H1-8

Summary

H1-8 (H1.8 linker histone, HGNC:18463) is a protein-coding gene on chromosome 3q22.1, encoding Histone H1.8 (Q8IZA3). May play a key role in the control of gene expression during oogenesis and early embryogenesis, presumably through the perturbation of chromatin structure.

Histones are basic nuclear proteins that are responsible for the nucleosome structure of the chromosomal fiber in eukaryotes. Nucleosomes consist of approximately 146 bp of DNA wrapped around a histone octamer composed of pairs of each of the four core histones (H2A, H2B, H3, and H4). The chromatin fiber is further compacted through the interaction of a linker histone, H1, with the DNA between the nucleosomes to form higher order chromatin structures. The protein encoded is a replication-independent histone that is a member of the histone H1 family. This gene contains introns, unlike most histone genes. The related mouse gene is expressed only in oocytes.

Source: NCBI Gene 132243 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 76 total
• MANE Select transcript: NM_153833

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18463
Approved symbol	H1-8
Name	H1.8 linker histone
Location	3q22.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000178804
Ensembl biotype	protein_coding
Entrez	132243

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000324382, ENST00000503977

RefSeq mRNA: 2 — MANE Select: NM_153833 NM_001308262, NM_153833

CCDS: CCDS3064, CCDS77815

Canonical transcript exons

ENST00000324382 — 5 exons

Exon	Start	End
ENSE00001227239	129550745	129550809
ENSE00001227255	129547391	129547680
ENSE00001227280	129543175	129543306
ENSE00002066758	129551107	129551467
ENSE00003634846	129549001	129549364

Expression profiles

Bgee: expression breadth broad, 22 present calls, max score 99.49.

Top tissues by expression

218 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	99.49	gold quality
secondary oocyte	CL:0000655	98.84	gold quality
buccal mucosa cell	CL:0002336	73.48	silver quality
left testis	UBERON:0004533	68.03	gold quality
tendon of biceps brachii	UBERON:0008188	67.89	silver quality
right testis	UBERON:0004534	66.15	gold quality
testis	UBERON:0000473	65.53	gold quality
trabecular bone tissue	UBERON:0002483	64.74	gold quality
vena cava	UBERON:0004087	63.36	gold quality
myocardium	UBERON:0002349	62.50	gold quality
upper leg skin	UBERON:0004262	59.14	silver quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	58.93	gold quality
cartilage tissue	UBERON:0002418	58.41	gold quality
pons	UBERON:0000988	58.26	gold quality
nasal cavity epithelium	UBERON:0005384	57.85	gold quality
heart right ventricle	UBERON:0002080	57.33	gold quality
biceps brachii	UBERON:0001507	56.59	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	55.79	gold quality
medial globus pallidus	UBERON:0002477	55.33	gold quality
Brodmann (1909) area 46	UBERON:0006483	54.87	gold quality
lower lobe of lung	UBERON:0008949	54.54	silver quality
pericardium	UBERON:0002407	53.81	gold quality
decidua	UBERON:0002450	53.12	gold quality
globus pallidus	UBERON:0001875	52.06	gold quality
vastus lateralis	UBERON:0001379	50.43	gold quality
quadriceps femoris	UBERON:0001377	50.19	gold quality
visceral pleura	UBERON:0002401	49.99	gold quality
mammalian vulva	UBERON:0000997	49.76	gold quality
adult organism	UBERON:0007023	47.55	gold quality
deltoid	UBERON:0001476	47.50	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.39

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

18 targeting H1-8, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-3915	99.45	68.49	1905
HSA-MIR-4316	99.37	65.75	1360
HSA-MIR-10522-5P	99.26	68.50	2087
HSA-MIR-1264	99.25	66.81	1317
HSA-MIR-1294	98.91	69.26	1030
HSA-MIR-9986	98.91	69.28	1024
HSA-MIR-3161	98.71	67.14	816
HSA-MIR-2278	97.30	66.19	1130
HSA-MIR-5579-3P	97.00	68.81	1111

Literature-anchored findings (GeneRIF, showing 2)

• Structure and gene expression of osH1. (PMID:12711322)
• After intracytoplasmic sperm injection, the assembly of H1FOO on sperm chromatin during decondensation seems to occur very quickly, and hH1FOO protein is localized in all oocytes from primordial to Graafian follicles. (PMID:19147139)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	h1m	ENSDARG00000102892
mus_musculus	H1f8	ENSMUSG00000042279
rattus_norvegicus	H1f8	ENSRNOG00000025251
caenorhabditis_elegans		WBGENE00001853
caenorhabditis_elegans		WBGENE00001854
caenorhabditis_elegans		WBGENE00001855
caenorhabditis_elegans	hil-5	WBGENE00001856
caenorhabditis_elegans		WBGENE00001857

Paralogs (9): H1-3 (ENSG00000124575), H1-1 (ENSG00000124610), H1-4 (ENSG00000168298), H1-5 (ENSG00000184357), H1-10 (ENSG00000184897), H1-7 (ENSG00000187166), H1-6 (ENSG00000187475), H1-2 (ENSG00000187837), H1-0 (ENSG00000189060)

Protein

Protein identifiers

Histone H1.8 — Q8IZA3 (reviewed: Q8IZA3)

Alternative names: Histone H1oo, Oocyte-specific histone H1, Oocyte-specific linker histone H1

All UniProt accessions (1): Q8IZA3

UniProt curated annotations — full annotation on UniProt →

Function. May play a key role in the control of gene expression during oogenesis and early embryogenesis, presumably through the perturbation of chromatin structure. Essential for meiotic maturation of germinal vesicle-stage oocytes. The somatic type linker histone H1c is rapidly replaced by H1oo in a donor nucleus transplanted into an oocyte. The greater mobility of H1oo as compared to H1c may contribute to this rapid replacement and increased instability of the embryonic chromatin structure. The rapid replacement of H1c with H1oo may play an important role in nuclear remodeling.

Subcellular location. Cytoplasm. Nucleus. Chromosome.

Tissue specificity. Oocyte-specific.

Similarity. Belongs to the histone H1/H5 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8IZA3-1	1	yes
Q8IZA3-2	2

RefSeq proteins (2): NP_001295191, NP_722575* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005818	Histone_H1/H5_H15	Domain
IPR036388	WH-like_DNA-bd_sf	Homologous_superfamily
IPR036390	WH_DNA-bd_sf	Homologous_superfamily

Pfam: PF00538

UniProt features (17 total): compositionally biased region 10, region of interest 2, chain 1, domain 1, splice variant 1, sequence variant 1, short sequence motif 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IZA3-F1	60.53	0.20

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9821993	Replacement of protamines by nucleosomes in the male pronucleus

MSigDB gene sets: 59 (showing top): GOBP_CHROMOSOME_ORGANIZATION, GOBP_REGULATION_OF_DNA_RECOMBINATION, GOBP_NEGATIVE_REGULATION_OF_DNA_RECOMBINATION, GOBP_CHROMOSOME_CONDENSATION, GOBP_PROTEIN_DNA_COMPLEX_ORGANIZATION, chr3q22, GOBP_CHROMATIN_REMODELING, GOBP_EPIGENETIC_REGULATION_OF_GENE_EXPRESSION, GOBP_MEIOTIC_CELL_CYCLE, GOMF_CHROMATIN_BINDING, GOCC_PROTEIN_DNA_COMPLEX, GOCC_NUCLEOLUS, GOBP_DNA_METABOLIC_PROCESS, GOMF_NUCLEOSOME_BINDING, GOMF_CHROMATIN_DNA_BINDING

GO Biological Process (5): nucleosome assembly (GO:0006334), chromosome condensation (GO:0030261), epigenetic regulation of gene expression (GO:0040029), negative regulation of DNA recombination (GO:0045910), meiotic cell cycle (GO:0051321)

GO Molecular Function (4): double-stranded DNA binding (GO:0003690), structural constituent of chromatin (GO:0030527), nucleosomal DNA binding (GO:0031492), DNA binding (GO:0003677)

GO Cellular Component (5): nucleosome (GO:0000786), nucleus (GO:0005634), cytoplasm (GO:0005737), extracellular exosome (GO:0070062), chromosome (GO:0005694)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Maternal to zygotic transition (MZT)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
chromatin	2
chromatin organization	1
nucleosome organization	1
protein-DNA complex assembly	1
chromosome organization	1
chromatin remodeling	1
regulation of gene expression	1
regulation of DNA recombination	1
DNA recombination	1
negative regulation of DNA metabolic process	1
cell cycle	1
sexual reproduction	1
reproductive process	1
meiotic nuclear division	1
DNA binding	1
structural molecule activity	1
chromatin DNA binding	1
nucleosome binding	1
nucleic acid binding	1
protein-DNA complex	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1
extracellular vesicle	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

1036 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
H1-8	H1-6	P22492	976
H1-8	H3-4	Q16695	959
H1-8	H1-7	Q75WM6	948
H1-8	H1-10	Q92522	942
H1-8	H1-5	P16401	857
H1-8	H1-1	Q02539	856
H1-8	H1-0	P07305	803
H1-8	H1-3	P16402	749
H1-8	H1-4	P10412	745
H1-8	H1-2	P16403	711
H1-8	RPS23	P39028	676
H1-8	OSBP	P22059	659
H1-8	ZAR1	Q86SH2	647
H1-8	GDF9	O60383	597
H1-8	FIGLA	Q6QHK4	570

IntAct

3 interactions, top by confidence:

A	B	Type	Score
RPL22	H1-8	psi-mi:“MI:0915”(physical association)	0.400
H1-8	RRP8	psi-mi:“MI:0914”(association)	0.350

BioGRID (48): H1FOO (Proximity Label-MS), ZNF22 (Affinity Capture-MS), RPS3 (Affinity Capture-MS), BRIX1 (Affinity Capture-MS), HIST1H1C (Affinity Capture-MS), RPL17 (Affinity Capture-MS), RPL15 (Affinity Capture-MS), RPL8 (Affinity Capture-MS), RPL7A (Affinity Capture-MS), RPF1 (Affinity Capture-MS), NOP2 (Affinity Capture-MS), NMNAT1 (Affinity Capture-MS), RPL27 (Affinity Capture-MS), SURF6 (Affinity Capture-MS), KIAA0020 (Affinity Capture-MS)

ESM2 similar proteins: A0A8V8TNH8, A0A8V8TPE2, A1L443, A5D7L8, A6NDY2, A6NIJ5, A6NJQ4, A6NKC0, A6NNJ1, A7E321, A8MWA6, A8MX19, A8MXJ8, A8MXZ1, D6RGX4, O08784, P0C7V4, P0C7W8, P0C7W9, P0C7X0, P0DV73, P0DV74, P0DV75, P0DV76, Q13428, Q14684, Q2TBX7, Q2YDF7, Q3HNG7, Q5RB69, Q5RCJ6, Q5SV97, Q5T8A7, Q5VZR2, Q5XIB5, Q658T7, Q6A025, Q6ZMY3, Q6ZUT6, Q75WM6

Diamond homologs: A7MAZ5, D3ZBN0, G3N131, O01833, O16277, O17536, P02251, P02252, P02253, P02255, P02256, P02257, P02258, P02259, P06144, P06348, P06350, P06513, P06893, P06894, P06895, P07305, P07796, P08284, P08285, P08286, P08287, P08288, P09426, P09987, P10412, P10771, P10922, P15796, P15864, P15865, P15866, P15867, P15869, P15870

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

76 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	62
Likely benign	12
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

970 predictions. Top by Δscore:

Variant	Effect	Δscore
3:129543302:GCCAG:G	donor_gain	1.0000
3:129547681:G:GG	donor_gain	1.0000
3:129543303:CCAGG:C	donor_loss	0.9900
3:129543304:CAGG:C	donor_loss	0.9900
3:129543307:G:GA	donor_loss	0.9900
3:129543308:T:A	donor_loss	0.9900
3:129547389:A:AG	acceptor_gain	0.9900
3:129547389:AGGCC:A	acceptor_loss	0.9900
3:129547390:G:GG	acceptor_gain	0.9900
3:129547679:AAGTA:A	donor_loss	0.9900
3:129547680:AGTA:A	donor_loss	0.9900
3:129547681:GTA:G	donor_loss	0.9900
3:129547682:TA:T	donor_loss	0.9900
3:129547683:AA:A	donor_loss	0.9900
3:129548999:A:AG	acceptor_gain	0.9900
3:129549000:G:GG	acceptor_gain	0.9900
3:129549000:GTTA:G	acceptor_gain	0.9900
3:129549268:A:T	donor_gain	0.9900
3:129550720:T:G	acceptor_gain	0.9900
3:129550721:A:AG	acceptor_gain	0.9900
3:129550722:A:G	acceptor_gain	0.9900
3:129546705:GACCT:G	donor_gain	0.9800
3:129547390:GGCCC:G	acceptor_gain	0.9800
3:129547584:G:GG	donor_gain	0.9800
3:129547679:AA:A	donor_gain	0.9800
3:129549000:GTT:G	acceptor_gain	0.9800
3:129549267:G:GT	donor_gain	0.9800
3:129547389:AG:A	acceptor_gain	0.9700
3:129547390:GG:G	acceptor_gain	0.9700
3:129547390:GGCC:G	acceptor_gain	0.9700

AlphaMissense

2219 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:129547675:T:C	F125L	0.999
3:129547676:T:C	F125S	0.999
3:129547677:C:A	F125L	0.999
3:129547677:C:G	F125L	0.999
3:129547475:T:C	M58T	0.998
3:129547532:T:A	I77N	0.998
3:129547676:T:G	F125C	0.998
3:129547532:T:G	I77S	0.997
3:129547544:T:A	I81N	0.997
3:129547604:T:A	L101Q	0.997
3:129547638:G:C	R112S	0.997
3:129547638:G:T	R112S	0.997
3:129547544:T:C	I81T	0.996
3:129547613:G:A	G104D	0.996
3:129547631:T:A	L110H	0.996
3:129547637:G:C	R112T	0.996
3:129547637:G:T	R112M	0.996
3:129547670:G:A	G123D	0.996
3:129547532:T:C	I77T	0.995
3:129547544:T:G	I81S	0.995
3:129547604:T:C	L101P	0.995
3:129547612:G:C	G104R	0.995
3:129547476:G:A	M58I	0.994
3:129547476:G:C	M58I	0.994
3:129547476:G:T	M58I	0.994
3:129547592:T:C	L97P	0.994
3:129547600:G:C	A100P	0.994
3:129547669:G:C	G123R	0.994
3:129547486:G:C	A62P	0.993
3:129547596:G:C	K98N	0.993

dbSNP variants (sampled 300 via entrez): RS1000836528 (3:129545706 C>T), RS1000991740 (3:129545922 G>A), RS1001038587 (3:129550521 G>A), RS1001323148 (3:129546941 T>A), RS1001773921 (3:129551957 C>T), RS1002352072 (3:129544229 G>A), RS1002688853 (3:129545732 G>T), RS1002745091 (3:129551826 G>T), RS1002839992 (3:129547835 C>T), RS1002941808 (3:129542743 A>C), RS1002991989 (3:129548211 G>C), RS1003166320 (3:129551597 T>C,G), RS1003258579 (3:129547460 C>A,T), RS1003687454 (3:129543923 G>A), RS1003688019 (3:129544188 G>A)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST005956_82	Waist-to-hip ratio adjusted for BMI	2.000000e-07
GCST005958_5	Waist-to-hip ratio adjusted for BMI (age >50)	4.000000e-10
GCST005962_16	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	2.000000e-11
GCST008153_60	Lean body mass	2.000000e-07
GCST012229_46	Hip index	1.000000e-12
GCST90020024_1256	A body shape index	4.000000e-08

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0004995	lean body mass
EFO:0008039	BMI-adjusted hip circumference
EFO:0007789	BMI-adjusted waist circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

13 total (human), top 13 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
propionaldehyde	decreases expression	1
sodium arsenite	increases expression	1
CGP 52608	affects binding, increases reaction	1
theaflavin-3,3’-digallate	affects expression	1
Resveratrol	affects cotreatment, decreases expression	1
Acetaminophen	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	decreases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Valproic Acid	increases methylation	1
Aflatoxin B1	increases methylation	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.