HOGA1 4-hydroxy-2-oxoglutarate aldolase 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: HOGA1provided by HGNC
Official Full Name: 4-hydroxy-2-oxoglutarate aldolase 1provided by HGNC
Primary source: HGNC:HGNC:25155
See related: Ensembl:ENSG00000241935 MIM:613597; AllianceGenome:HGNC:25155
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: HP3; NPL2; DHDPS2; DHDPSL; C10orf65
Summary: The authors of PMID:20797690 cloned this gene while searching for genes in a region of chromosome 10 linked to primary hyperoxalurea type III. They noted that even though the encoded protein has been described as a mitochondrial dihydrodipicolinate synthase-like enzyme, it shares little homology with E. coli dihydrodipicolinate synthase (Dhdps), particularly in the putative substrate-binding region. Moreover, neither lysine biosynthesis nor sialic acid metabolism, for which Dhdps is responsible, occurs in vertebrate mitochondria. They propose that this gene encodes mitochondrial 4-hydroxyl-2-oxoglutarate aldolase (EC 4.1.3.16), which catalyzes the final step in the metabolic pathway of hydroxyproline, releasing glyoxylate and pyruvate. This gene is predominantly expressed in the liver and kidney, and mutations in this gene are found in patients with primary hyperoxalurea type III. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Nov 2010]
Expression: Biased expression in kidney (RPKM 27.4), liver (RPKM 9.9) and 5 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 10q24.2

Exon count:: 7

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	10	NC_000010.11 (97584389..97612802)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	10	NC_060934.1 (98464572..98493008)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	10	NC_000010.10 (99344146..99372559)

Chromosome 10 - NC_000010.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

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Expression

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See details

Project title: HPA RNA-seq normal tissues 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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

HOGA1 variants in Chinese patients with primary hyperoxaluria type 3: genetic features and genotype-phenotype relationships.
Title: HOGA1 variants in Chinese patients with primary hyperoxaluria type 3: genetic features and genotype-phenotype relationships.
Kidney cysts in patients with HOGA1 variants.
Title: Kidney cysts in patients with HOGA1 variants.
HOGA1 gene pathogenic variants in primary hyperoxaluria type III: Spectrum of pathogenic sequence variants, and phenotypic association.
Title: HOGA1 gene pathogenic variants in primary hyperoxaluria type III: Spectrum of pathogenic sequence variants, and phenotypic association.
Extended genetic analysis of exome sequencing for primary hyperoxaluria in pediatric urolithiasis patients with hyperoxaluria.
Title: Extended genetic analysis of exome sequencing for primary hyperoxaluria in pediatric urolithiasis patients with hyperoxaluria.
Mutations in HOGA1 do Not Confer a Dominant Phenotype Manifesting as Kidney Stone Disease.
Title: Mutations in HOGA1 do Not Confer a Dominant Phenotype Manifesting as Kidney Stone Disease.
Study found that primary hyperoxaluria type 3 (PH3) was significantly diagnosed in Chinese children with urolithiasis. Nine novel HOGA1 mutations were identified in association with PH3, which provide a first-line investigation in Chinese PH3 patients. The eGFR was normal in all children with PH3. This finding contrasts with the early impairment of renal function in PH1 and PH2.
Title: Nine novel HOGA1 gene mutations identified in primary hyperoxaluria type 3 and distinct clinical and biochemical characteristics in Chinese children.
Biophysical and structural studies showed that pyruvate was a competitive inhibitor of HOGA1 with an inhibition constant in the micromolar range.
Title: Regulation of human 4-hydroxy-2-oxoglutarate aldolase by pyruvate and α-ketoglutarate: implications for primary hyperoxaluria type-3.
Potential mutation hot spot region (c.834_834+1) in the Chinese population and two novel mutations were found.
Title: Mutation Hot Spot Region in the HOGA1 Gene Associated with Primary Hyperoxaluria Type 3 in the Chinese Population.
Results show that HOGA1 harboring mutations found in primary hyperoxaluria is thermally unstable and targeted for proteolytic degradation leading to an absolute loss of function.
Title: Cellular degradation of 4-hydroxy-2-oxoglutarate aldolase leads to absolute deficiency in primary hyperoxaluria type 3.
Among the seven patients identified with HOGA1 mutations the median onset of clinical symptoms was 1.8 years. Five patients initially presented with urolithiasis, and two other patients presented with urinary tract infection.
Title: Renal function can be impaired in children with primary hyperoxaluria type 3.

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

Associated conditions

Description	Tests
Primary hyperoxaluria type 3 MedGen: C3150878 OMIM: 613616 GeneReviews: Primary Hyperoxaluria Type 3	not available

EBI GWAS Catalog

Description
Genome-wide association study identifies multiple loci influencing human serum metabolite levels. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH41894 (e-PCR)
- UniSTS:48901

RH48677 (e-PCR)
- UniSTS:38949

RH140725 (e-PCR)
- UniSTS:222791

SHGC-155735 (e-PCR)
- UniSTS:183921

STS-R89840 (e-PCR)
- UniSTS:52898

RH92617 (e-PCR)
- UniSTS:85750

RH94255 (e-PCR)
- UniSTS:87804

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables (4S)-4-hydroxy-2-oxoglutarate aldolase activity	IEA Inferred from Electronic Annotation more info
enables (R,S)-4-hydroxy-2-oxoglutarate aldolase activity	IBA Inferred from Biological aspect of Ancestor more info
enables (R,S)-4-hydroxy-2-oxoglutarate aldolase activity	IDA Inferred from Direct Assay more info	PubMed
enables (R,S)-4-hydroxy-2-oxoglutarate aldolase activity	ISS Inferred from Sequence or Structural Similarity more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein homodimerization activity	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in 4-hydroxyproline catabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in glyoxylate catabolic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in glyoxylate catabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in glyoxylate metabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in oxalate metabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in pyruvate biosynthetic process	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
located_in mitochondrial matrix	TAS Traceable Author Statement more info
located_in mitochondrion	HTP more info	PubMed
is_active_in mitochondrion	IBA Inferred from Biological aspect of Ancestor more info
located_in mitochondrion	ISS Inferred from Sequence or Structural Similarity more info	PubMed

General protein information

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Preferred Names: 4-hydroxy-2-oxoglutarate aldolase, mitochondrial

Names: DHDPS-like protein; N-acetylneuraminate pyruvate lyase 2 (putative); dihydrodipicolinate synthase-like, mitochondrial; dihydrodipicolinate synthetase homolog 2; probable 2-keto-4-hydroxyglutarate aldolase; probable 4-hydroxy-2-oxoglutarate aldolase, mitochondrial; probable KHG-aldolase; protein 569272

NP_001128142.1

EC 4.1.3.16

NP_612422.2

EC 4.1.3.16

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.

Genomic

NG_027922.1 RefSeqGene

Range

5045..33458

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001134670.2 → NP_001128142.1 4-hydroxy-2-oxoglutarate aldolase, mitochondrial isoform 2

See identical proteins and their annotated locations for NP_001128142.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks multiple consecutive exons in the coding region, compared to variant 1, resulting in a protein (isoform 2) that lacks a large region of the central protein when compared to isoform 1.

Source sequence(s)

BC011916

Consensus CDS

CCDS44469.1

UniProtKB/Swiss-Prot

Q86XE5

Related

ENSP00000359681.4, ENST00000370647.8

Conserved Domains (2) summary

cd00408
Location:70 → 158

DHDPS-like; Dihydrodipicolinate synthase family

cl21457
Location:35 → 61

TIM_phosphate_binding; TIM barrel proteins share a structurally conserved phosphate binding motif and in general share an eight beta/alpha closed barrel structure. Specific for this family is the conserved phosphate binding site at the edges of strands 7 and 8. The phosphate ...
NM_138413.4 → NP_612422.2 4-hydroxy-2-oxoglutarate aldolase, mitochondrial isoform 1

See identical proteins and their annotated locations for NP_612422.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).

Source sequence(s)

BC011916, BC045550

Consensus CDS

CCDS7467.1

UniProtKB/Swiss-Prot

A8K075, Q5T680, Q5T684, Q711P0, Q86XE5, Q8N9F2, Q96EV5

Related

ENSP00000359680.4, ENST00000370646.9

Conserved Domains (1) summary

cd00408
Location:38 → 321

DHDPS-like; Dihydrodipicolinate synthase family