XIST

Summary

XIST (X inactive specific transcript, HGNC:12810) is a long non-coding RNA gene on chromosome Xq13.2. It is haploinsufficient (ClinGen: sufficient evidence).

X inactivation is an early developmental process in mammalian females that transcriptionally silences one of the pair of X chromosomes, thus providing dosage equivalence between males and females. The process is regulated by several factors, including a region of chromosome X called the X inactivation center (XIC). The XIC comprises several non-coding and protein-coding genes, and this gene was the first non-coding gene identified within the XIC. This gene is expressed exclusively from the XIC of the inactive X chromosome, and is essential for the initiation and spread of X-inactivation. The transcript is a spliced RNA. Alternatively spliced transcript variants have been identified, but their full length sequences have not been determined. Mutations in the XIST promoter cause familial skewed X inactivation.

Source: NCBI Gene 7503 — 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 sufficient evidence, triplosensitivity no evidence

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12810
Approved symbol	XIST
Name	X inactive specific transcript
Location	Xq13.2
Locus type	RNA, long non-coding
Status	Approved
Aliases	NCRNA00001, DXS1089, swd66, LINC00001
Ensembl gene	ENSG00000229807
Ensembl biotype	lncRNA
OMIM	314670
Entrez	7503
RNAcentral	URS0000D5BF26 — lncRNA, 19236 nt, 1 organism(s)

Gene structure

Transcript identifiers

Ensembl transcripts: 33 — 33 lncRNA

ENST00000416330, ENST00000417942, ENST00000421322, ENST00000429829, ENST00000433732, ENST00000434839, ENST00000445814, ENST00000602495, ENST00000602587, ENST00000602863, ENST00000635841, ENST00000647696, ENST00000647913, ENST00000648091, ENST00000648607, ENST00000648829, ENST00000648927, ENST00000648970, ENST00000648991, ENST00000649353, ENST00000649757, ENST00000650186, ENST00000650366, ENST00000650548, ENST00000650627, ENST00000650637, ENST00000665247, ENST00000666309, ENST00000666954, ENST00000669898, ENST00000841934, ENST00000841935, ENST00000841936

RefSeq mRNA: 0 — MANE Select: None

Canonical transcript exons

ENST00000416330 — 4 exons

Exon	Start	End
ENSE00001641042	73822071	73822216
ENSE00001721892	73826738	73826889
ENSE00001766342	73820653	73821029
ENSE00001793550	73826115	73826347

Expression profiles

Bgee: expression breadth ubiquitous, 244 present calls, max score 99.79.

FANTOM5 (CAGE): breadth broad, TPM avg 78.7916 / max 11397.5721, expressed in 815 samples.

FANTOM5 promoters (80 alternative TSS)

Promoter ID	TPM avg	Samples expressed
199743	47.5193	773
199632	8.2357	539
199738	3.3334	351
199742	2.5733	452
199664	1.5915	378
199737	1.3517	184
199670	1.2217	338
199631	0.9562	196
199728	0.6829	272
199667	0.5674	164

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tibia	UBERON:0000979	99.79	gold quality
skin of hip	UBERON:0001554	99.79	gold quality
ileal mucosa	UBERON:0000331	99.78	gold quality
right uterine tube	UBERON:0001302	99.70	gold quality
mammalian vulva	UBERON:0000997	99.67	gold quality
germinal epithelium of ovary	UBERON:0001304	99.60	gold quality
pericardium	UBERON:0002407	99.60	gold quality
mammary duct	UBERON:0001765	99.56	gold quality
epithelium of mammary gland	UBERON:0003244	99.56	gold quality
left ovary	UBERON:0002119	99.40	gold quality
right ovary	UBERON:0002118	99.36	gold quality
lower esophagus mucosa	UBERON:0035834	99.30	gold quality
body of uterus	UBERON:0009853	99.29	gold quality
uterine cervix	UBERON:0000002	99.26	gold quality
endocervix	UBERON:0000458	99.26	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	99.23	gold quality
myometrium	UBERON:0001296	99.21	gold quality
left uterine tube	UBERON:0001303	99.12	gold quality
uterus	UBERON:0000995	99.08	gold quality
endometrium	UBERON:0001295	99.05	gold quality
ectocervix	UBERON:0012249	98.99	gold quality
mucosa of stomach	UBERON:0001199	98.84	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	98.59	gold quality
vagina	UBERON:0000996	98.36	gold quality
decidua	UBERON:0002450	98.24	gold quality
ovary	UBERON:0000992	98.08	gold quality
adult organism	UBERON:0007023	98.00	gold quality
female reproductive system	UBERON:0000474	97.85	gold quality
bone marrow cell	CL:0002092	97.55	gold quality
granulocyte	CL:0000094	97.45	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-10662	yes	1792.21
E-GEOD-180759	yes	1156.77
E-HCAD-30	no	1814.96
E-MTAB-11268	no	1433.25
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTCF, DNMT1, DNMT3A, DNMT3B, EED, FOXB1

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• role in inducing chromosome inactivation in postdifferentiation human HT-1080 cells (PMID:12072569)
• Multiple X chromosomes in testicular germ cell tumors were predominantly hypomethylated and active regardless of XIST expression. (PMID:12629412)
• point mutations in the XIST promoter reveal a correlation between CTCF binding and pre-emptive choices of X chromosome inactivation (PMID:15731119)
• In human cells maintenance of XIST methylation is controlled differently than global genomic methylation and in the absence of both DNMT1 and DNMT3B. (PMID:16769694)
• results indicate XIST RNA’s nuclear localization is mediated by nuclear retention rather than export followed by import; evidence presented that TAP/NXF1 binds poorly to XIST RNA suggesting reduced TAP/NFX1 binding may contribute to its nuclear retention (PMID:17333237)
• Inducible XIST-dependent X-chromosome inactivation in somatic cells is reversible. (PMID:17537922)
• by combining multiple approaches to assess the genetics and epigenetics of a large series of BRCA1 primary tumors, we can conclude definitively that BRCA1 is not required for XIST RNA coating of the X chromosome (PMID:17545591)
• we demonstrated by quantitative RT-PCR an active XIST RNA expression in blood lymphocytes from Klinefelter patients, comparable to that observed in control females and over 30,000-fold greater than in control males (PMID:18854511)
• The observations sheds light on a possible previously uncharacterized mechanism of breast carcinogenesis mediated by XIST misbehaviour, particularly in BRCA1-related cancers. (PMID:19440381)
• This study advances understanding of RNA chromosome binding and the roles of aurora B kinase and demonstrates a novel approach to manipulate and study XIST RNA. (PMID:19704020)
• XIST methylation is 18% in sex-determining region of the Y chromosome (SRY)-positive XX-males, and thus they are severely hypomethylated compared to (SRY-) XX-males, Klinefelter men and female controls. (PMID:19812237)
• 2-D structure of the A region of Xist RNA; conclude that while some segments of the A region allow the binding of particular PRC2 components, the entire A region is required for efficient association of the entire complex (PMID:20052282)
• identification of three previously unknown hypersensitive sites surrounding the human XIST locus. (PMID:20211024)
• It is not yet known whether X chromosome duplication, XIST dysregulation, and over-expression of X-linked genes represent important factors in tumorgenesis. (PMID:21212949)
• study demonstrates the 2 well-studied regulatory long non-coding RNAs HOTAIR and XIST are targets of site-specific cytosine methylation; cytosine methylation in the XIST A structure strongly affects binding to the chromatin-modifying complex PRC2 in vitro (PMID:23595112)
• A reduction of H3K27me3 at Xist promoter regions leads to elevated levels of urinary Xist, which may be used as a biomarker to detect membranous nephropathy. (PMID:25157805)
• Differentially methylated sites within XIST marks the location of an alternative promoter, P2, that generates a transcript of unknown function. (PMID:25200388)
• YY1 is the first autosomal activating factor involved in a fundamental and conserved pathway of Xist regulation that ensures the asymmetric transcriptional upregulation of the master regulator of X-chromosome inactivation. (PMID:25209548)
• DLG1, XIST, DDX3Y and RPS4Y1 genes can classify samples into different group clearly, and they are regarded as high confidence distinct gene biomarkers of Parkinson disease. (PMID:25275262)
• We show that reduction of DICER1 in human female cells increases XIST transcripts without compromising the binding of the XIST and histone tail modifications on the Xi chromosome. (PMID:25428210)
• miR-152 mediates the tumor-suppressive effects that knockdown of XIST exerts in glioblastoma stem cells. (PMID:25578780)
• Xist, an essential lncRNA for X chromosome inactivation (XCI), interacts with 81 proteins from chromatin modification, nuclear matrix, and RNA remodeling pathways. (PMID:25843628)
• Combination of XIST and HIF1A-AS1 had a higher positive diagnostic efficiency of NSCLC than XIST or HIF1A-AS1 alone. (PMID:26339353)
• over-expression of XIST and some X-linked escapee genes may be a common mechanism for development of psychiatric disorders between the patients with rare genetic diseases (XXY or XXX) and the general population of female psychiatric patients (PMID:26425698)
• The non-coding RNA XIST functions as a cis-acting silencer when expressed from nine different locations throughout the genome (PMID:26429547)
• we show that XIST and 53BP1 can be used to identify BRCA1-like breast cancer patients that have higher event rates and poor outcome after HD chemotherapy. (PMID:26637364)
• This analysis also identified new structural elements in Xist that are evolutionarily conserved, including a new element proximal to the C repeats that is important for Xist function. (PMID:26646615)
• XCI involves the concerted action of non-coding RNAs (ncRNAs), including the well-known Xist RNA (PMID:26659486)
• all female human embryonic stem cell (hESC) lines used expressed negligible levels of endogenous XIST , suggesting they had undergone post-XCI XIST loss.This highlights the poor utility of hESC lines as models for the study of XIST biology (PMID:26662182)
• Knockdown of XIST could upregulate the expression of miR-92b to promote hepatocellular carcinoma cell proliferation and metastasis. (PMID:27100897)
• Data suggest a tumor suppressor role of Xist in inhibiting AKT activation via regulation of non-X-chromosome gene PHLPP1 expression. (PMID:27248326)
• XIST functioned as an oncogene in nasopharyngeal carcinoma through up-regulating E2F3 in part through ‘spongeing’ miR-34a-5p. (PMID:27461945)
• Long noncoding RNA XIST acts as an oncogene in non-small cell lung cancer by epigenetically repressing KLF2 expression. (PMID:27501756)
• Study shows that human nuclei undergo a progressive loss of H3K27me3 and XIST from the inactive X chromosome (Xi) and selectively re-express certain human Xi genes. (PMID:27507283)
• data reveal a pathway of m(6)A formation and recognition required for XIST-mediated transcriptional repression (PMID:27602518)
• Data demonstrated that lncRNA XIST was significantly overexpressed in gastric cancer tissues and cell lines. Its overexpression was closely associated with an aggressive tumor phenotype and adverse prognosis. Its knockdown suppressed cell proliferation, migration and invasion through its regulation of miR-101 to modulate EZH2 in gastric cancer cells. (PMID:27620004)
• Data suggest a role of XIST- correlated small RNA XPi2 in modulating the G-quadruplex formation which may play some essential roles in the KRAS- associated carcinogenesis. (PMID:27880931)
• Data demonstrated that lncRNA XIST is up-regulated in gastric cancer tissues and cell lines and associated with tumor size. Its inhibition decreased tumor growth and invasion in vivo through the miR-497/MACC1 axis. (PMID:27911852)
• These findings therefore suggest a mechanism involving antagonistic activity of XIST and XACT in controlling X chromosome activity in early human embryos. (PMID:27989768)
• Authors revealed that there was reciprocal repression between XIST and miR-139-5p. PDK1 was identified as a direct target of miR-139-5p and proposed that XIST was responsible for hepatocellular carcinoma cell proliferation, and XIST exerted its function through the miR-139-5p/PDK1 axis. (PMID:28231734)

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.