PYCR1

pyrroline-5-carboxylate reductase 1

Basic information

Region (hg38): 17:81932383-81942412

Links

ENSG00000183010 ∙ NCBI:5831 ∙ OMIM:179035 ∙ HGNC:9721 ∙ Uniprot:P32322 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• geroderma osteodysplastica (Supportive), mode of inheritance: AR
• autosomal recessive cutis laxa type 2B (Supportive), mode of inheritance: AR
• autosomal recessive cutis laxa type 2B (Definitive), mode of inheritance: AR
• autosomal recessive cutis laxa type 2B (Definitive), mode of inheritance: AR
• autosomal recessive cutis laxa type 2B (Strong), mode of inheritance: AR
• PYCR1-related de Barsy syndrome (Strong), mode of inheritance: AR
• PYCR1-related de Barsy syndrome (Strong), mode of inheritance: AR
• autosomal recessive cutis laxa type 2B (Strong), mode of inheritance: AR
• autosomal recessive cutis laxa type 2B (Strong), mode of inheritance: AR
• PYCR1-related de Barsy syndrome (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cutis laxa, autosomal recessive, type IIB; Cutis laxa, autosomal recessive type IIIB	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; Dermatologic; Musculoskeletal; Neurologic	4076251; 11424136; 16045708; 18304158; 18348262; 19576563; 19401719; 19648921; 21204221; 21567914; 21834030; 22052856

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PYCR1 gene.

• not provided (192 variants)
• Cutis laxa (50 variants)
• Autosomal recessive cutis laxa type 2B (22 variants)
• Inborn genetic diseases (21 variants)
• not specified (18 variants)
• PYCR1-related de Barsy syndrome (8 variants)
• Wiedemann-Rautenstrauch-like progeroid syndrome (6 variants)
• PYCR1-related condition (4 variants)
• Autosomal recessive cutis laxa type 2B;PYCR1-related de Barsy syndrome (3 variants)
• Cutis laxa, recessive (3 variants)
• PYCR1-related de Barsy syndrome;Autosomal recessive cutis laxa type 2B (2 variants)
• Abnormality of connective tissue (1 variants)
• Microcephaly (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PYCR1 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	40	3	45
missense	6	7	82	2	3	100
nonsense		2	1			3
start loss						0
frameshift	3	4				7
inframe indel			2			2
splice donor/acceptor (+/-2bp)	3	3				6
splice region			7	7		14
non coding			22	29	7	58
Total	12	16	109	71	13

Highest pathogenic variant AF is 0.000125

Variants in PYCR1

This is a list of pathogenic ClinVar variants found in the PYCR1 region.

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

Position	Type	Phenotype	Significance	ClinVar
17-81932445-G-A		Cutis laxa	Uncertain significance (Jan 12, 2018)
17-81932468-G-A		Cutis laxa, recessive	Uncertain significance (Jun 14, 2016)
17-81932515-C-A		Cutis laxa	Uncertain significance (Jan 13, 2018)
17-81932592-C-T		Cutis laxa	Uncertain significance (Jan 13, 2018)
17-81932710-C-G		Cutis laxa	Uncertain significance (Jan 13, 2018)
17-81932732-C-T		Cutis laxa	Uncertain significance (Jan 13, 2018)
17-81932737-G-A		Cutis laxa	Uncertain significance (Jan 13, 2018)
17-81932774-G-A		Cutis laxa	Uncertain significance (Jan 12, 2018)
17-81932862-G-C		Cutis laxa	Uncertain significance (Jan 13, 2018)
17-81932907-C-A		Cutis laxa	Uncertain significance (Aug 01, 2018)
17-81932942-C-T		Cutis laxa	Benign (Jul 26, 2018)
17-81932969-A-G		Cutis laxa	Uncertain significance (Jan 13, 2018)
17-81932985-G-A		Cutis laxa	Uncertain significance (Jan 12, 2018)
17-81933017-CCT-C		Cutis laxa, recessive	Uncertain significance (Jun 14, 2016)
17-81933019-T-A		Cutis laxa	Uncertain significance (Jan 13, 2018)
17-81933064-G-A		Cutis laxa	Uncertain significance (Jan 13, 2018)
17-81933110-C-T		Cutis laxa	Uncertain significance (Jan 13, 2018)
17-81933146-G-A		Cutis laxa	Benign (Jan 13, 2018)
17-81933152-C-G		Cutis laxa	Uncertain significance (Jan 13, 2018)
17-81933225-C-T			Uncertain significance (Feb 25, 2022)
17-81933226-C-T			Likely benign (Apr 15, 2023)
17-81933227-G-A			Uncertain significance (Jul 04, 2022)
17-81933240-T-G		Inborn genetic diseases	Uncertain significance (May 11, 2022)
17-81933242-C-T			Uncertain significance (Jul 19, 2022)
17-81933243-G-A			Uncertain significance (Aug 15, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PYCR1	protein_coding	protein_coding	ENST00000329875	7	10029

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000199	0.739	125475	0	31	125506	0.000124

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.173	187	194	0.965	0.0000130	2039
Missense in Polyphen		49	65.038	0.75341		662
Synonymous	0.170	81	83.0	0.976	0.00000613	684
Loss of Function	0.988	7	10.4	0.670	5.54e-7	118

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000153	0.000152
Ashkenazi Jewish	0.00	0.00
East Asian	0.000601	0.000599
Finnish	0.0000475	0.0000462
European (Non-Finnish)	0.0000553	0.0000529
Middle Eastern	0.000601	0.000599
South Asian	0.000331	0.000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Housekeeping enzyme that catalyzes the last step in proline biosynthesis. Can utilize both NAD and NADP, but has higher affinity for NAD. Involved in the cellular response to oxidative stress. {ECO:0000269|PubMed:16730026, ECO:0000269|PubMed:19648921}.
• Disease: DISEASE: Cutis laxa, autosomal recessive, 2B (ARCL2B) [MIM:612940]: A disorder characterized by an excessive congenital skin wrinkling, a large fontanelle with delayed closure, a typical facial appearance with downslanting palpebral fissures, a general connective tissue weakness, and varying degrees of growth and developmental delay and neurological abnormalities. Patients do not manifest metabolic abnormalities. {ECO:0000269|PubMed:19576563, ECO:0000269|PubMed:19648921}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Cutis laxa, autosomal recessive, 3B (ARCL3B) [MIM:614438]: A disorder characterized by an aged appearance with distinctive facial features, sparse hair, ophthalmologic abnormalities, intrauterine growth retardation, and cutis laxa. {ECO:0000269|PubMed:19648921, ECO:0000269|PubMed:22052856}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Arginine and proline metabolism - Homo sapiens (human);Amino Acid metabolism;Urea cycle and metabolism of amino groups;Metabolism of amino acids and derivatives;Metabolism;Urea cycle and metabolism of arginine, proline, glutamate, aspartate and asparagine;lysine degradation II (pipecolate pathway);Arginine Proline metabolism;proline biosynthesis;Amino acid synthesis and interconversion (transamination) (Consensus)

Recessive Scores

• pRec: 0.263

Intolerance Scores

• loftool: 0.449
• rvis_EVS: -0.53
• rvis_percentile_EVS: 20.7

Haploinsufficiency Scores

• pHI: 0.140
• hipred: N
• hipred_score: 0.170
• ghis: 0.538

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.996

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pycr1
• Phenotype: homeostasis/metabolism phenotype

Zebrafish Information Network

• Gene name: pycr1b
• Affected structure: post-vent region
• Phenotype tag: abnormal
• Phenotype quality: increased curvature

Gene ontology

• Biological process: proline biosynthetic process;cellular amino acid biosynthetic process;cellular response to oxidative stress;regulation of mitochondrial membrane potential;oxidation-reduction process;L-proline biosynthetic process;negative regulation of hydrogen peroxide-induced cell death
• Cellular component: mitochondrion;mitochondrial matrix
• Molecular function: pyrroline-5-carboxylate reductase activity;protein binding;identical protein binding