PHF1

Chr 6

PHD finger protein 1

Also known as: MTF2L2, PCL1, TDRD19C, hPHF1

NCBI Gene: 5252ENSG00000112511UniProt: O43189

This gene encodes a Polycomb group protein. The protein is a component of a histone H3 lysine-27 (H3K27)-specific methyltransferase complex, and functions in transcriptional repression of homeotic genes. The protein is also recruited to double-strand breaks, and reduced protein levels results in X-ray sensitivity and increased homologous recombination. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2009]

77
ClinVar variants
5
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— PHF1
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
5 Pathogenic / Likely Pathogenic· 65 VUS of 77 total submissions
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
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.
0.20LOEUF
pLI 1.000
Z-score 4.83
OE 0.06 (0.03–0.20)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

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.
1.80Z-score
OE missense 0.73 (0.65–0.81)
248 obs / 341.5 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.0.06 (0.03–0.20)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.73 (0.65–0.81)
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.0.99
0≤1.21.6
LoF obs/exp: 2 / 31.0Missense obs/exp: 248 / 341.5Syn Z: 0.08

ClinVar Variant Classifications

77 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic4
Likely Pathogenic1
VUS65
Likely Benign7
4
Pathogenic
1
Likely Pathogenic
65
VUS
7
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
4
0
4
Likely Pathogenic
0
0
1
0
1
VUS
0
56
9
0
65
Likely Benign
0
6
0
1
7
Benign
0
0
0
0
0
Total06214177

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

View in ClinVar →

Protein Context — Lollipop Plot

PHF1 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Phosphorylated tau interactome in the human Alzheimer's disease brain.
Drummond E et al.·Brain
2020
Ossifying fibromyxoid tumours: A case series.
Pozas J et al.·Eur J Cancer
2025Cohort
Traumatic brain injury or head impacts from contact sports are associated with tau astrogliopathy.
Arena JD et al.·Brain
2025
Structural basis for histone variant H3tK27me3 recognition by PHF1 and PHF19.
Dong C et al.·Elife
2020
A novel MBTD1-PHF1 gene fusion in endometrial stromal sarcoma: A case report and literature review.
Han L et al.·Genes Chromosomes Cancer
2020Review
Glial reactivity and T cell infiltration in frontotemporal lobar degeneration with tau pathology.
Hartnell IJ et al.·Brain
2024
Expanding the molecular signatures of malignant ossifying fibromyxoid tumours with two novel gene fusions: PHF1::FOXR1 and PHF1::FOXR2.
Srivastava P et al.·Histopathology
2023Case report
Immunohistochemical evaluation of a trial of gantenerumab or solanezumab in dominantly inherited Alzheimer disease.
Chen CD et al.·Acta Neuropathol
2025
Tissue-Specific Tumour Suppressor and Oncogenic Activities of the Polycomb-like Protein MTF2.
Ngubo M et al.·Genes (Basel)
2023Review
Novel recurrent PHF1-TFE3 fusions in ossifying fibromyxoid tumors.
Suurmeijer AJH et al.·Genes Chromosomes Cancer
2019Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Ossification-deficient atypical ossifying fibromyxoid tumor of submandibular gland with PHF1::EP400 fusion: diagnostic challenges.
Sun Y et al.·Oral Maxillofac Surg
2025
Uterine Mesenchymal Neoplasm With BRD8::PHF1 Fusion: Low-grade Endometrial Stromal Sarcoma or Uterine Ossifying Fibromyxoid Tumor?
O'Neill N et al.·Int J Gynecol Pathol
2026
pS396/pS404 (PHF1) tau vaccine outperforms pS199/pS202 (AT8) in rTg4510 tauopathy model.
Hulse JP et al.·NPJ Vaccines
2025🔓 Open AccessFunctional
PHF1::TFE3-positive fibromyxoid sarcoma? Report of 2 cases and review of 13 cases of PHF1::TFE3-positive ossifying fibromyxoid tumor in the literature.
Wei S et al.·Am J Clin Pathol
2025Review
Aggressive Malignant Ossifying Fibromyxoid Tumor With a Rare PHF1::FOXR2 Fusion: A Case Report and Literature Review.
Syrnioti A et al.·Int J Surg Pathol
2025Review
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