HOGA1

4-hydroxy-2-oxoglutarate aldolase 1

Basic information

Region (hg38): 10:97584322-97612802

Previous symbols: [ "C10orf65", "DHDPSL" ]

Links

ENSG00000241935 ∙ NCBI:112817 ∙ OMIM:613597 ∙ HGNC:25155 ∙ Uniprot:Q86XE5 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• primary hyperoxaluria type 3 (Definitive), mode of inheritance: AR
• primary hyperoxaluria type 3 (Supportive), mode of inheritance: AR
• primary hyperoxaluria type 3 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hyperoxaluria, primary, type III	AD/AR	Renal	Increased fluid intake in order to promote hydration as well as medical therapy (eg, neutral phosphate therapy, citrate medications, thiazides) may be beneficial	Biochemical; Renal	20797690; 21896830; 22781098; 22688746; 22391140

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the HOGA1 gene.

• not provided (277 variants)
• Primary hyperoxaluria type 3 (214 variants)
• Inborn genetic diseases (19 variants)
• Primary hyperoxaluria (7 variants)
• not specified (5 variants)
• HOGA1-related condition (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HOGA1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				104	3	107
missense	4	34	60	6		104
nonsense	10	5				15
start loss	3					3
frameshift	13	12				25
inframe indel	1		2			3
splice donor/acceptor (+/-2bp)	1	15				16
splice region	1	1	3	20	1	26
non coding			39	27	16	82
Total	32	66	101	137	19

Highest pathogenic variant AF is 0.00151

Variants in HOGA1

This is a list of pathogenic ClinVar variants found in the HOGA1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
10-97584425-G-A		Primary hyperoxaluria type 3	Benign/Likely benign (Nov 12, 2018)
10-97584480-G-A		Primary hyperoxaluria type 3	Uncertain significance (Jan 12, 2018)
10-97584705-T-G			Pathogenic (Jul 25, 2023)
10-97584706-G-A		Primary hyperoxaluria type 3	Pathogenic (Oct 27, 2023)
10-97584706-G-T			Pathogenic (Jul 22, 2021)
10-97584709-G-GGGTCT		Primary hyperoxaluria type 3	Pathogenic/Likely pathogenic (Feb 24, 2023)
10-97584712-T-C			Likely benign (Dec 03, 2021)
10-97584721-C-T		Primary hyperoxaluria type 3	Likely benign (Nov 01, 2023)
10-97584723-G-C		Primary hyperoxaluria type 3	Uncertain significance (Oct 27, 2023)
10-97584724-GTCT-G		Primary hyperoxaluria type 3	Uncertain significance (Dec 19, 2017)
10-97584733-G-A			Likely benign (Sep 25, 2021)
10-97584736-G-A			Likely benign (Dec 03, 2021)
10-97584736-G-T		Primary hyperoxaluria type 3	Uncertain significance (Mar 02, 2022)
10-97584742-G-A		Primary hyperoxaluria type 3	Conflicting classifications of pathogenicity (Jan 04, 2024)
10-97584742-G-T			Likely benign (Mar 12, 2021)
10-97584744-T-A		Primary hyperoxaluria type 3	Uncertain significance (Oct 27, 2023)
10-97584745-A-G			Likely benign (Jul 09, 2023)
10-97584754-C-T			Likely benign (Jan 31, 2024)
10-97584757-G-A			Likely benign (Mar 28, 2023)
10-97584766-T-C			Likely benign (Jul 30, 2023)
10-97584767-G-A		Primary hyperoxaluria type 3	Uncertain significance (Dec 18, 2019)
10-97584768-TG-T			Pathogenic (Feb 17, 2020)
10-97584769-G-A			Likely benign (Jul 20, 2021)
10-97584772-G-A			Likely benign (Aug 16, 2023)
10-97584778-G-A			Pathogenic (Jan 04, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HOGA1	protein_coding	protein_coding	ENST00000370646	7	28480

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.58e-14	0.00373	125677	1	70	125748	0.000282

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.279	217	206	1.05	0.0000128	2115
Missense in Polyphen		81	77.025	1.0516		787
Synonymous	0.710	75	83.2	0.901	0.00000538	686
Loss of Function	-0.874	19	15.3	1.24	8.32e-7	155

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000521	0.000518
Ashkenazi Jewish	0.00	0.00
East Asian	0.000943	0.000925
Finnish	0.00	0.00
European (Non-Finnish)	0.000267	0.000264
Middle Eastern	0.000943	0.000925
South Asian	0.000429	0.000392
Other	0.000326	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the final step in the metabolic pathway of hydroxyproline. {ECO:0000269|PubMed:20797690, ECO:0000269|PubMed:21998747}.
• Disease: DISEASE: Hyperoxaluria primary 3 (HP3) [MIM:613616]: A disorder phenotypically similar to hyperoxaluria type 1 and type 2. It is characterized by increase in urinary oxalate excretion and mild glycolic aciduria. Clinical manifestations include calcium oxalate urolithiasis, hematuria, pain, and/or urinary tract infection. {ECO:0000269|PubMed:20797690}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Arginine and proline metabolism - Homo sapiens (human);Glyoxylate and dicarboxylate metabolism - Homo sapiens (human);Metabolism of amino acids and derivatives;Metabolism;4-hydroxyproline degradation;Glyoxylate metabolism and glycine degradation (Consensus)

Recessive Scores

• pRec: 0.146

Intolerance Scores

• rvis_EVS: -1
• rvis_percentile_EVS: 8.32

Haploinsufficiency Scores

• pHI: 0.0918
• hipred: N
• hipred_score: 0.251
• ghis: 0.516

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.114

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Hoga1
• Phenotype: homeostasis/metabolism phenotype; renal/urinary system phenotype; liver/biliary system phenotype

Gene ontology

• Biological process: glyoxylate catabolic process;4-hydroxyproline catabolic process;oxalate metabolic process;pyruvate biosynthetic process;glyoxylate metabolic process
• Cellular component: mitochondrion;mitochondrial matrix
• Molecular function: protein binding;4-hydroxy-2-oxoglutarate aldolase activity;protein homodimerization activity