STARD5

Summary

STARD5 (StAR related lipid transfer domain containing 5, HGNC:18065) is a protein-coding gene on chromosome 15q25.1, encoding StAR-related lipid transfer protein 5 (Q9NSY2). May be involved in the intracellular transport of sterols or other lipids.

Proteins containing a steroidogenic acute regulatory-related lipid transfer (START) domain are often involved in the trafficking of lipids and cholesterol between diverse intracellular membranes. This gene is a member of the StarD subfamily that encodes START-related lipid transfer proteins. The protein encoded by this gene is a cholesterol transporter and is also able to bind and transport other sterol-derived molecules related to the cholesterol/bile acid biosynthetic pathways such as 25-hydroxycholesterol. Its expression is upregulated during endoplasmic reticulum (ER) stress. The protein is thought to act as a cytosolic sterol transporter that moves cholesterol between intracellular membranes such as from the cytoplasm to the ER and from the ER to the Golgi apparatus. Alternative splicing of this gene produces multiple transcript variants.

Source: NCBI Gene 80765 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 33 total
• MANE Select transcript: NM_181900

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18065
Approved symbol	STARD5
Name	StAR related lipid transfer domain containing 5
Location	15q25.1
Locus type	gene with protein product
Status	Approved
Aliases	MGC10327
Ensembl gene	ENSG00000172345
Ensembl biotype	protein_coding
OMIM	607050
Entrez	80765

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 2 protein_coding, 2 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000302824, ENST00000325346, ENST00000559913, ENST00000560156, ENST00000560723, ENST00000560916, ENST00000913840

RefSeq mRNA: 1 — MANE Select: NM_181900 NM_181900

CCDS: CCDS10318

Canonical transcript exons

ENST00000302824 — 6 exons

Exon	Start	End
ENSE00001716823	81309053	81313403
ENSE00001891841	81324001	81324141
ENSE00003546337	81318409	81318502
ENSE00003546959	81322899	81322948
ENSE00003668579	81322408	81322540
ENSE00003676609	81319339	81319456

Expression profiles

Bgee: expression breadth ubiquitous, 192 present calls, max score 93.65.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.6081 / max 2489.6330, expressed in 1629 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
151229	8.7530	1410
151230	1.6020	1054
151228	1.2530	453

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	93.65	gold quality
skin of abdomen	UBERON:0001416	93.46	gold quality
skin of leg	UBERON:0001511	93.44	gold quality
zone of skin	UBERON:0000014	91.26	gold quality
ectocervix	UBERON:0012249	88.73	gold quality
mucosa of transverse colon	UBERON:0004991	88.31	gold quality
rectum	UBERON:0001052	87.59	gold quality
lower esophagus mucosa	UBERON:0035834	87.11	gold quality
vagina	UBERON:0000996	87.07	gold quality
endocervix	UBERON:0000458	86.90	gold quality
body of uterus	UBERON:0009853	86.61	gold quality
upper leg skin	UBERON:0004262	86.41	gold quality
esophagus mucosa	UBERON:0002469	86.39	gold quality
granulocyte	CL:0000094	85.52	gold quality
transverse colon	UBERON:0001157	84.23	gold quality
liver	UBERON:0002107	84.19	gold quality
small intestine Peyer’s patch	UBERON:0003454	83.19	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.08	gold quality
stromal cell of endometrium	CL:0002255	83.07	gold quality
upper arm skin	UBERON:0004263	83.03	gold quality
spleen	UBERON:0002106	81.81	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	81.77	gold quality
mammalian vulva	UBERON:0000997	81.26	gold quality
left uterine tube	UBERON:0001303	80.91	gold quality
gingival epithelium	UBERON:0001949	80.53	gold quality
small intestine	UBERON:0002108	80.22	gold quality
gall bladder	UBERON:0002110	80.03	gold quality
esophagus	UBERON:0001043	79.96	gold quality
minor salivary gland	UBERON:0001830	79.89	gold quality
right hemisphere of cerebellum	UBERON:0014890	79.36	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.41

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): XBP1

miRNA regulators (miRDB)

30 targeting STARD5, 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-6740-5P	100.00	65.64	932
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-155-5P	99.35	70.16	1509
HSA-MIR-2115-3P	99.31	69.68	2026
HSA-MIR-6808-5P	99.31	66.23	2150
HSA-MIR-6893-5P	99.31	66.25	2119
HSA-MIR-5693	99.24	66.67	1106
HSA-MIR-4477B	99.23	70.49	1733
HSA-MIR-593-3P	99.22	67.28	1327
HSA-MIR-361-5P	98.95	70.16	1340
HSA-MIR-6829-5P	98.86	65.12	1480
HSA-MIR-6761-5P	98.71	68.03	1504
HSA-MIR-624-3P	98.37	67.06	1067
HSA-MIR-3074-3P	97.83	67.26	922
HSA-MIR-3921	97.81	67.45	1431
HSA-MIR-4653-5P	97.22	67.72	1429
HSA-MIR-514A-3P	96.43	67.77	1048
HSA-MIR-514B-3P	96.43	67.77	1048
HSA-MIR-5586-3P	95.51	67.00	805
HSA-MIR-4693-3P	95.23	65.92	735
HSA-MIR-6717-5P	91.67	66.93	68

Literature-anchored findings (GeneRIF, showing 6)

• StarD4 is regulated by sterols via SREBP-2, and StarD5 is activated by ER stress cholesterol metabolism; they serve different functions (PMID:15760897)
• demonstrated StarD5 protein in liver cytosolic fractions only, suggesting StarD5 as a directional cytosolic sterol carrier (PMID:15897605)
• The presence of StarD5 different human liver cells that are related to inflammatory processes provides new clues to its role of in free sterol transport in the cells and in lipid-mediated atherogenesis. (PMID:16534142)
• Data support STARD5 functioning in kidney, specifically within proximal tubule cells, and suggest a role in ER-associated cholesterol transport. (PMID:19474188)
• Studies show the 3 steroidogenic acute regulatory-related lipid transfer (START) domain proteins StarD4, StarD5 and StarD6 have a similar lipid binding pocket specific for sterols (cholesterol in particular), but differing regulation and localization. (PMID:24440759)
• Genetically regulated expression underlies cellular sensitivity to chemotherapy in diverse populations. (PMID:33575800)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	stard5	ENSDARG00000076117
mus_musculus	Stard5	ENSMUSG00000046027
rattus_norvegicus	Stard5	ENSRNOG00000025052
drosophila_melanogaster	Start1	FBGN0035028
caenorhabditis_elegans		WBGENE00010505
caenorhabditis_elegans		WBGENE00017826

Paralogs (5): STARD3NL (ENSG00000010270), STARD3 (ENSG00000131748), STAR (ENSG00000147465), STARD4 (ENSG00000164211), STARD6 (ENSG00000174448)

Protein

Protein identifiers

StAR-related lipid transfer protein 5 — Q9NSY2 (reviewed: Q9NSY2)

Alternative names: START domain-containing protein 5

All UniProt accessions (2): Q9NSY2, H0YLW4

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in the intracellular transport of sterols or other lipids. May bind cholesterol or other sterols.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NSY2-1	1	yes
Q9NSY2-3	2

RefSeq proteins (1): NP_871629* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002913	START_lipid-bd_dom	Domain
IPR023393	START-like_dom_sf	Homologous_superfamily
IPR043556	StARD5/6	Family

Pfam: PF01852

UniProt features (21 total): strand 10, helix 5, splice variant 2, chain 1, domain 1, turn 1, sequence variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2R55	X-RAY DIFFRACTION	2.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NSY2-F1	97.04	0.97

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-159418	Recycling of bile acids and salts
R-HSA-1430728	Metabolism
R-HSA-194068	Bile acid and bile salt metabolism
R-HSA-556833	Metabolism of lipids
R-HSA-8957322	Metabolism of steroids

MSigDB gene sets: 200 (showing top): TGGTGCT_MIR29A_MIR29B_MIR29C, GCANCTGNY_MYOD_Q6, MORF_BRCA1, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, MORF_RAD51L3, GOBP_ORGANIC_HYDROXY_COMPOUND_TRANSPORT, RICKMAN_TUMOR_DIFFERENTIATED_WELL_VS_POORLY_DN, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM4, BOYAULT_LIVER_CANCER_SUBCLASS_G23_DN, CAIRO_HEPATOBLASTOMA_DN, MODULE_88, LIU_CMYB_TARGETS_UP, GOBP_STEROL_TRANSPORT, MORF_ATF2

GO Biological Process (2): cholesterol import (GO:0070508), lipid transport (GO:0006869)

GO Molecular Function (3): cholesterol binding (GO:0015485), cholesterol transfer activity (GO:0120020), lipid binding (GO:0008289)

GO Cellular Component (1): cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Bile acid and bile salt metabolism	1
Metabolism of steroids	1
Metabolism	1
Metabolism of lipids	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cholesterol transport	1
transport	1
lipid localization	1
sterol binding	1
alcohol binding	1
cholesterol binding	1
sterol transfer activity	1
binding	1
cytoplasm	1
cellular anatomical structure	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

1 interactions, top by confidence:

A	B	Type	Score
	PLEKHG3	psi-mi:“MI:0914”(association)	0.350

BioGRID (2): STARD5 (Two-hybrid), STARD5 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A1A4M6, A5GFX0, A5PJU6, O46689, O88736, P49675, P51557, P53808, P59095, P59096, P70114, P79245, P97826, Q28918, Q28996, Q3U1V6, Q4R5S9, Q58DB0, Q5BKH5, Q5IH13, Q5IH14, Q5R8P9, Q64421, Q6GM21, Q6IQS6, Q6NTS7, Q6P9U4, Q6TMK8, Q8R1R3, Q8VE85, Q8WYK0, Q90673, Q90ZB9, Q94E75, Q96DR4, Q96N28, Q99JV5, Q99NB7, Q9CYY7, Q9DBK0

Diamond homologs: A1A4M6, P59095, P59096, Q5R8P9, Q96DR4, Q99JV5, Q9EPQ7, Q9NSY2, Q61542, F7B909, O46689, O95772, P49675, P51557, P58864, P70114, P79245, P97826, Q14849, Q28918, Q28996, Q90ZB9, Q9DCI3, Q9DE06, Q9DEB4, Q9DFS4, Q9DG08, Q9DG09, Q9DG10

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	24
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

841 predictions. Top by Δscore:

Variant	Effect	Δscore
15:81319457:C:CC	acceptor_gain	1.0000
15:81322401:GACTT:G	donor_loss	1.0000
15:81322402:ACTTA:A	donor_loss	1.0000
15:81322403:CTTA:C	donor_loss	1.0000
15:81322404:TTA:T	donor_loss	1.0000
15:81322405:T:TG	donor_loss	1.0000
15:81322406:A:AC	donor_gain	1.0000
15:81322407:C:CC	donor_gain	1.0000
15:81322407:C:CT	donor_loss	1.0000
15:81322407:CGT:C	donor_gain	1.0000
15:81323995:A:AC	donor_gain	1.0000
15:81323996:C:CC	donor_gain	1.0000
15:81323999:A:AC	donor_gain	1.0000
15:81324000:C:CC	donor_gain	1.0000
15:81324000:CG:C	donor_gain	1.0000
15:81324005:T:TA	donor_gain	1.0000
15:81324006:C:A	donor_gain	1.0000
15:81324018:T:TA	donor_gain	1.0000
15:81319260:T:A	donor_gain	0.9900
15:81319332:CACT:C	donor_loss	0.9900
15:81319333:ACTC:A	donor_loss	0.9900
15:81319334:CTCA:C	donor_loss	0.9900
15:81319335:TCACC:T	donor_loss	0.9900
15:81319336:CA:C	donor_loss	0.9900
15:81319337:A:AC	donor_gain	0.9900
15:81319337:A:C	donor_loss	0.9900
15:81319338:C:CC	donor_gain	0.9900
15:81319338:C:CG	donor_loss	0.9900
15:81319453:GGGT:G	acceptor_gain	0.9900
15:81319455:GTCTG:G	acceptor_loss	0.9900

AlphaMissense

1393 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:81319391:A:C	F116L	0.997
15:81319391:A:T	F116L	0.997
15:81319393:A:G	F116L	0.997
15:81322455:A:G	W79R	0.997
15:81322455:A:T	W79R	0.997
15:81322453:C:A	W79C	0.996
15:81322453:C:G	W79C	0.996
15:81318433:C:T	G157D	0.994
15:81319397:T:A	R114S	0.993
15:81319397:T:G	R114S	0.993
15:81324021:A:G	W27R	0.993
15:81324021:A:T	W27R	0.993
15:81318451:C:T	G151E	0.992
15:81322535:C:G	R52P	0.992
15:81324019:C:A	W27C	0.992
15:81324019:C:G	W27C	0.992
15:81319392:A:G	F116S	0.991
15:81319407:A:T	I111N	0.991
15:81322910:A:C	F46L	0.990
15:81322910:A:T	F46L	0.990
15:81322912:A:G	F46L	0.990
15:81319346:A:C	S131R	0.989
15:81319346:A:T	S131R	0.989
15:81319348:T:G	S131R	0.989
15:81319407:A:G	I111T	0.989
15:81322451:T:A	D80V	0.989
15:81322452:C:G	D80H	0.989
15:81322539:A:C	Y51D	0.989
15:81319398:C:G	R114T	0.988
15:81319392:A:C	F116C	0.987

dbSNP variants (sampled 300 via entrez): RS1000452661 (15:81321585 A>G), RS1000571148 (15:81325593 A>T), RS1000698066 (15:81320135 T>C), RS1000872851 (15:81317331 T>C), RS1000912680 (15:81323606 T>A,C,G), RS1000921345 (15:81325824 A>C,G), RS1001194358 (15:81323361 C>A,T), RS1001322447 (15:81323400 GAA>G), RS1001374331 (15:81323110 A>G), RS1001502582 (15:81311875 A>G), RS1001696333 (15:81322846 T>G), RS1002001476 (15:81316958 G>A,C), RS1002199901 (15:81318165 A>C), RS1002378831 (15:81321604 G>A,T), RS1002436469 (15:81324140 A>C,G,T)

Disease associations

OMIM: gene MIM:607050 | 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

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, increases expression, decreases expression, affects cotreatment	4
bisphenol A	affects cotreatment, increases expression	2
Arsenic	decreases expression, increases abundance, increases expression, affects cotreatment	2
Estradiol	affects cotreatment, decreases expression	2
alpha phellandrene	increases expression	1
triphenyl phosphate	affects expression	1
trichostatin A	affects expression	1
butyraldehyde	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
CGP 52608	affects binding, increases reaction	1
perfluoro-n-nonanoic acid	decreases expression	1
bisphenol S	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, increases expression	1
(+)-JQ1 compound	increases expression	1
Temozolomide	decreases expression	1
Sunitinib	increases expression	1
Acetaminophen	increases expression	1
Air Pollutants	increases abundance, affects expression	1
Amiodarone	increases expression	1
Benzo(a)pyrene	decreases methylation, increases methylation	1
Cadmium	decreases expression, increases abundance	1
Cisplatin	affects cotreatment, increases expression	1
Dexamethasone	increases expression, affects cotreatment	1
Doxorubicin	decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Indomethacin	affects cotreatment, increases expression	1
Lipopolysaccharides	affects response to substance, increases expression	1
Methyl Methanesulfonate	increases expression	1
Ozone	affects expression, increases abundance	1
Selenium	affects cotreatment, increases expression	1

Clinical trials (associated diseases)

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