PHACTR1

Chr 6

phosphatase and actin regulator 1

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

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]

GeneReviewsResearchGenerating clinical summary…
DNmechanismLOEUF 0.92
Clinical SummaryPHACTR1
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.64) — some intolerance to loss-of-function variants.
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ClinVar Variants
7 unique Pathogenic / Likely Pathogenic· 92 VUS of 156 total submissions
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GeneReview available — PHACTR1
Authoritative clinical overview · Recommended first read
Open GeneReview ↗
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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 OE?0.00 (0.000.92)
00.351.4
Missense OE?0.79 (0.660.96)
00.61.4
Synonymous OE?0.92
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

This gene — mechanism propensity

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.1

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

References

  1. 1.PMID 30256902

ClinVar Variant Classifications

156 submitted variants in ClinVar

Classification Summary

Pathogenic3
Likely Pathogenic4
VUS92
Likely Benign35
Benign12
Conflicting1
3
Pathogenic
4
Likely Pathogenic
92
VUS
35
Likely Benign
12
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
3
0
0
3
Likely Pathogenic
0
3
1
0
4
VUS
8
81
3
0
92
Likely Benign
1
5
6
23
35
Benign
0
3
5
4
12
Conflicting
1
Total9951527147

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

View in ClinVar →

27 pathogenic / likely-pathogenic (of 34) ClinVar copy-number / structural variants overlap PHACTR1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

PHACTR1 · 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

No active trials found for this gene.

Search ClinicalTrials.gov →