PHYH

Summary

PHYH (phytanoyl-CoA 2-hydroxylase, HGNC:8940) is a protein-coding gene on chromosome 10p13, encoding Phytanoyl-CoA dioxygenase, peroxisomal (O14832). Catalyzes the 2-hydroxylation of not only racemic phytanoyl-CoA and the isomers of 3-methylhexadecanoyl-CoA, but also a variety of other mono-branched 3-methylacyl-CoA esters (with a chain length of at least seven carbon atoms) and straight-chain acyl-CoA esters (with a chain le….

This gene is a member of the PhyH family and encodes a peroxisomal protein that is involved in the alpha-oxidation of 3-methyl branched fatty acids. Specifically, this protein converts phytanoyl-CoA to 2-hydroxyphytanoyl-CoA. Mutations in this gene have been associated with Refsum disease (RD) and deficient protein activity has been associated with Zellweger syndrome and rhizomelic chondrodysplasia punctata. Alternate transcriptional splice variants, encoding different isoforms, have been characterized.

Source: NCBI Gene 5264 — RefSeq curated summary.

At a glance

• Gene–disease (curated): phytanoyl-CoA hydroxylase deficiency (Definitive, ClinGen) — +1 more curated relationship
• Clinical variants (ClinVar): 503 total — 34 pathogenic, 33 likely-pathogenic
• Phenotypes (HPO): 54
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• MANE Select transcript: NM_006214

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8940
Approved symbol	PHYH
Name	phytanoyl-CoA 2-hydroxylase
Location	10p13
Locus type	gene with protein product
Status	Approved
Aliases	PAHX, RD, PHYH1
Ensembl gene	ENSG00000107537
Ensembl biotype	protein_coding
OMIM	602026
Entrez	5264

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 19 protein_coding, 2 retained_intron

ENST00000263038, ENST00000396913, ENST00000396920, ENST00000453759, ENST00000463730, ENST00000464049, ENST00000479604, ENST00000858005, ENST00000858006, ENST00000858007, ENST00000858008, ENST00000858009, ENST00000858010, ENST00000858011, ENST00000858012, ENST00000858013, ENST00000858014, ENST00000858015, ENST00000928060, ENST00000943580, ENST00000943581

RefSeq mRNA: 6 — MANE Select: NM_006214 NM_001037537, NM_001323080, NM_001323082, NM_001323083, NM_001323084, NM_006214

CCDS: CCDS41489, CCDS7097

Canonical transcript exons

ENST00000263038 — 9 exons

Exon	Start	End
ENSE00000915175	13280976	13281110
ENSE00000915178	13291831	13291912
ENSE00001094769	13288360	13288541
ENSE00001166150	13277799	13278354
ENSE00001526751	13299968	13300064
ENSE00003470677	13298187	13298245
ENSE00003503294	13295496	13295606
ENSE00003542857	13294428	13294596
ENSE00003789589	13283690	13283839

Expression profiles

Bgee: expression breadth ubiquitous, 296 present calls, max score 99.25.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.0577 / max 203.0628, expressed in 1763 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
108295	9.3244	1710
108297	1.6015	1083
108298	0.7468	275
108296	0.3850	170

Top tissues by expression

300 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
vastus lateralis	UBERON:0001379	99.25	gold quality
biceps brachii	UBERON:0001507	99.22	gold quality
quadriceps femoris	UBERON:0001377	99.13	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	99.07	gold quality
nephron tubule	UBERON:0001231	98.96	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	98.81	gold quality
amniotic fluid	UBERON:0000173	98.80	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.79	gold quality
body of tongue	UBERON:0011876	98.75	gold quality
muscle organ	UBERON:0001630	98.71	gold quality
skeletal muscle organ	UBERON:0014892	98.71	gold quality
gastrocnemius	UBERON:0001388	98.69	gold quality
skeletal muscle tissue	UBERON:0001134	98.68	gold quality
heart right ventricle	UBERON:0002080	98.65	gold quality
diaphragm	UBERON:0001103	98.63	gold quality
muscle of leg	UBERON:0001383	98.61	gold quality
triceps brachii	UBERON:0001509	98.61	gold quality
deltoid	UBERON:0001476	98.35	gold quality
liver	UBERON:0002107	98.34	gold quality
right lobe of liver	UBERON:0001114	98.30	gold quality
gluteal muscle	UBERON:0002000	98.15	gold quality
jejunal mucosa	UBERON:0000399	98.08	gold quality
left ventricle myocardium	UBERON:0006566	98.01	gold quality
kidney epithelium	UBERON:0004819	97.99	gold quality
muscle tissue	UBERON:0002385	97.71	gold quality
myocardium	UBERON:0002349	97.42	gold quality
tibialis anterior	UBERON:0001385	97.37	gold quality
adult mammalian kidney	UBERON:0000082	97.28	gold quality
adrenal tissue	UBERON:0018303	97.27	gold quality
renal glomerulus	UBERON:0000074	97.24	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	11.48
E-CURD-11	no	275.93

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

31 targeting PHYH, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-29B-2-5P	99.67	68.98	1726
HSA-MIR-452-5P	99.65	69.63	1762
HSA-MIR-4676-3P	99.65	69.31	1733
HSA-MIR-892C-3P	99.65	69.38	1745
HSA-MIR-425-5P	99.59	67.67	900
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-6839-3P	99.39	68.86	1301
HSA-MIR-1276	99.36	68.18	1642
HSA-MIR-4506	99.34	67.47	526
HSA-MIR-4777-5P	99.33	67.53	1148
HSA-MIR-4652-3P	99.33	70.02	2742
HSA-MIR-2115-3P	99.31	69.68	2026
HSA-MIR-6739-3P	99.22	68.84	1843
HSA-MIR-625-5P	99.02	68.64	2031
HSA-MIR-1257	98.97	68.02	1133
HSA-MIR-361-5P	98.95	70.16	1340
HSA-MIR-374A-3P	98.87	67.82	1531
HSA-MIR-367-5P	98.84	67.18	902
HSA-MIR-629-5P	98.78	68.72	1032
HSA-MIR-1267	98.24	69.05	837
HSA-MIR-4665-5P	97.91	67.69	1536
HSA-MIR-10526-3P	97.86	64.97	1342
HSA-MIR-938	97.41	68.28	656
HSA-MIR-216B-5P	97.16	66.76	1126
HSA-MIR-6886-3P	96.96	66.36	844
HSA-MIR-4436B-5P	96.71	68.37	1346
HSA-MIR-4529-3P	96.40	66.46	582

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 8)

• substrate specificity of PAHX is broader than expected, so Refsum disease might be characterized by an accumulation of not only phytanic acid but also other 3-alkyl-branched fatty acids (PMID:12923223)
• Ten novel PHYH mutations found in Refsum disease patients. (PMID:14974078)
• demonstrate that both unprocessed and processed forms are able to hydroxylate a range of CoA derivatives; site-directed mutagenesis was used to support proposals for the identity of the iron binding istes of PAHX (PMID:15930519)
• manner in which phytanoyl-CoA 2-hydroxylase (PAHX) binds to iron(II) and 2-oxoglutarate at its active site distinguishes it from that of the other human 2-oxoglutarate (2OG)-dependent oxygenase (PMID:16186124)
• In the absence of elevated phytanic acid concentrations, clinical neurologic abnormalities in heterozygous relatives of Refsum patients are not attributable to heterozygosity for PAHX mutations. (PMID:18612766)
• 3 heterozygous variants: c.85C>T (p.Pro29Ser), c.135-2A>G, and c.768del63bp (p.Phe257Glnfs*16) were found in a family with Refsum’s disease. (PMID:28681609)
• Prognostic role of PHYH for overall survival (OS) in clear cell renal cell carcinoma (ccRCC). (PMID:33468235)
• PHYH c.678+5G>T Leads to In-Frame Exon Skipping and Is Associated With Attenuated Refsum Disease. (PMID:38411969)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	phyh	ENSDARG00000086740
mus_musculus	Phyh	ENSMUSG00000026664
rattus_norvegicus	Phyh	ENSRNOG00000018044
caenorhabditis_elegans		WBGENE00013999
caenorhabditis_elegans		WBGENE00014000

Protein

Protein identifiers

Phytanoyl-CoA dioxygenase, peroxisomal — O14832 (reviewed: O14832)

Alternative names: Phytanic acid oxidase, Phytanoyl-CoA alpha-hydroxylase

All UniProt accessions (4): O14832, B1ALH6, C9IYS5, C9JR86

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the 2-hydroxylation of not only racemic phytanoyl-CoA and the isomers of 3-methylhexadecanoyl-CoA, but also a variety of other mono-branched 3-methylacyl-CoA esters (with a chain length of at least seven carbon atoms) and straight-chain acyl-CoA esters (with a chain length longer than four carbon atoms). Does not hydroxylate long and very long straight chain acyl-CoAs or 2-methyl- and 4-methyl-branched acyl-CoAs.

Subunit / interactions. Interacts with FKBP52. Interacts with PHYHIP.

Subcellular location. Peroxisome.

Tissue specificity. Expressed in liver, kidney, and T-cells, but not in spleen, brain, heart, lung and skeletal muscle.

Disease relevance. Refsum disease (RD) [MIM:266500] A rare autosomal recessive peroxisomal disorder characterized by the accumulation of the branched-chain fatty acid, phytanic acid, in blood and tissues. Cardinal clinical features are retinitis pigmentosa, peripheral neuropathy, cerebellar ataxia, and elevated protein levels in the cerebrospinal fluid (CSF). Half of all patients exhibit generalized, mild to moderate ichthyosis resembling ichthyosis vulgaris. Less constant features are nerve deafness, anosmia, skeletal abnormalities, cataracts and cardiac impairment. The disease is caused by variants affecting the gene represented in this entry.

Pathway. Lipid metabolism; fatty acid metabolism.

Similarity. Belongs to the PhyH family.

Isoforms (2)

UniProt ID	Names	Canonical?
O14832-1	1	yes
O14832-2	2

RefSeq proteins (6): NP_001032626, NP_001310009, NP_001310011, NP_001310012, NP_001310013, NP_006205* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008775	Phytyl_CoA_dOase-like	Family
IPR047128	PhyH	Family

Pfam: PF05721

Enzyme classification (BRENDA):

• EC 1.14.11.18 — phytanoyl-CoA dioxygenase (BRENDA: 6 organisms, 28 substrates, 6 inhibitors, 2 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

2 substrates with measured Km, best-characterized 2. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
2-OXOGLUTARATE	0.049	1
3-METHYLHEXADECANOYL-COA	0.0408	1

Catalyzed reactions (Rhea), 12 shown:

• phytanoyl-CoA + 2-oxoglutarate + O2 = 2-hydroxyphytanoyl-CoA + succinate + CO2 (RHEA:16065)
• 3-methylhexadecanoyl-CoA + 2-oxoglutarate + O2 = 2-hydroxy-3-methylhexadecanoyl-CoA + succinate + CO2 (RHEA:44000)
• hexadecanoyl-CoA + 2-oxoglutarate + O2 = 2-hydroxyhexadecanoyl-CoA + succinate + CO2 (RHEA:54596)
• octanoyl-CoA + 2-oxoglutarate + O2 = 2-hydroxyoctanoyl-CoA + succinate + CO2 (RHEA:54600)
• decanoyl-CoA + 2-oxoglutarate + O2 = 2-hydroxydecanoyl-CoA + succinate + CO2 (RHEA:54604)
• 3-methylbutanoyl-CoA + 2-oxoglutarate + O2 = 2-hydroxy-3-methylbutanoyl-CoA + succinate + CO2 (RHEA:54612)
• heptadecanoyl-CoA + 2-oxoglutarate + O2 = 2-hydroxyheptadecanoyl-CoA + succinate + CO2 (RHEA:54616)
• eicosanoyl-CoA + 2-oxoglutarate + O2 = 2-hydroxyeicosanoyl-CoA + succinate + CO2 (RHEA:54620)
• octadecanoyl-CoA + 2-oxoglutarate + O2 = 2-hydroxyoctadecanoyl-CoA + succinate + CO2 (RHEA:54624)
• dodecanoyl-CoA + 2-oxoglutarate + O2 = 2-hydroxydodecanoyl-CoA + succinate + CO2 (RHEA:54628)
• tetradecanoyl-CoA + 2-oxoglutarate + O2 = 2-hydroxytetradecanoyl-CoA + succinate + CO2 (RHEA:54632)
• hexanoyl-CoA + 2-oxoglutarate + O2 = 2-hydroxyhexanoyl-CoA + succinate + CO2 (RHEA:55172)

UniProt features (58 total): sequence variant 18, strand 14, binding site 9, helix 9, modified residue 5, transit peptide 1, chain 1, splice variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2A1X	X-RAY DIFFRACTION	2.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O14832-F1	86.33	0.68

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (9): 275; 120; 157; 175–177; 175; 177; 193; 264; 266

Post-translational modifications (5): 59, 108, 231, 252, 317

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-389599	Alpha-oxidation of phytanate
R-HSA-9033241	Peroxisomal protein import
R-HSA-9033500	TYSND1 cleaves peroxisomal proteins

MSigDB gene sets: 324 (showing top): GOBP_LIPID_MODIFICATION, MODULE_93, GOBP_FATTY_ACID_CATABOLIC_PROCESS, CHIARADONNA_NEOPLASTIC_TRANSFORMATION_KRAS_DN, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_PAIRED_DONORS_WITH_INCORPORATION_OR_REDUCTION_OF_MOLECULAR_OXYGEN, DITTMER_PTHLH_TARGETS_UP, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, RODWELL_AGING_KIDNEY_NO_BLOOD_DN, GOBP_DICARBOXYLIC_ACID_METABOLIC_PROCESS, YORDY_RECIPROCAL_REGULATION_BY_ETS1_AND_SP100_DN, CAIRO_HEPATOBLASTOMA_CLASSES_DN, chr10p13, GOBP_SHORT_CHAIN_FATTY_ACID_METABOLIC_PROCESS, RUTELLA_RESPONSE_TO_CSF2RB_AND_IL4_UP, GOBP_ORGANIC_ACID_CATABOLIC_PROCESS

GO Biological Process (6): fatty acid alpha-oxidation (GO:0001561), 2-oxoglutarate metabolic process (GO:0006103), isoprenoid metabolic process (GO:0006720), 2-oxobutyrate catabolic process (GO:0019606), methyl-branched fatty acid metabolic process (GO:0097089), fatty acid metabolic process (GO:0006631)

GO Molecular Function (9): ferrous iron binding (GO:0008198), carboxylic acid binding (GO:0031406), L-ascorbic acid binding (GO:0031418), phytanoyl-CoA dioxygenase activity (GO:0048244), catalytic activity (GO:0003824), protein binding (GO:0005515), oxidoreductase activity (GO:0016491), metal ion binding (GO:0046872), dioxygenase activity (GO:0051213)

GO Cellular Component (4): peroxisome (GO:0005777), peroxisomal matrix (GO:0005782), cytosol (GO:0005829), 9+0 non-motile cilium (GO:0097731)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Peroxisomal lipid metabolism	1
Protein localization	1
Peroxisomal protein import	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
lipid metabolic process	2
fatty acid catabolic process	1
fatty acid oxidation	1
dicarboxylic acid metabolic process	1
short-chain fatty acid catabolic process	1
fatty acid metabolic process	1
monocarboxylic acid metabolic process	1
iron ion binding	1
anion binding	1
organic acid binding	1
vitamin binding	1
carboxylic acid binding	1
monosaccharide binding	1
heterocyclic compound binding	1
2-oxoglutarate-dependent dioxygenase activity	1
molecular_function	1
binding	1
catalytic activity	1
cation binding	1
oxidoreductase activity	1
microbody	1
peroxisome	1
microbody lumen	1
cytoplasm	1
cellular anatomical structure	1
non-motile cilium	1

Protein interactions and networks

STRING

1667 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PHYH	PHYHIP	Q92561	986
PHYH	PEX7	O00628	945
PHYH	PEX5	P50542	860
PHYH	PEX6	Q13608	821
PHYH	GLMN	Q92990	713
PHYH	AGPS	O00116	711
PHYH	FKBP4	Q02790	705
PHYH	ACOX3	O15254	690
PHYH	ACSL6	Q9UKU0	690
PHYH	HACL1	Q9UJ83	678
PHYH	GNPAT	O15228	658
PHYH	PEX13	Q92968	656
PHYH	AMACR	Q9UHK6	610
PHYH	ACAA1	P09110	606
PHYH	FKBP1A	P20071	605

IntAct

76 interactions, top by confidence:

A	B	Type	Score
FAM9B	PHYH	psi-mi:“MI:0915”(physical association)	0.780
PHYH	FAM9B	psi-mi:“MI:0915”(physical association)	0.780
COPS3	PHYH	psi-mi:“MI:0915”(physical association)	0.680
PHYH	MAGEA11	psi-mi:“MI:0915”(physical association)	0.670
MAGEA11	PHYH	psi-mi:“MI:0915”(physical association)	0.670
INADL	PHYH	psi-mi:“MI:0915”(physical association)	0.560
EPHB2	PHYH	psi-mi:“MI:0915”(physical association)	0.560
TRAF5	PHYH	psi-mi:“MI:0915”(physical association)	0.560
RNF112	PHYH	psi-mi:“MI:0915”(physical association)	0.560
PIAS1	PHYH	psi-mi:“MI:0915”(physical association)	0.560
CDC23	PHYH	psi-mi:“MI:0915”(physical association)	0.560
MALT1	PHYH	psi-mi:“MI:0915”(physical association)	0.560
EDRF1	PHYH	psi-mi:“MI:0915”(physical association)	0.560
LHX6	PHYH	psi-mi:“MI:0915”(physical association)	0.560
KLHL20	PHYH	psi-mi:“MI:0915”(physical association)	0.560
CRLF3	PHYH	psi-mi:“MI:0915”(physical association)	0.560
ASIC4	PHYH	psi-mi:“MI:0915”(physical association)	0.560
OTUD7B	PHYH	psi-mi:“MI:0915”(physical association)	0.560
ABHD17C	PHYH	psi-mi:“MI:0915”(physical association)	0.560
SPMIP4	PHYH	psi-mi:“MI:0915”(physical association)	0.560
TRIM74	PHYH	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (34): FAM9B (Two-hybrid), PHYH (Two-hybrid), PHYH (Synthetic Growth Defect), PHYH (Two-hybrid), FAM9B (Two-hybrid), PHYH (Affinity Capture-MS), PHYH (Two-hybrid), PHYH (Affinity Capture-MS), PHYH (Affinity Capture-MS), PHYH (Proximity Label-MS), PHYH (Reconstituted Complex), TOM1L1 (Two-hybrid), INADL (Two-hybrid), MAGEA11 (Two-hybrid), PHYH (Two-hybrid)

ESM2 similar proteins: A8MRC7, B9N1F9, B9SQI7, F4I8M8, F4J0A8, F4JAU3, F4JNU8, F4JZ24, O14832, O18778, O35386, O82730, P00860, P08196, P09057, P11515, P11926, P14019, P21529, P27117, P27119, P27120, P31166, P32826, P37271, P37272, P37891, P49085, P49293, P52712, P53797, Q09131, Q24JN5, Q41005, Q52QW5, Q56WF8, Q5Z5B7, Q6NQB7, Q8L970, Q8LAN3

Diamond homologs: O14832, O18778, O35386, O62515, P57093, Q10E49, Q65WW7, P0C660, Q0IIB1, Q54XH6, Q5BJP9, Q5SRE7, Q5U3U0, Q9DB26, Q9NAM7, Q9ZVF6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

503 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	34
Likely pathogenic	33
Uncertain significance	176
Likely benign	185
Benign	31

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1379590	NM_006214.4(PHYH):c.133C>T (p.Gln45Ter)	Pathogenic
1404181	NM_006214.4(PHYH):c.679-1dup	Pathogenic
1460457	NC_000010.10:g.(?13333811)(13333932_?)del	Pathogenic
1948044	NM_006214.4(PHYH):c.639_640del (p.His213fs)	Pathogenic
2114712	NM_006214.4(PHYH):c.732_739del (p.Arg245fs)	Pathogenic
2136846	NM_006214.4(PHYH):c.457del (p.Ala153fs)	Pathogenic
2425532	NC_000010.10:g.(?13340167)(13340265_?)del	Pathogenic
2425533	NC_000010.10:g.(?13340167)(13342042_?)del	Pathogenic
2782463	NM_006214.4(PHYH):c.127C>T (p.Gln43Ter)	Pathogenic
2800295	NM_006214.4(PHYH):c.520del (p.Leu174fs)	Pathogenic
2806346	NM_006214.4(PHYH):c.412G>T (p.Glu138Ter)	Pathogenic
2810432	NM_006214.4(PHYH):c.802C>T (p.Gln268Ter)	Pathogenic
2812949	NM_006214.4(PHYH):c.493dup (p.Ser165fs)	Pathogenic
2817687	NM_006214.4(PHYH):c.709C>T (p.Gln237Ter)	Pathogenic
2834074	NM_006214.4(PHYH):c.717C>G (p.Tyr239Ter)	Pathogenic
2840913	NM_006214.4(PHYH):c.733_734delinsTA (p.Arg245Ter)	Pathogenic
2861585	NM_006214.4(PHYH):c.817G>T (p.Gly273Ter)	Pathogenic
3244975	NC_000010.10:g.(?13320301)(13342042_?)del	Pathogenic
3244976	NC_000010.10:g.(?13341948)(13342042_?)del	Pathogenic
3244977	NC_000010.10:g.(?13330340)(13342042_?)del	Pathogenic
3244978	NC_000010.10:g.(?13320301)(13340265_?)del	Pathogenic
3244979	NC_000010.10:g.(?13336408)(13337626_?)del	Pathogenic
3244980	NC_000010.10:g.(?13330340)(13337626_?)del	Pathogenic
3244982	NC_000010.10:g.(?13325670)(13330561_?)del	Pathogenic
3244983	NC_000010.10:g.(?13320301)(13325859_?)del	Pathogenic
3359073	NM_006214.4(PHYH):c.336del (p.Pro113fs)	Pathogenic
379919	NM_006214.4(PHYH):c.840C>A (p.Cys280Ter)	Pathogenic
4804693	NM_006214.4(PHYH):c.425del (p.Tyr142fs)	Pathogenic
498045	NM_006214.4(PHYH):c.235C>T (p.Gln79Ter)	Pathogenic
7581	NM_006214.4(PHYH):c.135-2A>G	Pathogenic

SpliceAI

1456 predictions. Top by Δscore:

Variant	Effect	Δscore
10:13280971:CATA:C	donor_loss	1.0000
10:13280972:ATAC:A	donor_loss	1.0000
10:13280973:TACC:T	donor_loss	1.0000
10:13280975:CCTTC:C	donor_loss	1.0000
10:13281031:T:TA	donor_gain	1.0000
10:13281120:G:C	acceptor_gain	1.0000
10:13283685:CTTA:C	donor_loss	1.0000
10:13283686:TTA:T	donor_loss	1.0000
10:13283687:TACC:T	donor_loss	1.0000
10:13283688:A:AC	donor_gain	1.0000
10:13283689:C:CC	donor_gain	1.0000
10:13283689:CCTT:C	donor_gain	1.0000
10:13283835:CCCCC:C	acceptor_gain	1.0000
10:13283836:CCCC:C	acceptor_gain	1.0000
10:13283836:CCCCC:C	acceptor_gain	1.0000
10:13283837:CCC:C	acceptor_gain	1.0000
10:13283837:CCCC:C	acceptor_gain	1.0000
10:13283838:CC:C	acceptor_gain	1.0000
10:13283838:CCC:C	acceptor_gain	1.0000
10:13283839:CC:C	acceptor_gain	1.0000
10:13283840:C:CC	acceptor_gain	1.0000
10:13283841:T:A	acceptor_loss	1.0000
10:13288355:CCTA:C	donor_loss	1.0000
10:13288356:CTAC:C	donor_loss	1.0000
10:13288357:TA:T	donor_loss	1.0000
10:13288358:ACC:A	donor_loss	1.0000
10:13294461:ATCTT:A	donor_gain	1.0000
10:13294462:T:C	donor_gain	1.0000
10:13295489:A:AC	donor_gain	1.0000
10:13295490:C:CC	donor_gain	1.0000

AlphaMissense

2256 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:13288515:G:C	H175D	0.998
10:13288508:T:G	D177A	0.997
10:13283728:G:C	H264D	0.996
10:13288508:T:A	D177V	0.996
10:13288461:A:G	W193R	0.995
10:13288461:A:T	W193R	0.995
10:13288507:G:C	D177E	0.995
10:13288507:G:T	D177E	0.995
10:13288508:T:C	D177G	0.995
10:13288509:C:G	D177H	0.994
10:13288465:G:C	C191W	0.993
10:13288515:G:T	H175N	0.992
10:13288524:G:C	H172D	0.992
10:13288513:G:C	H175Q	0.991
10:13288513:G:T	H175Q	0.991
10:13295547:C:T	G65E	0.991
10:13295548:C:A	G65W	0.991
10:13283726:G:C	H264Q	0.990
10:13283726:G:T	H264Q	0.990
10:13283819:G:C	F233L	0.990
10:13283819:G:T	F233L	0.990
10:13283821:A:G	F233L	0.990
10:13288510:C:A	Q176H	0.990
10:13288510:C:G	Q176H	0.990
10:13281098:G:C	H281D	0.989
10:13283694:C:G	R275P	0.989
10:13283733:A:G	L262P	0.989
10:13288469:A:T	V190D	0.989
10:13291844:T:A	K161N	0.989
10:13291844:T:G	K161N	0.989

dbSNP variants (sampled 300 via entrez): RS1000072598 (10:13294251 T>C), RS1000073599 (10:13281862 C>T), RS1000175856 (10:13301661 C>A), RS1000197335 (10:13288721 G>C), RS1000463042 (10:13299479 A>T), RS1000614853 (10:13301416 G>A,T), RS1000717412 (10:13289044 G>A), RS1000983932 (10:13292599 T>C), RS1001099834 (10:13297120 G>A), RS1001177749 (10:13300638 C>A,T), RS1001210381 (10:13300409 G>A), RS1001353405 (10:13292284 T>A,C), RS1001376281 (10:13297790 T>C,G), RS1001565819 (10:13289757 C>A), RS1001610221 (10:13280401 T>G)

Disease associations

OMIM: gene MIM:602026 | disease phenotypes: MIM:266500, MIM:600964, MIM:268000, MIM:277440

GenCC curated gene-disease

Disease	Classification	Inheritance
adult Refsum disease	Definitive	Autosomal recessive
phytanoyl-CoA hydroxylase deficiency	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
phytanoyl-CoA hydroxylase deficiency	Definitive	AR

Mondo (7): adult Refsum disease (MONDO:0009958), inherited retinal dystrophy (MONDO:0019118), retinitis pigmentosa (MONDO:0019200), phytanoyl-CoA hydroxylase deficiency (MONDO:0100258), vitamin D-dependent rickets, type 2A (MONDO:0010186), optic atrophy (MONDO:0003608), intellectual disability (MONDO:0001071)

Orphanet (5): Adult Refsum disease (Orphanet:773), OBSOLETE: Inherited retinal disorder (Orphanet:71862), Retinitis pigmentosa (Orphanet:791), Hypocalcemic vitamin D-resistant rickets (Orphanet:93160), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

54 total (30 of 54 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000083	Renal insufficiency
HP:0000407	Sensorineural hearing impairment
HP:0000458	Anosmia
HP:0000478	Abnormality of the eye
HP:0000488	Retinopathy
HP:0000496	Abnormality of eye movement
HP:0000504	Abnormality of vision
HP:0000505	Visual impairment
HP:0000508	Ptosis
HP:0000510	Rod-cone dystrophy
HP:0000518	Cataract
HP:0000529	Progressive visual loss
HP:0000546	Retinal degeneration
HP:0000568	Microphthalmia
HP:0000616	Miosis
HP:0000639	Nystagmus
HP:0000662	Nyctalopia
HP:0000958	Dry skin
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001265	Hyporeflexia
HP:0001635	Congestive heart failure
HP:0001638	Cardiomyopathy
HP:0001640	Cardiomegaly
HP:0001744	Splenomegaly
HP:0001760	Abnormal foot morphology
HP:0001761	Pes cavus
HP:0001765	Hammertoe
HP:0001939	Abnormality of metabolism/homeostasis

GWAS associations

0 associations (top):

MeSH disease descriptors (7)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D009896	Optic Atrophy	C10.292.700.225; C11.640.451
D012035	Refsum Disease	C10.228.140.163.100.813; C10.500.300.780; C10.574.500.495.780; C10.668.829.800.300.780; C16.131.666.300.780; C16.320.400.375.780; C16.320.565.189.813; C16.320.565.663.760; C18.452.132.100.813; C18.452.648.189.813; C18.452.648.663.760
D058499	Retinal Dystrophies	C11.768.585.658
D012174	Retinitis Pigmentosa	C11.270.684; C11.768.585.658.500; C16.320.290.684
C535517	Refsum disease with increased pipecolic acidemia (supp.)
C562794	Vitamin D-Dependent Rickets, Type 2A (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

43 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases methylation, affects expression, decreases expression, decreases methylation	3
bisphenol A	affects expression, increases expression	2
trichostatin A	affects cotreatment, decreases expression	2
Air Pollutants	increases abundance, increases expression, decreases expression	2
Cisplatin	increases expression, affects expression, affects cotreatment	2
Doxorubicin	affects expression, decreases expression	2
Cyclosporine	decreases expression	2
Particulate Matter	increases abundance, increases expression, decreases expression	2
aristolochic acid I	increases expression	1
GSK-J4	decreases expression	1
dicrotophos	decreases expression	1
sodium arsenite	increases expression	1
periodate-oxidized adenosine	affects expression	1
beta-methylcholine	affects expression	1
CD 437	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	affects cotreatment, increases expression	1
bisphenol AF	increases expression	1
Decitabine	affects expression	1
Acetaminophen	increases expression	1
Amitriptyline	increases expression	1
Arsenic	affects methylation	1
trans-1,4-Bis(2-chlorobenzaminomethyl)cyclohexane Dihydrochloride	increases expression	1
Chlorpromazine	increases expression	1
Clomipramine	increases expression	1
Ethyl Methanesulfonate	increases expression	1
Fluorouracil	affects response to substance	1
Ivermectin	decreases expression	1
Methotrexate	increases expression	1

Clinical trials (associated diseases)

262 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00717080	PHASE4	COMPLETED	The Role of Capsular Tension Ring (CTR) in Anterior Capsular Contraction
NCT04224207	PHASE3	COMPLETED	Management of Retinitis Pigmentosa by Mesenchymal Stem Cells by Wharton’s Jelly Derived Mesenchymal Stem Cells
NCT07082855	PHASE3	NOT_YET_RECRUITING	A Multicenter, Randomized, Double-Blind, Controlled Clinical Study of Minocycline for the Treatment of Retinitis Pigmentosa
NCT00000114	PHASE3	COMPLETED	Randomized Trial of Vitamin A and Vitamin E Supplementation for Retinitis Pigmentosa
NCT00000116	PHASE3	COMPLETED	Randomized Trial of DHA for Retinitis Pigmentosa Patients Receiving Vitamin A
NCT00346333	PHASE3	COMPLETED	Clinical Trial of Lutein for Patients With Retinitis Pigmentosa Receiving Vitamin A
NCT01786395	PHASE3	TERMINATED	Phase III Efficacy and Safety Clinical Study of UF-021 for Treatment of Retinitis Pigmentosa
NCT04636853	PHASE3	COMPLETED	CB-PRP in Retinitis Pigmentosa and Dry Age-related Macular Degeneration
NCT05537220	PHASE3	ACTIVE_NOT_RECRUITING	Oral N-acetylcysteine for Retinitis Pigmentosa
NCT05800301	PHASE3	COMPLETED	Management of Retinitis Pigmentosa Via Combination of Wharton’s Jelly-derived Mesenchymal Stem Cells and Magnovision
NCT05926583	PHASE3	ACTIVE_NOT_RECRUITING	A Study of AAV5-hRKp.RPGR for the Treatment of Japanese Participants With X-linked Retinitis Pigmentosa
NCT06388200	PHASE3	ACTIVE_NOT_RECRUITING	A Phase 3 Study Of OCU400 Gene Therapy for the Treatment Of Retinitis Pigmentosa
NCT07290530	PHASE3	NOT_YET_RECRUITING	24-Month Trial of NPI-001 for the Preservation of Photoreceptors in Retinitis Pigmentosa Associated With Usher Syndrome
NCT03763227	PHASE2	COMPLETED	Intravitreal Ranibizumab (Lucentis®) in the Treatment of Non-leaking Macular Cysts in Retinal Dystrophy
NCT04068207	PHASE2	COMPLETED	Minocycline Treatment in Retinitis Pigmentosa
NCT04945772	PHASE2	COMPLETED	Efficacy and Safety of MCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE]
NCT00100230	PHASE2	COMPLETED	DHA and X-Linked Retinitis Pigmentosa
NCT00447980	PHASE2	COMPLETED	A Study of Encapsulated Cell Technology (ECT) Implant for Participants With Early Stage Retinitis Pigmentosa
NCT00447993	PHASE2	COMPLETED	A Study of Encapsulated Cell Technology (ECT) Implant for Patients With Late Stage Retinitis Pigmentosa
NCT01233609	PHASE2	COMPLETED	Trial of Oral Valproic Acid for Retinitis Pigmentosa
NCT01399515	PHASE2	COMPLETED	Efficacy and Safety of Oral Valproic Acid for Retinitis Pigmentosa
NCT01530659	PHASE2	COMPLETED	Retinal Imaging in CNTF -Releasing Encapsulated Cell Implant Treated Patients for Early-stage Retinitis Pigmentosa
NCT01560715	PHASE2	COMPLETED	Autologous Bone Marrow-Derived Stem Cells Transplantation For Retinitis Pigmentosa
NCT02609165	PHASE2	COMPLETED	Nerve Growth Factor Eye Drops Treatment in Patients With Retinitis Pigmentosa and Cystoid Macular Edema
NCT02661711	PHASE2	COMPLETED	Aflibercept for Macular Oedema With Underlying Retinitis Pigmentosa (AMOUR) Study
NCT02804360	PHASE2	UNKNOWN	Intravitreal Dexamethasone Implant in Retinitis Pigmentosa-related Macular Edema- a Retrospective Study
NCT02837640	PHASE2	UNKNOWN	Studying a Potential Protective Effect of L-Dopa on Retinitis Pigmentosa
NCT03073733	PHASE2	COMPLETED	Safety and Efficacy of Intravitreal Injection of Human Retinal Progenitor Cells in Adults With Retinitis Pigmentosa
NCT04356716	PHASE2	COMPLETED	Sildenafil for Treatment of Choroidal Ischemia
NCT04604899	PHASE2	COMPLETED	Safety of Repeat Intravitreal Injection of Human Retinal Progenitor Cells (jCell) in Adult Subjects With Retinitis Pigmentosa
NCT04763369	PHASE2	UNKNOWN	Investigation of Therapeutic Efficacy and Safety of UMSCs for the Management of Retinitis Pigmentosa (RP)
NCT04864496	PHASE2	UNKNOWN	Effects of Treatment With N- Acetylcysteine on Visual Outcomes in Patients With Retinitis Pigmentosa
NCT05085964	PHASE2	TERMINATED	An Open-Label Extension Study to Evaluate Safety & Tolerability of QR-421a in Subjects With Retinitis Pigmentosa
NCT05392179	PHASE2	COMPLETED	A Study in Subjects With Retinitis Pigmentosa
NCT06627179	PHASE2	RECRUITING	Study to Evaluate Ultevursen in Subjects With Retinitis Pigmentosa (RP) Due to Mutations in Exon 13 of the USH2A Gene
NCT06628947	PHASE2	RECRUITING	A Phase II Study of Intravitreal KIO-301 in Patients With Late-stage Retinitis Pigmentosa
NCT06912633	PHASE2	RECRUITING	Safety of a Single, Intravitreal Injection of 6.0M jCell (Famzeretcel) in Retinitis Pigmentosa (RP)
NCT05902962	PHASE1	COMPLETED	SAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects
NCT06319872	PHASE1	RECRUITING	The Effects of Disulfiram (Antabuse®) on Visual Acuity in Patients With Retinal Degeneration
NCT06455826	PHASE1	COMPLETED	MAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects (Wallaby)