), late endosome (GO:0005770), endoplasmic reticulum membrane (GO:0005789), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Metabolism of steroid hormones	1
Metabolism of steroids	1
Metabolism	1
Metabolism of lipids	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
binding	2
cytoplasm	2
primary metabolic process	1
C21-steroid hormone biosynthetic process	1
ketone biosynthetic process	1
progesterone metabolic process	1
olefinic compound biosynthetic process	1
intracellular transport	1
lipid metabolic process	1
sterol metabolic process	1
secondary alcohol metabolic process	1
sterol transport	1
transport	1
lipid localization	1
metabolic process	1
sterol binding	1
alcohol binding	1
identical protein binding	1
protein dimerization activity	1
cholesterol binding	1
sterol transfer activity	1
nuclear lumen	1
intracellular anatomical structure	1
intracellular membrane-bounded organelle	1
lysosome	1
lytic vacuole membrane	1
endomembrane system	1
cytoplasmic vesicle	1
late endosome	1
endosome membrane	1
organelle	1
organelle membrane contact site	1
endosome	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1

Protein interactions and networks

STRING

1350 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
STARD3	VAPA	Q9P0L0	945
STARD3	PCTP	Q9UKL6	938
STARD3	NPC2	P61916	926
STARD3	NPC1	O15118	863
STARD3	GRB7	Q14451	817
STARD3	PGAP3	Q96FM1	803
STARD3	VAPB	O95292	802
STARD3	MOSPD2	Q8NHP6	744
STARD3	OSBPL5	Q9H0X9	733
STARD3	CERT1	Q9Y5P4	729
STARD3	ZFYVE27	Q5T4F4	723
STARD3	GSTP1	P09211	689
STARD3	MIEN1	Q9BRT3	675
STARD3	TCAP	O15273	674
STARD3	OSBP	P22059	673

IntAct

112 interactions, top by confidence:

A	B	Type	Score
VAPB	FAM83G	psi-mi:“MI:0914”(association)	0.730
NIPAL1	ESYT2	psi-mi:“MI:0914”(association)	0.640
STARD3	MOSPD2	psi-mi:“MI:0915”(physical association)	0.600
STARD3	MOSPD2	psi-mi:“MI:0403”(colocalization)	0.600
AKT1	MAPK13	psi-mi:“MI:0914”(association)	0.600
STARD3	CBARP	psi-mi:“MI:0915”(physical association)	0.590
GOPC	STARD3	psi-mi:“MI:0915”(physical association)	0.560
STARD3	GOPC	psi-mi:“MI:0915”(physical association)	0.560
AQP6	STARD3	psi-mi:“MI:0915”(physical association)	0.560
STARD3	RNF170	psi-mi:“MI:0915”(physical association)	0.560
AKT1	STARD3	psi-mi:“MI:0915”(physical association)	0.540
AKT1	STARD3	psi-mi:“MI:2364”(proximity)	0.540
MME	TMEM223	psi-mi:“MI:0914”(association)	0.530
MANSC1	KLRG2	psi-mi:“MI:0914”(association)	0.530
SLC15A1	METTL15	psi-mi:“MI:0914”(association)	0.530
SPACA1	GOLIM4	psi-mi:“MI:0914”(association)	0.530
TSPYL6	NME4	psi-mi:“MI:0914”(association)	0.530
SDF4	GTPBP6	psi-mi:“MI:0914”(association)	0.530
CHRM3	PLD2	psi-mi:“MI:0914”(association)	0.530
SLC15A4	PGRMC1	psi-mi:“MI:0914”(association)	0.530
UNC93B1	GPR89A	psi-mi:“MI:0914”(association)	0.530

BioGRID (119): GOPC (Two-hybrid), STARD3 (Affinity Capture-MS), STARD3 (Affinity Capture-MS), STARD3 (Affinity Capture-MS), STARD3 (Affinity Capture-MS), STARD3 (Affinity Capture-MS), STARD3 (Two-hybrid), C19orf26 (Affinity Capture-MS), STARD3 (Affinity Capture-MS), STARD3 (Affinity Capture-MS), STARD3 (Affinity Capture-MS), STARD3 (Affinity Capture-MS), STARD3 (Affinity Capture-MS), STARD3 (Affinity Capture-MS), STARD3 (Affinity Capture-MS)

ESM2 similar proteins: A5GFX0, A8Y5H7, F7B909, O59707, P35200, P49675, P51557, P59095, P59096, P70114, Q03606, Q04006, Q05776, Q0V9N0, Q14849, Q16KN5, Q28996, Q29JQ0, Q4R5S9, Q54G07, Q54VC7, Q58DB0, Q5BKH5, Q5EA59, Q5RBI4, Q61542, Q6GM21, Q6NTS7, Q6P9U4, Q6TMK8, Q8GXB1, Q8TB40, Q8VD66, Q8VE85, Q8WTS1, Q92503, Q96N28, Q9CYY7, Q9DE06, Q9DEB4

Diamond homologs: F7B909, O46689, O95772, P49675, P51557, P58864, P70114, P79245, P97826, Q14849, Q28918, Q28996, Q61542, Q90ZB9, Q9DCI3, Q9DE06, Q9DEB4, Q9DFS4, Q9DG08, Q9DG09, Q9DG10, Q9W145, A1A4M6, Q5R8P9, Q9EPQ7, Q9NSY2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	58
Likely benign	7
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2743 predictions. Top by Δscore:

Variant	Effect	Δscore
17:39637229:CAGGT:C	donor_loss	1.0000
17:39637230:AGG:A	donor_loss	1.0000
17:39637232:GT:G	donor_loss	1.0000
17:39653747:GAAT:G	donor_gain	1.0000
17:39653751:G:GG	donor_gain	1.0000
17:39657003:CACA:C	acceptor_loss	1.0000
17:39657004:ACAG:A	acceptor_loss	1.0000
17:39657005:CA:C	acceptor_loss	1.0000
17:39657006:A:AG	acceptor_gain	1.0000
17:39657006:A:C	acceptor_loss	1.0000
17:39657007:G:GT	acceptor_gain	1.0000
17:39657007:GA:G	acceptor_gain	1.0000
17:39657007:GACC:G	acceptor_gain	1.0000
17:39657007:GACCA:G	acceptor_gain	1.0000
17:39657081:TCTTT:T	donor_gain	1.0000
17:39657084:TT:T	donor_gain	1.0000
17:39657086:G:GG	donor_gain	1.0000
17:39657770:A:AG	acceptor_gain	1.0000
17:39657771:CCA:C	acceptor_loss	1.0000
17:39657772:CAG:C	acceptor_loss	1.0000
17:39657773:A:AC	acceptor_loss	1.0000
17:39657773:A:AG	acceptor_gain	1.0000
17:39657774:G:A	acceptor_loss	1.0000
17:39657774:G:GG	acceptor_gain	1.0000
17:39657850:GCG:G	donor_gain	1.0000
17:39657853:G:GC	donor_loss	1.0000
17:39657853:G:GG	donor_gain	1.0000
17:39657854:T:TC	donor_loss	1.0000
17:39658404:GCT:G	acceptor_gain	1.0000
17:39658462:T:TA	acceptor_gain	1.0000

AlphaMissense

2870 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:39658462:T:A	W163R	1.000
17:39658462:T:C	W163R	1.000
17:39660500:T:A	W310R	1.000
17:39660500:T:C	W310R	1.000
17:39660502:G:C	W310C	1.000
17:39660502:G:T	W310C	1.000
17:39660880:T:A	V342D	1.000
17:39660889:G:T	R345M	1.000
17:39660985:T:C	F347L	1.000
17:39660987:C:A	F347L	1.000
17:39660987:C:G	F347L	1.000
17:39662321:T:A	W404R	1.000
17:39662321:T:C	W404R	1.000
17:39653706:T:C	F59L	0.999
17:39653708:C:A	F59L	0.999
17:39653708:C:G	F59L	0.999
17:39653733:T:A	W68R	0.999
17:39653733:T:C	W68R	0.999
17:39657991:A:C	S132R	0.999
17:39657993:T:A	S132R	0.999
17:39657993:T:G	S132R	0.999
17:39659482:G:A	G242R	0.999
17:39659482:G:C	G242R	0.999
17:39659482:G:T	G242W	0.999
17:39659491:G:C	A245P	0.999
17:39659533:T:A	W259R	0.999
17:39659533:T:C	W259R	0.999
17:39660227:T:A	V271E	0.999
17:39660269:T:C	L285P	0.999
17:39660461:T:G	Y297D	0.999

dbSNP variants (sampled 300 via entrez): RS1000039681 (17:39644840 C>T), RS1000053669 (17:39636700 G>A), RS1000112577 (17:39658138 G>A,T), RS1000466803 (17:39641312 A>G), RS1000525268 (17:39662894 G>A), RS1000596874 (17:39661613 G>A), RS1000673575 (17:39647869 G>A), RS1000764833 (17:39653423 G>A,T), RS1000896254 (17:39650546 G>A), RS1000965624 (17:39659747 T>C,G), RS1001042272 (17:39656679 C>T), RS1001158945 (17:39655027 C>G), RS1001285094 (17:39648970 G>A,C), RS1001310711 (17:39636024 C>A,T), RS1001319726 (17:39651766 A>G)

Disease associations

OMIM: gene MIM:607048 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

28 associations (top):

Study	Trait	p-value
GCST000624_15	Ulcerative colitis	3.000000e-08
GCST000755_5	HDL cholesterol	3.000000e-14
GCST002223_56	HDL cholesterol	3.000000e-17
GCST004232_20	HDL cholesterol levels	1.000000e-21
GCST005312_39	Menopause (age at onset)	2.000000e-09
GCST006436_12	Triglyceride levels	2.000000e-09
GCST007235_3	Pancreatic ductal adenocarcinoma	1.000000e-06
GCST007564_21	Asthma or allergic disease (pleiotropy)	4.000000e-17
GCST008070_27	HDL cholesterol levels	2.000000e-10
GCST008070_91	HDL cholesterol levels	1.000000e-08
GCST008075_167	HDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	8.000000e-28
GCST008075_22	HDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	2.000000e-28
GCST008084_233	HDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	6.000000e-38
GCST008084_32	HDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	4.000000e-35
GCST008085_134	HDL cholesterol levels in current drinkers	2.000000e-17
GCST008085_17	HDL cholesterol levels in current drinkers	8.000000e-17
GCST008757_30	Alcohol consumption	1.000000e-09
GCST008809_9	Smoking behaviour (cigarettes smoked per day)	3.000000e-08
GCST008916_10	Asthma	5.000000e-09
GCST008916_21	Asthma	2.000000e-62
GCST008916_45	Asthma	3.000000e-10
GCST008916_86	Asthma	2.000000e-14
GCST009368_66	HDL cholesterol levels x long total sleep time interaction (2df test)	3.000000e-12
GCST009798_16	Asthma	8.000000e-27
GCST010002_123	Refractive error	1.000000e-24
GCST010083_58	Hemoglobin levels	4.000000e-11
GCST010241_120	Apolipoprotein A1 levels	2.000000e-34
GCST010242_526	HDL cholesterol levels	2.000000e-51

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004704	age at menopause
EFO:0004530	triglyceride measurement
EFO:0004329	alcohol drinking
EFO:0006525	cigarettes per day measurement
EFO:0004509	hemoglobin measurement
EFO:0004614	apolipoprotein A 1 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523297 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

16 total (human), top 16 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, decreases expression, affects cotreatment, increases abundance	3
Arsenic	affects cotreatment, increases abundance, increases expression, decreases expression	2
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
Sunitinib	increases expression	1
Air Pollutants	affects expression, increases abundance	1
Vehicle Emissions	decreases expression, increases abundance	1
Benzo(a)pyrene	decreases methylation	1
Lead	affects methylation	1
Ozone	affects expression, increases abundance	1
Smoke	decreases expression	1
Urethane	increases expression	1
Valproic Acid	increases expression, increases methylation	1
Vanadates	decreases expression	1
8-Bromo Cyclic Adenosine Monophosphate	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

ChEMBL screening assays

5 unique, capped per target: 5 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4433689	Binding	Inhibition of recombinant human His-tagged StAR-related lipid transfer protein 3 START domain expressed in Escherichia coli BL21(DE3) cells assessed as reduction of protein interaction with cholesterol using 3-hexanoyl-NBD Cholesterol as su	First-of-its-kind STARD3 Inhibitor: In Silico Identification and Biological Evaluation as Anticancer Agent. — ACS Med Chem Lett

Cellosaurus cell lines

16 cell lines: 16 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_0179	BT-474	Cancer cell line	Female
CVCL_4V65	BT474-5FU[r]	Cancer cell line	Female
CVCL_4Y08	BT-474/CMV-Luc	Cancer cell line	Female
CVCL_A2GH	LR-BT474	Cancer cell line	Female
CVCL_A4AK	BT-474 Tam2	Cancer cell line	Female
CVCL_A4CL	BT-474 Ecadherin EmGFP	Cancer cell line	Female
CVCL_AQ07	BT-474 Clone 5	Cancer cell line	Female
CVCL_AR86	BT-474 Tam1	Cancer cell line	Female
CVCL_AR96	BT-474 EEI	Cancer cell line	Female
CVCL_C9CU	BT-474-Luc2	Cancer cell line	Female

Clinical trials (associated diseases)

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