PHC3

protein-coding

polyhomeotic homolog 3, the group of Sterile alpha motif domain containing

Gene summary

Predicted to enable chromatin binding activity and histone binding activity. Predicted to be involved in negative regulation of DNA-templated transcription. Located in nucleoplasm. Part of PRC1 complex. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_024947.4

Inheritance

—

ClinVar variants

U:129B:1

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.02

Max pathogenic AF

—

Genomic locus

chr3:170,086,732-170,181,749

External References & Databases

Ensembl (ENSG00000173889)

Transcript & Mutation Effects

hg38 • Region Span ~95.0 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 PHC3 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 119

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_024947.4. 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 clinvar	1 clinvar		3
missense			122 clinvar			122
nonsense			1 clinvar			1
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	129	1	0	130

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 60 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_024947.4	RefSeq	NP_079223.3	15	MANE Select
ENST00000495893.7	Ensembl	ENSP00000420294.1	15	MANE Select
NM_001308116.2	RefSeq	NP_001295045.1	14	Standard
NM_001437995.1	RefSeq	NP_001424924.1	16	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Signal Transduction
Gene expression (Transcription)
RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known
Transcriptional Regulation by E2F6
Generic Transcription Pathway

Biological Process

multicellular organism development
negative regulation of G0 to G1 transition

Molecular Function

DNA binding
protein binding
zinc ion binding

Cellular Component

nucleus
nucleoplasm
PcG protein complex
PRC1 complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000495893
Coding exons: 15
Length: 95018
Individuals with no LoFs: 124581
Homozygous LoFs: 0
Heterozygous LoFs: 3
Defined: 124584
p: 0.0000120

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.72	425	537	0.791	0.0000282	6436
Missense (PolyPhen)		189	273.09	0.69208		3317
Synonymous	-1.55	217	190	1.14	0.00000940	2048
Loss of Function	6.36	1	49.1	0.0204	0.00000263	532

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000056	0.000056	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.0000089	0.0000089	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Component of a Polycomb group (PcG) multiprotein PRC1- like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development. PcG PRC1 complex acts via chromatin remodeling and modification of histones; it mediates monoubiquitination of histone H2A 'Lys-119', rendering chromatin heritably changed in its expressibility. {ECO:0000269|PubMed:12167701}.;

Recessive Scores

pRec: 0.150

Intolerance Scores

LoFtool: 0.227
RVIS EVS: -0.46
RVIS percentile EVS: 23.63

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.947

Gene Damage Prediction

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