PHF21A

PHD finger protein 21A, the group of PHD finger proteins

Basic information

Region (hg38): 11:45929318-46121454

Links

ENSG00000135365 ∙ NCBI:51317 ∙ OMIM:608325 ∙ HGNC:24156 ∙ Uniprot:Q96BD5 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Potocki-Shaffer syndrome (Strong), mode of inheritance: AD
• intellectual developmental disorder with behavioral abnormalities and craniofacial dysmorphism with or without seizures (Moderate), mode of inheritance: AD
• intellectual developmental disorder with behavioral abnormalities and craniofacial dysmorphism with or without seizures (Strong), mode of inheritance: AD
• complex neurodevelopmental disorder (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder with behavioral abnormalities and craniofacial dysmorphism with or without seizures	AD	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	Craniofacial; Musculoskeletal; Neurologic	30487643; 31649809

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PHF21A gene.

• not provided (131 variants)
• Intellectual developmental disorder with behavioral abnormalities and craniofacial dysmorphism with or without seizures (26 variants)
• Inborn genetic diseases (21 variants)
• not specified (5 variants)
• PHF21A-related condition (2 variants)
• See cases (2 variants)
• Intellectual disability (1 variants)
• Autism spectrum disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PHF21A 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				33	8	41
missense			57	6	6	69
nonsense	5	1				6
start loss						0
frameshift	11	3				14
inframe indel			2	1		3
splice donor/acceptor (+/-2bp)		5				5
splice region			1	6	5	12
non coding			4	8	6	18
Total	16	9	63	48	20

Variants in PHF21A

This is a list of pathogenic ClinVar variants found in the PHF21A region.

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

Position	Type	Phenotype	Significance	ClinVar
11-45933982-C-T			Uncertain significance (Dec 22, 2023)
11-45933987-T-G			Uncertain significance (Oct 27, 2023)
11-45933998-C-T			Likely benign (Mar 21, 2022)
11-45933999-G-A		PHF21A-related disorder	Likely benign (Jan 29, 2024)
11-45934018-AG-A		Inborn genetic diseases	Likely pathogenic (May 08, 2019)
11-45934021-G-A		Inborn genetic diseases	Uncertain significance (Feb 26, 2024)
11-45934031-C-T			Likely benign (Dec 06, 2023)
11-45934033-G-A			Uncertain significance (Oct 17, 2022)
11-45934034-C-T		PHF21A-related disorder	Likely benign (Dec 01, 2023)
11-45934035-G-A			Uncertain significance (Dec 30, 2023)
11-45934045-C-T			Benign (Jan 29, 2024)
11-45934046-G-A			Likely benign (Aug 17, 2023)
11-45934054-C-T			Benign (Nov 07, 2023)
11-45934054-CA-C			Pathogenic (Aug 23, 2023)
11-45934055-AG-A		Intellectual developmental disorder with behavioral abnormalities and craniofacial dysmorphism with or without seizures	Pathogenic (Aug 14, 2023)
11-45934057-G-T			Benign (Aug 22, 2022)
11-45934060-G-C			Uncertain significance (Feb 09, 2023)
11-45934061-G-C			Likely benign (Jan 27, 2024)
11-45934062-G-A		Inborn genetic diseases	Benign/Likely benign (Jan 10, 2024)
11-45934062-G-C			Uncertain significance (Dec 20, 2023)
11-45934070-C-T			Likely benign (Feb 11, 2023)
11-45934071-G-A			Uncertain significance (Aug 14, 2023)
11-45934073-G-A			Likely benign (Nov 24, 2023)
11-45934077-T-C		PHF21A-related disorder	Benign (Jan 30, 2024)
11-45934081-A-G		Intellectual developmental disorder with behavioral abnormalities and craniofacial dysmorphism with or without seizures	Uncertain significance (Mar 26, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PHF21A	protein_coding	protein_coding	ENST00000418153	16	192115

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.00000170	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.86	223	380	0.587	0.0000201	4444
Missense in Polyphen		68	153.12	0.44411		1865
Synonymous	1.17	124	142	0.875	0.00000789	1366
Loss of Function	5.64	0	37.1	0.00	0.00000192	395

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Component of the BHC complex, a corepressor complex that represses transcription of neuron-specific genes in non-neuronal cells. The BHC complex is recruited at RE1/NRSE sites by REST and acts by deacetylating and demethylating specific sites on histones, thereby acting as a chromatin modifier. In the BHC complex, it may act as a scaffold. Inhibits KDM1A-mediated demethylation of 'Lys-4' of histone H3 in vitro, suggesting a role in demethylation regulation. {ECO:0000269|PubMed:16140033}.
• Pathway: Factors involved in megakaryocyte development and platelet production;HDACs deacetylate histones;Chromatin modifying enzymes;Hemostasis;Chromatin organization (Consensus)

Recessive Scores

• pRec: 0.131

Intolerance Scores

• loftool: 0.0517
• rvis_EVS: -0.62
• rvis_percentile_EVS: 17.31

Haploinsufficiency Scores

• pHI: 0.459
• hipred: Y
• hipred_score: 0.853
• ghis: 0.611

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: H
• gene_indispensability_pred: E
• gene_indispensability_score: 0.801

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Phf21a
• 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: phf21ab
• Affected structure: aortic arch
• Phenotype tag: abnormal
• Phenotype quality: hypoplastic

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;blood coagulation;histone deacetylation
• Cellular component: histone deacetylase complex;nucleoplasm;DNA repair complex
• Molecular function: DNA binding;chromatin binding;histone deacetylase activity;protein binding;metal ion binding