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 (378 variants)
not_specified (203 variants)
not_provided (37 variants)
OPLAH-related_disorder (26 variants)
EBV-positive_nodal_T-_and_NK-cell_lymphoma (1 variants)
See_cases (1 variants)
Familial_sleep-related_hypermotor_epilepsy (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. These statistics are base on transcript: NM_000017570.5. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			5 clinvar	93 clinvar	11 clinvar	109
missense	1 clinvar	3 clinvar	287 clinvar	26 clinvar	13 clinvar	330
nonsense	8 clinvar	7 clinvar				15
start loss						0
frameshift	9 clinvar	8 clinvar	1 clinvar			18
splice donor/acceptor (+/-2bp)	1 clinvar	5 clinvar				6
Total	19	23	293	119	24

Highest pathogenic variant AF is 0.000039694452

Loading clinvar variants...

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
ghis

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