H1-4

H1.4 linker histone, cluster member, the group of H1 histones

Basic information

Region (hg38): 6:26156329-26157115

Previous symbols: [ "H1F4", "HIST1H1E" ]

Links

ENSG00000168298 ∙ NCBI:3008 ∙ OMIM:142220 ∙ HGNC:4718 ∙ Uniprot:P10412 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Rahman syndrome (Definitive), mode of inheritance: AD
• Rahman syndrome (Strong), mode of inheritance: AD
• syndromic intellectual disability (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Rahman syndrome	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	28475857

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the H1-4 gene.

• Rahman syndrome (15 variants)
• not provided (12 variants)
• HIST1H1E-related neurodevelopmental disorder with multiple anomalies (1 variants)
• Auditory neuropathy spectrum disorder (1 variants)
• H1-4-related disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the H1-4 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				28	4	32
missense			34	27	1	62
nonsense						0
start loss			1			1
frameshift	19	8	5			32
inframe indel	1		2			3
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			1			1
Total	20	8	43	55	5

Highest pathogenic variant AF is 0.0000132

Variants in H1-4

This is a list of pathogenic ClinVar variants found in the H1-4 region.

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

Position	Type	Phenotype	Significance	ClinVar
6-26156385-T-C			Uncertain significance (May 01, 2022)
6-26156390-C-G		H1-4-related disorder	Uncertain significance (Sep 16, 2024)
6-26156392-T-A			Uncertain significance (Nov 22, 2022)
6-26156396-C-A			Likely benign (Dec 21, 2018)
6-26156401-C-T		not specified	Conflicting classifications of pathogenicity (Mar 01, 2024)
6-26156404-C-T			Uncertain significance (Apr 01, 2022)
6-26156405-G-A			Likely benign (May 01, 2023)
6-26156419-C-T		not specified	Likely benign (Dec 27, 2022)
6-26156422-C-T		not specified	Uncertain significance (Jan 26, 2022)
6-26156428-C-T		not specified	Likely benign (Sep 28, 2022)
6-26156430-C-CCTGCCGAGAAGA			Uncertain significance (Apr 07, 2023)
6-26156439-A-G		not specified	Uncertain significance (Dec 03, 2020)
6-26156443-C-T		not specified	Likely benign (Dec 19, 2022)
6-26156445-C-T		not specified	Conflicting classifications of pathogenicity (Jan 01, 2024)
6-26156446-C-T		not specified	Likely benign (May 23, 2024)
6-26156447-C-T			Likely benign (Oct 29, 2018)
6-26156464-G-T		not specified	Uncertain significance (May 15, 2024)
6-26156473-C-T		not specified	Uncertain significance (Feb 21, 2024)
6-26156475-G-T			Uncertain significance (Mar 20, 2023)
6-26156478-G-A		not specified	Uncertain significance (Dec 03, 2021)
6-26156479-C-G		not specified	Likely benign (Jan 04, 2022)
6-26156479-C-T		not specified	Likely benign (Jun 23, 2023)
6-26156483-C-G		H1-4-related disorder	Benign/Likely benign (Jan 01, 2024)
6-26156484-A-C		not specified	Uncertain significance (Jan 16, 2024)
6-26156494-C-T		not specified	Likely benign (Mar 18, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
H1-4	protein_coding	protein_coding	ENST00000304218	1	785

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.186	0.658	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-6.72	340	127	2.68	0.00000551	1373
Missense in Polyphen		27	23.319	1.1578		276
Synonymous	-16.8	217	56.6	3.83	0.00000264	482
Loss of Function	0.913	1	2.58	0.387	9.94e-8	67

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: Histone H1 protein binds to linker DNA between nucleosomes forming the macromolecular structure known as the chromatin fiber. Histones H1 are necessary for the condensation of nucleosome chains into higher-order structured fibers. Acts also as a regulator of individual gene transcription through chromatin remodeling, nucleosome spacing and DNA methylation (By similarity). {ECO:0000250}.
• Disease: DISEASE: Rahman syndrome (RMNS) [MIM:617537]: An autosomal dominant syndrome characterized by intellectual disability and overgrowth manifesting as increased birth length, height, weight, and/or head circumference. {ECO:0000269|PubMed:28475857}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Pathways Affected in Adenoid Cystic Carcinoma;Formation of Senescence-Associated Heterochromatin Foci (SAHF);DNA Damage/Telomere Stress Induced Senescence;Cellular Senescence;Cellular responses to stress;Activation of DNA fragmentation factor;Apoptosis induced DNA fragmentation;Apoptotic execution phase;Apoptosis;Programmed Cell Death;Cellular responses to external stimuli;Signaling events mediated by HDAC Class III (Consensus)

Recessive Scores

• pRec: 0.228

Intolerance Scores

• loftool: 0.421
• rvis_EVS: -1.2
• rvis_percentile_EVS: 5.83

Haploinsufficiency Scores

• pHI: 0.497
• ghis: 0.474

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.999

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Hist1h1e
• Phenotype: endocrine/exocrine gland phenotype; growth/size/body region phenotype; immune system phenotype; embryo phenotype; hematopoietic system phenotype; 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); normal 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); reproductive system phenotype; limbs/digits/tail phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan)

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;nucleosome assembly;regulation of transcription, DNA-templated;nucleosome positioning;chromosome condensation;negative regulation of chromatin silencing;negative regulation of DNA recombination;histone H3-K4 trimethylation;histone H3-K27 trimethylation
• Cellular component: nuclear nucleosome;nucleus;nuclear heterochromatin
• Molecular function: double-stranded DNA binding;RNA binding;calcium ion binding;protein binding;ATP binding;GTP binding;AMP binding;chromatin DNA binding;nucleosomal DNA binding;dATP binding;ADP binding