PHACTR1

Chr 6AD

phosphatase and actin regulator 1

Also known as: DEE70, EIEE70, RPEL, RPEL1, dJ257A7.2

NCBI Gene: 221692ENSG00000112137UniProt: Q9C0D0

The protein encoded by this gene is a member of the phosphatase and actin regulator family of proteins. This family member can bind actin and regulate the reorganization of the actin cytoskeleton. It plays a role in tubule formation and in endothelial cell survival. Polymorphisms in this gene are associated with susceptibility to myocardial infarction, coronary artery disease and cervical artery dissection. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Apr 2016]

Primary Disease Associations & Inheritance

Developmental and epileptic encephalopathy 70MIM #618298
AD
175
ClinVar variants
34
Pathogenic / LP
0.64
pLI score
0
Active trials
Clinical Summary— PHACTR1
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.64) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
34 Pathogenic / Likely Pathogenic· 95 VUS of 175 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.92LOEUF
pLI 0.635
Z-score 1.67
OE 0.00 (0.00–0.92)
Moderately constrained

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.71Z-score
OE missense 0.79 (0.66–0.96)
73 obs / 92.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.00 (0.00–0.92)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.79 (0.66–0.96)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.92
0≤1.21.6
LoF obs/exp: 0 / 3.2Missense obs/exp: 73 / 92.1Syn Z: 0.40

ClinVar Variant Classifications

175 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic28
Likely Pathogenic6
VUS95
Likely Benign33
Benign12
Conflicting1
28
Pathogenic
6
Likely Pathogenic
95
VUS
33
Likely Benign
12
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
3
25
0
28
Likely Pathogenic
0
3
3
0
6
VUS
6
77
12
0
95
Likely Benign
1
5
6
21
33
Benign
0
3
5
4
12
Conflicting
—1
Total7915125175

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

View in ClinVar →

Protein Context — Lollipop Plot

PHACTR1 · protein map & ClinVar variants

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

Gene2Phenotype Curations

PHACTR1-related neurodevelopment disorder

strong
ADDominant NegativeAltered Gene Product Structure
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Developmental and epileptic encephalopathy 70

MIM #618298

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — PHACTR1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Genotype and phenotype correlation of PHACTR1-related neurological disorders.
Xu Z et al.·J Med Genet
2024
Unveiling migraine subtype heterogeneity and risk loci: integrated genome-wide association study and single-cell transcriptomics discovery.
Wei S et al.·J Headache Pain
2025
Genes and Weightlifting Performance.
Kikuchi N et al.·Genes (Basel)
2021
Genomics of Fibromuscular Dysplasia.
Di Monaco S et al.·Int J Mol Sci
2018Review
Genetic Study of PHACTR1 and Fibromuscular Dysplasia, Meta-Analysis and Effects on Clinical Features of Patients: The ARCADIA-POL Study.
Warchol-Celinska E et al.·Hypertension
2020Meta-analysis
PHACTR1 splicing isoforms and eQTLs in atherosclerosis-relevant human cells.
Codina-Fauteux VA et al.·BMC Med Genet
2018
Genetic and environmental risk factors for atherosclerosis regulate transcription of phosphatase and actin regulating gene PHACTR1.
Reschen ME et al.·Atherosclerosis
2016
Deficiency of macrophage PHACTR1 impairs efferocytosis and promotes atherosclerotic plaque necrosis.
Kasikara C et al.·J Clin Invest
2021
Fibromuscular Dysplasia and Its Neurologic Manifestations: A Systematic Review.
Touzé E et al.·JAMA Neurol
2019Review
Genetic Variants in PHACTR1 & LPL Mediate Restenosis Risk in Coronary Artery Patients.
Al Hageh C et al.·Vasc Health Risk Manag
2023Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools