PHF12

Chr 17

PHD finger protein 12

Also known as: PF1

NCBI Gene: 57649ENSG00000109118UniProt: Q96QT6

Enables phosphatidylinositol binding activity and transcription corepressor activity. Involved in negative regulation of DNA-templated transcription. Acts upstream of or within negative regulation of transcription by RNA polymerase II. Located in nucleoplasm. Part of Sin3-type complex and transcription repressor complex. [provided by Alliance of Genome Resources, Jul 2025]

0
Active trials
7
Pathogenic / LP
103
ClinVar variants
0
Pubs (1 yr)
2.4
Missense Z
0.14
LOEUF· LoF intolerant
Clinical Summary— PHF12
🧬
Gene-Disease Validity (ClinGen)
complex neurodevelopmental disorder · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
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
7 Pathogenic / Likely Pathogenic· 91 VUS of 103 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.14LOEUF
pLI 1.000
Z-score 6.07
OE 0.04 (0.02–0.14)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint
2.43Z-score
OE missense 0.72 (0.67–0.78)
439 obs / 607.5 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.04 (0.02–0.14)
0≤0.351.4
Missense OE0.72 (0.67–0.78)
0≤0.61.4
Synonymous OE0.83
0≤1.21.6
LoF obs/exp: 2 / 46.8Missense obs/exp: 439 / 607.5Syn Z: 2.08
LOF
DN
0.2598th %ile
GOF
0.2099th %ile
LOF
0.84top 5%

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

LOFprediction above median · LOEUF 0.14

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

103 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic6
Likely Pathogenic1
VUS91
Likely Benign2
Benign3
6
Pathogenic
1
Likely Pathogenic
91
VUS
2
Likely Benign
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
6
0
6
Likely Pathogenic
0
0
1
0
1
VUS
1
82
8
0
91
Likely Benign
0
1
0
1
2
Benign
0
1
0
2
3
Total184153103

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

View in ClinVar →

PHF12 · protein map & ClinVar variants

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

Gene2Phenotype Curations

PHF12-related developmental disorder

strong
ADLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
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 2 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