PHYHIP

Chr 8

phytanoyl-CoA 2-hydroxylase interacting protein

Also known as: DYRK1AP3, PAHX-AP, PAHXAP1

NCBI Gene: 9796ENSG00000168490UniProt: Q92561

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.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
5
Pubs (1 yr)
82
P/LP submissions
0%
P/LP missense
0.44
LOEUF
LOF
Mechanism· predicted
Clinical Summary— PHYHIP
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.86) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
82 unique Pathogenic / Likely Pathogenic· 36 VUS of 122 total submissions
Explore recent and relevant literature in Research Assistant →

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 OE0.09 (0.03–0.44)
0≤0.351.4
Missense OE0.37 (0.30–0.44)
0≤0.61.4
Synonymous OE1.12
0≤1.21.6
LoF obs/exp: 1 / 10.8Missense obs/exp: 77 / 209.8Syn Z: -0.94
DN
0.3395th %ile
GOF
0.4085th %ile
LOF
0.73top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.44

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

122 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic78
Likely Pathogenic4
VUS36
78
Pathogenic
4
Likely Pathogenic
36
VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
78
0
78
Likely Pathogenic
0
0
4
0
4
VUS
0
27
9
0
36
Likely Benign
0
0
0
0
0
Benign
0
0
0
0
0
Total027910118

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

PHYHIP · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 4 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients