PHF2

protein-coding

PHD finger protein 2, the group of MicroRNA protein coding host genes|Lysine demethylases|PHD finger proteins

Gene summary

This gene encodes a protein which contains a zinc finger-like PHD (plant homeodomain) finger, distinct from other classes of zinc finger motifs, and a hydrophobic and highly conserved domain. The PHD finger shows the typical Cys4-His-Cys3 arrangement. PHD finger genes are thought to belong to a diverse group of transcriptional regulators possibly affecting eukaryotic gene expression by influencing chromatin structure. [provided by RefSeq, Jul 2008]

MANE transcript

NM_005392.4

Inheritance

—

ClinVar variants

P:1U:138B:30

Top phenotype

PHF2-related disorder

gnomAD constraint

pLI —, LoF o/e 0.08

Max pathogenic AF

—

Genomic locus

chr9:93,576,584-93,679,587

External References & Databases

Ensembl (ENSG00000197724)

Transcript & Mutation Effects

hg38 • Region Span ~103.0 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PHF2 variants in ClinVar

6 Conditions Cataloged

not specifiedTotal: 124

not providedTotal: 19

PHF2-related disorderTotal: 19

Autism spectrum disorderTotal: 2

Neurodevelopmental disorderTotal: 1

Prostate cancerTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005392.4. 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			6 clinvar	12 clinvar	8 clinvar	26
missense			125 clinvar	7 clinvar	3 clinvar	135
nonsense		1 clinvar				1
start loss						0
frameshift			4 clinvar			4
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	1	138	19	11	169

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 24 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005392.4	RefSeq	NP_005383.3	22	MANE Select
ENST00000359246.9	Ensembl	ENSP00000352185.4	22	MANE Select
ENST00000610682.1	Ensembl	ENSP00000479936.1	8	Standard
ENST00000610682.2	Ensembl	ENSP00000479936.1	8	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

HDMs demethylate histones
Chromatin modifying enzymes
Chromatin organization

Biological Process

liver development
protein demethylation
histone H3-K9 demethylation
oxidation-reduction process
negative regulation of chromatin silencing at rDNA

Molecular Function

transcription coactivator activity
iron ion binding
protein binding
zinc ion binding
histone demethylase activity

Cellular Component

kinetochore
condensed chromosome kinetochore
nucleus
nucleoplasm
nucleolus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000359246
Coding exons: 22
Length: 103181
Individuals with no LoFs: 125732
Homozygous LoFs: 0
Heterozygous LoFs: 15
Defined: 125747
p: 0.0000596

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.49	389	637	0.610	0.0000401	7112
Missense (PolyPhen)		1	5.9297	0.16864		44
Synonymous	0.00914	288	288	0.999	0.0000210	2129
Loss of Function	6.16	4	51.9	0.0771	0.00000253	642

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00018	0.000062	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.00032	0.00032	rare
European (Non-Finnish)	0.0000088	0.0000088	rare
South Asian	0.000098	0.000065	rare
Other	0.00050	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Lysine demethylase that demethylates both histones and non-histone proteins. Enzymatically inactive by itself, and becomes active following phosphorylation by PKA: forms a complex with ARID5B and mediates demethylation of methylated ARID5B. Demethylation of ARID5B leads to target the PHF2-ARID5B complex to target promoters, where PHF2 mediates demethylation of dimethylated 'Lys-9' of histone H3 (H3K9me2), followed by transcription activation of target genes. The PHF2-ARID5B complex acts as a coactivator of HNF4A in liver. PHF2 is recruited to trimethylated 'Lys-4' of histone H3 (H3K4me3) at rDNA promoters and promotes expression of rDNA. {ECO:0000269|PubMed:20129925, ECO:0000269|PubMed:21167174, ECO:0000269|PubMed:21532585}.;

Recessive Scores

pRec: 0.111

Intolerance Scores

LoFtool: 0.352
RVIS EVS: -1.03
RVIS percentile EVS: 7.86

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.226

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	Medium	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High