PHF6

Chr X

PHD finger protein 6

Also known as: BFLS, BORJ, CENP-31

NCBI Gene: 84295ENSG00000156531UniProt: Q8IWS0

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]

GeneReviewsResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtBoerjeson-Forssman-Lehmann syndrome

Clinical highlights

Gene-disease validity (ClinGen)
Borjeson-Forssman-Lehmann syndrome · XLDefinitivesufficient evidence for diagnostic panels
Interpreting a novel variant
Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.
1
Active trials
58
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.17
LOEUF· LoF intol.
LOF
Mechanism· G2P
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GeneReview available — PHF6
Authoritative clinical overview · Recommended first read
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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

PHF6 · protein map & ClinVar variants

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

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