PHACTR2

Chr 6

phosphatase and actin regulator 2

Also known as: C6orf56

NCBI Gene: 9749ENSG00000112419UniProt: O75167OMIM: 608724

PHACTR2 encodes a protein that binds actin and organizes the actin cytoskeleton, localizing to plasma membranes and platelet alpha granule membranes. This gene is highly constrained against loss-of-function variants and has been implicated in neurodegenerative conditions including Parkinson's disease and multiple sclerosis. The inheritance pattern for PHACTR2-related disorders has not been definitively established in pediatric populations.

OMIMResearchSummary from RefSeq
DNmechanismLOEUF 0.69
Clinical Summary— PHACTR2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
15 unique Pathogenic / Likely Pathogenic· 25 VUS of 41 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.69LOEUF
pLI 0.000
Z-score 3.01
OE 0.45 (0.31–0.69)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.81Z-score
OE missense 0.88 (0.80–0.96)
299 obs / 341.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.45 (0.31–0.69)
0≤0.351.4
Missense OE0.88 (0.80–0.96)
0≤0.61.4
Synonymous OE1.03
0≤1.21.6
LoF obs/exp: 16 / 35.3Missense obs/exp: 299 / 341.2Syn Z: -0.23
DN
0.6842th %ile
GOF
0.5170th %ile
LOF
0.4430th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

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.

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

ClinVar Variant Classifications

41 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic15
VUS25
Likely Benign1
15
Pathogenic
25
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
15
0
15
Likely Pathogenic
0
0
0
0
0
VUS
0
24
1
0
25
Likely Benign
0
0
1
0
1
Benign
0
0
0
0
0
Total02417041

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

View in ClinVar →

Protein Context — Lollipop Plot

PHACTR2 · 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

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 5 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