H1-4 (H1.4 linker histone, cluster member)

Gene

• Entrez ID: 3008
• Gene name: H1.4 linker histone, cluster member
• Gene symbol: H1-4
• Synonyms (NCBI Gene): H1.4, H1E, H1F4, H1s-4, HIST1H1E, RMNS, dJ221C16.5
• Chromosome: 6
• Chromosome location: 6p22.2
• Summary: Histones are basic nuclear proteins responsible for nucleosome structure of the chromosomal fiber in eukaryotes. Two molecules of each of the four core histones (H2A, H2B, H3, and H4) form an octamer, around which approximately 146 bp of DNA is wrapped in

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000122	Process	Negative regulation of transcription by RNA polymerase II	IEA
GO:0000785	Component	Chromatin	IEA
GO:0000786	Component	Nucleosome	IEA
GO:0000791	Component	Euchromatin	IBA
GO:0000792	Component	Heterochromatin	IDA	15911621
GO:0003677	Function	DNA binding	IEA
GO:0003690	Function	Double-stranded DNA binding	IBA
GO:0003723	Function	RNA binding	HDA	22681889
GO:0005515	Function	Protein binding	IPI	17474147, 17540172, 28514442, 30021884, 33961781, 34232536, 34901782, 35271311, 36217030, 36950384
GO:0005634	Component	Nucleus	IBA
GO:0005634	Component	Nucleus	IDA	17540172
GO:0005634	Component	Nucleus	IEA
GO:0005694	Component	Chromosome	IEA
GO:0006325	Process	Chromatin organization	IEA
GO:0006334	Process	Nucleosome assembly	IEA
GO:0006357	Process	Regulation of transcription by RNA polymerase II	IEA
GO:0030261	Process	Chromosome condensation	IBA
GO:0030527	Function	Structural constituent of chromatin	IEA
GO:0031490	Function	Chromatin DNA binding	IEA
GO:0031490	Function	Chromatin DNA binding	IMP	15911621
GO:0031492	Function	Nucleosomal DNA binding	IBA
GO:0042826	Function	Histone deacetylase binding	IPI	15469825
GO:0045910	Process	Negative regulation of DNA recombination	IBA

Other IDs

• MIM: 142220
• HGNC: 4718
• e!Ensembl: ENSG00000168298

Protein

• UniProt ID: P10412
• Protein name: Histone H1.4 (Histone H1b) (Histone H1s-4)
• Protein 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. Also acts as a
• PDB: 3TZD, 5JJZ, 6H8P, 7K5Y, 7K63, 7PET, 7PEU, 7PEX, 7PEZ, 7PF0, 7PF2, 7PF3, 7PF5, 7PF6, 7PFA, 7PFC, 7PFD, 7PFE, 7PFT, 7PFU, 7PFV, 7PFW, 7PFX, 8H1T, 8VG2, 9DDE
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00538	Linker_histone	37 → 108	linker histone H1 and H5 family	Domain

• Sequence:

  MSETAPAAPAAPAPAEKTPVKKKARKSAGAAKRKASGPPVSELITKAVAASKERSGVSLA
  ALKKALAAAGYDVEKNNSRIKLGLKSLVSKGTLVQTKGTGASGSFKLNKKAASGEAKPKA
  KKAGAAKAKKPAGAAKKPKKATGAATPKKSAKKTPKKAKKPAAAAGAKKAKSPKKAKAAK
  PKKAPKSPAKAKAVKPKAAKPKTAKPKAAKPKKAAAKKK

• Sequence length: 219

Pathways

Reactome:

Apoptosis induced DNA fragmentation
Formation of Senescence-Associated Heterochromatin Foci (SAHF)

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Auditory neuropathy spectrum disorder	Pathogenic	rs1131690806	RCV003984842	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
H1-4-related disorder	Pathogenic	rs2480693825	RCV003397600	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
HIST1H1E-related neurodevelopmental disorder with multiple anomalies	Pathogenic	rs768525914	RCV002508301	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Multiple myeloma	Likely pathogenic	rs951047896	RCV000984116	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Neurodevelopmental disorder	Likely pathogenic; Pathogenic	rs1581429554	RCV001375002	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Pitt-Hopkins syndrome	Pathogenic	rs1131690806	RCV005861115	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Rahman syndrome	Likely pathogenic; Pathogenic	rs2113827331, rs2113826976, rs2113826875, rs1208228105, rs2480693529, rs2480693538, rs1131690805, rs1131690806, rs1131690807, rs1554162872, rs1554162894, rs1581429403, rs1581429431, rs1581429434, rs1581429514, rs1581429554, rs1764194669, rs768525914, rs1764194450	RCV002071029 RCV002226978 RCV002250041 RCV003444042 RCV003885398 RCV003988612 RCV000492231 RCV000492407 RCV000492643 RCV001281387 RCV001281390 RCV000984019 RCV000984021 RCV000984020 RCV000984022 RCV000984023 RCV000986122 RCV001281388 RCV001253099 RCV001281386	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
AUTOSOMAL DOMINANT INTELLECTUAL DISABILITY, CRANIOFACIAL DYSMORPHISM, MACROCEPHALY, HYPOTONIA SYNDROME DUE TO H1.4 LINKER HISTONE, CLUSTER MEMBER MUTATION	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AUTOSOMAL DOMINANT INTELLECTUAL DISABILITY-CRANIOFACIAL DYSMORPHISM-MACROCEPHALY-HYPOTONIA SYNDROME DUE TO H1-4 MUTATION	—	Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CARCINOMA, ADENOID CYSTIC	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Developmental disorder	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
INSOMNIA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NEURODEVELOPMENTAL DISORDERS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PROSTATE CANCER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PROSTATE CARCINOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SCHIZOPHRENIA	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Syndromic intellectual disability	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Acquired Kyphoscoliosis	Acquired Kyphoscoliosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Adenoid Cystic Carcinoma	Adenocarcinoma	CTD_human_DG	23685749		★☆☆☆☆ Found in Text Mining only
Astigmatism	Astigmatism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Autism Spectrum Disorders	Autism Spectrum Disorder	BEFREE	29704315		★☆☆☆☆ Found in Text Mining only
Autistic Disorder	Autism	BEFREE	29704315		★☆☆☆☆ Found in Text Mining only
Colorectal Carcinoma	Colorectal Cancer	UNIPROT_DG			★☆☆☆☆ Found in Text Mining only
Congenital Camptodactyly	Congenital Camptodactyly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital clubfoot	Congenital Clubfoot	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital kyphoscoliosis	Congenital kyphoscoliosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Developmental Disabilities	Development Disorder	BEFREE	28475857		★☆☆☆☆ Found in Text Mining only
Dysmorphic features	Dysmorphic Features	CLINVAR_DG	23945933, 25081361, 28475857		★☆☆☆☆ Found in Text Mining only
Global developmental delay	Developmental Delay	HPO_DG			★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Mental retardation	BEFREE	29383847, 29704315, 31400068, 31447100		★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Mental retardation	HPO_DG			★☆☆☆☆ Found in Text Mining only
Macrocephaly	Macrocephaly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of pancreas	Pancreatic cancer	BEFREE	2018521		★☆☆☆☆ Found in Text Mining only
Neonatal Hypotonia	Hypotonia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Nevus	Nevus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Non-obstructive azoospermia	Non-obstructive azoospermia	BEFREE	26199320		★☆☆☆☆ Found in Text Mining only
Pancreatic carcinoma	Pancreatic carcinoma	BEFREE	2018521		★☆☆☆☆ Found in Text Mining only
Pervasive Development Disorder	Autism spectrum disorder	BEFREE	29704315		★☆☆☆☆ Found in Text Mining only
Premature aging syndrome	Premature aging	BEFREE	31447100		★☆☆☆☆ Found in Text Mining only
RAHMAN SYNDROME	RAHMAN SYNDROME	GENOMICS_ENGLAND_DG	28475857		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
RAHMAN SYNDROME	RAHMAN SYNDROME	CLINVAR_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Schizophrenia	Schizophrenia	BEFREE	25048004		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Schizophrenia	Schizophrenia	PSYGENET_DG	25048004		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Strabismus	Strabismus	HPO_DG			★☆☆☆☆ Found in Text Mining only