STAR

steroidogenic acute regulatory protein, the group of StAR related lipid transfer domain containing

Basic information

Region (hg38): 8:38142699-38150992

Links

ENSG00000147465 ∙ NCBI:6770 ∙ OMIM:600617 ∙ HGNC:11359 ∙ Uniprot:P49675 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• congenital lipoid adrenal hyperplasia due to STAR deficency (Definitive), mode of inheritance: AR
• congenital lipoid adrenal hyperplasia due to STAR deficency (Definitive), mode of inheritance: AR
• congenital lipoid adrenal hyperplasia due to STAR deficency (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Lipoid adrenal hyperplasia	AR	Endocrine; Genitourinary; Oncologic	Due to the severity of disease, most individuals present as phenotypic females with fatal salt-wasting adrenal crises if untreated in early infancy (patients may also present later in life with milder forms of disease), and medical treatment (eg, with glucocorticoid and mineralcorticoid replacement) may be beneficial; Treatment of genitourinary anomalies (eg, with surgery, including related to the risk of malignancy in genotypic males) may be indicated in some individuals	Endocrine; Genitourinary; Oncologic	13968788; 4685387; 3841304; 2419119; 1661294; 7892608; 7547998; 8948562; 9077535; 10323391; 11061515; 16968793; 21057961; 21691971; 21714456; 21846663; 22028173; 22083155; 22249004

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the STAR gene.

• not provided (234 variants)
• Congenital lipoid adrenal hyperplasia due to STAR deficency (119 variants)
• Inborn genetic diseases (7 variants)
• not specified (4 variants)
• Congenital adrenal hyperplasia (4 variants)
• STAR-related condition (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the STAR gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				90	1	91
missense	2	11	27	2	1	43
nonsense	9	3				12
start loss						0
frameshift	16	20				36
inframe indel			1			1
splice donor/acceptor (+/-2bp)	4	13				17
splice region				17		17
non coding			33	24	11	68
Total	31	47	61	116	13

Highest pathogenic variant AF is 0.000105

Variants in STAR

This is a list of pathogenic ClinVar variants found in the STAR region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
8-38142716-T-C		Congenital lipoid adrenal hyperplasia due to STAR deficency	Uncertain significance (Jan 12, 2018)
8-38142730-G-T		Congenital lipoid adrenal hyperplasia due to STAR deficency	Uncertain significance (Jan 13, 2018)
8-38142749-T-C		Congenital lipoid adrenal hyperplasia due to STAR deficency	Benign (Jan 12, 2018)
8-38142760-G-C		Congenital lipoid adrenal hyperplasia due to STAR deficency	Uncertain significance (Jan 12, 2018)
8-38142800-C-T		Congenital lipoid adrenal hyperplasia due to STAR deficency	Uncertain significance (Jan 12, 2018)
8-38142801-G-A		Congenital lipoid adrenal hyperplasia due to STAR deficency	Uncertain significance (Jan 13, 2018)
8-38142888-GA-G		Congenital adrenal hyperplasia	Uncertain significance (Jun 14, 2016)
8-38143151-A-T		Congenital lipoid adrenal hyperplasia due to STAR deficency	Uncertain significance (Jan 12, 2018)
8-38143286-T-C		Congenital lipoid adrenal hyperplasia due to STAR deficency	Benign (Jan 13, 2018)
8-38143292-T-C		Congenital lipoid adrenal hyperplasia due to STAR deficency	Uncertain significance (Jan 13, 2018)
8-38143305-AT-A		Congenital adrenal hyperplasia	Benign (Jun 14, 2016)
8-38143305-A-ATTT		Congenital adrenal hyperplasia	Uncertain significance (Jun 14, 2016)
8-38143324-TG-T		Congenital adrenal hyperplasia	Uncertain significance (Jun 14, 2016)
8-38143343-G-A		Congenital lipoid adrenal hyperplasia due to STAR deficency	Uncertain significance (Jan 12, 2018)
8-38143360-G-A		Congenital lipoid adrenal hyperplasia due to STAR deficency	Uncertain significance (Jan 13, 2018)
8-38143376-G-A		Congenital lipoid adrenal hyperplasia due to STAR deficency	Uncertain significance (Jan 13, 2018)
8-38143393-G-A		Congenital lipoid adrenal hyperplasia due to STAR deficency	Uncertain significance (Jan 13, 2018)
8-38143455-C-T		Congenital lipoid adrenal hyperplasia due to STAR deficency	Uncertain significance (Jan 13, 2018)
8-38143456-G-A		Congenital lipoid adrenal hyperplasia due to STAR deficency	Uncertain significance (Jan 13, 2018)
8-38143477-T-C		Congenital lipoid adrenal hyperplasia due to STAR deficency	Uncertain significance (Jan 13, 2018)
8-38143505-C-T		Congenital lipoid adrenal hyperplasia due to STAR deficency	Uncertain significance (Jan 13, 2018)
8-38143574-G-C		Congenital lipoid adrenal hyperplasia due to STAR deficency	Uncertain significance (Jan 13, 2018)
8-38143575-G-T		Congenital lipoid adrenal hyperplasia due to STAR deficency	Uncertain significance (Jan 13, 2018)
8-38143585-G-A		Congenital lipoid adrenal hyperplasia due to STAR deficency	Uncertain significance (Jan 13, 2018)
8-38143717-T-C		Congenital lipoid adrenal hyperplasia due to STAR deficency	Uncertain significance (Jan 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
STAR	protein_coding	protein_coding	ENST00000276449	7	7617

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
8.77e-11	0.0429	125682	0	66	125748	0.000262

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.0892	172	169	1.02	0.0000109	1867
Missense in Polyphen		29	32.947	0.88021		376
Synonymous	-1.01	73	62.8	1.16	0.00000387	547
Loss of Function	-0.198	15	14.2	1.06	7.09e-7	154

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000767	0.000767
Ashkenazi Jewish	0.00	0.00
East Asian	0.00118	0.00114
Finnish	0.000185	0.000185
European (Non-Finnish)	0.000115	0.000114
Middle Eastern	0.00118	0.00114
South Asian	0.0000327	0.0000327
Other	0.000817	0.000815

dbNSFP

Source: dbNSFP

• Function: 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.
• Pathway: Cortisol synthesis and secretion - Homo sapiens (human);Aldosterone synthesis and secretion - Homo sapiens (human);Cushing,s syndrome - Homo sapiens (human);Cholesterol metabolism - Homo sapiens (human);Ovarian steroidogenesis - Homo sapiens (human);Corticotropin-releasing hormone signaling pathway;Metabolism of lipids;Metabolism;Pregnenolone biosynthesis;Metabolism of steroid hormones;Metabolism of steroids;Steroid hormones (Consensus)

Recessive Scores

• pRec: 0.430

Intolerance Scores

• loftool: 0.351
• rvis_EVS: -0.12
• rvis_percentile_EVS: 45.13

Haploinsufficiency Scores

• pHI: 0.243
• hipred: N
• hipred_score: 0.251
• ghis: 0.416

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.867

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Star
• Phenotype: mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; growth/size/body region phenotype; endocrine/exocrine gland phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: steroid biosynthetic process;bile acid biosynthetic process;C21-steroid hormone biosynthetic process;estrogen biosynthetic process;brain development;response to nutrient;cholesterol metabolic process;glucocorticoid metabolic process;male gonad development;response to herbicide;response to ionizing radiation;response to lead ion;positive regulation of gene expression;response to activity;diterpenoid metabolic process;insecticide metabolic process;biphenyl metabolic process;dibenzo-p-dioxin metabolic process;phenol-containing compound metabolic process;phthalate metabolic process;intracellular cholesterol transport;cellular response to insulin stimulus;response to nicotine;cellular response to interferon-alpha;response to hydrogen peroxide;circadian sleep/wake cycle, REM sleep;negative regulation of neuron apoptotic process;response to estrogen;response to leptin;cellular response to fibroblast growth factor stimulus;response to ethanol;regulation of neuronal synaptic plasticity;positive regulation of neurogenesis;regulation of steroid biosynthetic process;response to corticosterone;response to fungicide;testosterone biosynthetic process;positive regulation of bile acid biosynthetic process;cellular response to lipopolysaccharide;cellular response to antibiotic;cellular response to cadmium ion;cellular response to alkaloid;cellular response to cAMP;cellular response to glucose stimulus;cellular response to interferon-gamma;cellular response to follicle-stimulating hormone stimulus;cellular response to luteinizing hormone stimulus;cellular response to growth hormone stimulus;cellular response to dexamethasone stimulus;cellular response to transforming growth factor beta stimulus;cellular response to epinephrine stimulus
• Cellular component: mitochondrion;mitochondrial intermembrane space;cytosol;mitochondrial crista;neuron projection;neuronal cell body
• Molecular function: protein binding;cholesterol binding;cholesterol transporter activity