PHC1

polyhomeotic homolog 1, the group of Sterile alpha motif domain containing

Basic information

Region (hg38): 12:8913896-8941467

Previous symbols: [ "EDR1" ]

Links

ENSG00000111752

∙ NCBI:1911 ∙ OMIM:602978 ∙ HGNC:3182 ∙ Uniprot:P78364 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

microcephaly 11, primary, autosomal recessive (Limited), mode of inheritance: AR
autosomal recessive primary microcephaly (Supportive), mode of inheritance: AR
microcephaly 11, primary, autosomal recessive (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Microcephaly 11, primary, autosomal recessive	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	23418308

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PHC1 gene.

not_specified (126 variants)
not_provided (18 variants)
PHC1-related_disorder (6 variants)
Microcephaly_11,_primary,_autosomal_recessive (5 variants)
Primary_microcephaly (1 variants)
Intellectual_disability (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PHC1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000004426.3. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	10 clinvar		11
missense		1 clinvar	120 clinvar	4 clinvar	1 clinvar	126
nonsense	1 clinvar			1 clinvar		2
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	1	1	121	15	1

Highest pathogenic variant AF is 0.000001422196

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PHC1	protein_coding	protein_coding	ENST00000543824	14	27572

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.999	0.000619	125744	0	4	125748	0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.92	375	495	0.757	0.0000266	6373
Missense in Polyphen		85	112.03	0.7587		1396
Synonymous	-0.115	191	189	1.01	0.0000101	2071
Loss of Function	5.40	5	43.4	0.115	0.00000207	485

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000124	0.000123
Ashkenazi Jewish	0.0000997	0.0000992
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00000881	0.00000879
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

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. Required for proper control of cellular levels of GMNN expression. {ECO:0000269|PubMed:23418308}.;
Disease: DISEASE: Microcephaly 11, primary, autosomal recessive (MCPH11) [MIM:615414]: A form of microcephaly, a disease defined as a head circumference more than 3 standard deviations below the age- related mean. Brain weight is markedly reduced and the cerebral cortex is disproportionately small. {ECO:0000269|PubMed:23418308}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: Signal Transduction;Gene expression (Transcription);RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known;the prc2 complex sets long-term gene silencing through modification of histone tails;Transcriptional Regulation by E2F6;Generic Transcription Pathway;Oxidative Stress Induced Senescence;SUMOylation of DNA damage response and repair proteins;Cellular Senescence;SUMOylation of chromatin organization proteins;Cellular responses to stress;SUMOylation of RNA binding proteins;Post-translational protein modification;SUMO E3 ligases SUMOylate target proteins;Metabolism of proteins;RNA Polymerase II Transcription;SUMOylation;Cellular responses to external stimuli;Regulation of PTEN gene transcription;PTEN Regulation;PIP3 activates AKT signaling;Intracellular signaling by second messengers;Transcriptional regulation by RUNX1 (Consensus)

Recessive Scores

pRec: 0.147

Intolerance Scores

loftool: 0.395
rvis_EVS: 0.05
rvis_percentile_EVS: 57.48

Haploinsufficiency Scores

pHI: 0.489
hipred: Y
hipred_score: 0.572
ghis: 0.512

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.745

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Phc1
Phenotype: endocrine/exocrine gland phenotype; growth/size/body region phenotype; craniofacial phenotype; hearing/vestibular/ear phenotype; limbs/digits/tail phenotype; digestive/alimentary phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; embryo phenotype; skeleton phenotype; immune system phenotype; vision/eye phenotype;

Gene ontology

Biological process: multicellular organism development;histone ubiquitination;negative regulation of G0 to G1 transition
Cellular component: nucleus;nucleoplasm;PcG protein complex;PRC1 complex
Molecular function: DNA binding;protein binding;zinc ion binding