Details for: SERAC1

Gene ID: 84947

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: SERAC1

Ensembl ID: ENSG00000122335

Description: serine active site containing 1

Cell Significance Landscape

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • interneuron CL0000099
    CSI 3.42
    rCSI 6.87%
    PRS 89.03
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 3.3
    rCSI 5.55%
    PRS 83.81
  • pancreatic A cell CL0000171
    CSI 3.28
    rCSI 3.44%
    PRS 94.74
  • pancreatic D cell CL0000173
    CSI 3.27
    rCSI 3.21%
    PRS 94.58
  • cerebral cortex endothelial cell CL1001602
    CSI 2.6
    rCSI 4.5%
    PRS 89.67
  • astrocyte of the cerebral cortex CL0002605
    CSI 2.6
    rCSI 5.83%
    PRS 84.02
  • retinal bipolar neuron CL0000748
    CSI 2.42
    rCSI 4.53%
    PRS 87.04
  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 2.21
    rCSI 2%
    PRS 92.68
  • VIP GABAergic cortical interneuron CL4023016
    CSI 2.01
    rCSI 2.4%
    PRS 83.76
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 1.95
    rCSI 2.43%
    PRS 81.61
  • ependymal cell CL0000065
    CSI 1.88
    rCSI 3.81%
    PRS 78.96
  • sst GABAergic cortical interneuron CL4023017
    CSI 1.83
    rCSI 2.36%
    PRS 84.69
  • glycinergic amacrine cell CL4030028
    CSI 1.83
    rCSI 4.76%
    PRS 88.59
  • medium spiny neuron CL1001474
    CSI 1.65
    rCSI 14.18%
    PRS 87.32
  • glutamatergic neuron CL0000679
    CSI 1.53
    rCSI 3.15%
    PRS 83.82
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 1.52
    rCSI 2.68%
    PRS 83.16
  • amacrine cell CL0000561
    CSI 1.42
    rCSI 4.1%
    PRS 86.89
  • retinal ganglion cell CL0000740
    CSI 1.36
    rCSI 3%
    PRS 85.33
  • parietal epithelial cell CL1000452
    CSI 1.3
    rCSI 3.47%
    PRS 89.87
  • sncg GABAergic cortical interneuron CL4023015
    CSI 1.26
    rCSI 2.03%
    PRS 84.71
  • pancreatic ductal cell CL0002079
    CSI 1.21
    rCSI 2.36%
    PRS 94.55
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 1.17
    rCSI 2.84%
    PRS 81.61
  • GABAergic interneuron CL0011005
    CSI 0.99
    rCSI 15.67%
    PRS 93.79
  • dopaminergic neuron CL0000700
    CSI 0.78
    rCSI 4.4%
    PRS 84.98
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 0.74
    rCSI 2.81%
    PRS 83.89
  • megakaryocyte CL0000556
    CSI 0.73
    rCSI 3.17%
    PRS 93.79
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 0.65
    rCSI 2.04%
    PRS 86.57
  • L6b glutamatergic cortical neuron CL4023038
    CSI 0.63
    rCSI 1.97%
    PRS 84.75
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 0.61
    rCSI 2.2%
    PRS 81.92
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 0.38
    rCSI 2.23%
    PRS 84.07
  • indirect pathway medium spiny neuron CL4023029
    CSI 0.38
    rCSI 9.08%
    PRS 81.55
  • direct pathway medium spiny neuron CL4023026
    CSI 0.29
    rCSI 6.83%
    PRS 81.57

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

Comma-separated if multiple.
Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [SERAC1](/details-gene/84947), or Serine Active Site Containing 1, is a protein-coding gene located on chromosome 6q25.3. It plays a crucial role in intracellular lipid metabolism, specifically in phospholipid remodeling and cholesterol transport. Functional annotations localize the SERAC1 protein to the endoplasmic reticulum and the mitochondria-associated endoplasmic reticulum membrane (MAM), a critical site for lipid exchange. **Overall**, its expression is most significant in metabolically active cells, particularly various neuronal subtypes such as [interneurons](/details-cell/CL0000099) and specialized endocrine cells like [pancreatic A cells](/details-cell/CL0000171). Mutations in [SERAC1](/details-gene/84947) are associated with a severe neurological disorder characterized by dystonia, deafness, and mitochondrial dysfunction, underscoring its essential role in maintaining cellular lipid homeostasis, particularly within the central nervous system ([Link](https://doi.org/10.1038/ng.2325)). ## Cellular Roles and Expression Landscape The expression profile of [SERAC1](/details-gene/84947) highlights its importance in the central nervous system and in endocrine tissues that require high metabolic and secretory activity. **Overall**, the gene shows the highest significance in various neuronal populations. It is a top marker for multiple GABAergic cortical interneuron subtypes, including [lamp5](/details-cell/CL4023011), [VIP](/details-cell/CL4023016), [pvalb](/details-cell/CL4023018), and [sst](/details-cell/CL4023017), as well as [glutamatergic neurons](/details-cell/CL0000679). Its high CSI score in general [interneurons](/details-cell/CL0000099) (CSI: 3.42), [retinal bipolar neurons](/details-cell/CL0000748) (CSI: 2.42), and [medium spiny neurons](/details-cell/CL1001474) (CSI: 1.65) suggests a fundamental role in maintaining neuronal function across diverse brain regions. The gene is also highly significant in supporting cells of the CNS, including [cerebral cortex endothelial cells](/details-cell/CL1001602) (CSI: 2.60) and [astrocytes of the cerebral cortex](/details-cell/CL0002605) (CSI: 2.60), indicating its broad importance for the neurovascular unit and glial cell function. Beyond the nervous system, [SERAC1](/details-gene/84947) is prominently expressed in pancreatic endocrine cells, with high significance in both [pancreatic A cells](/details-cell/CL0000171) (CSI: 3.28) and [pancreatic D cells](/details-cell/CL0000173) (CSI: 3.27). This pattern is consistent with its role in lipid metabolism, which is essential for the synthesis, packaging, and secretion of hormones. ## Pathways and Molecular Function The function of [SERAC1](/details-gene/84947) is intrinsically linked to lipid biosynthesis and transport. Gene Ontology annotations indicate its involvement in [phosphatidylglycerol acyl-chain remodeling](/details-ontology/GO:0036148), the broader [phospholipid biosynthetic process](/details-ontology/GO:0008654), and [intracellular cholesterol transport](/details-ontology/GO:0032367). Its cellular localization is critical to these functions. The SERAC1 protein is found in the [endoplasmic reticulum](/details-ontology/GO:0005783), the [mitochondrion](/details-ontology/GO:0005739), and notably at the [mitochondria-associated endoplasmic reticulum membrane contact site](/details-ontology/GO:0044233). This interface is a key hub for lipid exchange between the two organelles, which is essential for mitochondrial function and cellular energy homeostasis. The clinical observation that [SERAC1](/details-gene/84947) mutations impair mitochondrial function and cholesterol trafficking directly supports this molecular role ([Link](https://doi.org/10.1038/ng.2325)). Its additional annotation to the [extracellular matrix](/details-ontology/GO:0031012) may suggest a less characterized role in modulating the cellular microenvironment. ## Research Directions The well-defined role of [SERAC1](/details-gene/84947) in lipid metabolism, combined with its specific expression pattern, provides a strong basis for further investigation into its cell-type-specific functions and its potential as a therapeutic target. **Proposed Hypotheses:** 1. Given its high expression across multiple neuronal subtypes and its function in phospholipid remodeling, [SERAC1](/details-gene/84947) may be essential for maintaining the unique lipid composition of synaptic membranes and vesicles, thereby regulating synaptic transmission fidelity and plasticity. 2. The high significance of [SERAC1](/details-gene/84947) in [pancreatic A cells](/details-cell/CL0000171) and [D cells](/details-cell/CL0000173) suggests its lipid-modifying activity is critical for the biogenesis and exocytosis of hormone-containing granules (e.g., glucagon and somatostatin). Disruption of [SERAC1](/details-gene/84947) in these cells could lead to impaired glucose homeostasis. **Experimental Approach:** To test the first hypothesis regarding the role of [SERAC1](/details-gene/84947) in synaptic function, a cell-type-specific conditional knockout mouse model could be generated (e.g., using a Vgat-Cre driver to target GABAergic interneurons). Primary neuronal cultures or acute brain slices from these mice could be analyzed. Electrophysiological recordings (patch-clamp) would be used to measure key parameters of synaptic transmission, such as vesicle release probability and postsynaptic current kinetics. In parallel, lipidomics analysis of isolated synaptosomes from the targeted brain region would identify specific changes in the synaptic membrane and vesicle lipidome resulting from [SERAC1](/details-gene/84947) ablation. **Therapeutic Potential:** As [SERAC1](/details-gene/84947) mutations cause a loss-of-function recessive disorder, therapeutic strategies would focus on restoration rather than inhibition. The gene's critical role in fundamental cellular processes within essential cell types like neurons makes it an unsuitable target for inhibitors. Instead, [SERAC1](/details-gene/84947) represents a candidate for gene replacement therapy. AAV-based vectors capable of crossing the blood-brain barrier could be engineered to deliver a functional copy of the [SERAC1](/details-gene/84947) cDNA to affected neuronal populations. This approach could potentially correct the underlying metabolic defects and alleviate the severe neurological symptoms associated with SERAC1-related disease.

Genular Protein ID: 514593898

Symbol: SRAC1_HUMAN

Name: Protein SERAC1

UniProtKB Accession Codes:

Q96JX3 Q49AT1 Q5VTX3 Q6PKF3

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 5 ESTHER 1 Ensembl 2 ExpressionAtlas 1 GO 9 Gene3D 2 GeneCards 1 GeneReviews 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 4 KEGG 1 MANE-Select 1 MIM 3 MINT 1 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 1 OrthoDB 1 PANTHER 2 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 3 Pumba 1 RNAct 1 RefSeq 1 STRING 1 SUPFAM 2 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 14574404

Title: The DNA sequence and analysis of human chromosome 6.

PubMed ID: 14574404

DOI: 10.1038/nature02055

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 23707711

Title: Exome sequencing identifies a new mutation in SERAC1 in a patient with 3-methylglutaconic aciduria.

PubMed ID: 23707711

DOI: 10.1016/j.ymgme.2013.04.021

PubMed ID: 22683713

Title: Mutations in the phospholipid remodeling gene SERAC1 impair mitochondrial function and intracellular cholesterol trafficking and cause dystonia and deafness.

PubMed ID: 22683713

DOI: 10.1038/ng.2325

PubMed ID: 28778788

Title: Novel mutations in SERAC1 gene in two Indian patients presenting with dystonia and intellectual disability.

PubMed ID: 28778788

DOI: 10.1016/j.ejmg.2017.07.013

Sequence Information:

  • Length: 654
  • Mass: 74147
  • Checksum: B40F3B41C0FBEDDE
  • Sequence:
    • MSLAAYCVIC CRRIGTSTSP PKSGTHWRDI RNIIKFTGSL ILGGSLFLTY EVLALKKAVT 
LDTQVVEREK MKSYIYVHTV SLDKGENHGI AWQARKELHK AVRKVLATSA KILRNPFADP 
FSTVDIEDHE CAVWLLLRKS KSDDKTTRLE AVREMSETHH WHDYQYRIIA QACDPKTLIG 
LARSEESDLR FFLLPPPLPS LKEDSSTEEE LRQLLASLPQ TELDECIQYF TSLALSESSQ 
SLAAQKGGLW CFGGNGLPYA ESFGEVPSAT VEMFCLEAIV KHSEISTHCD KIEANGGLQL 
LQRLYRLHKD CPKVQRNIMR VIGNMALNEH LHSSIVRSGW VSIMAEAMKS PHIMESSHAA 
RILANLDRET VQEKYQDGVY VLHPQYRTSQ PIKADVLFIH GLMGAAFKTW RQQDSEQAVI 
EKPMEDEDRY TTCWPKTWLA KDCPALRIIS VEYDTSLSDW RARCPMERKS IAFRSNELLR 
KLRAAGVGDR PVVWISHSMG GLLVKKMLLE ASTKPEMSTV INNTRGIIFY SVPHHGSRLA 
EYSVNIRYLL FPSLEVKELS KDSPALKTLQ DDFLEFAKDK NFQVLNFVET LPTYIGSMIK 
LHVVPVESAD LGIGDLIPVD VNHLNICKPK KKDAFLYQRT LQFIREALAK DLEN