PHRF1

protein-coding

PHD and ring finger domains 1, the group of Ring finger proteins|Protein phosphatase 1 regulatory subunits|PHD finger proteins

Gene summary

Predicted to enable RNA polymerase binding activity. Predicted to be involved in protein ubiquitination. Located in membrane. [provided by Alliance of Genome Resources, Jul 2025]

Previous symbols:

RNF221

MANE transcript

NM_001286581.2

Inheritance

—

ClinVar variants

U:370B:63

Top phenotype

PHRF1-related disorder

gnomAD constraint

pLI —, LoF o/e 0.25

Max pathogenic AF

—

Genomic locus

chr11:576,470-612,222

External References & Databases

Ensembl (ENSG00000070047)

Transcript & Mutation Effects

hg38 • Region Span ~35.8 kb

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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 PHRF1 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 396

not providedTotal: 12

PHRF1-related disorderTotal: 12

Aganglionic megacolonTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001286581.2. 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	10 clinvar	1 clinvar	17
missense			361 clinvar	47 clinvar	3 clinvar	411
nonsense			2 clinvar			2
start loss						0
frameshift				2 clinvar		2
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	370	59	4	433

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 73 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001286581.2	RefSeq	NP_001273510.1	17	MANE Select
ENST00000264555.10	Ensembl	ENSP00000264555.5	17	MANE Select
NM_001286582.2	RefSeq	NP_001273511.1	17	Standard
NM_001286583.2	RefSeq	NP_001273512.1	17	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

transcription by RNA polymerase II
mRNA processing

Molecular Function

protein domain specific binding
metal ion binding
RNA polymerase binding

Cellular Component

membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000416188
Coding exons: 17
Length: 35737
Individuals with no LoFs: 124718
Homozygous LoFs: 1
Heterozygous LoFs: 163
Defined: 124882
p: 0.000657

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-1.56	1207	1.06e+3	1.14	0.0000744	10505
Missense (PolyPhen)		339	329.87	1.0277		3160
Synonymous	-4.34	597	476	1.25	0.0000367	3556
Loss of Function	5.40	15	60.2	0.249	0.00000392	634

Population LoF Frequency

Population	CAF	p-value	Status
African	0.015	0.0067	notable
Latino/Admixed American	0.0014	0.00072	notable
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000056	0.000056	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00027	0.00019	rare
South Asian	0.00020	0.00016	rare
Other	0.0012	0.00099	notable

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.110

Intolerance Scores

LoFtool: 0.131
RVIS EVS: -1.58
RVIS percentile EVS: 3.13

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.299

Gene Damage Prediction

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