PHF19

Chr 9

PHD finger protein 19

Also known as: MTF2L1, PCL3, TDRD19B

PHF19 encodes a Polycomb group protein that binds methylated histones and recruits the PRC2 complex to regulate gene silencing during development, particularly in the transition from active to repressed chromatin states in embryonic stem cells. Mutations cause autosomal dominant intellectual disability with developmental delay and behavioral abnormalities. This gene is highly constrained against loss-of-function variants, indicating that haploinsufficiency is likely not tolerated in the general population.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.22
Clinical SummaryPHF19
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
22 unique Pathogenic / Likely Pathogenic· 46 VUS of 87 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint
0.22LOEUF
pLI 0.999
Z-score 5.00
OE 0.09 (0.040.22)
Highly constrained

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

Missense Constraint
3.35Z-score
OE missense 0.49 (0.430.56)
166 obs / 339.6 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.09 (0.040.22)
00.351.4
Missense OE0.49 (0.430.56)
00.61.4
Synonymous OE0.89
01.21.6
LoF obs/exp: 3 / 34.9Missense obs/exp: 166 / 339.6Syn Z: 0.98
DN
0.2399th %ile
GOF
0.2497th %ile
LOF
0.78top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.22

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

87 submitted variants in ClinVar

Classification Summary

Pathogenic21
Likely Pathogenic1
VUS46
Likely Benign1
21
Pathogenic
1
Likely Pathogenic
46
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
21
0
21
Likely Pathogenic
0
0
1
0
1
VUS
0
45
1
0
46
Likely Benign
0
1
0
0
1
Benign
0
0
0
0
0
Total04623069

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

View in ClinVar →

Protein Context — Lollipop Plot

PHF19 · 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.

Search ClinicalTrials.gov →
Clinical Literature
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