PHYH

Chr 10AR

phytanoyl-CoA 2-hydroxylase

Also known as: LN1, LNAP1, PAHX, PHYH1, RD

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. [provided by RefSeq, Jul 2008]

GeneReviewsOMIMResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Refsum diseaseMIM #266500
AR

Clinical highlights

Gene-disease validity (ClinGen)
phytanoyl-CoA hydroxylase deficiency · ARDefinitivesufficient evidence for diagnostic panels
Interpreting a novel variant
Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.
4
Active trials
10
Pubs (1 yr)
P/LP submissions
P/LP missense
1.12
LOEUF
LOF
Mechanism· G2P
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GeneReview available — PHYH
Authoritative clinical overview · Recommended first read
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
1.12LOEUF
pLI 0.000
Z-score 1.20
OE 0.68 (0.431.12)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?
0.03Z-score
OE missense 0.99 (0.881.12)
194 obs / 195.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.68 (0.431.12)
00.351.4
Missense OE?0.99 (0.881.12)
00.61.4
Synonymous OE?0.96
01.21.6
LoF obs/exp: 11 / 16.2Missense obs/exp: 194 / 195.2Syn Z: 0.29

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

PHYH · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.