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STARD4 StAR related lipid transfer domain containing 4 [ Homo sapiens (human) ]

Gene ID: 134429, updated on 3-Apr-2024

Summary

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Official Symbol
STARD4provided by HGNC
Official Full Name
StAR related lipid transfer domain containing 4provided by HGNC
Primary source
HGNC:HGNC:18058
See related
Ensembl:ENSG00000164211 MIM:607049; AllianceGenome:HGNC:18058
Gene type
protein coding
RefSeq status
VALIDATED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Summary
Cholesterol homeostasis is regulated, at least in part, by sterol regulatory element (SRE)-binding proteins (e.g., SREBP1; MIM 184756) and by liver X receptors (e.g., LXRA; MIM 602423). Upon sterol depletion, LXRs are inactive and SREBPs are cleaved, after which they bind promoter SREs and activate genes involved in cholesterol biosynthesis and uptake. Sterol transport is mediated by vesicles or by soluble protein carriers, such as steroidogenic acute regulatory protein (STAR; MIM 600617). STAR is homologous to a family of proteins containing a 200- to 210-amino acid STAR-related lipid transfer (START) domain, including STARD4 (Soccio et al., 2002 [PubMed 12011452]).[supplied by OMIM, Mar 2008]
Expression
Ubiquitous expression in duodenum (RPKM 9.8), small intestine (RPKM 9.3) and 22 other tissues See more
Orthologs
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Genomic context

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See STARD4 in Genome Data Viewer
Location:
5q22.1
Exon count:
7
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 5 NC_000005.10 (111496033..111512535, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 5 NC_060929.1 (112006333..112022835, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 5 NC_000005.9 (110831731..110848233, complement)

Chromosome 5 - NC_000005.10Genomic Context describing neighboring genes Neighboring gene RPS3A pseudogene 21 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22890 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16229 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22891 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16230 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16231 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16232 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22892 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22893 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22894 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22897 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22896 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22895 Neighboring gene calcium/calmodulin dependent protein kinase IV Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr5:110644539-110645132 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr5:110783389-110783979 Neighboring gene ReSE screen-validated silencer GRCh37_chr5:110838395-110838556 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22898 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22899 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16233 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22900 Neighboring gene uncharacterized LOC105369177 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22901 Neighboring gene STARD4 antisense RNA 1 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr5:110865742-110866941 Neighboring gene uncharacterized LOC124901042

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. [Steroidogenic acute regulatory protein-related lipid transfer 4 (StarD4) promotes breast cancer cell proliferation and its mechanism]. Huang T, et al. Sheng Wu Yi Xue Gong Cheng Xue Za Zhi, 2021 Dec 25. PMID 34970895, Free PMC Article
  2. STARD4 promotes breast cancer cell malignancy. Zhang M, et al. Oncol Rep, 2020 Dec. PMID 33125124, Free PMC Article
  3. Stable reduction of STARD4 alters cholesterol regulation and lipid homeostasis. Iaea DB, et al. Biochim Biophys Acta Mol Cell Biol Lipids, 2020 Apr. PMID 31917335, Free PMC Article
  4. Structural analysis of human sterol transfer protein STARD4. Tan L, et al. Biochem Biophys Res Commun, 2019 Dec 3. PMID 31607485
  5. Role of STARD4 in sterol transport between the endocytic recycling compartment and the plasma membrane. Iaea DB, et al. Mol Biol Cell, 2017 Apr 15. PMID 28209730, Free PMC Article

See all (26) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. SREBF2-STARD4 axis confers sorafenib resistance in hepatocellular carcinoma by regulating mitochondrial cholesterol homeostasis.
    Title: SREBF2-STARD4 axis confers sorafenib resistance in hepatocellular carcinoma by regulating mitochondrial cholesterol homeostasis.
  2. [Steroidogenic acute regulatory protein-related lipid transfer 4 (StarD4) promotes breast cancer cell proliferation and its mechanism].
    Title: [Steroidogenic acute regulatory protein-related lipid transfer 4 (StarD4) promotes breast cancer cell proliferation and its mechanism].
  3. STARD4 promotes breast cancer cell malignancy.
    Title: STARD4 promotes breast cancer cell malignancy.
  4. STARD4 has a conserved alpha-helix/beta-grip fold with a deep hydrophobic pocket.STARD4 binds sterol in the pocket and transport sterol between liposomes. Sterol binding requires a conformational change to form a complementary pocket.
    Title: Structural analysis of human sterol transfer protein STARD4.
  5. Knockdown of STARD4, a sterol transporter, leads to large changes in the lipidome. STARD4-KD cells also have large changes in their mRNA profile. There is an increase in cellular cholesterol, including in late endosomes. These results indicate that STARD4 plays important roles in lipid homeostasis.
    Title: Stable reduction of STARD4 alters cholesterol regulation and lipid homeostasis.
  6. This study shows that nonvesicular sterol transport mechanisms and STARD4 in particular account for a large fraction of sterol transport between the plasma membrane and the ERC.
    Title: Role of STARD4 in sterol transport between the endocytic recycling compartment and the plasma membrane.
  7. 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.
    Title: The StarD4 subfamily of steroidogenic acute regulatory-related lipid transfer (START) domain proteins: new players in cholesterol metabolism.
  8. The data indicate a role for STARD4 in nonvesicular transport of cholesterol from the plasma membrane and the endocytic recycling compartment to the endoplasmic reticulum and perhaps other intracellular compartments as well.
    Title: STARD4 knockdown in HepG2 cells disrupts cholesterol trafficking associated with the plasma membrane, ER, and ERC.
  9. cholesterol transport mediated by STARD4 is an important component of the cholesterol homeostasis regulatory machinery
    Title: STARD4 abundance regulates sterol transport and sensing.
  10. Study provide strong evidence for StarD4 as a highly regulated, non-vesicular, directional, intracellular transporter of cholesterol which plays a key role in the maintenance of intracellular cholesterol homeostasis.
    Title: Subcellular localization and regulation of StarD4 protein in macrophages and fibroblasts.
Submit: New GeneRIF Correction See all GeneRIFs (17)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables cholesterol binding IBA
Inferred from Biological aspect of Ancestor
more info
  
enables cholesterol binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables cholesterol transfer activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables cholesterol transfer activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
Process Evidence Code Pubs
involved_in cholesterol import IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in cholesterol import IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in cholesterol transport involved in cholesterol storage IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in cholesterol transport involved in cholesterol storage IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in intermembrane lipid transfer IEA
Inferred from Electronic Annotation
more info
  
involved_in intracellular cholesterol transport IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in intracellular cholesterol transport IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in positive regulation of bile acid biosynthetic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in positive regulation of cholesterol metabolic process IDA
Inferred from Direct Assay
more info
 PubMed 
Component Evidence Code Pubs
located_in cytoplasm IDA
Inferred from Direct Assay
more info
 PubMed 
located_in cytoplasmic vesicle IDA
Inferred from Direct Assay
more info
 PubMed 
is_active_in cytosol IBA
Inferred from Biological aspect of Ancestor
more info
  
is_active_in endoplasmic reticulum IBA
Inferred from Biological aspect of Ancestor
more info
  

General protein information

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Preferred Names
stAR-related lipid transfer protein 4
Names
START domain containing 4, sterol regulated
START domain-containing protein 4
StAR-related lipid transfer (START) domain containing 4

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

  1. NM_001308056.2 → NP_001294985.1  stAR-related lipid transfer protein 4 isoform a

    See identical proteins and their annotated locations for NP_001294985.1

    Status: VALIDATED

    Description
    Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Both variants 1 and 2 encode isoform a.
    Source sequence(s)
    AK026207, AK054566, AK125317, AL710253, BI091150, BU607573, DB475661
    Consensus CDS
    CCDS4104.1
    UniProtKB/Swiss-Prot
    Q86TN9, Q96DR4
    UniProtKB/TrEMBL
    A8K2P7
    Related
    ENSP00000427478.2, ENST00000505803.5
    Conserved Domains (1) summary
    cl14643
    Location:5 → 205
    SRPBCC; START/RHO_alpha_C/PITP/Bet_v1/CoxG/CalC (SRPBCC) ligand-binding domain superfamily

  2. NM_001308057.2 → NP_001294986.1  stAR-related lipid transfer protein 4 isoform b

    See identical proteins and their annotated locations for NP_001294986.1

    Status: VALIDATED

    Description
    Transcript Variant: This variant (3) contains alternate 3' exon structure, resulting in an alternate 3' coding region and 3' UTR, compared to variant 1. The encoded isoform (b) has a distinct C-terminus and is shorter than isoform a. Both variants 3 and 4 encode isoform b.
    Source sequence(s)
    AK308851, BC042956
    Consensus CDS
    CCDS78046.1
    UniProtKB/Swiss-Prot
    Q96DR4
    Related
    ENSP00000427639.1, ENST00000502322.5
    Conserved Domains (1) summary
    cl14643
    Location:5 → 137
    SRPBCC; START/RHO_alpha_C/PITP/Bet_v1/CoxG/CalC (SRPBCC) ligand-binding domain superfamily

  3. NM_001308058.2 → NP_001294987.1  stAR-related lipid transfer protein 4 isoform b

    See identical proteins and their annotated locations for NP_001294987.1

    Status: VALIDATED

    Description
    Transcript Variant: This variant (4) differs in the 5' UTR and contains alternate 3' exon structure, resulting in an alternate 3' coding region and 3' UTR, compared to variant 1. The encoded isoform (b) has a distinct C-terminus and is shorter than isoform a. Both variants 3 and 4 encode isoform b.
    Source sequence(s)
    AK308851, BC042956, DB475661, DT220890
    Consensus CDS
    CCDS78046.1
    UniProtKB/Swiss-Prot
    Q96DR4
    Conserved Domains (1) summary
    cl14643
    Location:5 → 137
    SRPBCC; START/RHO_alpha_C/PITP/Bet_v1/CoxG/CalC (SRPBCC) ligand-binding domain superfamily

  4. NM_001308059.2 → NP_001294988.1  stAR-related lipid transfer protein 4 isoform c

    See identical proteins and their annotated locations for NP_001294988.1

    Status: VALIDATED

    Description
    Transcript Variant: This variant (5) contains an additional exon, resulting in differences in the 5' UTR and translation initiation at a downstream in-frame start codon, compared to variant 1. The encoded isoform (c) is shorter at the N-terminus, compared to isoform a. Both variants 5 and 6 encode isoform c.
    Source sequence(s)
    AK026207, AK054566, AK125317, BI091150, BP234859, BU607573, DB475661
    UniProtKB/Swiss-Prot
    Q96DR4
    Conserved Domains (1) summary
    cl14643
    Location:1 → 123
    SRPBCC; START/RHO_alpha_C/PITP/Bet_v1/CoxG/CalC (SRPBCC) ligand-binding domain superfamily

  5. NM_001308060.2 → NP_001294989.1  stAR-related lipid transfer protein 4 isoform d

    See identical proteins and their annotated locations for NP_001294989.1

    Status: VALIDATED

    Description
    Transcript Variant: This variant (7) lacks two internal exons, resulting in differences in the 5' UTR and translation initiation at a downstream in-frame start codon, compared to variant 1. The encoded isoform (d) is shorter at the N-terminus, compared to isoform a.
    Source sequence(s)
    AK026207, AK054566, AK125317, AK315863, BI091150, BU607573, DB475661
    UniProtKB/TrEMBL
    B0AZS2, Q86T95
    Conserved Domains (1) summary
    cl14643
    Location:1 → 107
    SRPBCC; START/RHO_alpha_C/PITP/Bet_v1/CoxG/CalC (SRPBCC) ligand-binding domain superfamily

  6. NM_001308061.2 → NP_001294990.1  stAR-related lipid transfer protein 4 isoform c

    See identical proteins and their annotated locations for NP_001294990.1

    Status: VALIDATED

    Description
    Transcript Variant: This variant (6) lacks an internal exon, resulting in differences in the 5' UTR and translation initiation at a downstream in-frame start codon, compared to variant 1. The encoded isoform (c) is shorter at the N-terminus, compared to isoform a. Both variants 5 and 6 encode isoform c.
    Source sequence(s)
    AK026207, AK054566, AK125317, BI091150, BP247836, BU607573, DB475661
    UniProtKB/Swiss-Prot
    Q96DR4
    Conserved Domains (1) summary
    cl14643
    Location:1 → 123
    SRPBCC; START/RHO_alpha_C/PITP/Bet_v1/CoxG/CalC (SRPBCC) ligand-binding domain superfamily

  7. NM_139164.3 → NP_631903.1  stAR-related lipid transfer protein 4 isoform a

    See identical proteins and their annotated locations for NP_631903.1

    Status: VALIDATED

    Description
    Transcript Variant: This variant (1) encodes the longest isoform (a). Both variants 1 and 2 encode isoform a.
    Source sequence(s)
    AK026207, AK054566, AK125317, BI091150, BU607573, DB475661
    Consensus CDS
    CCDS4104.1
    UniProtKB/Swiss-Prot
    Q86TN9, Q96DR4
    UniProtKB/TrEMBL
    A8K2P7
    Related
    ENSP00000296632.3, ENST00000296632.8
    Conserved Domains (1) summary
    cl14643
    Location:5 → 205
    SRPBCC; START/RHO_alpha_C/PITP/Bet_v1/CoxG/CalC (SRPBCC) ligand-binding domain superfamily

RNA

  1. NR_131752.2 RNA Sequence

    Status: VALIDATED

    Description
    Transcript Variant: This variant (8) lacks an alternate internal exon and contains alternate 3' exon structure, compared to variant 1. This variant is represented as non-coding because the predicted protein does not meet RefSeq quality criteria.
    Source sequence(s)
    AK308851, BC042956, DB475661

  2. NR_131753.2 RNA Sequence

    Status: VALIDATED

    Description
    Transcript Variant: This variant (9) contains alternate 3' exon structure, compared to variant 1. This variant is represented as non-coding because the predicted protein does not meet RefSeq quality criteria.
    Source sequence(s)
    BC019632, BC042956, DB475661
    Related
    ENST00000509887.5

  3. NR_131754.2 RNA Sequence

    Status: VALIDATED

    Description
    Transcript Variant: This variant (10) uses an alternate splice site in the 5' terminal exon and also in an internal exon, compared to variant 1. This variant is represented as non-coding because the predicted protein does not meet RefSeq quality criteria.
    Source sequence(s)
    AK026207, AK054566, AK125317, BI091150, BU607573

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000005.10 Reference GRCh38.p14 Primary Assembly

    Range
    111496033..111512535 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_017009043.3 → XP_016864532.1  stAR-related lipid transfer protein 4 isoform X3

    UniProtKB/TrEMBL
    B0AZS2, Q86T95
    Conserved Domains (1) summary
    cl14643
    Location:1 → 107
    SRPBCC; START/RHO_alpha_C/PITP/Bet_v1/CoxG/CalC (SRPBCC) ligand-binding domain superfamily

  2. XM_017009044.3 → XP_016864533.1  stAR-related lipid transfer protein 4 isoform X2

    Conserved Domains (1) summary
    cl14643
    Location:1 → 123
    SRPBCC; START/RHO_alpha_C/PITP/Bet_v1/CoxG/CalC (SRPBCC) ligand-binding domain superfamily

  3. XM_047416728.1 → XP_047272684.1  stAR-related lipid transfer protein 4 isoform X3

    UniProtKB/TrEMBL
    B0AZS2

  4. XM_024454364.2 → XP_024310132.1  stAR-related lipid transfer protein 4 isoform X1

    Conserved Domains (1) summary
    cl14643
    Location:5 → 132
    SRPBCC; START/RHO_alpha_C/PITP/Bet_v1/CoxG/CalC (SRPBCC) ligand-binding domain superfamily

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060929.1 Alternate T2T-CHM13v2.0

    Range
    112006333..112022835 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054351637.1 → XP_054207612.1  stAR-related lipid transfer protein 4 isoform X3

    UniProtKB/TrEMBL
    B0AZS2

  2. XM_054351635.1 → XP_054207610.1  stAR-related lipid transfer protein 4 isoform X2

  3. XM_054351636.1 → XP_054207611.1  stAR-related lipid transfer protein 4 isoform X3

    UniProtKB/TrEMBL
    B0AZS2

  4. XM_054351634.1 → XP_054207609.1  stAR-related lipid transfer protein 4 isoform X1

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q96DR4.1 GenPept UniProtKB/Swiss-Prot:Q96DR4

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