PRODH2

proline dehydrogenase 2

Basic information

Region (hg38): 19:35799988-35813299

Links

ENSG00000250799 ∙ NCBI:58510 ∙ OMIM:616377 ∙ HGNC:17325 ∙ Uniprot:Q9UF12 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hydroxyprolinemia (Limited), mode of inheritance: AR

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PRODH2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PRODH2 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					2	2
missense			53	3		56
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			1	2		3
Total	0	0	54	5	2

Variants in PRODH2

This is a list of pathogenic ClinVar variants found in the PRODH2 region.

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

Position	Type	Phenotype	Significance	ClinVar
19-35800060-C-T			Uncertain significance (Oct 01, 2022)
19-35800073-G-A		not specified	Uncertain significance (Jun 29, 2023)
19-35800112-G-A		not specified	Uncertain significance (Sep 22, 2021)
19-35800120-T-A		not specified	Uncertain significance (Jan 03, 2024)
19-35800132-C-A		not specified	Uncertain significance (Sep 11, 2024)
19-35800132-C-T		not specified	Uncertain significance (Aug 16, 2022)
19-35800141-T-C		not specified	Uncertain significance (Apr 13, 2023)
19-35800145-C-A		not specified	Uncertain significance (May 11, 2022)
19-35800146-C-G		not specified	Uncertain significance (Nov 01, 2022)
19-35800150-C-T		not specified	Uncertain significance (Dec 19, 2023)
19-35800172-C-T		not specified	Uncertain significance (Oct 09, 2024)
19-35800187-A-T		not specified	Uncertain significance (Jul 26, 2024)
19-35800214-C-T		not specified	Uncertain significance (May 22, 2024)
19-35802258-A-C		not specified	Uncertain significance (Jan 21, 2025)
19-35802273-C-T		not specified	Uncertain significance (May 15, 2023)
19-35802983-C-A		not specified	Uncertain significance (Jun 10, 2024)
19-35803025-A-G		not specified	Uncertain significance (Aug 19, 2024)
19-35803034-T-C		not specified	Likely benign (Aug 11, 2022)
19-35803037-C-T		not specified	Likely benign (Dec 03, 2024)
19-35803049-G-A		not specified	Uncertain significance (Jun 16, 2023)
19-35803070-C-T		not specified	Uncertain significance (Jul 06, 2021)
19-35803071-G-A		not specified	Uncertain significance (Feb 27, 2023)
19-35803071-G-C		not specified	Uncertain significance (May 13, 2024)
19-35806422-G-A		PRODH2-related disorder	Likely benign (Aug 22, 2019)
19-35806461-T-C		not specified	Uncertain significance (Aug 20, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PRODH2	protein_coding	protein_coding	ENST00000301175	11	13312

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.45e-13	0.127	125441	1	305	125747	0.00122

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.118	314	320	0.981	0.0000204	3348
Missense in Polyphen		85	101.71	0.83573		1064
Synonymous	0.205	136	139	0.978	0.00000862	1178
Loss of Function	0.798	22	26.4	0.832	0.00000148	269

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000689	0.000678
Ashkenazi Jewish	0.000299	0.000298
East Asian	0.00191	0.00190
Finnish	0.00620	0.00616
European (Non-Finnish)	0.000882	0.000871
Middle Eastern	0.00191	0.00190
South Asian	0.000269	0.000261
Other	0.00114	0.00114

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Dehydrogenase that converts trans-4-L-hydroxyproline to delta-1-pyrroline-3-hydroxy-5-carboxylate (Hyp) using ubiquinone- 10 as the terminal electron acceptor. Can also use proline as a substrate but with a very much lower efficiency. Does not react with other diastereomers of Hyp: trans-4-D-hydroxyproline and cis- 4-L-hydroxyproline. Ubiquininone analogs such as menadione, duroquinone and ubiquinone-1 react more efficiently than oxygen as the terminal electron acceptor during catalysis. {ECO:0000269|PubMed:25697095}.
• Pathway: Arginine and proline metabolism - Homo sapiens (human);Proline catabolism;Histidine, lysine, phenylalanine, tyrosine, proline and tryptophan catabolism;Metabolism of amino acids and derivatives;Metabolism;4-hydroxyproline degradation;Glyoxylate metabolism and glycine degradation (Consensus)

Intolerance Scores

• loftool: 0.930
• rvis_EVS: 0.27
• rvis_percentile_EVS: 70.73

Haploinsufficiency Scores

• hipred: N
• hipred_score: 0.146
• ghis: 0.427

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.219

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Prodh2

Gene ontology

• Biological process: proline catabolic process;proline catabolic process to glutamate;glyoxylate metabolic process;oxidation-reduction process
• Cellular component: mitochondrion;mitochondrial inner membrane
• Molecular function: proline dehydrogenase activity;oxidoreductase activity, acting on the CH-NH group of donors;FAD binding