H19

Summary

H19 (H19 imprinted maternally expressed transcript, HGNC:4713) is a long non-coding RNA gene on chromosome 11p15.5.

This gene is located in an imprinted region of chromosome 11 near the insulin-like growth factor 2 (IGF2) gene. This gene is only expressed from the maternally-inherited chromosome, whereas IGF2 is only expressed from the paternally-inherited chromosome. The product of this gene is a long non-coding RNA which functions as a tumor suppressor. Mutations in this gene have been associated with Beckwith-Wiedemann Syndrome and Wilms tumorigenesis. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 283120 — RefSeq curated summary.

At a glance

• Gene type: non-coding (lncRNA) — no protein product; not a drug target. Variant/disease associations are omitted (they would be positional, from an overlapping protein-coding gene).
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4713
Approved symbol	H19
Name	H19 imprinted maternally expressed transcript
Location	11p15.5
Locus type	RNA, long non-coding
Status	Approved
Aliases	D11S813E, ASM, ASM1, NCRNA00008, LINC00008, MIR675HG, GMRSP
Ensembl gene	ENSG00000130600
Ensembl biotype	lncRNA
OMIM	103280
Entrez	283120
RNAcentral	URS00026A1E43 — lncRNA, 2315 nt, 1 organism(s)

Gene structure

Transcript identifiers

Ensembl transcripts: 46 — 39 lncRNA, 7 retained_intron

ENST00000411861, ENST00000412788, ENST00000414790, ENST00000417089, ENST00000422826, ENST00000428066, ENST00000431095, ENST00000436715, ENST00000439725, ENST00000442037, ENST00000447298, ENST00000643292, ENST00000691195, ENST00000701032, ENST00000702588, ENST00000710448, ENST00000710480, ENST00000710481, ENST00000710482, ENST00000710483, ENST00000710484, ENST00000710485, ENST00000710488, ENST00000710489, ENST00000710490, ENST00000710491, ENST00000710492, ENST00000710493, ENST00000710495, ENST00000710496, ENST00000710497, ENST00000786877, ENST00000786878, ENST00000786879, ENST00000786880, ENST00000786881, ENST00000786882, ENST00000786883, ENST00000786884, ENST00000786885, ENST00000786886, ENST00000786887, ENST00000786888, ENST00000786889, ENST00000786890, ENST00000786891

RefSeq mRNA: 0 — MANE Select: None

Canonical transcript exons

ENST00000411861 — 4 exons

Exon	Start	End
ENSE00001124535	1996079	1996191
ENSE00001616130	1995176	1995998
ENSE00003403127	1996287	1996421
ENSE00004163885	1996518	1997842

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 100.00.

FANTOM5 (CAGE): breadth broad, TPM avg 34.9525 / max 6417.4272, expressed in 644 samples.

FANTOM5 promoters (26 alternative TSS)

Promoter ID	TPM avg	Samples expressed
118115	9.3091	407
118116	3.5478	272
118078	3.3755	339
118090	3.2878	326
118107	2.0834	249
118079	1.5041	253
118089	1.3965	215
118102	1.3289	212
118086	1.2662	214
118085	1.0805	197

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
placenta	UBERON:0001987	100.00	gold quality
adrenal tissue	UBERON:0018303	99.94	gold quality
hindlimb stylopod muscle	UBERON:0004252	99.79	gold quality
apex of heart	UBERON:0002098	99.66	gold quality
right adrenal gland cortex	UBERON:0035827	99.65	gold quality
gastrocnemius	UBERON:0001388	99.64	gold quality
left adrenal gland cortex	UBERON:0035825	99.63	gold quality
metanephros cortex	UBERON:0010533	99.59	gold quality
left adrenal gland	UBERON:0001234	99.58	gold quality
muscle of leg	UBERON:0001383	99.57	gold quality
right adrenal gland	UBERON:0001233	99.55	gold quality
adrenal gland	UBERON:0002369	99.55	gold quality
skeletal muscle tissue	UBERON:0001134	99.54	gold quality
left uterine tube	UBERON:0001303	99.48	gold quality
heart left ventricle	UBERON:0002084	99.36	gold quality
omental fat pad	UBERON:0010414	99.31	gold quality
fallopian tube	UBERON:0003889	99.26	gold quality
endocervix	UBERON:0000458	99.19	gold quality
right atrium auricular region	UBERON:0006631	99.18	gold quality
right ovary	UBERON:0002118	99.05	gold quality
right lobe of liver	UBERON:0001114	98.97	gold quality
adipose tissue	UBERON:0001013	98.91	gold quality
liver	UBERON:0002107	98.87	gold quality
right uterine tube	UBERON:0001302	98.80	gold quality
mucosa of stomach	UBERON:0001199	98.79	gold quality
ectocervix	UBERON:0012249	98.79	gold quality
lower esophagus muscularis layer	UBERON:0035833	98.79	gold quality
lower esophagus	UBERON:0013473	98.77	gold quality
heart	UBERON:0000948	98.74	gold quality
subcutaneous adipose tissue	UBERON:0002190	98.57	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-10287	yes	131.87
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

2 targets.

Target	Regulation
CDX2	Activation
IGF2	Repression

Upstream regulators (CollecTRI, top): CTCF, DDX5, E2F1, E2F6, ESR1, GLI1, HMGA1, HMGA2, JUNB, MYC, MYOD1, PGR, PLAG1, SOX9, SP1, TCF3, TFAP2A, TFEB, TP53, ZBTB7A

Functional genomics

ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• epigenetic alterations of H19 and LIT1 distinguish patients with Beckwith-Wiedemann syndrome with cancer and birth defects (PMID:11813134)
• Association of H19 promoter methylation with the expression of H19 gene in adrenocortical tumors. (PMID:11889182)
• Insertional mutagenesis identified nucleosome positioning sequences (NPSs) allow the remarkably precise distribution of target sites for the chromatin insulator protein CTCF to nucleosome linker sequences in the H19 ICR. (PMID:11971967)
• An overload of H19 transcript is associated with cells exhibiting higher tumorigenic phenotypes and therefore the H19 gene has oncogenic properties in breast epithelial cells. (PMID:12419837)
• Association of in vitro fertilization with Beckwith-Wiedemann syndrome and epigenetic alterations of LIT1 and H19 (PMID:12439823)
• Regulation of the H19 imprinting gene expression in human nasopharyngeal carcinoma by methylation. (PMID:12569573)
• Alterations in the H19 imprinted region occur in juvenile nasopharyngeal angiofibroma . (PMID:12605037)
• Reduced expression of H19 was seen in bone marrow cells from chronic myeloproliferative disorders. This may play an important role in the pathogenesis and growth regulatory dysfunction in these disorders. (PMID:12682647)
• MAP-kinase ERK-1/2 pathway and phosphatidylinositol-3 kinase pathway influenced H19 RNA expression. Significant overexpression of H19 RNA and its increased sensitivity to starvation/cytokine regulation in rheumatoid arthritis suggests pathogenetic role. (PMID:12937131)
• imprinting defects associated with disturbed spermatogenesis. methylation of the H19 gene changed in oligozoospermic patients. (PMID:15158633)
• Here we show that inherited microdeletions in the H19 differentially methylated region (DMR) that abolish two CTCF target sites cause this disease. (PMID:15314640)
• there is a disturbed regulation of the IGF-2/H19 locus in myeloid leukemias which is not caused by loss of imprinting (PMID:15645136)
• The common H19 2992T allele, in the mother or offspring, may confer reduced fetal growth restraint, as indicated by associations with larger offspring birth size, higher cord blood IGF-II levels, and lower compensatory early postnatal catch-up weight gain (PMID:15885138)
• Positive correlations between elevated IGF2 expression and hypermethylation of CCCTC transcription factor binding sites 1 and 6 at the H19 proximal imprint center (P = 0.05 and 0.02, respectively) was identified. (PMID:16603642)
• Results demonstrate correct genetic imprints for H19 even in spermatogonia selected from seminiferous tubules exhibiting spermatogenic arrest at the level of spermatogonia. (PMID:16608903)
• An adolescent female had premature ovarian failure and features of BWS syndrome. (PMID:16708166)
• IGF2 gain of imprinting and H19 loss of imprinting are common in hepatocellular carcinoma (PMID:17294726)
• H19 RNA harbors pro-tumorigenic properties, thus the H19 gene behaves as an oncogene and may serve as a potential new target for anti-tumor therapy (PMID:17786216)
• analysis of IGF2 and H19 loss of imprinting in bladder cancer (PMID:18006818)
• In 30% of patients, differentially methylated IGF2/H19 imprinting center region (ICR1) on chromosome 11p15 was found to be hypomethylated, as determined by Southern blot analysis of an HpaII restriction site close to third CTCF-binding site within ICR1 (PMID:18159214)
• Methylation-imprinting defects at the IGF2-H19 locus can result from inherited mutations of the imprinting center and have high recurrence risk or arise independently from the sequence context and generally not transmitted to the progeny. (PMID:18245780)
• An SNP polymorphism in the non-protein-encoding H19 gene is associated with a decreased risk of developing non-muscle-invasive bladder cancer. This association was found for only heterozygotes, not for homozygotes. (PMID:18262338)
• Of the informative human hepatocellular carcinoma samples 47.06% (8 of 17) demonstrated a gain of imprinting of IGF2, and 21.74% (5 of 23) of the informative HCC samples demonstrated a loss of imprinting of H19. (PMID:18358696)
• there were no differences in the genotype and allele distribution of H19 polymorphism frequencies between females with idiopathic recurrent spontaneous abortion and controls (PMID:18573128)
• Results decribethe loss IGF2/H19 imprinting,loss of heterozygosity of IGF2R and CTCF, and incidental H. pylori infections in laryngeal squamous cell carcinoma. (PMID:18604514)
• Hypermethylation of H19 in a patient with a cardiac tumor but phenotypically without features of Beckwith-Wiedemann syndrome. (PMID:18627058)
• CTCFL/BORIS is a methylation-independent DNA-binding protein that preferentially binds to the paternal H19 differentially methylated region (PMID:18632606)
• H19 is a maternally expressed imprinted mRNA that is closely involved in regulating the IGF2 gene. The genotype-associated breast cancer risk varied by radiation dosage for the rs2107425 snp . (PMID:18708391)
• Hypomethylation of the paternally derived H19 is associated with Silver-Russell syndrome. (PMID:18709478)
• The association of specific anomalies of the spine, elbows, hands and feet, and genital defects in SRS with severe H19 hypomethylation. (PMID:19017756)
• findings demonstrate that hypomethylation of H19 or IGF2 alone appears to be sufficient to cause Silver-Russell syndrome(SRS); germ cell mosaicism & vertical transmission from an affected father to his child shows a recurrence risk for epimutations in SRS (PMID:19066168)
• biallelic expression of H19 gene exists in some cases at early stage of normal pregnancy & changes into monoallelic expression near 10 weeks of gestation. (PMID:19342096)
• data indicated that Hcy could induce hypomethylation of the sixth CTCF-binding sites upstream of H19, which is an important regulating area for the imprinting expression of IGF2 and H19 (PMID:19499149)
• Report aberrant epigenetic modifications in the CTCF binding domain of the IGF2/H19 gene in prostate cancer compared with benign prostate hyperplasia. (PMID:19513555)
• Loss of imprinting can be identified in pre-eclamptic placentas and is associated with maternal blood pressure. (PMID:19570415)
• Data found biallelic expression of the H19 gene in one induced pluripotent stem cell line and analysis of the DNA methylation levels of the promoter region of the H19 gene found that the cell line had undergone extensive DNA demethylation. (PMID:19711451)
• Epimutations on chromosome 11p15 can be most efficiently detected in Russell-Silver syndrome patients by screening for DNA methylation defects at the H19 promoter or the distal region of imprinting center ICR. (PMID:19876907)
• Expression profiles of human VIGILIN, H19, and IGF2 mRNA increased with cell-cycle prograssion. (PMID:19950580)
• cohesin has a critical role in maintaining CTCF-mediated chromatin conformation at the at the IGF2-H19 locus locus and disruption of this conformation coincides with changes in IGF2 expression. (PMID:19956766)
• frequent combined aberrant methylation of the IGF2-H19 locus and LINE1 in the vast majority of ovarian carcinoma samples suggests that these changes are important events in tumorigenesis (PMID:19956846)

Cross-species orthologs

0 orthologs

Protein

Non-coding RNA — no protein product; not a drug target.

Function

No curated pathway, Gene-Ontology, or interaction data.

Disease & clinical

No curated disease, variant, or cancer-driver associations.

Drugs & pharmacology

No drug or pharmacology data — not an established drug target.