OPLAH

5-oxoprolinase, ATP-hydrolysing, the group of MicroRNA protein coding host genes

Basic information

Region (hg38): 8:144051266-144063965

Links

ENSG00000178814 ∙ NCBI:26873 ∙ OMIM:614243 ∙ HGNC:8149 ∙ Uniprot:O14841 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• 5-oxoprolinase deficiency (Strong), mode of inheritance: AR
• 5-oxoprolinase deficiency (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
5-oxoprolinase deficiency	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Biochemical; Gastrointestinal; Renal	6113726; 6790862; 8127060; 21651516
Transient neonatal hypoglycemia has been reported

ClinVar

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

• 5-Oxoprolinase deficiency (12 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the OPLAH 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			7	72	17	96
missense		1	185	23	14	223
nonsense	6	4				10
start loss						0
frameshift	6	1				7
inframe indel						0
splice donor/acceptor (+/-2bp)	1	3				4
splice region			5	13	2	20
non coding			7	31	7	45
Total	13	9	199	126	38

Highest pathogenic variant AF is 0.0000591

Variants in OPLAH

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

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

Position	Type	Phenotype	Significance	ClinVar
8-144051332-G-T			Likely benign (Dec 01, 2022)
8-144051350-A-G		5-Oxoprolinase deficiency	Likely benign (Aug 09, 2022)
8-144051362-G-A		5-Oxoprolinase deficiency	Likely benign (Jan 22, 2024)
8-144051370-G-A		5-Oxoprolinase deficiency	Uncertain significance (Nov 22, 2022)
8-144051371-C-T		5-Oxoprolinase deficiency	Likely benign (Feb 03, 2023)
8-144051372-T-A		5-Oxoprolinase deficiency	Benign/Likely benign (Sep 30, 2023)
8-144051373-C-T		5-Oxoprolinase deficiency	Likely benign (Dec 12, 2023)
8-144051385-G-A		5-Oxoprolinase deficiency	Likely benign (Feb 02, 2023)
8-144051397-G-GCGACACCGGCGGTGGGGCGGGGT		OPLAH-related disorder	Likely pathogenic (Sep 27, 2024)
8-144051406-G-A		not specified	Uncertain significance (Jan 05, 2022)
8-144051440-A-G		5-Oxoprolinase deficiency	Likely benign (Aug 09, 2022)
8-144051448-C-G		5-Oxoprolinase deficiency	Uncertain significance (Mar 27, 2022)
8-144051480-C-G			Likely benign (Sep 01, 2023)
8-144051482-CG-C		5-Oxoprolinase deficiency	Benign (Dec 29, 2023)
8-144051482-C-CG		5-Oxoprolinase deficiency	Benign (Jan 29, 2024)
8-144051484-G-C		5-Oxoprolinase deficiency	Uncertain significance (Jun 15, 2022)
8-144051485-G-A		5-Oxoprolinase deficiency	Likely benign (Jun 05, 2022)
8-144051487-G-T		5-Oxoprolinase deficiency	Likely benign (Nov 29, 2022)
8-144051488-G-C		5-Oxoprolinase deficiency	Benign/Likely benign (Jan 17, 2024)
8-144051489-GGGC-G		5-Oxoprolinase deficiency	Likely benign (Dec 30, 2023)
8-144051490-GGC-G		5-Oxoprolinase deficiency	Likely benign (Jan 25, 2024)
8-144051491-GC-G		5-Oxoprolinase deficiency	Benign (Jan 25, 2024)
8-144051492-C-G		5-Oxoprolinase deficiency	Benign (Jan 31, 2024)
8-144051721-G-A		5-Oxoprolinase deficiency	Benign/Likely benign (Jul 30, 2021)
8-144051732-G-A		5-Oxoprolinase deficiency	Likely benign (Sep 21, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
OPLAH	protein_coding	protein_coding	ENST00000426825	27	12569

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
6.97e-17	0.935	19252	105234	34	124520	0.607

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.265	816	838	0.974	0.0000570	8098
Missense in Polyphen		328	369.13	0.88857		3532
Synonymous	-0.0242	368	367	1.00	0.0000260	2807
Loss of Function	2.33	34	52.2	0.652	0.00000272	559

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	2.00	1.49
Ashkenazi Jewish	1.00	0.686
East Asian	1.00	0.695
Finnish	1.00	0.305
European (Non-Finnish)	1.00	0.602
Middle Eastern	1.00	0.695
South Asian	1.00	0.789
Other	1.00	0.649

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the cleavage of 5-oxo-L-proline to form L- glutamate coupled to the hydrolysis of ATP to ADP and inorganic phosphate.
• Disease: DISEASE: 5-oxoprolinase deficiency (OPLAHD) [MIM:260005]: A disorder characterized by calcium oxalate/carbonate urolithiasis, and excessive urinary 5-oxo-L-proline. Affected individuals have recurrent episodes of vomiting, diarrhea, and abdominal pain. {ECO:0000269|PubMed:21651516}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Glutathione metabolism - Homo sapiens (human);Gamma-glutamyl-transpeptidase deficiency;5-oxoprolinase deficiency;Gamma-Glutamyltransferase Deficiency;Glutathione Metabolism;Glutathione Synthetase Deficiency;5-Oxoprolinuria;Glutathione metabolism;Glutathione conjugation;Phase II - Conjugation of compounds;Biological oxidations;Metabolism;γ-glutamyl cycle;Glutathione synthesis and recycling (Consensus)

Recessive Scores

• pRec: 0.186

Haploinsufficiency Scores

• pHI: 0.118
• hipred: N
• hipred_score: 0.315

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Oplah
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); limbs/digits/tail phenotype

Gene ontology

• Biological process: glutathione metabolic process;glutathione biosynthetic process
• Cellular component: cytosol
• Molecular function: ATP binding;5-oxoprolinase (ATP-hydrolyzing) activity