OPLAH

protein-coding

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

Gene summary

The protein encoded by this gene acts as a homodimer, using ATP hydrolysis to catalyze the conversion of 5-oxo-L-proline to L-glutamate. Defects in this gene are a cause of 5-oxoprolinase deficiency (OPLAHD). [provided by RefSeq, Jun 2012]

MANE transcript

NM_017570.5

Inheritance

ClinVar variants

P:48U:330B:159

Top phenotype

5-oxoprolinase deficiency

gnomAD constraint

pLI —, LoF o/e 0.65

Max pathogenic AF

—

Genomic locus

chr8:144,051,266-144,063,965

External References & Databases

Ensembl (ENSG00000178814)

Transcript & Mutation Effects

hg38 • Region Span ~12.7 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

5-oxoprolinase deficiencySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009825

Submitter: Labcorp Genetics (formerly Invitae)

5-oxoprolinase deficiencyMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0009825

Submitter: PanelApp Australia

5-oxoprolinase deficiencySUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009825

Submitter: Orphanet

Clinical Genomic Database (CGD)

5-oxoprolinase deficiencyAR

Manifestation: Biochemical; Gastrointestinal; Renal

Intervention: General

Rationale: 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

Comments: Transient neonatal hypoglycemia has been reported

Refs: 6113726; 6790862; 8127060; 21651516

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to OPLAH variants in ClinVar

7 Conditions Cataloged

5-Oxoprolinase deficiencyTotal: 417

not specifiedTotal: 223

not providedTotal: 43

OPLAH-related disorderTotal: 26

EBV-positive nodal T- and NK-cell lymphomaTotal: 1

Familial sleep-related hypermotor epilepsyTotal: 1

See casesTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_017570.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			7 clinvar	109 clinvar	11 clinvar	127
missense	1 clinvar	4 clinvar	311 clinvar	26 clinvar	13 clinvar	355
nonsense	8 clinvar	8 clinvar	2 clinvar			18
start loss						0
frameshift	11 clinvar	9 clinvar	3 clinvar			23
splice donor/acceptor (+/-2bp)	1 clinvar	6 clinvar	7 clinvar			14
Total	21	27	330	135	24	537

Highest pathogenic variant AF is 0.00006299282

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 80 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_017570.5	RefSeq	NP_060040.1	26	MANE Select
ENST00000618853.5	Ensembl	ENSP00000480476.1	26	MANE Select
ENST00000567871.2	Ensembl	ENSP00000481640.2	5	Standard
ENST00000894953.1	Ensembl	ENSP00000565012.1	26	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Glutathione metabolism - Homo sapiens (human)
Gamma-glutamyl-transpeptidase deficiency
5-oxoprolinase deficiency
Gamma-Glutamyltransferase Deficiency
Glutathione Metabolism

Biological Process

glutathione metabolic process
glutathione biosynthetic process

Molecular Function

ATP binding
5-oxoprolinase (ATP-hydrolyzing) activity

Cellular Component

cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000426825
Coding exons: 27
Length: 12569
Individuals with no LoFs: 19252
Homozygous LoFs: 105234
Heterozygous LoFs: 34
Defined: 124520
p: 0.607

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.265	816	838	0.974	0.0000570	8098
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	1.0	0.49	notable
Latino/Admixed American	1.0	0.80	notable
Ashkenazi Jewish	1.0	0.69	notable
East Asian	1.0	0.69	notable
Finnish	1.0	0.30	notable
European (Non-Finnish)	1.0	0.60	notable
South Asian	1.0	0.79	notable
Other	1.0	0.65	notable

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec: 0.186

Gene Damage Prediction

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