PHACTR1

Chr 6AD

phosphatase and actin regulator 1

The protein binds actin monomers and regulates actin cytoskeleton dynamics, cell motility, endothelial cell survival, and cortical neuron migration and dendrite arborization. Mutations cause developmental and epileptic encephalopathy 70, inherited in an autosomal dominant pattern.

OMIMResearchSummary from RefSeq, OMIM, UniProt
DNmechanismADLOEUF 0.921 OMIM phenotype
Clinical SummaryPHACTR1
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.64) — some intolerance to loss-of-function variants.
Some data sources returned errors (1)

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.92LOEUF
pLI 0.635
Z-score 1.67
OE 0.00 (0.000.92)
Moderately constrained

Typical tolerance to LoF variation

Missense Constraint
0.71Z-score
OE missense 0.79 (0.660.96)
73 obs / 92.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.00 (0.000.92)
00.351.4
Missense OE0.79 (0.660.96)
00.61.4
Synonymous OE0.92
01.21.6
LoF obs/exp: 0 / 3.2Missense obs/exp: 73 / 92.1Syn Z: 0.40
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongPHACTR1-related neurodevelopment disorderDNAD
DN
0.5771th %ile
GOF
0.5563th %ile
LOF
0.61top 25%

The Badonyi & Marsh model scores loss-of-function highest, but genomic evidence most strongly supports dominant-negative as the primary mechanism.

DN1 literature citation

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Literature Evidence

DNIn addition, expression of the mutations in mice induced migration defects and caused abnormal cortical architecture in a dominant-negative manner.PMID:30256902

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants 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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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