PHYKPL

5-phosphohydroxy-L-lysine phospho-lyase

Basic information

Region (hg38): 5:178208471-178232802

Previous symbols: [ "AGXT2L2" ]

Links

ENSG00000175309 ∙ NCBI:85007 ∙ OMIM:614683 ∙ HGNC:28249 ∙ Uniprot:Q8IUZ5 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• phosphohydroxylysinuria (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Phosphohydroxylysinuria	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	2387074; 23242558
Individuals have been described with multiple phenotypes, but the overall consequences are unclear

ClinVar

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

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PHYKPL 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						0
missense			54	5		59
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			10			10
Total	0	0	64	5	0

Variants in PHYKPL

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

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

Position	Type	Phenotype	Significance	ClinVar
5-178209393-C-T		not specified	Uncertain significance (Jun 07, 2024)
5-178209394-G-A		not specified	Uncertain significance (Mar 19, 2024)
5-178209403-G-A		not specified	Uncertain significance (Oct 06, 2023)
5-178210138-G-T		not specified	Uncertain significance (Nov 12, 2024)
5-178210162-G-A		not specified	Uncertain significance (Aug 04, 2023)
5-178210224-G-A		not specified	Uncertain significance (Sep 17, 2021)
5-178210243-A-G		not specified	Uncertain significance (Jun 02, 2023)
5-178210245-T-C		not specified	Uncertain significance (Jun 16, 2024)
5-178210248-G-A		not specified	Uncertain significance (May 29, 2024)
5-178210260-G-A		not specified	Uncertain significance (Jun 16, 2023)
5-178211944-C-G		not specified	Likely benign (Nov 30, 2022)
5-178211959-T-C		not specified	Uncertain significance (Nov 08, 2022)
5-178211961-T-C		not specified	Uncertain significance (Dec 28, 2024)
5-178211964-T-A		Phosphohydroxylysinuria	Uncertain significance (Nov 30, 2022)
5-178213000-C-T		not specified	Uncertain significance (Apr 04, 2024)
5-178213008-C-T		not specified	Likely benign (Dec 03, 2021)
5-178213038-G-C		not specified	Uncertain significance (Aug 29, 2024)
5-178213043-A-T		not specified	Uncertain significance (Jun 29, 2023)
5-178213075-T-C		not specified	Uncertain significance (Jul 25, 2023)
5-178213087-C-T		not specified	Likely benign (Aug 02, 2021)
5-178213100-C-T		PHYKPL-related disorder	Likely benign (May 11, 2020)
5-178214812-C-A		not specified	Uncertain significance (Oct 22, 2021)
5-178214854-T-A		not specified	Uncertain significance (Aug 20, 2023)
5-178214869-T-C		not specified	Uncertain significance (Jan 19, 2024)
5-178215286-C-T		not specified	Uncertain significance (Sep 04, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PHYKPL	protein_coding	protein_coding	ENST00000308158	12	24295

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.77e-14	0.0263	125602	0	146	125748	0.000581

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.476	295	273	1.08	0.0000163	2938
Missense in Polyphen		104	100.39	1.036		1020
Synonymous	-0.657	124	115	1.08	0.00000759	886
Loss of Function	0.170	21	21.9	0.961	9.29e-7	259

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000601	0.000601
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.000925	0.000925
Finnish	0.000748	0.000739
European (Non-Finnish)	0.000632	0.000624
Middle Eastern	0.000925	0.000925
South Asian	0.000719	0.000719
Other	0.000844	0.000815

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the pyridoxal-phosphate-dependent breakdown of 5-phosphohydroxy-L-lysine, converting it to ammonia, inorganic phosphate and 2-aminoadipate semialdehyde. {ECO:0000269|PubMed:22241472}.
• Disease: DISEASE: Phosphohydroxylysinuria (PHLU) [MIM:615011]: A condition characterized by elevated phosphohydroxylysine in the urine. There is no clinical phenotype associated with this finding other than the urinary metabolites. {ECO:0000269|PubMed:23242558}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Lysine degradation - Homo sapiens (human);Lysine catabolism;Collagen degradation;Histidine, lysine, phenylalanine, tyrosine, proline and tryptophan catabolism;Metabolism of amino acids and derivatives;Extracellular matrix organization;Metabolism;Degradation of the extracellular matrix (Consensus)

Recessive Scores

• pRec: 0.122

Intolerance Scores

• rvis_EVS: 0.09
• rvis_percentile_EVS: 60.57

Haploinsufficiency Scores

• pHI: 0.132
• hipred: N
• hipred_score: 0.197
• ghis: 0.496

Essentials

• essential_gene_CRISPR: N
• essential_gene_gene_trap: N

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Phykpl
• Phenotype: vision/eye phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: lysine catabolic process;collagen catabolic process
• Cellular component: mitochondrial matrix
• Molecular function: protein binding;transaminase activity;lyase activity;pyridoxal phosphate binding;identical protein binding