PHF19

Chr 9

PHD finger protein 19

Also known as: MTF2L1, PCL3, TDRD19B

NCBI Gene: 26147 ENSG00000119403 UniProt: Q5T6S3

Enables methylated histone binding activity. Involved in negative regulation of gene expression, epigenetic. Located in ESC/E(Z) complex. [provided by Alliance of Genome Resources, Apr 2025]

Active trials

Pathogenic / LP

ClinVar variants

Pubs (1 yr)

3.3

Missense Z· constrained

0.22

LOEUF· LoF intolerant

Clinical Summary— PHF19

⚡

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.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

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.

0.22LOEUF

pLI 0.999

Z-score 5.00

OE 0.09 (0.04–0.22)

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.

3.35Z-score

OE missense 0.49 (0.43–0.56)

166 obs / 339.6 exp

Constrained

Highly missense-constrained (top ~0.1%)

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.0.09 (0.04–0.22)

0≤0.351.4

Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.49 (0.43–0.56)

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.0.89

0≤1.21.6

LoF obs/exp: 3 / 34.9Missense obs/exp: 166 / 339.6Syn Z: 0.98

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.