STAR

Summary

STAR (steroidogenic acute regulatory protein, HGNC:11359) is a protein-coding gene on chromosome 8p11.23, encoding Steroidogenic acute regulatory protein, mitochondrial (P49675). Plays a key role in steroid hormone synthesis by enhancing the metabolism of cholesterol into pregnenolone.

The protein encoded by this gene plays a key role in the acute regulation of steroid hormone synthesis by enhancing the conversion of cholesterol into pregnenolone. This protein permits the cleavage of cholesterol into pregnenolone by mediating the transport of cholesterol from the outer mitochondrial membrane to the inner mitochondrial membrane. Mutations in this gene are a cause of congenital lipoid adrenal hyperplasia (CLAH), also called lipoid CAH. A pseudogene of this gene is located on chromosome 13.

Source: NCBI Gene 6770 — RefSeq curated summary.

At a glance

• Gene–disease (curated): congenital lipoid adrenal hyperplasia due to STAR deficency (Definitive, GenCC)
• GWAS associations: 3
• Clinical variants (ClinVar): 458 total — 45 pathogenic, 50 likely-pathogenic
• Phenotypes (HPO): 40
• Druggable target: yes
• MANE Select transcript: NM_000349

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11359
Approved symbol	STAR
Name	steroidogenic acute regulatory protein
Location	8p11.23
Locus type	gene with protein product
Status	Approved
Aliases	STARD1
Ensembl gene	ENSG00000147465
Ensembl biotype	protein_coding
OMIM	600617
Entrez	6770

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 5 protein_coding, 1 retained_intron

ENST00000276449, ENST00000520114, ENST00000521236, ENST00000522050, ENST00000927192, ENST00000971759

RefSeq mRNA: 1 — MANE Select: NM_000349 NM_000349

CCDS: CCDS6102

Canonical transcript exons

ENST00000276449 — 7 exons

Exon	Start	End
ENSE00000980249	38145963	38146147
ENSE00000980250	38145222	38145315
ENSE00001325953	38148200	38148327
ENSE00002130335	38142700	38144386
ENSE00002137623	38150755	38150952
ENSE00003523986	38148641	38148754
ENSE00003574459	38146289	38146447

Expression profiles

Bgee: expression breadth ubiquitous, 184 present calls, max score 99.95.

FANTOM5 (CAGE): breadth broad, TPM avg 3.5257 / max 2215.3401, expressed in 290 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
92730	2.6183	144
92732	0.4917	167
92731	0.2952	87
92729	0.1204	49

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right adrenal gland	UBERON:0001233	99.95	gold quality
right adrenal gland cortex	UBERON:0035827	99.94	gold quality
left adrenal gland	UBERON:0001234	99.93	gold quality
adrenal cortex	UBERON:0001235	99.92	gold quality
left adrenal gland cortex	UBERON:0035825	99.91	gold quality
adrenal tissue	UBERON:0018303	99.88	gold quality
adrenal gland	UBERON:0002369	98.93	gold quality
left ovary	UBERON:0002119	98.68	gold quality
right ovary	UBERON:0002118	97.79	gold quality
ovary	UBERON:0000992	95.19	gold quality
right testis	UBERON:0004534	91.72	gold quality
left testis	UBERON:0004533	90.63	gold quality
testis	UBERON:0000473	89.98	gold quality
adult organism	UBERON:0007023	78.42	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	74.84	silver quality
left uterine tube	UBERON:0001303	74.51	gold quality
cervix squamous epithelium	UBERON:0006922	74.48	gold quality
prefrontal cortex	UBERON:0000451	73.84	gold quality
stromal cell of endometrium	CL:0002255	73.64	gold quality
oocyte	CL:0000023	73.50	gold quality
endothelial cell	CL:0000115	73.44	silver quality
hypothalamus	UBERON:0001898	72.49	gold quality
decidua	UBERON:0002450	72.19	silver quality
skin of abdomen	UBERON:0001416	72.01	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	71.09	silver quality
right frontal lobe	UBERON:0002810	71.02	gold quality
Brodmann (1909) area 9	UBERON:0013540	70.56	gold quality
cingulate cortex	UBERON:0003027	70.51	gold quality
germinal epithelium of ovary	UBERON:0001304	70.27	silver quality
anterior cingulate cortex	UBERON:0009835	70.24	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-GEOD-124263	yes	1516.32
E-MTAB-8381	no	765.43
E-ANND-3	no	2.19

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AHR, AR, CEBPA, CEBPB, CEBPG, CLOCK, CNBP, CREB1, CREM, DGKQ, DLX5, ESR1, FOS, FOXL2, GATA4, GATA6, HDAC1, JUN, KLF13, KLF4, KLF9, NFYA, NR0B1, NR4A1, NR5A1, NR5A2, PAX6, PPARG, SF1, SMAD3, SP1, SP3, SREBF1, SREBF2, SSRP1, TCF21, TCF3, YY1

miRNA regulators (miRDB)

35 targeting STAR, 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-4534	99.99	66.58	1907
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-4276	99.56	67.66	2514
HSA-MIR-5584-5P	99.49	68.22	2814
HSA-MIR-32-3P	99.36	68.20	2517
HSA-MIR-1257	98.97	68.02	1133
HSA-MIR-4716-5P	98.82	68.57	1168
HSA-MIR-4763-5P	98.75	63.89	854
HSA-MIR-6769B-5P	98.73	64.91	1092
HSA-MIR-5094	98.63	67.11	1062
HSA-MIR-934	98.49	70.44	581
HSA-MIR-6792-5P	98.39	68.16	1330
HSA-MIR-4691-3P	98.11	66.83	1204
HSA-MIR-6769A-5P	97.99	64.16	851
HSA-MIR-6511B-5P	97.98	65.64	823
HSA-MIR-6811-5P	97.98	64.96	848
HSA-MIR-3129-3P	97.85	67.63	1246
HSA-MIR-5583-5P	97.85	67.61	1243
HSA-MIR-7111-3P	97.80	66.75	1467
HSA-MIR-4642	97.52	67.60	916
HSA-MIR-6818-5P	97.50	67.10	1167
HSA-MIR-526B-5P	97.41	67.99	1074
HSA-MIR-6509-5P	97.39	68.27	969
HSA-MIR-219B-3P	97.31	66.96	672

Literature-anchored findings (GeneRIF, showing 40)

• StAR protein is an absolute requirement in the rate-limiting step in steroidogenesis, the transfer of cholesterol into the mitochondria [review] (PMID:12044915)
• StAR can transfer cholesterol between synthetic membranes without other protein components found in mitochondria (PMID:12372832)
• StAR requires structural alterations to allow cholesterol binding, most evidently by C-terminal alpha-helix above U-shaped beta-barrel. Unfolding of helix probable and leads to 2% subpopulation of partially unfolded StAR. (PMID:12530644)
• modulation of DAX-1 and steroidogenic factor-1 intracellular levels in granulosa cells suggests that these transcription factors could be involved in mitogen-activated protein kinase suppression of steroidogenic acute regulatory protein expression (PMID:12727988)
• Steroidogenic acute regulatory protein expression in the normal human brain and intracranial tumors. (PMID:12834921)
• hCG-stimulated steroidogenic response in the mid- and late luteal phase is correlated with increased StAR mRNA and protein abundance (PMID:12843197)
• StAR binding protein binds StAR protein in cells and enhances the ability of StAR protein to promote syntheses of steroid hormones. (PMID:12909641)
• increased histone H3 acetylation involving the EP2 receptor, protein kinase A, CREB, and CREB binding protein is responsible for PGE(2)-induced StAR gene activation in endometriotic stromal cells. (PMID:12933667)
• angiotensin II-dependent activation of steroidogenic acute regulatory protein transcription requires janus kinase 2 and calcium (PMID:14565954)
• This mutation gives rise to a truncated StAR protein, which lacks an important N-terminal region and the entire lipid transfer domain. (PMID:14764819)
• LRH-1 could be the major transcription factor responsible for the rapid and significant increase in ovarian StAR gene expression after ovulation. (PMID:15181096)
• Mutated in congenital lipoid adrenal hyperplasia. (PMID:15546900)
• Jak2 is novel pathway in Ang II-dependent activation of StAR expression and steroidogenesis in adrenocortical cells and is requirement for ongoing protein synthesis in Ang II-mediated StAR transcription. (PMID:15666812)
• Studies summarized in this review describe the critical role of the StAR protein in the regulation of steroid hormone biosynthesis. (PMID:15777208)
• importance of StAR-dependent steroidogenesis during fetal development and early infancy. new, prevalent StAR mutation (L260P) for the Swiss population. (PMID:15985476)
• presence of mature StAR in the luteal cell cytoplasm is consonant with the notion that StAR acts on the outer mitochondrial membrane to effect sterol import, and that StAR may interact with other cytoplasmic proteins involved in cholesterol metabolism (PMID:16162390)
• StAR activity requires a pH-dependent molten globule transition on the OMM (PMID:16234239)
• Results describe a novel cytosine/thymidine polymorphism of the human steroidogenic acute regulatory (StAR) gene promoter located 3 bp downstream of the steroidogenic factor-1 (SF-1)-binding site and 9 bp upstream of the TATA box (ATTTAAG). (PMID:16901925)
• 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)
• PPAR-gamma, insulin receptor with its signaling pathways, and StAR protein constitute a novel human ovarian regulatory system with complex interactions among its components (PMID:17374711)
• StAR appears to act in concert with the peripheral benzodiazepine receptor, but the precise itinerary of a cholesterol molecule entering the mitochondrion remains unclear. (PMID:17433772)
• In most Palestinian cases of congenital lipoid adrenal hyperplasia, a founder c.201_202delCT mutation in StAR is the cause (PMID:17666473)
• Cholesterol sulphate affects the production of steroid hormones by reducing StAR protein level in adrenocortical cells. (PMID:18000307)
• phenotypic variations of 46, XX girls with mutations in the gene for StAR; majority of StAR 46,XX females developed irregular menses and ovarian cysts [review] (PMID:18084157)
• No difference in StAR and P450scc protein levels in granulosa cells obtained from older low-responder in vitro fertilization patients with that of young good-responder patients. (PMID:18191841)
• phosphorylated StAR interacts with voltage-dependent anion channel 1 (VDAC1) on the OMM, which then facilitates processing of the 37-kDa phospho-StAR to the 32-kDa intermediate. (PMID:18250166)
• provide evidence for differential cholesterol binding of the two most closely related START domain proteins STARD1 and STARD3 (PMID:18331352)
• StAR can readily bind to cholesterol with an apparent affinity that commensurates with monomeric cholesterol solubility in water. The proper function of the C-terminal alpha-helix is essential for the binding process (PMID:18341481)
• Orexin effects on StAR gene expression were primarily, but not exclusively, acting through the orexin receptor type 1. (PMID:18450961)
• Cholesterol sulfate has an inhibitory effect on progesterone production by regulating the expression of StAR and P450scc gene expression. (PMID:18490834)
• Data show that StAR mRNA was found throughout the whole adrenal cortex attached to adrenocortical adenomas, but not in the medulla. (PMID:18505908)
• PGE(2)-induced StAR promoter activity appears to be regulated by CREB and C/EBPbeta in a cooperative manner in ectopic human endometriotic stromal cells, providing a molecular framework for the etiology of endometriosis. (PMID:18583320)
• Differential expression of steroidogenic factors 1 and 2, cytochrome p450scc, and steroidogenic acute regulatory protein in the pancreas. (PMID:18665078)
• The mechanism of specific binding of fere cholesterol by the STAR protein: evidence for a role of the C-terminal alpha-helix in the gating of the binding site. (PMID:18729825)
• Case Report: Conception and pregnancy outcome in a patient with 11-bp deletion of the steroidogenic acute regulatory protein gene. (PMID:18829024)
• Overexpression of mitochondrial cholesterol delivery protein, StAR, decreases intracellular lipids and inflammatory factors secretion in macrophages. (PMID:18945429)
• Endometriotic cells contain the full complement of steroidogenic genes for de novo synthesis of estradiol from cholesterol, which is stimulated by PGE2 via enhanced binding of SF1 to promoters of StAR and aromatase genes in a synchronous fashion. (PMID:19001523)
• both SF1 and LRH1 can transcriptionally cooperate with the AP-1 family members c-JUN and c-FOS, known to be associated with enhanced proliferation of endometrial carcinoma cells, to further enhance activation of the STAR, HSD3B2, and CYP19A1 PII promoters (PMID:19022561)
• A structural in silico analysis of StAR, is presented. (PMID:19095060)
• StAR overexpression in non-alcoholic fatty liver disease suggests that mitochondrial free cholesterol may be involved in disease progression. (PMID:19231010)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	star	ENSDARG00000006137
mus_musculus	Star	ENSMUSG00000031574
rattus_norvegicus	Star	ENSRNOG00000015052
drosophila_melanogaster	Start1	FBGN0035028
caenorhabditis_elegans		WBGENE00010505
caenorhabditis_elegans		WBGENE00017826

Paralogs (5): STARD3NL (ENSG00000010270), STARD3 (ENSG00000131748), STARD4 (ENSG00000164211), STARD5 (ENSG00000172345), STARD6 (ENSG00000174448)

Protein

Protein identifiers

Steroidogenic acute regulatory protein, mitochondrial — P49675 (reviewed: P49675)

Alternative names: START domain-containing protein 1

All UniProt accessions (5): P49675, A0A0S2Z4E8, E5RH12, H0YB94, Q6IBK0

UniProt curated annotations — full annotation on UniProt →

Function. Plays a key role in steroid hormone synthesis by enhancing the metabolism of cholesterol into pregnenolone. Mediates the transfer of cholesterol from the outer mitochondrial membrane to the inner mitochondrial membrane where it is cleaved to pregnenolone.

Subunit / interactions. May interact with TSPO.

Subcellular location. Mitochondrion outer membrane. Mitochondrion matrix.

Tissue specificity. Expressed in gonads, adrenal cortex and kidney.

Disease relevance. Adrenal hyperplasia 1 (AH1) [MIM:201710] The most severe form of adrenal hyperplasia. It is a condition characterized by onset of profound adrenocortical insufficiency shortly after birth, hyperpigmentation reflecting increased production of pro-opiomelanocortin, elevated plasma renin activity as a consequence of reduced aldosterone synthesis, and male pseudohermaphroditism resulting from deficient fetal testicular testosterone synthesis. Affected individuals are phenotypic females irrespective of gonadal sex, and frequently die in infancy if mineralocorticoid and glucocorticoid replacement are not instituted. The disease is caused by variants affecting the gene represented in this entry.

Pathway. Steroid metabolism; cholesterol metabolism.

RefSeq proteins (1): NP_000340* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000799	StAR-like	Family
IPR002913	START_lipid-bd_dom	Domain
IPR023393	START-like_dom_sf	Homologous_superfamily
IPR029866	StAR	Family

Pfam: PF01852

Catalyzed reactions (Rhea), 1 shown:

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

UniProt features (31 total): strand 11, sequence variant 10, helix 4, modified residue 2, transit peptide 1, chain 1, domain 1, turn 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
6T5H	X-RAY DIFFRACTION	2.04
6T5F	X-RAY DIFFRACTION	2.63
3P0L	X-RAY DIFFRACTION	3.4
5OMA	X-RAY DIFFRACTION	3.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P49675-F1	82.71	0.69

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 (2): 57, 195

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-196108	Pregnenolone biosynthesis
R-HSA-9837999	Mitochondrial protein degradation
R-HSA-1430728	Metabolism
R-HSA-196071	Metabolism of steroid hormones
R-HSA-392499	Metabolism of proteins
R-HSA-556833	Metabolism of lipids
R-HSA-8957322	Metabolism of steroids

MSigDB gene sets: 0 (showing top):

GO Biological Process (10): steroid biosynthetic process (GO:0006694), glucocorticoid biosynthetic process (GO:0006704), cholesterol metabolic process (GO:0008203), intracellular cholesterol transport (GO:0032367), regulation of steroid biosynthetic process (GO:0050810), positive regulation of bile acid biosynthetic process (GO:0070859), lipid metabolic process (GO:0006629), lipid transport (GO:0006869), glucocorticoid metabolic process (GO:0008211), sterol transport (GO:0015918)

GO Molecular Function (4): cholesterol binding (GO:0015485), cholesterol transfer activity (GO:0120020), protein binding (GO:0005515), lipid binding (GO:0008289)

GO Cellular Component (4): mitochondrion (GO:0005739), mitochondrial outer membrane (GO:0005741), mitochondrial intermembrane space (GO:0005758), mitochondrial matrix (GO:0005759)

Reactome top-level categories

Rollup of top-5 pathways:

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
steroid metabolic process	2
binding	2
lipid biosynthetic process	1
glucocorticoid metabolic process	1
steroid hormone biosynthetic process	1
sterol metabolic process	1
secondary alcohol metabolic process	1
intracellular anatomical structure	1
cholesterol transport	1
intracellular sterol transport	1
steroid biosynthetic process	1
regulation of steroid metabolic process	1
regulation of lipid biosynthetic process	1
bile acid biosynthetic process	1
positive regulation of steroid biosynthetic process	1
positive regulation of small molecule metabolic process	1
regulation of bile acid biosynthetic process	1
primary metabolic process	1
transport	1
lipid localization	1
lipid transport	1
organic hydroxy compound transport	1
sterol binding	1
alcohol binding	1
cholesterol binding	1
sterol transfer activity	1
cytoplasm	1
intracellular membrane-bounded organelle	1
mitochondrial membrane	1
organelle outer membrane	1
mitochondrial envelope	1
organelle envelope lumen	1
mitochondrion	1
intracellular organelle lumen	1

Protein interactions and networks

STRING

1194 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
STAR	TSPO	P30536	994
STAR	VDAC1	P21796	958
STAR	CYP11A1	P05108	954
STAR	CYP17A1	P05093	945
STAR	CYP11B2	P19099	922
STAR	NR5A1	Q13285	920
STAR	HSD3B1	P14060	896
STAR	TOMM22	Q9NS69	892
STAR	FDX1	P10109	891
STAR	CYP19A1	P11511	877
STAR	NR0B1	P51843	874
STAR	PRKACA	P17612	864
STAR	PRKACG	P22612	864
STAR	PRKACB	P22694	864
STAR	CYP11B1	P15538	843

IntAct

36 interactions, top by confidence:

A	B	Type	Score
STAR	MAGEA11	psi-mi:“MI:0915”(physical association)	0.720
MAGEA11	STAR	psi-mi:“MI:0915”(physical association)	0.720
MAGEA11	STAR	psi-mi:“MI:0915”(physical association)	0.560
STAR	MAGEA11	psi-mi:“MI:0915”(physical association)	0.560
STAR	AGTRAP	psi-mi:“MI:0915”(physical association)	0.560
STAR	RABEP1	psi-mi:“MI:0915”(physical association)	0.560
STAR	DGAT2L6	psi-mi:“MI:0915”(physical association)	0.560
SMPD2	STAR	psi-mi:“MI:0915”(physical association)	0.560
STAR	CMTM4	psi-mi:“MI:0915”(physical association)	0.560
STAR	STX8	psi-mi:“MI:0915”(physical association)	0.560
HTT	STAR	psi-mi:“MI:0915”(physical association)	0.560
STAR	CCHCR1	psi-mi:“MI:0915”(physical association)	0.400
STAR	AGTRAP	psi-mi:“MI:0915”(physical association)	0.000
STAR	MAGEA11	psi-mi:“MI:0915”(physical association)	0.000
STAR	RABEP1	psi-mi:“MI:0915”(physical association)	0.000
STAR	SMPD2	psi-mi:“MI:0915”(physical association)	0.000
STAR	DGAT2L6	psi-mi:“MI:0915”(physical association)	0.000
STAR	CMTM4	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (16): STAR (Reconstituted Complex), STAR (Biochemical Activity), STAR (Two-hybrid), MAGEA11 (Two-hybrid), MAGEA11 (Two-hybrid), NUCB2 (Two-hybrid), CCHCR1 (Two-hybrid), CCHCR1 (Affinity Capture-Western), STAR (Two-hybrid), FEZ1 (Two-hybrid), STAR (Two-hybrid), STX8 (Two-hybrid), AGTRAP (Two-hybrid), CMTM4 (Two-hybrid), DGAT2L6 (Two-hybrid)

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: 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

11 interactions.

A	Effect	B	Mechanism
CEBPA	“up-regulates quantity by expression”	STAR	“transcriptional regulation”
CEBPB	“up-regulates quantity by expression”	STAR	“transcriptional regulation”
FOXL2	“down-regulates quantity by repression”	STAR	“transcriptional regulation”
NR5A1	“up-regulates quantity by expression”	STAR	“transcriptional regulation”
NR5A2	“up-regulates quantity by expression”	STAR	“transcriptional regulation”
JUN	“up-regulates quantity by expression”	STAR	“transcriptional regulation”
FOS	“up-regulates quantity by expression”	STAR	“transcriptional regulation”
LONP1	“down-regulates quantity by destabilization”	STAR	cleavage
CLOCK/BMAL1	“up-regulates quantity by expression”	STAR	“transcriptional regulation”
STAR	“up-regulates quantity”	cholesterol	relocalization

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	45
Likely pathogenic	50
Uncertain significance	128
Likely benign	185
Benign	11

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1068479	NM_000349.3(STAR):c.76C>T (p.Gln26Ter)	Pathogenic
1071071	NM_000349.3(STAR):c.784del (p.Gln262fs)	Pathogenic
1076650	NM_000349.3(STAR):c.719del (p.Thr240fs)	Pathogenic
1412308	NM_000349.3(STAR):c.701_702dup (p.Ser235fs)	Pathogenic
1439981	NM_000349.3(STAR):c.319A>T (p.Lys107Ter)	Pathogenic
1452094	NM_000349.3(STAR):c.441G>A (p.Trp147Ter)	Pathogenic
1456378	NM_000349.3(STAR):c.129del (p.Thr44fs)	Pathogenic
1459786	NM_000349.3(STAR):c.94dup (p.Ser32fs)	Pathogenic
1691341	NM_000349.3(STAR):c.65-12_68del	Pathogenic
2039092	NM_000349.3(STAR):c.661_713dup (p.Leu239fs)	Pathogenic
2101047	NM_000349.3(STAR):c.707_708delinsCTT (p.Lys236fs)	Pathogenic
2120151	NM_000349.3(STAR):c.401_402del (p.Leu133_Tyr134insTer)	Pathogenic
2136659	NM_000349.3(STAR):c.407del (p.Glu136fs)	Pathogenic
2739260	NM_000349.3(STAR):c.637A>T (p.Lys213Ter)	Pathogenic
2760056	NM_000349.3(STAR):c.73dup (p.Gln25fs)	Pathogenic
2782096	NM_000349.3(STAR):c.402T>A (p.Tyr134Ter)	Pathogenic
2824358	NM_000349.3(STAR):c.173_177del (p.Leu58fs)	Pathogenic
2830333	NM_000349.3(STAR):c.723G>A (p.Trp241Ter)	Pathogenic
2840692	NM_000349.3(STAR):c.60dup (p.Lys21fs)	Pathogenic
2995568	NM_000349.3(STAR):c.472C>T (p.Gln158Ter)	Pathogenic
3000732	NM_000349.3(STAR):c.306+1del	Pathogenic
35553	NM_000349.3(STAR):c.577C>T (p.Arg193Ter)	Pathogenic
3648473	NM_000349.3(STAR):c.398_404del (p.Leu133fs)	Pathogenic
370502	NM_000349.3(STAR):c.629_630del (p.Pro210fs)	Pathogenic
4735320	NM_000349.3(STAR):c.130_134del (p.Pro43_Thr44insTer)	Pathogenic
4818220	NM_000349.3(STAR):c.465+2T>A	Pathogenic
4819786	NM_000349.3(STAR):c.490dup (p.Thr164fs)	Pathogenic
550550	NM_000349.3(STAR):c.544C>T (p.Arg182Cys)	Pathogenic
550998	NM_000349.3(STAR):c.64+1G>T	Pathogenic
553713	NM_000349.3(STAR):c.229C>T (p.Gln77Ter)	Pathogenic

SpliceAI

737 predictions. Top by Δscore:

Variant	Effect	Δscore
8:38146145:GACC:G	acceptor_loss	1.0000
8:38146146:ACCTA:A	acceptor_loss	1.0000
8:38146148:C:CA	acceptor_loss	1.0000
8:38146285:TCA:T	donor_loss	1.0000
8:38146286:CACCT:C	donor_loss	1.0000
8:38146288:C:T	donor_loss	1.0000
8:38146329:T:TA	donor_gain	1.0000
8:38146443:TTGTC:T	acceptor_gain	1.0000
8:38146444:TGTC:T	acceptor_gain	1.0000
8:38146445:GTC:G	acceptor_gain	1.0000
8:38146445:GTCCT:G	acceptor_loss	1.0000
8:38146446:TC:T	acceptor_gain	1.0000
8:38146447:CC:C	acceptor_gain	1.0000
8:38146447:CCTG:C	acceptor_loss	1.0000
8:38146449:T:C	acceptor_loss	1.0000
8:38146452:C:CT	acceptor_gain	1.0000
8:38146453:A:T	acceptor_gain	1.0000
8:38148195:CTTA:C	donor_loss	1.0000
8:38148196:TTA:T	donor_loss	1.0000
8:38148197:TACC:T	donor_loss	1.0000
8:38148198:A:AC	donor_gain	1.0000
8:38148199:C:CG	donor_gain	1.0000
8:38148199:CCT:C	donor_gain	1.0000
8:38148199:CCTG:C	donor_gain	1.0000
8:38148750:CAGCC:C	acceptor_gain	1.0000
8:38148751:AGCC:A	acceptor_gain	1.0000
8:38148752:GCC:G	acceptor_gain	1.0000
8:38148753:CC:C	acceptor_gain	1.0000
8:38148753:CCC:C	acceptor_gain	1.0000
8:38148753:CCCTG:C	acceptor_loss	1.0000

AlphaMissense

1880 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:38146315:A:G	W147R	0.998
8:38146315:A:T	W147R	0.998
8:38145245:A:G	W241R	0.997
8:38145245:A:T	W241R	0.997
8:38145963:C:A	R217M	0.997
8:38146313:C:A	W147C	0.997
8:38146313:C:G	W147C	0.997
8:38146394:G:C	F120L	0.997
8:38146394:G:T	F120L	0.997
8:38146396:A:G	F120L	0.997
8:38148220:A:G	W96R	0.997
8:38148220:A:T	W96R	0.997
8:38145315:C:A	R217S	0.996
8:38145315:C:G	R217S	0.996
8:38146061:A:C	F184L	0.996
8:38146061:A:T	F184L	0.996
8:38146063:A:G	F184L	0.996
8:38146069:G:T	R182S	0.995
8:38146389:A:G	L122P	0.995
8:38148218:C:A	W96C	0.995
8:38148218:C:G	W96C	0.995
8:38144319:A:G	L271P	0.994
8:38145241:A:G	L242P	0.994
8:38145963:C:G	R217T	0.994
8:38144330:A:C	F267L	0.993
8:38144330:A:T	F267L	0.993
8:38144332:A:G	F267L	0.993
8:38146055:G:C	S186R	0.993
8:38146055:G:T	S186R	0.993
8:38146057:T:G	S186R	0.993

dbSNP variants (sampled 300 via entrez): RS1000574169 (8:38151422 T>C), RS1000602830 (8:38146693 T>C), RS1000622605 (8:38145029 A>G,T), RS1000644495 (8:38152662 G>A), RS1000738247 (8:38145333 C>G), RS1001203436 (8:38149665 C>T), RS1001356534 (8:38147828 A>G), RS1001387551 (8:38148103 G>A), RS1001468266 (8:38143719 A>G), RS1001718266 (8:38149428 A>T), RS1002883542 (8:38142367 A>G), RS1002995468 (8:38150503 G>C,T), RS1003169711 (8:38143465 C>G,T), RS1003699775 (8:38149342 T>A), RS1003923195 (8:38145158 A>G,T)

Disease associations

OMIM: gene MIM:600617 | disease phenotypes: MIM:201710, MIM:300707

GenCC curated gene-disease

Disease	Classification	Inheritance
congenital lipoid adrenal hyperplasia due to STAR deficency	Definitive	Autosomal recessive

Mondo (2): congenital lipoid adrenal hyperplasia due to STAR deficency (MONDO:0008725), syndactyly-telecanthus-anogenital and renal malformations syndrome (MONDO:0010408)

Orphanet (3): Congenital adrenal hyperplasia (Orphanet:418), Congenital lipoid adrenal hyperplasia due to STAR deficency (Orphanet:90790), Syndactyly-telecanthus-anogenital and renal malformations syndrome (Orphanet:140952)

HPO phenotypes

40 total (30 of 40 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000010	Recurrent urinary tract infections
HP:0000027	Azoospermia
HP:0000028	Cryptorchidism
HP:0000047	Hypospadias
HP:0000098	Tall stature
HP:0000127	Renal salt wasting
HP:0000826	Precocious puberty
HP:0000840	Adrenogenital syndrome
HP:0000846	Adrenal insufficiency
HP:0000851	Congenital hypothyroidism
HP:0001249	Intellectual disability
HP:0001325	Hypoglycemic coma
HP:0001508	Failure to thrive
HP:0001639	Hypertrophic cardiomyopathy
HP:0001824	Weight loss
HP:0002013	Vomiting
HP:0002014	Diarrhea
HP:0002019	Constipation
HP:0002039	Anorexia
HP:0002153	Hyperkalemia
HP:0002173	Hypoglycemic seizures
HP:0002445	Tetraplegia
HP:0002574	Episodic abdominal pain
HP:0002615	Hypotension
HP:0002719	Recurrent infections
HP:0002902	Hyponatremia
HP:0002960	Autoimmunity
HP:0004319	Decreased circulating aldosterone concentration
HP:0007440	Generalized hyperpigmentation

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST002209_4	Orthostatic hypotension	4.000000e-06
GCST005312_24	Menopause (age at onset)	7.000000e-22
GCST006803_65	Schizophrenia	6.000000e-10

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004704	age at menopause

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C567475	Toe Syndactyly, Telecanthus, and Anogenital and Renal Malformations (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067601 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Colforsin	decreases reaction, increases expression, affects cotreatment	14
8-Bromo Cyclic Adenosine Monophosphate	decreases reaction, increases expression, affects reaction	8
bisphenol A	decreases expression, decreases reaction, increases expression	5
Benzo(a)pyrene	affects expression, decreases expression, decreases methylation, increases methylation	3
Bucladesine	decreases reaction, affects cotreatment, decreases expression, increases expression	3
Diethylhexyl Phthalate	increases expression, decreases expression, decreases reaction, affects cotreatment	3
Flame Retardants	increases expression, affects cotreatment, decreases expression	3
Valproic Acid	decreases reaction, increases expression, decreases expression	3
1-Methyl-3-isobutylxanthine	decreases reaction, increases expression, affects cotreatment	3
triphenyl phosphate	affects cotreatment, affects expression, decreases reaction, increases expression	2
perfluorooctane sulfonic acid	increases expression, affects cotreatment	2
27-hydroxycholesterol	increases expression, increases reaction, increases abundance	2
entinostat	increases expression, affects cotreatment	2
torcetrapib	decreases reaction, increases expression	2
Resveratrol	decreases expression, decreases reaction, increases expression, affects cotreatment	2
Ethanol	decreases expression	2
Atrazine	decreases reaction, increases expression, increases reaction	2
Cholesterol	increases transport, affects transport	2
Copper	affects expression, affects cotreatment, decreases expression	2
Dexamethasone	decreases expression, increases reaction, affects cotreatment, increases expression	2
Dibutyl Phthalate	decreases expression, affects cotreatment, decreases reaction, increases expression	2
Mitotane	increases expression, decreases expression, decreases reaction	2
Nicotine	decreases expression, increases methylation, decreases reaction	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tretinoin	decreases expression, increases expression	2
Dinoprostone	decreases reaction, increases reaction, decreases expression, increases expression, affects binding	2
Mifepristone	decreases expression, decreases reaction	2
Cyclosporine	decreases expression	2
Halogenated Diphenyl Ethers	increases expression, decreases expression	2
aristolochic acid I	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5550808	Binding	Binding affinity to STARD1 (unknown origin)	Fluorescent probes and degraders of the sterol transport protein Aster-A. — Bioorg Med Chem

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2HH	Abcam HeLa STAR KO	Cancer cell line	Female

Clinical trials (associated diseases)

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