PHC1

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

Basic information

Region (hg38): 12:8913895-8941467

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.

• Inborn genetic diseases (38 variants)
• not provided (34 variants)
• not specified (17 variants)
• Microcephaly 11, primary, autosomal recessive (9 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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	6	5	12
missense			49	3	3	55
nonsense	1					1
start loss						0
frameshift						0
inframe indel					1	1
splice donor/acceptor (+/-2bp)						0
splice region			1		1	2
non coding				1	18	19
Total	1	0	50	10	27

Variants in PHC1

This is a list of pathogenic ClinVar variants found in the PHC1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
12-8917690-A-C		not specified	Uncertain significance (May 17, 2023)
12-8917735-G-A		not specified	Uncertain significance (Oct 17, 2023)
12-8917739-G-C		not specified	Uncertain significance (Nov 18, 2022)
12-8917748-C-T		Microcephaly 11, primary, autosomal recessive	Uncertain significance (May 14, 2018)
12-8917770-T-A		Microcephaly 11, primary, autosomal recessive	Benign (Sep 05, 2021)
12-8917777-C-T		Microcephaly 11, primary, autosomal recessive	Pathogenic (-)
12-8917778-G-A		not specified	Uncertain significance (Jun 18, 2020)
12-8917982-T-C			Benign (Jun 19, 2021)
12-8919566-C-T			Benign (Jun 19, 2021)
12-8919803-C-T		not specified	Likely benign (Feb 20, 2017)
12-8919860-C-A		PHC1-related disorder	Likely benign (May 01, 2019)
12-8921004-G-A		not specified	Uncertain significance (Dec 18, 2023)
12-8921043-A-C		not specified	Uncertain significance (Jun 21, 2022)
12-8921058-A-G		not specified	Uncertain significance (May 23, 2023)
12-8921072-A-G		not specified	Uncertain significance (Feb 10, 2017)
12-8921619-T-C		not specified	Uncertain significance (Aug 08, 2023)
12-8921661-C-T		not specified	Uncertain significance (May 17, 2023)
12-8921663-C-T		Microcephaly 11, primary, autosomal recessive	Benign (Sep 05, 2021)
12-8921679-A-G		not specified	Uncertain significance (Apr 25, 2022)
12-8922418-G-T			Benign (Jun 19, 2021)
12-8922662-C-T		not specified	Uncertain significance (May 04, 2015)
12-8922710-G-A		not specified	Uncertain significance (Nov 23, 2021)
12-8922797-C-T		not specified	Likely benign (Oct 12, 2020)
12-8930161-C-T			Benign (Jun 19, 2021)
12-8930259-A-G			Benign (Jun 19, 2021)

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