H4C11

H4 clustered histone 11, the group of H4 histones

Basic information

Region (hg38): 6:27824092-27824480

Previous symbols: [ "H4FE", "HIST1H4J" ]

Links

ENSG00000197238 ∙ NCBI:8363 ∙ OMIM:602826 ∙ HGNC:4785 ∙ Uniprot:P62805 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Tessadori-van Haaften neurodevelopmental syndrome 2 (Limited), mode of inheritance: AD
• Tessadori-van Haaften neurodevelopmental syndrome 2 (Moderate), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Tessadori-Bicknell-van Haaften neurodevelopmental syndrome 2	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	31804630

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the H4C11 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the H4C11 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				2	1	3
missense		1	9			10
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					2	2
Total	0	1	9	2	3

Variants in H4C11

This is a list of pathogenic ClinVar variants found in the H4C11 region.

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

Position	Type	Phenotype	Significance	ClinVar
6-27824133-C-T			Benign (Oct 01, 2022)
6-27824175-G-A		not specified	Likely benign (May 30, 2024)
6-27824205-C-G		not specified	Uncertain significance (Oct 16, 2024)
6-27824230-C-T		Tessadori-van Haaften neurodevelopmental syndrome 2	Likely pathogenic (Dec 27, 2023)
6-27824245-C-T			Uncertain significance (Jan 20, 2023)
6-27824260-C-T			Uncertain significance (Oct 01, 2021)
6-27824277-C-G		not specified	Uncertain significance (Dec 08, 2023)
6-27824277-C-T			Likely benign (Feb 01, 2025)
6-27824290-C-A		not specified	Uncertain significance (Oct 09, 2024)
6-27824372-C-T		Tessadori-van Haaften neurodevelopmental syndrome 2	Uncertain significance (Dec 19, 2024)
6-27824380-G-C		not specified	Uncertain significance (May 24, 2023)
6-27824385-G-A			Likely benign (Dec 31, 2019)
6-27824393-C-G		Tessadori-van Haaften neurodevelopmental syndrome 2	Uncertain significance (Nov 21, 2024)
6-27824398-A-C		Tessadori-van Haaften neurodevelopmental syndrome 1	Pathogenic (Feb 22, 2022)
6-27824398-A-G		Tessadori-van Haaften neurodevelopmental syndrome 2	Pathogenic (Jan 20, 2023)
6-27824408-G-A		Tessadori-van Haaften neurodevelopmental syndrome 2	Uncertain significance (Dec 22, 2023)
6-27824419-T-C		not specified	Uncertain significance (Jul 11, 2023)
6-27824443-C-T			Benign (Dec 08, 2020)
6-27824450-T-C			Benign (Dec 08, 2020)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
H4C11	protein_coding	protein_coding	ENST00000355057	1	374

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.387	0.485	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.682	44	58.7	0.750	0.00000275	642
Missense in Polyphen		17	17.453	0.97406		214
Synonymous	-8.19	77	24.9	3.09	0.00000120	232
Loss of Function	0.901	0	0.946	0.00	3.86e-8	19

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: Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.
• Disease: DISEASE: Note=Chromosomal aberrations involving HISTONE H4 is a cause of B-cell non-Hodgkin lymphomas (B-cell NHL). Translocation t(3;6)(q27;p21), with BCL6. {ECO:0000269|PubMed:12414651}.
• Pathway: Systemic lupus erythematosus - Homo sapiens (human);Viral carcinogenesis - Homo sapiens (human);Alcoholism - Homo sapiens (human);Histone Modifications;HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA);B-WICH complex positively regulates rRNA expression;ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression;Positive epigenetic regulation of rRNA expression;SIRT1 negatively regulates rRNA expression;DNA Repair;NoRC negatively regulates rRNA expression;Negative epigenetic regulation of rRNA expression;Signaling by WNT;Signal Transduction;DNA methylation;Epigenetic regulation of gene expression;Gene expression (Transcription);Nonhomologous End-Joining (NHEJ);DNA Double-Strand Break Repair;Generic Transcription Pathway;Oxidative Stress Induced Senescence;Senescence-Associated Secretory Phenotype (SASP);Cellular Senescence;Homology Directed Repair;SUMOylation of chromatin organization proteins;Cellular responses to stress;Post-translational protein modification;SUMO E3 ligases SUMOylate target proteins;HDACs deacetylate histones;Metabolism of proteins;Reproduction;HDMs demethylate histones;RNA Polymerase I Promoter Clearance;PKMTs methylate histone lysines;RNA Polymerase I Promoter Opening;RNA Polymerase II Transcription;G2/M DNA damage checkpoint;RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function;RMTs methylate histone arginines;Chromatin modifying enzymes;G2/M Checkpoints;Cell Cycle Checkpoints;RNA Polymerase I Transcription;Amyloid fiber formation;RNA Polymerase I Chain Elongation;Meiotic recombination;SUMOylation;Meiotic synapsis;Meiosis;Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3;RHO GTPases activate PKNs;Nucleosome assembly;HATs acetylate histones;Cellular responses to external stimuli;RHO GTPase Effectors;Signaling by Rho GTPases;Packaging Of Telomere Ends;Telomere Maintenance;Chromosome Maintenance;Deposition of new CENPA-containing nucleosomes at the centromere;Condensation of Prophase Chromosomes;Signaling by Nuclear Receptors;Chromatin organization;Mitotic Prophase;M Phase;Estrogen-dependent gene expression;Transcriptional regulation by small RNAs;RUNX1 regulates transcription of genes involved in differentiation of HSCs;Cell Cycle;Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks;DNA Double Strand Break Response;Cell Cycle, Mitotic;ESR-mediated signaling;Transcriptional regulation by RUNX1;Processing of DNA double-strand break ends;Formation of the beta-catenin:TCF transactivating complex;TCF dependent signaling in response to WNT;Signaling events mediated by HDAC Class III;Gene Silencing by RNA;PRC2 methylates histones and DNA (Consensus)

Intolerance Scores

• loftool: 0.716
• rvis_EVS: -0.05
• rvis_percentile_EVS: 49.39

Haploinsufficiency Scores

• pHI: 0.531
• hipred: N
• hipred_score: 0.272
• ghis: 0.565

Essentials

• essential_gene_CRISPR: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.965

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Hist1h4f