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
Phenotypes
GenCC
Source:
- Rahman syndrome (Definitive), mode of inheritance: AD
- Rahman syndrome (Strong), mode of inheritance: AD
- syndromic intellectual disability (Definitive), mode of inheritance: AD
- Rahman syndrome (Strong), mode of inheritance: AD
- Rahman syndrome (Strong), mode of inheritance: AD
Clinical Genomic Database
Source:
| 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
- not_specified (112 variants)
- not_provided (86 variants)
- Rahman_syndrome (34 variants)
- H1-4-related_disorder (15 variants)
- Inborn_genetic_diseases (5 variants)
- Syndromic_intellectual_disability (2 variants)
- Neurodevelopmental_disorder (1 variants)
- Auditory_neuropathy_spectrum_disorder (1 variants)
- See_cases (1 variants)
- Pitt-Hopkins_syndrome (1 variants)
- Multiple_myeloma (1 variants)
- Developmental_disorder (1 variants)
- HIST1H1E-related_neurodevelopmental_disorder_with_multiple_anomalies (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. These statistics are base on transcript: NM_000005321.3. 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 | 33 | 36 | ||||
| missense | 76 | 52 | 134 | |||
| nonsense | 0 | |||||
| start loss | 1 | 1 | ||||
| frameshift | 22 | 10 | 15 | 47 | ||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 26 | 12 | 92 | 85 | 3 |
Highest pathogenic variant AF is 0.0000043571
Loading clinvar variants...
GnomAD
Source:
| 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:
- 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
- hipred
- hipred_score
- 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