Details for: HIGD1B

Gene ID: 51751

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: HIGD1B

Ensembl ID: ENSG00000131097

Description: HIG1 hypoxia inducible domain family member 1B

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • retinal blood vessel endothelial cell CL0002585
    CSI 20.76
    rCSI 33.15%
    PRS 97.39
  • lung pericyte CL0009089
    CSI 18.01
    rCSI 47.53%
    PRS 98.01
  • perivascular cell CL4033054
    CSI 16.46
    rCSI 22.49%
    PRS 97.99
  • tracheobronchial smooth muscle cell CL0019019
    CSI 13.16
    rCSI 23.21%
    PRS 97.68
  • vascular leptomeningeal cell CL4023051
    CSI 11.38
    rCSI 19.96%
    PRS 94.61
  • microcirculation associated smooth muscle cell CL0008035
    CSI 9.13
    rCSI 26.44%
    PRS 95.95
  • cerebral cortex endothelial cell CL1001602
    CSI 7.23
    rCSI 12.5%
    PRS 93.75
  • myofibroblast cell CL0000186
    CSI 5.79
    rCSI 8.02%
    PRS 94.6
  • vascular associated smooth muscle cell CL0000359
    CSI 5.49
    rCSI 17.81%
    PRS 95.84
  • ependymal cell CL0000065
    CSI 5.14
    rCSI 10.43%
    PRS 84.57
  • contractile cell CL0000183
    CSI 3.89
    rCSI 11.48%
    PRS 96.52
  • melanocyte of skin CL1000458
    CSI 2.48
    rCSI 3.38%
    PRS 74.73
  • basal cell of epidermis CL0002187
    CSI 2.34
    rCSI 4.15%
    PRS 74.23
  • renal interstitial pericyte CL1001318
    CSI 1.6
    rCSI 4.41%
    PRS 95.5
  • blood vessel smooth muscle cell CL0019018
    CSI 0.58
    rCSI 4.68%
    PRS 95.74

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.

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  • 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 [HIGD1B](/details-gene/51751), or HIG1 Hypoxia Inducible Domain Family Member 1B, is a protein-coding gene located on chromosome 17q21.31. Functionally, it is annotated as a mitochondrial membrane protein involved in the assembly of the mitochondrial respirasome ([GO:0097250](https://www.ebi.ac.uk/QuickGO/term/GO:0097250)). Expression data indicates a highly specialized role for [HIGD1B](/details-gene/51751), with significant expression concentrated in cells associated with the vasculature and perivascular tissues. Its prominent role in cell types such as [retinal blood vessel endothelial cells](/details-cell/CL0002585) and [lung pericytes](/details-cell/CL0009089) suggests that it is a key component in maintaining the metabolic integrity and function of blood vessel walls. ## Cellular Roles and Expression Landscape The expression profile of [HIGD1B](/details-gene/51751) points to a crucial function within the circulatory system's cellular architecture. **Overall**, the gene shows the highest significance in cells that form or support blood vessels. The top-ranked cell type is the [retinal blood vessel endothelial cell](/details-cell/CL0002585) (CSI: 20.76), followed closely by various types of perivascular and smooth muscle cells, including [lung pericyte](/details-cell/CL0009089) (CSI: 18.01), [perivascular cell](/details-cell/CL4033054) (CSI: 16.46), and [tracheobronchial smooth muscle cell](/details-cell/CL0019019) (CSI: 13.16). This consistent high expression across different vascular beds, including those in the retina, lung, and brain ([cerebral cortex endothelial cell](/details-cell/CL1001602)), suggests a fundamental role in vascular biology rather than a tissue-specific one. Its strong presence in contractile cells such as [vascular associated smooth muscle cells](/details-cell/CL0000359) and [myofibroblast cells](/details-cell/CL0000186) further supports its involvement in processes requiring high metabolic output, such as vasoconstriction and tissue remodeling. The data collectively positions [HIGD1B](/details-gene/51751) as a key metabolic regulator in the endothelial and mural cells that constitute the vascular wall. ## Pathways and Molecular Function The known molecular functions of [HIGD1B](/details-gene/51751) are directly related to mitochondrial bioenergetics. Gene Ontology annotations place it within the [mitochondrion](/details-cell/GO:0005739) as an integral [membrane](/details-cell/GO:0016020) protein. Its primary annotated biological process is [mitochondrial respirasome assembly](/details-cell/GO:0097250). The respirasome is a supercomplex of electron transport chain components that optimizes cellular respiration and ATP production. This function aligns perfectly with the gene's cellular expression pattern. Endothelial cells, pericytes, and smooth muscle cells have high energy demands to maintain vascular barrier integrity, regulate blood flow, and respond to physiological stimuli. The involvement of [HIGD1B](/details-gene/51751) in the efficient assembly of the respiratory chain suggests it is essential for meeting these energetic requirements, particularly under conditions of fluctuating oxygen levels, which are common in the vascular microenvironment. ## Research Directions The specific expression of [HIGD1B](/details-gene/51751) in vascular cells, coupled with its role in mitochondrial respiration, provides a strong basis for further investigation into its role in both vascular health and disease. **Proposed Testable Hypotheses:** 1. [HIGD1B](/details-gene/51751) is essential for maintaining endothelial barrier function and metabolic homeostasis, and its downregulation under pathological conditions (e.g., chronic hypoxia or inflammation) contributes to endothelial dysfunction and vascular leakage. 2. In pericytes and vascular smooth muscle cells, [HIGD1B](/details-gene/51751) regulates cellular contractility and proliferation by ensuring adequate ATP supply, and its deficiency may contribute to vascular remodeling seen in diseases like hypertension or atherosclerosis. **Suggested Experimental Approach:** To test the first hypothesis regarding the role of [HIGD1B](/details-gene/51751) in endothelial function, a CRISPR-Cas9-mediated knockout could be generated in a human endothelial cell line, such as HUVECs. The metabolic profile of these knockout cells versus wild-type controls could be quantified using a Seahorse XF Analyzer to measure the oxygen consumption rate (OCR). To assess barrier integrity, cells could be grown on Transwell inserts, and transendothelial electrical resistance (TEER) could be measured following exposure to inflammatory stimuli like TNF-alpha or hypoxic conditions. A significant drop in OCR and TEER in knockout cells would support the hypothesis. **Therapeutic Potential:** Given that endothelial metabolic dysfunction is a hallmark of numerous cardiovascular diseases, [HIGD1B](/details-gene/51751) presents a potential therapeutic target. Because its function is to support mitochondrial efficiency, **activation** or enhancement of HIGD1B activity, rather than inhibition, would likely be the desired therapeutic strategy. A small molecule capable of stabilizing the HIGD1B protein or promoting its integration into respirasomes could potentially restore metabolic function in compromised endothelial cells, offering a novel approach for treating conditions like atherosclerosis, diabetic vasculopathy, or pulmonary arterial hypertension.

Genular Protein ID: 3886961190

Symbol: HIG1B_HUMAN

Name: HIG1 domain family member 1B

UniProtKB Accession Codes:

Q9P298 D3DX57 Q9P297

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 BMRB 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 5 Ensembl 2 EvolutionaryTrace 1 ExpressionAtlas 1 GO 3 Gene3D 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 2 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 1 PDBsum 1 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 RefSeq 8 SMR 1 STRING 1 SignaLink 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

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: 22609626

Title: Facile backbone structure determination of human membrane proteins by NMR spectroscopy.

PubMed ID: 22609626

DOI: 10.1038/nmeth.2033

Sequence Information:

  • Length: 99
  • Mass: 11058
  • Checksum: 2B5AF9EE5F27FB05
  • Sequence:
    • MSANRRWWVP PDDEDCVSEK LLRKTRESPL VPIGLGGCLV VAAYRIYRLR SRGSTKMSIH 
LIHTRVAAQA CAVGAIMLGA VYTMYSDYVK RMAQDAGEK