PHF10
protein-codingPHD finger protein 10, the group of PHD finger proteins|BAF complex|PBAF complex
Gene summary
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]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~21.7 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0019042
Submitter: LiferaOmics
Genetic evidence – Published (AR scope) No scorable published cases of biallelic (autosomal recessive) PHF10 variants causing neurodevelopmental disorder were identified in the literature. Published genetic evidence total = 0 / 12 Published (AD context; not scored for AR) PMID: 37500730 – Large cohort analysis of mSWI/SNF (BAF) complex genes in neurodevelopmental disorders. PHF10 is discussed in the context of chromatin remodeling and enrichment of pathogenic variants in neurodevelopmental cohorts; however, this publication does not report biallelic PHF10 cases nor establish an autosomal recessive disease mechanism. Therefore, it is not scorable under the AR model. AD-context / complex-level evidence total (not scored for AR) = 0 Genetic evidence – Our cases Family 1- One proband. Case-level (biallelic predicted null in AR model; homozygous scored once; consanguinity −0.5 applied) = (1.5 − 0.5) = 1.0; segregation = 0; case-control =0 Family 1 total = 1.0 Family 2-one proband. Case-level (biallelic predicted null in AR model; homozygous scored once; consanguinity −0.5 applied) = (1.5 − 0.5) = 1.0; segregation (affected sibling; conservative assignment) = 0.5; case-control = 0 Family 2 total = 1.5 Total genetic evidence (published AR + our cases) 0 (published AR) + 2.5 (our cases) = 2.5 / 12 Experimental evidence – Published PMID: 37500730 – Demonstrates that PHF10 is a component of the mSWI/SNF (BAF) chromatin remodeling complex, which plays a critical role in neurodevelopment, neural progenitor regulation, and transcriptional control. While this publication does not establish an autosomal recessive PHF10 disorder, it supports strong biological plausibility that disruption of PHF10 function could impair neurodevelopment. Gene function / biological plausibility = 0.5 Experimental evidence total = 0.5 / 6 Overall score Genetic evidence = 2.5 Experimental evidence = 0.5 Overall score = 3.0 / 18
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to PHF10 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_018288.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | 1 | 1 | 4 | ||
| missense | 57 | 1 | 58 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 63 | 2 | 1 | 66 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_060758.2 | 12 | MANE Select | |
| Ensembl | ENSP00000341805.4 | 12 | MANE Select | |
| RefSeq | NP_579866.2 | 12 | Standard | |
| Ensembl | ENSP00000355743.4 | 12 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Hepatocellular carcinoma - Homo sapiens (human)
Biological Process
- nervous system development
- histone acetylation
- negative regulation of transcription, DNA-templated
- positive regulation of transcription by RNA polymerase II
Molecular Function
- histone acetyltransferase activity
- histone binding
- metal ion binding
Cellular Component
- histone acetyltransferase complex
- nuclear chromatin
- nucleus
- npBAF complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000339209
- Coding exons
- 12
- Length
- 20151
- Individuals with no LoFs
- 125713
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 35
- Defined
- 125748
- p
- 0.000139
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.79 | 173 | 253 | 0.684 | 0.0000129 | 3252 |
| Missense (PolyPhen) | 33 | 62.399 | 0.52886 | 776 | ||
| Synonymous | -0.159 | 84 | 82.2 | 1.02 | 0.00000371 | 898 |
| Loss of Function | 3.01 | 11 | 28.3 | 0.389 | 0.00000152 | 359 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00019 | 0.00018 | rare |
| Latino/Admixed American | 0.000091 | 0.000087 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0.00014 | 0.00014 | rare |
| European (Non-Finnish) | 0.00016 | 0.00015 | rare |
| South Asian | 0.00013 | 0.00013 | rare |
| Other | 0.00065 | 0.00065 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Involved in transcription activity regulation by chromatin remodeling. Belongs to the neural progenitors-specific chromatin remodeling complex (npBAF complex) and is required for the proliferation of neural progenitors. During neural development a switch from a stem/progenitor to a post-mitotic chromatin remodeling mechanism occurs as neurons exit the cell cycle and become committed to their adult state. The transition from proliferating neural stem/progenitor cells to post-mitotic neurons requires a switch in subunit composition of the npBAF and nBAF complexes. As neural progenitors exit mitosis and differentiate into neurons, npBAF complexes which contain ACTL6A/BAF53A and PHF10/BAF45A, are exchanged for homologous alternative ACTL6B/BAF53B and DPF1/BAF45B or DPF3/BAF45C subunits in neuron- specific complexes (nBAF). The npBAF complex is essential for the self-renewal/proliferative capacity of the multipotent neural stem cells. The nBAF complex along with CREST plays a role regulating the activity of genes essential for dendrite growth (By similarity). {ECO:0000250}.;
Recessive Scores
- pRec
- 0.107
Intolerance Scores
- LoFtool
- 0.284
- RVIS EVS
- -0.43
- RVIS percentile EVS
- 25.15
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.973
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |