STAR
protein-codingsteroidogenic acute regulatory protein, the group of StAR related lipid transfer domain containing
Gene summary
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. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~8.3 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0008725
Submitter: G2P
Inheritance Pattern: AR
Disease ID:MONDO:0008725
Submitter: Myriad Women's Health
Inheritance Pattern: AR
Disease ID:MONDO:0008725
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0008725
Submitter: Natera
Inheritance Pattern: AR
Disease ID:MONDO:0008725
Submitter: Labcorp Genetics (formerly Invitae)
Clinical Genomic Database (CGD)
Manifestation: Endocrine; Genitourinary; Oncologic
Intervention: Endocrine; Genitourinary; Oncologic
Rationale: 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
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to STAR variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_000349.3. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 5 | 125 | 1 | 131 | ||
| missense | 6 | 17 | 93 | 4 | 1 | 121 |
| nonsense | 13 | 6 | 19 | |||
| start loss | 0 | |||||
| frameshift | 37 | 28 | 65 | |||
| splice donor/acceptor (+/-2bp) | 4 | 20 | 24 | |||
| Total | 60 | 71 | 98 | 129 | 2 | 360 |
Highest pathogenic variant AF is 0.00005886012
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_000340.2 | 7 | MANE Select | |
| Ensembl | ENSP00000276449.3 | 7 | MANE Select | |
| Ensembl | ENSP00000430030.1 | 2 | Standard | |
| Ensembl | ENSP00000429009.1 | 5 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- 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)
Biological Process
- steroid biosynthetic process
- bile acid biosynthetic process
- C21-steroid hormone biosynthetic process
- estrogen biosynthetic process
- brain development
Molecular Function
- protein binding
- cholesterol binding
- cholesterol transporter activity
Cellular Component
- mitochondrion
- mitochondrial intermembrane space
- cytosol
- mitochondrial crista
- neuron projection
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000276449
- Coding exons
- 7
- Length
- 7617
- Individuals with no LoFs
- 125682
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 66
- Defined
- 125748
- p
- 0.000262
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.0892 | 172 | 169 | 1.02 | 0.0000109 | 1867 |
| Missense (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 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00025 | 0.00025 | rare |
| Latino/Admixed American | 0.00052 | 0.00052 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.0012 | 0.0011 | notable |
| Finnish | 0.00018 | 0.00018 | rare |
| European (Non-Finnish) | 0.00011 | 0.00011 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0.00082 | 0.00081 | rare |
dbNSFP Gene Annotations
Source:
- 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.;
Recessive Scores
- pRec
- 0.430
Intolerance Scores
- LoFtool
- 0.351
- RVIS EVS
- -0.12
- RVIS percentile EVS
- 45.13
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.867
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |