PHF6

Chr XXLR

PHD finger protein 6

Also known as: BFLS, BORJ, CENP-31

NCBI Gene: 84295 ENSG00000156531 UniProt: Q8IWS0 OMIM: 300414

The protein contains two PHD-type zinc finger domains and localizes to the nucleolus where it functions in transcriptional regulation. Mutations cause Borjeson-Forssman-Lehmann syndrome, an X-linked recessive disorder characterized by cognitive disability, epilepsy, hypogonadism, hypometabolism, obesity, facial swelling, narrow palpebral fissures, and large ears. The pathogenic mechanism involves loss of function of this highly constrained protein.

OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

This gene is a member of the plant homeodomain (PHD)-like finger (PHF) family. It encodes a protein with two PHD-type zinc finger domains, indicating a potential role in transcriptional regulation, that localizes to the nucleolus. Mutations affecting the coding region of this gene or the splicing of the transcript have been associated with Borjeson-Forssman-Lehmann syndrome (BFLS), a disorder characterized by cognitive disability, epilepsy, hypogonadism, hypometabolism, obesity, swelling of subcutaneous tissue of the face, narrow palpebral fissures, and large ears. Alternate splicing results in multiple transcript variants, encoding different isoforms. [provided by RefSeq, Jun 2010]

OMIM ResearchGenerating clinical summary…

LOFmechanismXLRLOEUF 0.171 OMIM phenotype

Clinical Summary— PHF6

🧬

Gene-Disease Validity (ClinGen)

Borjeson-Forssman-Lehmann syndrome · XLDefinitive

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.

💊

Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.17LOEUF

pLI 0.998

Z-score 3.93

OE 0.00 (0.00–0.17)

Highly constrained

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

Missense Constraint?

2.28Z-score

OE missense 0.44 (0.35–0.55)

57 obs / 130.4 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.17)

0≤0.351.4

Missense OE?0.44 (0.35–0.55)

0≤0.61.4

Synonymous OE?1.10

0≤1.21.6

LoF obs/exp: 0 / 18.0Missense obs/exp: 57 / 130.4Syn Z: -0.50

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitivePHF6-related Boerjeson-Forssman-Lehmann syndromeLOFmonoallelic_X_heterozygous

This gene — mechanism propensity

0.17100th %ile

GOF

0.2098th %ile

LOF

0.79top 5%

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

LOFprediction above median · LOEUF 0.17 · ClinGen HI: Sufficient evidence for dosage pathogenicity

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