PHYHIP

Chr 8

phytanoyl-CoA 2-hydroxylase interacting protein

Also known as: DYRK1AP3, PAHX-AP, PAHXAP1

NCBI Gene: 9796 ENSG00000168490 UniProt: Q92561 OMIM: 608511

The PHYHIP protein enables protein tyrosine kinase binding and is involved in protein localization within the cytoplasm, with its interaction with PHYH suggesting a role in central nervous system development. This gene is highly constrained against loss-of-function variants (pLI 0.86, LOEUF 0.44), indicating that mutations are likely to cause significant developmental effects. However, specific disease associations and inheritance patterns for PHYHIP mutations have not yet been established in the clinical literature.

OMIM ResearchSummary from RefSeq, UniProt

Enables protein tyrosine kinase binding activity. Involved in intracellular protein localization. Located in mitochondrion and nucleoplasm. [provided by Alliance of Genome Resources, Jun 2026]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.44

LOEUF

LOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Missense constrained — critical functional residues

LoF Constraint?

0.44LOEUF

pLI 0.860

Z-score 2.77

OE 0.09 (0.03–0.44)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

3.26Z-score

OE missense 0.37 (0.30–0.44)

77 obs / 209.8 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.09 (0.03–0.44)

0≤0.351.4

Missense OE?0.37 (0.30–0.44)

0≤0.61.4

Synonymous OE?1.12

0≤1.21.6

LoF obs/exp: 1 / 10.8Missense obs/exp: 77 / 209.8Syn Z: -0.94

Background carrier burden — how many people carry a rare variant somewhere in PHYHIP?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 480

258 rare PASS variants

Rare truncating (LoF)

1 in 9,100

18 rare PASS variants

Rare synonymous (reference)

1 in 120

214 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PHYHIP. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 490	1 in 19,000
South Asian	~43k	1 in 320	≈ 1 in 22,000
Remaining (unassigned)	~30k	1 in 420	none seen
European (Finnish)	~27k	1 in 1,100	≈ 1 in 27,000
Admixed American	~22k	1 in 610	≈ 1 in 22,000
African / African American	~21k	1 in 460	1 in 4,000
East Asian	~20k	1 in 430	1 in 2,600
Ashkenazi Jewish	~13k	1 in 600	none seen
Middle Eastern	~2,884	≈ 1 in 580	≈ 1 in 1,400

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 4 coding exons well covered in gnomAD exomes and genomes.? see exons ↓