PHF10

Chr 6

PHD finger protein 10

Also known as: BAF45A, SMARCG4, XAP135

NCBI Gene: 55274 ENSG00000130024 UniProt: Q8WUB8 OMIM: 613069

PHF10 encodes a chromatin remodeling protein that belongs to the neural progenitor-specific BAF complex (npBAF) and regulates transcription by switching from stem cell to neuronal chromatin remodeling during brain development. Mutations cause Bainbridge-Ropers syndrome, an autosomal dominant neurodevelopmental disorder characterized by intellectual disability, developmental delay, autism spectrum disorder, and distinctive facial features. The gene shows tolerance to loss-of-function variants (low pLI score), suggesting the disorder may involve complex mechanisms affecting chromatin remodeling in developing neural tissue.

OMIM ResearchSummary from RefSeq, UniProt

This gene contains a predicted ORF that encodes a protein with two zinc finger domains. The function of the encoded protein is not known. Sequence analysis suggests that multiple alternatively spliced transcript variants are derived from this gene but the full-length nature of only two of them is known. These two splice variants encode different isoforms. A pseudogene for this gene is located on Xq28. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 0.64

Clinical Summary— PHF10

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

56 VUS of 77 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.64LOEUF

pLI 0.000

Z-score 3.01

OE 0.39 (0.24–0.64)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.79Z-score

OE missense 0.68 (0.60–0.78)

173 obs / 252.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.39 (0.24–0.64)

0≤0.351.4

Missense OE?0.68 (0.60–0.78)

0≤0.61.4

Synonymous OE?1.02

0≤1.21.6

LoF obs/exp: 11 / 28.3Missense obs/exp: 173 / 252.9Syn Z: -0.16

This gene — mechanism propensity

0.6453th %ile

GOF

0.5170th %ile

LOF

0.4332th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

77 submitted variants in ClinVar

ClinVar

Classification Summary

VUS56

Likely Benign2

Benign1

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	56	0	56
Likely Benign	1	1	2
Benign	0	1	1
Total	57	2	59

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

View in ClinVar →

78 pathogenic / likely-pathogenic (of 83) ClinVar copy-number / structural variants overlap PHF10 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →