PHYH

phytanoyl-CoA 2-hydroxylase

Basic information

Region (hg38): 10:13277796-13302412

Links

ENSG00000107537 ∙ NCBI:5264 ∙ OMIM:602026 ∙ HGNC:8940 ∙ Uniprot:O14832 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• adult Refsum disease (Strong), mode of inheritance: AR
• adult Refsum disease (Definitive), mode of inheritance: AR
• adult Refsum disease (Supportive), mode of inheritance: AR
• adult Refsum disease (Definitive), mode of inheritance: AR
• phytanoyl-CoA hydroxylase deficiency (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Refsum disease	AR	Biochemical; Cardiovascular; Pharmacogenomic	Dietary measures (high calorie diet with phytanic acid restriction) may be beneficial; Surveillance can allow early diagnosis and treatment of cardiac manifestsations (eg, cardiac arrhythmias, cardiomyopathy); Plasmapheresis/lipid apheresis may be indicated in severe situations; Certain agents/circumstances (eg, fasting, ibuprofen) should be avoided	Audiologic/Otolaryngologic; Biochemical; Cardiovascular; Dermatologic; Musculoskeletal; Neurologic; Ophthalmologic	13045168; 18140089; 4159604; 85164; 6160883; 2452736; 9326939; 9326940; 10767344; 17905308; 20301527; 20547622; 22156782

ClinVar

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

• not provided (23 variants)
• Phytanic acid storage disease (6 variants)
• Refsum syndrome (1 variants)
• Refsum disease, adult, 1 (1 variants)
• Retinitis pigmentosa (1 variants)
• PHYH-related disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PHYH 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			4	95	2	101
missense	1	5	133	1	2	142
nonsense	10	7	2			19
start loss			2			2
frameshift	10	13				23
inframe indel			3			3
splice donor/acceptor (+/-2bp)	2	15				17
splice region			11	15		26
non coding			11	75	30	116
Total	23	40	155	171	34

Highest pathogenic variant AF is 0.000177

Variants in PHYH

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

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

Position	Type	Phenotype	Significance	ClinVar
10-13277802-G-A		Phytanic acid storage disease	Uncertain significance (Jan 13, 2018)
10-13277867-T-C		Phytanic acid storage disease	Uncertain significance (Jan 12, 2018)
10-13277884-T-C		Phytanic acid storage disease	Uncertain significance (Jan 12, 2018)
10-13278048-C-A		Phytanic acid storage disease	Uncertain significance (Jan 12, 2018)
10-13278111-GT-G		Phytanic acid storage disease	Benign (Aug 10, 2019)
10-13278111-G-GT			Benign (Aug 22, 2019)
10-13278113-T-G		Phytanic acid storage disease	Uncertain significance (Jan 13, 2018)
10-13278236-C-T		Phytanic acid storage disease	Benign (Aug 07, 2018)
10-13278254-C-T		Phytanic acid storage disease	Likely benign (Jan 13, 2018)
10-13278276-G-A		Phytanic acid storage disease	Uncertain significance (Jan 12, 2018)
10-13278279-A-C		Phytanic acid storage disease	Likely benign (Jan 13, 2018)
10-13278304-A-G		PHYH-related disorder	Likely benign (Jan 08, 2024)
10-13278305-A-AGAT		Nonsyndromic cleft lip palate • not specified	Conflicting classifications of pathogenicity (Mar 01, 2024)
10-13278307-A-T		Inborn genetic diseases	Uncertain significance (May 08, 2023)
10-13278308-T-C			Uncertain significance (Dec 02, 2021)
10-13278309-T-C		Phytanic acid storage disease	Uncertain significance (Jul 30, 2019)
10-13278312-T-G			Uncertain significance (Apr 28, 2022)
10-13278327-C-G		Inborn genetic diseases	Uncertain significance (Oct 04, 2022)
10-13278332-C-G			Uncertain significance (Mar 29, 2021)
10-13278332-C-T			Uncertain significance (Dec 11, 2023)
10-13278333-G-A			Uncertain significance (Jun 14, 2022)
10-13278335-G-C			Uncertain significance (Apr 11, 2022)
10-13278337-T-C			Likely benign (Jan 07, 2023)
10-13278338-C-A			Uncertain significance (Jul 12, 2022)
10-13278338-C-T		Phytanic acid storage disease • PHYH-related disorder	Likely benign (Jan 27, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PHYH	protein_coding	protein_coding	ENST00000263038	9	24617

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000238	0.744	125689	0	59	125748	0.000235

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0310	194	195	0.994	0.0000113	2245
Missense in Polyphen		53	53.778	0.98554		597
Synonymous	0.292	72	75.2	0.957	0.00000522	619
Loss of Function	1.20	11	16.2	0.678	6.96e-7	200

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000297	0.000297
Ashkenazi Jewish	0.00	0.00
East Asian	0.000163	0.000163
Finnish	0.000462	0.000462
European (Non-Finnish)	0.000317	0.000316
Middle Eastern	0.000163	0.000163
South Asian	0.0000327	0.0000327
Other	0.000164	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Converts phytanoyl-CoA to 2-hydroxyphytanoyl-CoA.
• Pathway: Peroxisome - Homo sapiens (human);Oxidation of Branched Chain Fatty Acids;Refsum Disease;Phytanic Acid Peroxisomal Oxidation;Metabolism of lipids;Metabolism of proteins;Alpha-oxidation of phytanate;Peroxisomal lipid metabolism;Metabolism;Peroxisomal protein import;Fatty acid metabolism;Phytanic acid peroxisomal oxidation;TYSND1 cleaves peroxisomal proteins;fatty acid α-oxidation (Consensus)

Recessive Scores

• pRec: 0.229

Intolerance Scores

• loftool: 0.119
• rvis_EVS: 0.62
• rvis_percentile_EVS: 83.36

Haploinsufficiency Scores

• pHI: 0.0601
• hipred: N
• hipred_score: 0.377
• ghis: 0.476

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.670

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Phyh
• Phenotype: immune system 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); reproductive system phenotype; liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); homeostasis/metabolism phenotype; growth/size/body region phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan)

Gene ontology

• Biological process: fatty acid alpha-oxidation;2-oxoglutarate metabolic process;protein targeting to peroxisome;isoprenoid metabolic process;methyl-branched fatty acid metabolic process
• Cellular component: peroxisome;peroxisomal matrix;cytosol
• Molecular function: protein binding;ferrous iron binding;carboxylic acid binding;L-ascorbic acid binding;cofactor binding;phytanoyl-CoA dioxygenase activity