PHF2

Chr 9

PHD finger protein 2

Also known as: CENP-35, GRC5, JHDM1E, KDM7C

This gene encodes a lysine demethylase that removes methyl groups from histones and non-histone proteins, functioning as a transcriptional regulator that influences chromatin structure and gene expression. Mutations cause autosomal dominant neurodevelopmental disorders with intellectual disability and developmental delay. The gene is highly constrained against loss-of-function variants (pLI 1.0, LOEUF 0.18), indicating intolerance to protein-disrupting mutations.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.18
Clinical SummaryPHF2
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

Dual constrained — LoF & missense intolerant
LoF Constraint
0.18LOEUF
pLI 1.000
Z-score 6.16
OE 0.08 (0.040.18)
Highly constrained

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

Missense Constraint
3.49Z-score
OE missense 0.61 (0.560.66)
389 obs / 637.2 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.08 (0.040.18)
00.351.4
Missense OE0.61 (0.560.66)
00.61.4
Synonymous OE1.00
01.21.6
LoF obs/exp: 4 / 51.9Missense obs/exp: 389 / 637.2Syn Z: 0.01
DN
0.2798th %ile
GOF
0.2298th %ile
LOF
0.84top 5%

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

LOFprediction above median · LOEUF 0.18

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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

PHF2 · 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.

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Clinical Literature
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