PYCR2

pyrroline-5-carboxylate reductase 2, the group of MicroRNA protein coding host genes

Basic information

Region (hg38): 1:225919877-225924340

Links

ENSG00000143811 ∙ NCBI:29920 ∙ OMIM:616406 ∙ HGNC:30262 ∙ Uniprot:Q96C36 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal recessive primary microcephaly (Supportive), mode of inheritance: AR
• hypomyelinating leukodystrophy 10 (Definitive), mode of inheritance: AR
• hypomyelinating leukodystrophy 10 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Leukodystrophy, hypomyelinating 10	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	Craniofacial; Musculoskeletal; Neurologic	25865492

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PYCR2 gene.

• not provided (5 variants)
• Hypomyelinating leukodystrophy 10 (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PYCR2 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			1	26	3	30
missense		7	36		1	44
nonsense	2	1	1			4
start loss			2			2
frameshift	3	3				6
inframe indel			1			1
splice donor/acceptor (+/-2bp)	1	4				5
splice region			1	3	1	5
non coding			1	8	3	12
Total	6	15	42	34	7

Highest pathogenic variant AF is 0.0000263

Variants in PYCR2

This is a list of pathogenic ClinVar variants found in the PYCR2 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-225920477-G-C		not specified	Benign (Apr 10, 2023)
1-225920494-G-C		not specified • Hypomyelinating leukodystrophy 10	Benign/Likely benign (Jan 08, 2024)
1-225920500-C-T			Benign (Jan 29, 2024)
1-225920520-G-C		Inborn genetic diseases	Uncertain significance (Jan 27, 2022)
1-225920541-C-A			Uncertain significance (Aug 02, 2022)
1-225920552-C-T		Inborn genetic diseases	Uncertain significance (Dec 03, 2021)
1-225920577-C-T		Inborn genetic diseases	Uncertain significance (Jun 03, 2024)
1-225920601-C-G			Uncertain significance (Jul 15, 2022)
1-225920617-C-T			Likely benign (Sep 01, 2022)
1-225921192-C-T			Uncertain significance (Dec 02, 2021)
1-225921194-C-T		Hypomyelinating leukodystrophy 10	Benign (Jan 30, 2024)
1-225921199-T-G		Hypomyelinating leukodystrophy 10	Benign (Jan 30, 2024)
1-225921209-G-A		Hypomyelinating leukodystrophy 10	Pathogenic (Sep 01, 2022)
1-225921219-A-C			Uncertain significance (Sep 07, 2022)
1-225921220-CAGG-C			Uncertain significance (Dec 08, 2021)
1-225921232-A-G		Hypomyelinating leukodystrophy 10	Likely pathogenic (Mar 20, 2024)
1-225921243-G-A			Likely benign (Nov 29, 2017)
1-225921246-C-CAG		Hypomyelinating leukodystrophy 10	Pathogenic/Likely pathogenic (Nov 13, 2023)
1-225921253-C-T		Hypomyelinating leukodystrophy 10	Conflicting classifications of pathogenicity (-)
1-225921254-G-A		Hypomyelinating leukodystrophy 10	Pathogenic (May 07, 2015)
1-225921257-A-C		Hypomyelinating leukodystrophy 10	Uncertain significance (May 21, 2021)
1-225921258-G-A			Likely benign (Jul 17, 2023)
1-225921260-C-G			Uncertain significance (Jun 05, 2022)
1-225921294-G-T			Likely benign (Apr 10, 2022)
1-225921311-A-C		Hypomyelinating leukodystrophy 10	Pathogenic (Sep 16, 2016)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PYCR2	protein_coding	protein_coding	ENST00000343818	7	4401

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000207	0.476	125720	0	28	125748	0.000111

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.948	156	193	0.808	0.0000109	2053
Missense in Polyphen		34	61.079	0.55665		639
Synonymous	-0.520	92	85.9	1.07	0.00000542	691
Loss of Function	0.685	10	12.6	0.792	7.21e-7	135

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000729	0.000728
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.000139	0.000139
European (Non-Finnish)	0.0000619	0.0000615
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000653	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Housekeeping enzyme that catalyzes the last step in proline biosynthesis. In some cell types, such as erythrocytes, its primary function may be the generation of NADP(+). Can utilize both NAD and NADP. Has higher affinity for NADP, but higher catalytic efficiency with NADH (PubMed:2722838, PubMed:6894153). Involved in cellular response to oxidative stress (PubMed:25865492). {ECO:0000269|PubMed:25865492, ECO:0000269|PubMed:2722838, ECO:0000269|PubMed:6894153}.
• 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);Metabolism of amino acids and derivatives;Metabolism;proline biosynthesis;Amino acid synthesis and interconversion (transamination) (Consensus)

Recessive Scores

• pRec: 0.162

Intolerance Scores

• loftool: 0.338
• rvis_EVS: -0.71
• rvis_percentile_EVS: 14.4

Haploinsufficiency Scores

• pHI: 0.201
• hipred: N
• hipred_score: 0.146
• ghis: 0.618

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.969

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pycr2
• Phenotype: immune system phenotype; hematopoietic system phenotype

Gene ontology

• Biological process: proline biosynthetic process;cellular amino acid biosynthetic process;cellular response to oxidative stress;oxidation-reduction process;L-proline biosynthetic process
• Cellular component: mitochondrion;mitochondrial matrix
• Molecular function: pyrroline-5-carboxylate reductase activity;protein binding