PRODH

proline dehydrogenase 1

Basic information

Region (hg38): 22:18912777-18936553

Links

ENSG00000100033 ∙ NCBI:5625 ∙ OMIM:606810 ∙ HGNC:9453 ∙ Uniprot:O43272 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hyperprolinemia type 1 (Strong), mode of inheritance: AR
• hyperprolinemia type 1 (Definitive), mode of inheritance: AR
• hyperprolinemia type 1 (Supportive), mode of inheritance: AR
• hyperprolinemia type 1 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hyperprolinemia, type I	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; Neurologic	13910064; 14497974; 4299764; 11510941; 12217952; 12525555; 17412540; 18197084; 18806117; 20524212; 23462603

ClinVar

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

• Proline_dehydrogenase_deficiency (352 variants)
• Schizophrenia_4 (142 variants)
• not_provided (87 variants)
• Inborn_genetic_diseases (20 variants)
• not_specified (10 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PRODH gene is commonly pathogenic or not. These statistics are base on transcript: NM_000016335.6. 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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			4	81	8	93
missense	1	2	156	11	9	179
nonsense	4	2	2		1	9
start loss		2	1			3
frameshift	6	3	1			10
splice donor/acceptor (+/-2bp)		4	2			6
Total	11	13	166	92	18

Highest pathogenic variant AF is 0.00384334

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PRODH	protein_coding	protein_coding	ENST00000357068	14	23773

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
5.36e-12	0.359	116132	272	9341	125745	0.0390

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0649	307	310	0.990	0.0000202	3790
Missense in Polyphen		91	102.27	0.8898		1190
Synonymous	-0.792	138	127	1.09	0.00000868	1161
Loss of Function	1.15	21	27.5	0.764	0.00000130	333

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.139	0.139
Ashkenazi Jewish	0.0470	0.0469
East Asian	0.0304	0.0304
Finnish	0.0275	0.0274
European (Non-Finnish)	0.0378	0.0376
Middle Eastern	0.0304	0.0304
South Asian	0.0244	0.0243
Other	0.0533	0.0523

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Converts proline to delta-1-pyrroline-5-carboxylate.
• Disease: DISEASE: Hyperprolinemia 1 (HYRPRO1) [MIM:239500]: An inborn error of proline metabolism resulting in elevated levels of proline in the plasma and urine. The disorder is generally benign and most affected individuals are clinically asymptomatic. Some patients, however, have neurologic manifestations, including epilepsy and mental retardation. Association with certain forms of schizophrenia have been reported. {ECO:0000269|PubMed:12217952, ECO:0000269|PubMed:15662599, ECO:0000269|PubMed:17135275}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Schizophrenia 4 (SCZD4) [MIM:600850]: A complex, multifactorial psychotic disorder or group of disorders characterized by disturbances in the form and content of thought (e.g. delusions, hallucinations), in mood (e.g. inappropriate affect), in sense of self and relationship to the external world (e.g. loss of ego boundaries, withdrawal), and in behavior (e.g bizarre or apparently purposeless behavior). Although it affects emotions, it is distinguished from mood disorders in which such disturbances are primary. Similarly, there may be mild impairment of cognitive function, and it is distinguished from the dementias in which disturbed cognitive function is considered primary. Some patients manifest schizophrenic as well as bipolar disorder symptoms and are often given the diagnosis of schizoaffective disorder. {ECO:0000269|PubMed:11891283, ECO:0000269|PubMed:15662599}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.
• Pathway: Arginine and proline metabolism - Homo sapiens (human);Hyperornithinemia with gyrate atrophy (HOGA);Creatine deficiency, guanidinoacetate methyltransferase deficiency;L-arginine:glycine amidinotransferase deficiency;Hyperornithinemia-hyperammonemia-homocitrullinuria [HHH-syndrome];Guanidinoacetate Methyltransferase Deficiency (GAMT Deficiency);Prolinemia Type II;Prolidase Deficiency (PD);Arginine and Proline Metabolism;Hyperprolinemia Type I;Hyperprolinemia Type II;Ornithine Aminotransferase Deficiency (OAT Deficiency);Arginine: Glycine Amidinotransferase Deficiency (AGAT Deficiency);Proline catabolism;Histidine, lysine, phenylalanine, tyrosine, proline and tryptophan catabolism;Metabolism of amino acids and derivatives;Metabolism;proline degradation;Urea cycle and metabolism of arginine, proline, glutamate, aspartate and asparagine (Consensus)

Intolerance Scores

• loftool: 0.707
• rvis_EVS: 1.74
• rvis_percentile_EVS: 96.63

Haploinsufficiency Scores

• pHI: 0.661
• hipred: N
• hipred_score: 0.239
• ghis: 0.403

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.832

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Prodh
• Phenotype: pigmentation phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); skeleton phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); limbs/digits/tail phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: proline metabolic process;proline catabolic process;intrinsic apoptotic signaling pathway in response to oxidative stress;proline catabolic process to glutamate;positive regulation of cell death;4-hydroxyproline catabolic process;oxidation-reduction process
• Cellular component: mitochondrion;mitochondrial inner membrane;mitochondrial matrix
• Molecular function: proline dehydrogenase activity;FAD binding