HMGA2 (high mobility group AT-hook 2)

2015-10-01 Jian-Jun Wei Affiliation

Identity

HGNC

HMGA2

LOCATION

12q14.3

IMAGE

LEGEND

FISH Probe(s) - Courtesy Mariano Rocchi

LOCUSID

8091

ALIAS

BABL,HMGI-C,HMGIC,LIPO,SRS5,STQTL9

FUSION GENES

Show Gene Fusions

Abstract

HMGA2, the High Mobility Group A2 gene, is a non-histone and architectural transcription factor. As an oncofetal protein, HMGA2 plays an important role in development and contributes to the tumorigenesis of many epithelial and mesenchymal tumors. Upregulation of HMGA2 by non-random chromosomal translocations is common in mesenchymal tumors, whereas by the altered transcription regulation is likely the major mechanism in malignant epithelial tumors and it involves much more complex mechanisms. HMGA2 directly and indirectly regulates the multiple biological and oncogenic pathways. Its oncogenic property remains to be fully characterized.

DNA/RNA

HMGA2 has long UTR (about 3,000 nt). HMGA2 can be potentially regulated by multiple miRNAs and one of well characterized miRNAs is let-7 family which contains at least five predicted bindings sites. MIRLET7E (Let-7) repression of HMGA2 expression at transcription and translation has been demonstrated in several different studies (Lee and Dutta 2007, Wang et al. 2007, Peng et al. 2008). Inverse association of Let-7 and HMGA2 is an important regulation mechanism in normal development and abnormal tumorigensis (Park et al. 2007, Shell et al. 2007).

Description

5 exons, spans approximately 160 kb; a sixth alternative terminal exon within intron 3 has been described

Transcription

RNA: 4.1 kb. Transcription initiated from two different promoter regions. A polymorphic dinucleotide repeat upstream of the ATG start codon strongly regulates HMGA2 expression. Moreover, HMGA2 is controlled by negatively acting regulatory elements within the 3UTR

Proteins

Description

109 amino acids; three DNA binding domains (AT hooks) linked to the carboxy-terminal acidic domain that does not activate transcription.

HMGA2 can directly regulate expression of many genes. Specific recognition of AT-rich DNA sequences by HMGA2 was reporte by a SELEX study. The relative heights are proportional to their frequencies shown in the 71 SELEX sequences (Cui and Leng 2007).

Expression

Fetal tissues: expression in various tissues, prominent in kidney, liver and uterus; adult tissues: no expression except in lung and kidney; tumors: expression in benign mesenchymal tumor tissues correlated to 12q15 rearrangements; expressed in malignant tumours (e.g., in breast tumours, pancreas tumours, ovarian cancer, lung tumours, colorectal cancer, nerve system tumours, oral cavity squamous cell cancer).

Inverse expression pattern of HMGA2 and let-7 family in developmental and adulthood stages as well as neoplastic change (Park, Shell et al. 2007).

Localisation

nuclear

Immunohistochemistry shows that HMGA2 is specifically expressed and located in nucleus. Photomicrographs illustrate strong immunoreactivity for HMGA2 in leiomyoma with t(12;14) translocation and high grade serous ovarian carcinoma (Wu and Wei 2013, Bertsch et al. 2014).

Function

Architectural factor, non histone, preferential binding to AT rich sequences in the minor groove of DNA helix; the precise function remains to be elucidated; probable role in regulation of cell proliferation.

It is widely accepted that functional CDKN2A (p16INK4a) and RB1 (pRb) as well as the HMGA2, which accumulate at E2F target promoters during senescence, are critically required for SAHF arrangement (Narita et al. 2006).

Homology

Member of the HMGI protein family.

HMGA2 is regulated by non-coding miRNAs and coding genes. As a non-histone nuclear transcription regulator, HMGA2 has a broad influence in many gene expression, mainly target at epithelial-to-mesenchymal transition (EMT), cell proliferation, DNA damage repair, stem cell self-renewal and differentiation, as well as tumorigenesis of many benign and malignant mesenchymal and epithelial tumors (Wu and Wei 2013).

HMGA2 regulates stem cell potential for self-renewal. HMGA2 seems to be a major regulator of INK4a/ARF expression. HMGA2 reduces INK4A and ARF expression. HMGA2 binds to the Junb locus. As JUNB promotes INK4A/ARF expression in stem cells, thus promoting stem cell self-renewal. Increase in let-7 expression results in the downregulation of HMGA2 and the derepression of the INK4a/ARF and activation of p16INK4a expression in self-renewing cells. In Hmga2-deficient mice, it shows reduced stem cell numbers and self-renewal. Furthermore, p16(Ink4a) and p19(Arf) expression were increased in Hmga2-deficient fetal and young-adult stem cells, and deletion of p16(Ink4a) and/or p19(Arf) partially restored self-renewal capacity. (Yu et al. 2007, Nishino et al. 2008).

Mutations

Germinal

Deletion of HMGIC in mutant mice or transgenic knock out mice for the first two exons of HMGIC have the "pigmy" phenotype: low birth weight, craniofacial defects, adipocyte hypoplasia adult body weight about 40% of normal; mice with a partial or complete deficiency of HMGA2 resisted diet-induced obesity implicating a role of the gene in fat cell proliferation; truncations of mouse Hmga2 in transgenic mice result in somatic overgrowth and, in particular, increased abundance of fat and lipomas; overexpression of the HMGA2 gene in transgenic mice leads to the onset of pituary adenomas secreting prolactic and growth hormone; HMGA2-null mice had very few spermatids and complete absence of spermatozoa.
8-year-old boy had a de novo pericentric inversion of chromosome 12, with breakpoints at p11.22 and q14.3. The phenotype included extreme somatic overgrowth, advanced endochondral bone and dental ages, a cerebellar tumour, and multiple lipomas. His chromosomal inversion was found to truncate HMGA2, which maps to the 12q14.3 breakpoint.

Implicated in

Entity name

MESENCHYMAL BENIGN TUMORS as follows:

Entity name

Lipoma

Disease

benign adipocyte tumor

Prognosis

good

Cytogenetics

various rearrangements involving 12q15 (translocations, inversions, deletions...); reciprocal translocations involve 12q15 with different partners such as chromosomes 1, 2, 3, 7, 10, 11, 13, 15, 17, 21, X; the most frequent anomaly is t(3;12)(q27-28;q15); cryptic rearrangements, such as paracentric inversions not detectable by conventional cytogenetics but detectable by FISH, have been described

Hybrid gene

for t(3;12): HMGIC-LPP (LPP: lipoma preferred partner; 3q27-28); a gene located in 13q, LHFP (lipoma HMGIC fusion partner) was found to be fused with HMGIC in one case of lipoma; one lipoma displayed fusion of HMGA2 exon 4 with a sequence from intron 4, indicating abnormal splicing; HMGA2-CMKOR1 in three cases with aberrations involving 2q35-37 and 12q13-15; HMGA2-NFIB in one lipoma;

Fusion protein

HMGIC-LPP; the three AT hook domains at the aminoterminal of HMGIC are fused to the LIM domain of LPP; another fusion protein due to the fusion of HMGIC with a putative gene located at 15q24 predicted to encode a protein with a serine/threonine-rich domain has also been described

Oncogenesis

the relevance of the exact role LPP in the HMGA2-LPP fusion is not established yet, but the transactivation functions of the LPP LIM domains is retained in the fusion protein and the fusion protein can function as a transcription factor; the truncation of HMGA2 by itself may have a role in the tumorigenesis

Entity name

Uterine leiomyoma (uterine fibroids)

Disease

benign mesenchymal tumors

Prognosis

good

Cytogenetics

approximately 40% of uterine leiomyomas have structural chromosomal rearrangements, about 10% of which involve 12q15 (translocations, inversions, deletions...); the most frequent anomaly is t(12;14)(q15;q23-24)

Hybrid gene

in a majority of cases, there is no fusion gene: the breakpoint is located 10 kb up to 100 kb 5 to HMGIC; the recombinational repair gene RAD51B is a candidate to be the partner gene of HMGIC in t(12;14). In two cases (out of 81 primary tumors) exon 7 of RAD51B was fused in frame to either exon 2 or 3 of the HMGA2 gene; in one case with paracentric inversion, HMGIC exon 3 was fused to ALDH2 exon 13 (12q24.1); in one case (no cytogenetic analysis) HMGIC exon 3 was fused to COX6C 3 UTR (8q22-23); in one case, with apparently normal karyotype, exon 3 of HMGIC was fused to retrotransposon-like sequences RTVLH 3 LTRs; three fusion transcripts contained 3 cryptic exonic sequences present in intron 3 of the HMGA2 gene (breakpoints downstream of exons 3 or 4), suggesting that they are due to alternative splicing; one case displayed fusion of the first two exons of HMGA2 to the 3 portion of the CCNB1IP1/C14orf18/HEI10 gene

Fusion protein

HMGIC-ALDH2: ALDH2 contribution was only 10 amino acids;

HMGA2 and MED12 mutations are mutually exclusive and are the two independent factors for tumorigenesis of leiomyoma (Bertsch et al. 2014).

Oncogenesis

HMGIC-ALDH2: it is suggested that the truncation of HMGIC, rather than fusion may be responsible for tumorigenesis; the 3 untranslated region may stabilize the HMGIC messenger RNA

Entity name

Pleomorphic adenoma of the salivary gland (or mixed salivary gland tumor)

Disease

benign tumors from the major or minor salivary glands

Prognosis

good

Cytogenetics

approximately 12% of pleomorphic adenomas of salivary glands show abnormalities involving HMGIC in 12q15; the most frequent aberration is t(9;12)(p24.1;q15)

Hybrid gene

in t(9;12): HMGIC-NFIB fusion; another type of fusion HMGIC-FHIT (3p14.2) has also been described

Entity name

Pulmonary chondroid hamartoma of the lung

Disease

benign mesenchymal tumors of the lung

Prognosis

good

Cytogenetics

various rearrangements involving 12q15 leading to HMGIC dysregulation; cryptic rearrangements such as paracentric inversions not detectable by conventional cytogenetics but detectable by FISH have been described

Hybrid gene

in two cases with apparently normal karyotypes, exon 3 of HMGIC was fused to retrotransposon-like sequences RTVLH 3 LTRs; in cases with t(3;12)(q27-28;q14-15) (see lipomas), a fusion of HMGA2-LPP was described; only 1/61 cases with normal karyotype displayed HMGA2-LPP fusion; three cases with rearrangements involving 12q14-15 and 13q12-14 lacked rearrangements of HMGA2-LHFP;

Entity name

Endometrial polyps

Disease

uterine benign tumors

Prognosis

good

Cytogenetics

Entity name

Myofibroblastic inflammatory tumor

Disease

benign mesenchymal tumors

Prognosis

good

Cytogenetics

in one case, a complex rearrangement involving chromosomes 12 (in 12q15), 4 and 21 was described

Hybrid gene

an aberrant transcript was produced by the fusion of HMGIC exon 3 to an ectopic sequence originating from the third intron of HMGIC

Entity name

Chondrolipoangioma

Disease

a rare benign type of mesenchyomas composed predominantly of cartilage and adipose tissue with vascular elements and myxoid elements

Cytogenetics

One case demonstrated t(12;15)(q13;q26). FISH analysis revealed rearrangement of chromosomes 2, 12 and 15 and HMGA2.

Entity name

Chondromas

Disease

benign cartilage tumours

Cytogenetics

HMGA2 was expressed in 4/6 soft tissue chondromas (all with 12q-rearrangements cytogenetically), three cases showed truncated (exons 1-3) transcripts, one case displayed a t(3;12)(q27;q15) and RT-PCR demonstrated a HMGA2-LPP fusion transcript composed of HMGA2 exons 1-3 and LPP exons 9-11.

Entity name

Hyaline vascular Castlemans disease

Cytogenetics

one case with der(6)t(6;12)(q23;q15)del(12)(q15) is described.

Hybrid gene

a combined immunologic-cytogenetic approach demonstrated HMGA2 rearrangement in follicular dendritic cells

Entity name

Prolactinoma

Disease

prolactin-secreting pituary adenoma, non-metastasizing

Cytogenetics

trisomy 12 nonrandom finding in pituary adenomas

Hybrid gene

HMGA2 locus amplified in 7/8 prolactinomas

Entity name

Aggressive angiomyxoma of the vulva

Disease

myxoid mesenchymal neoplasm

Prognosis

infiltrative neoplasm, locally destructive recurrences, no metastatic potential

Cytogenetics

one case displayed t(8;12)(p12;q15)

Hybrid gene

FISH demonstrated a breakpoint 3 of the gene, the tumour expressed HMGA2

Entity name

MALIGNANT TUMORS as follows:

Entity name

Well-differentiated liposarcoma

Disease

malignant adipocyte tumor; peripheral or retroperitoneal location

Prognosis

rather good; borderline malignancy; locally aggressive, rarely metastasizes

Cytogenetics

supernumerary ring or giant marker chromosomes containing 12q14-15 amplification (surrounding MDM2); HMGIC is frequently amplified together with MDM2; rearrangement of HMGA2, in addition to amplification has been described

Hybrid gene

ectopic sequences from 12q14-15, 1q24, 11q14, and chromosome 2 was shown to be fused to HMGA2 exon 2 or 3

Entity name

Uterine leiomyosarcoma

Disease

malignant counterpart of uterine leiomyoma

Prognosis

poor

Cytogenetics

12q13-15 region is recurrently amplified

Hybrid gene

HMGA2 amplified within this region

Entity name

Osteosarcoma

Disease

malignant tumor

Hybrid gene

in one osteosarcoma cell line (OsA-Cl) the three DNA binding domains of HMGIC fused to the keratan sulfate protein glycan gene LUM (12q22-23); LUM was fused out of frame, and only 3 amino acids were fused to HMGIC; in addition, the rearranged gene was amplified

Entity name

Myelofibrosis with myeloid metaplasia

Disease

rare chronic myeloproliferative disorder

Prognosis

variable

Cytogenetics

one case with t(4;12)(q32;q15) and one case with t(5;12)(p14;q15)

Hybrid gene

FISH analysis suggested breakpoint in HMGA2, RT-PCR revealed that HMGA2 is expressed in blood mononuclear cells from patients with this disease

Entity name

Acute lymphoblastic leukaemia

Disease

Heterogenous disease that arises in precursor B or T cells

Cytogenetics

One case with a t(9;12)(p22;q14), frequent deletions at 12q14.3

Hybrid gene

t(9;12): FISH analysis indicated a breakpoint in the 5 region of the gene, RT-PCR showed overexpression of HMGA2 lacking the carboxyterminal tail; deletions covering the 5 end of HMGA2

Entity name

High-grade serous carcinoma of the fallopian tubes

Disease

Serous carcinoma arising from fallopian tube secretory epithelia.

Oncogenesis

Overexpression of HMGA2 regulated by several genetic mechanism, including CTNNB1 (β -Catenin), TGF- β, miRNAs. Currently well definied miRNAs including let-7 and MIR-182. MiR-182 promotes HMGA2 expression through negative regulation of BRCA1 (Moskwa et al. 2011, Liu et al. 2012). HMGA2 regulates several EMT genes including STC2 and LUM (Wu et al. 2011).
Overexpression of HMGA2 is associated with early tumorigenesis, tumor cell proliferation, invasion and worse outcome through regulation of cell cycle, epithelial to mesenchymal transition (Wu et al. 2011).

Entity name

Pancreatic carcinoma

Disease

Pancreatic ductal carcinoma.

Oncogenesis

Overexpression of HMGA2 promote EMT by regulation of SNAIL, SLUG, SIP1, TCF3 (E12/E47), and ZEB1 (Watanabe et al. 2009).
HMGA2 nuclear immunoreactivity correlates positively with lymph node metastases and high tumor grade (Hristov et al. 2009).

Entity name

Breast Cancer

Disease

Serous carcinoma arising from fallopian tube secretory epithelia.

Oncogenesis

HMGA2 gene and protein are highly expressed in metastatic breast cancer cells. HMGA2 as an important regulator of PAR1-mediated invasion.
Inhibition of PAR1 signaling suppresses HMGA2-driven invasion in breast cancer cells (Yang et al. 2015).

Entity name

Colon Cancer

Disease

Colonic adenocarcinoma.

Oncogenesis

HMGA2 delays the clearance of H2AFX(γ-H2AX) in colon cancer.
Overexpression of HMGA2 is associated with metastasis and unequivocally occurred in parallel with reduced survival rates of patients with colorectal carcinoma (Wang et al. 2011).

Entity name

Lung Cancer

Disease

Non-small-cell lung cancer (NSCLC)

Oncogenesis

HMGA2 can operate as competing endogenous RNA (ceRNA) for the let-7 microRNA (miRNA) family, suggesting that Hmga2 affects let-7 activity by altering miRNA targeting.
HMGA2 promotes the transformation of lung cancer cells independent of protein-coding function. Tgfbr3 expression is regulated by the Hmga2 ceRNA through differential recruitment to Argonaute 2 (AGO2), and TGF-β signalling driven by Tgfbr3 is important for Hmga2 to promote lung cancer progression (Kumar et al. 2014).

Breakpoints

Up to 21 partners have a breakpoint with HMGA2 are summarized. The majority of this non-random translocations were found to be in mesenchymal neoplasia (Wu and Wei 2013).

Article Bibliography

Pubmed ID	Last Year	Title	Authors
14647145	2003	An increased high-mobility group A2 expression level is associated with malignant phenotype in pancreatic exocrine tissue.	Abe N et al
15497774	2004	High mobility group I-C protein in astrocytoma and glioblastoma.	Akai T et al
10742101	2000	In vivo modulation of Hmgic reduces obesity.	Anand A et al
14603445	2004	Dysregulation and overexpression of HMGA2 in myelofibrosis with myeloid metaplasia.	Andrieux J et al
10747931	2000	Transgenic mice expressing a truncated form of the high mobility group I-C protein develop adiposity and an abnormally high prevalence of lipomas.	Arlotta P et al
7606786	1995	Disruption of the architectural factor HMGI-C: DNA-binding AT hook motifs fused in lipomas to distinct transcriptional regulatory domains.	Ashar HR et al
4081525	1985	Prevention from naturally acquired viral respiratory infection by interferon nasal spray.	Saito H et al
12569368	2003	Human HMGA2 promoter is coregulated by a polymorphic dinucleotide (TC)-repeat.	Borrmann L et al
12118328	2002	Fusion of RDC1 with HMGA2 in lipomas as the result of chromosome aberrations involving 2q35-37 and 12q13-15.	Broberg K et al
15650238	2004	HMGA molecules in neuroblastic tumors.	Cerignoli F et al
12032866	2002	HMGA1 and HMGA2 protein expression in mouse spermatogenesis.	Chieffi P et al
16125217	2005	Array comparative genomic hybridization analysis of uterine leiomyosarcoma.	Cho YL et al
11979097	2002	Hyaline vascular Castleman's disease with HMGIC rearrangement in follicular dendritic cells: molecular evidence of mesenchymal tumorigenesis.	Cokelaere K et al
15755872	2005	Transactivation functions of the tumor-specific HMGA2/LPP fusion protein are augmented by wild-type HMGA2.	Crombez KR et al
17956125	2007	Specific recognition of AT-rich DNA sequences by the mammalian high mobility group protein AT-hook 2: a SELEX study.	Cui T et al
17957144	2007	Let-7 prevents early cancer progression by suppressing expression of the embryonic gene HMGA2.	Park SM et al
14614053	2003	Fusion, disruption, and expression of HMGA2 in bone and soft tissue chondromas.	Dahlén A et al
1855228	1991	The Mary Lasker Conference, on growth factors in hormone-related tumors.	Mueller GC et al
12082634	2002	Overexpression of the HMGA2 gene in transgenic mice leads to the onset of pituitary adenomas.	Fedele M et al
11956103	2002	The High Mobility Group A2 gene is amplified and overexpressed in human prolactinomas.	Finelli P et al
10398424	1999	HMGIC expression in human adult and fetal tissues and in uterine leiomyomata.	Gattas GJ et al
11921278	2002	Sequencing of intron 3 of HMGA2 uncovers the existence of a novel exon.	Hauke S et al
11170289	2001	Chromosomal rearrangements leading to abnormal splicing within intron 4 of HMGIC?	Hauke S et al
9495195	1998	Chromosomal translocations in benign tumors: the HMGI proteins.	Hess JL et al
2769577	1989	Predictors of nutrition supplement use in the elderly. Part I: A review of the literature.	Cotugna N et al
16056249	2005	HMGA proteins in malignant peripheral nerve sheath tumor and synovial sarcoma: preferential expression of HMGA2 in malignant peripheral nerve sheath tumor.	Hui P et al
10686944	1999	Inflammatory myofibroblastic tumor with HMGIC rearrangement.	Kazmierczak B et al
8908160	1996	Amplification of a rearranged form of the high-mobility group protein gene HMGIC in OsA-CI osteosarcoma cells.	Kools PF et al
3886898	1985	Nutritional requirements of Plasmodium falciparum in culture. I. Exogenously supplied dialyzable components necessary for continuous growth.	Divo AA et al
11135440	2001	Three aberrant splicing variants of the HMGIC gene transcribed in uterine leiomyomas.	Kurose K et al
12505264	2002	Expression of the HMGA2-LPP fusion transcript in only 1 of 61 karyotypically normal pulmonary chondroid hamartomas.	Lemke I et al
15593017	2005	Constitutional rearrangement of the architectural factor HMGA2: a novel human phenotype including overgrowth and lipomas.	Ligon AH et al
22322863	2012	MiR-182 overexpression in tumourigenesis of high-grade serous ovarian carcinoma.	Liu Z et al
11391797	2001	Ectopic sequences from truncated HMGIC in liposarcomas are derived from various amplified chromosomal regions.	Meza-Zepeda LA et al
11223542	2001	Fusion of a sequence from HEI10 (14q11) to the HMGIC gene at 12q15 in a uterine leiomyoma.	Mine N et al
15026339	2004	Expression of mesenchyme-specific gene HMGA2 in squamous cell carcinomas of the oral cavity.	Miyazawa J et al
3249932	1988	[The effect of atropine, quinuclidinyl benzilate and their antidote tetrahydroaminoacridine on adhesion and spreading in cells cultured in vitro].	Kolárová J et al
1690178	1990	Expression of HRF20, a regulatory molecule of complement activation, on peripheral blood mononuclear cells.	Hideshima T et al
16133369	2005	Fusion of the HMGA2 and NFIB genes in lipoma.	Nilsson M et al
2582221	1985	Fc gamma-receptor blocking antibodies in hyperimmune and normal pooled gammaglobulin.	Templeton JG et al
11550285	2001	Chromosomal translocation t(8;12) induces aberrant HMGIC expression in aggressive angiomyxoma of the vulva.	Nucci MR et al
15495192	2005	Frequent deletions at 12q14.3 chromosomal locus in adult acute lymphoblastic leukemia.	Patel HS et al
18403645	2008	Antiproliferative effects by Let-7 repression of high-mobility group A2 in uterine leiomyoma.	Peng Y et al
8812423	1996	LPP, the preferred fusion partner gene of HMGIC in lipomas, is a novel member of the LIM protein gene family.	Petit MM et al
12851685	2003	HMGA2 locus rearrangement in a case of acute lymphoblastic leukemia.	Pierantoni GM et al
12649198	2003	Fusion transcripts involving HMGA2 are not a common molecular mechanism in uterine leiomyomata with rearrangements in 12q15.	Quade BJ et al
9598796	1998	The t(3;12)(q27;q14-q15) with underlying HMGIC-LPP fusion is not determining an adipocytic phenotype.	Rogalla P et al
11890997	2002	Absence of HMGIC-LHFP fusion in pulmonary chondroid hamartomas with aberrations involving chromosomal regions 12q13 through 15 and 13q12 through q14.	Rogalla P et al
8889500	1996	Translocation breakpoints upstream of the HMGIC gene in uterine leiomyomata suggest dysregulation of this gene by a mechanism different from that in lipomas.	Schoenberg Fejzo M et al
9892177	1999	Allelic knockout of novel splice variants of human recombination repair gene RAD51B in t(12;14) uterine leiomyomas.	Schoenmakers EF et al
2040910	1991	[Development of acute endolymphatic hydrops following secondary endolymphatic sac immune response. I: Short-term observation].	Tomiyama S et al
11135437	2001	Evidence for RAD51L1/HMGIC fusion in the pathogenesis of uterine leiomyoma.	Takahashi T et al
12021922	2002	Translocation of the HMGI-C ( HMGA2) gene in a benign mesenchymoma (chondrolipoangioma).	Van Dorpe J et al
17243163	2007	A micro-RNA signature associated with race, tumor size, and target gene activity in human uterine leiomyomas.	Wang T et al
3079060	1987	A controlled prospective trial of triple therapy with low-dose azathioprine, cyclosporine, and methylprednisolone in renal transplantation.	De Vecchi A et al
9087575	1997	Hidden paracentric inversions of chromosome arm 12q affecting the HMGIC gene.	Wanschura S et al
2665746	1989	Perturbations in nitrogen metabolism of brain and liver of rat following repeated benthiocarb administration.	Babu GR et al
23686260	2013	HMGA2 and high-grade serous ovarian carcinoma.	Wu J et al
21224353	2011	HMGA2 overexpression-induced ovarian surface epithelial transformation is mediated through regulation of EMT genes.	Wu J et al
26165842	2016	Dysregulated protease activated receptor 1 (PAR1) promotes metastatic phenotype in breast cancer through HMGA2.	Yang E et al
18083101	2007	let-7 regulates self renewal and tumorigenicity of breast cancer cells.	Yu F et al
7651535	1995	Mutation responsible for the mouse pygmy phenotype in the developmentally regulated factor HMGI-C.	Zhou X et al

Other Information

Locus ID:

NCBI: 8091
MIM: 600698
HGNC: 5009
Ensembl: ENSG00000149948

Variants:

dbSNP: 8091
ClinVar: 8091
TCGA: ENSG00000149948
COSMIC: HMGA2

RNA/Proteins

Gene ID	Transcript ID	Uniprot
ENSG00000149948	ENST00000354636	P52926
ENSG00000149948	ENST00000393577	F5H2A4
ENSG00000149948	ENST00000393578	P52926
ENSG00000149948	ENST00000403681	P52926
ENSG00000149948	ENST00000425208	P52926
ENSG00000149948	ENST00000536545	F5H6H0
ENSG00000149948	ENST00000537275	P52926
ENSG00000149948	ENST00000537429	P52926
ENSG00000149948	ENST00000539662	H0YFY4
ENSG00000149948	ENST00000541363	F5H2U8

Expression (GTEx)

Adipose - Subcutaneous

Adipose - Visceral

Adrenal Gland

Artery - Aorta

Artery - Tibial

Bladder

Brain - Amygdala

Brain - Anterior cingulate cortex

Brain - Caudate

Brain - Cerebellar Hemisphere

Brain - Cerebellum

Brain - Cortex

Brain - Frontal Cortex

Brain - Hippocampus

Brain - Hypothalamus

Brain - Nucleus accumbens

Brain - Putamen

Brain - Spinal cord

Brain - Substantia nigra

Breast - Mammary Tissue

Cells - Cultured fibroblasts

Cells - EBV - transformed lymphocytes

Cervix - Ectocervix

Cervix - Endocervix

Colon - Sigmoid

Colon - Transverse

Esophagus - Gastroesophageal Junction

Esophagus - Mucosa

Esophagus - Muscularis

Fallopian Tube

Heart - Atrial Appendage

Heart - Left Ventricle

Kidney - Cortex

Kidney - Medulla

Liver

Lung

Minor Salivary Gland

Muscle - Skeletal

Nerve - Tibial

Ovary

Pancreas

Pituitary

Prostate

Skin - Not Sun Exposed

Skin - Sun Exposed

Small Intestine - Terminal Ileum

Spleen

Stomach

Testis

Thyroid

Uterus

Vagina

Whole Blood

Pathways

Pathway	Source	External ID
Transcriptional misregulation in cancer	KEGG	ko05202
Transcriptional misregulation in cancer	KEGG	hsa05202
MicroRNAs in cancer	KEGG	hsa05206
MicroRNAs in cancer	KEGG	ko05206
Cellular responses to stress	REACTOME	R-HSA-2262752
Cellular Senescence	REACTOME	R-HSA-2559583
DNA Damage/Telomere Stress Induced Senescence	REACTOME	R-HSA-2559586
Formation of Senescence-Associated Heterochromatin Foci (SAHF)	REACTOME	R-HSA-2559584

Protein levels (Protein atlas)

Not detected

Low

Medium

High

References

Pubmed ID	Year	Title	Citations
37461232	2024	Keratin-Positive Giant Cell-Rich Tumor of Bone Harboring an HMGA2::NCOR2 Fusion: Two Cases, Including a Patient With Metastatic Disease, and Review of the Literature.	2
37822284	2024	CircDLGAP4 overexpression ameliorates neuronal injury in Parkinson's disease by binding to EIF4A3 and increasing HMGA2 expression.	0
37849332	2024	Expanding the histological spectrum of salivary gland neoplasms with HMGA2::WIF1 fusion emphasising their malignant potential: a report of eight cases.	0
38151824	2024	Exosomal circFAM63Bsuppresses bone regeneration of postmenopausal osteoporosis via regulating miR-578/HMGA2 axis.	1
38266920	2024	SOX10-Internal Tandem Duplications and PLAG1 or HMGA2 Fusions Segregate Eccrine-Type and Apocrine-Type Cutaneous Mixed Tumors.	0
38378354	2024	Effects of HMGA2 on the biological characteristics and stemness acquisition of gastric cancer cells.	0
38506034	2024	The role of HMGA2 in activating the IGFBP2 expression to promote angiogenesis and LUAD metastasis via the PI3K/AKT/VEGFA signaling pathway.	0
38516887	2024	Characterization of HMGA2 variants expands the spectrum of Silver-Russell syndrome.	0
38802807	2024	Association of deletion polymorphism rs10573247 in the HMGA2 gene with the risk of breast cancer: bioinformatic and experimental analyses.	0
38811851	2024	Chromatin modifier Hmga2 promotes adult hematopoietic stem cell function and blood regeneration in stress conditions.	0
37461232	2024	Keratin-Positive Giant Cell-Rich Tumor of Bone Harboring an HMGA2::NCOR2 Fusion: Two Cases, Including a Patient With Metastatic Disease, and Review of the Literature.	2
37822284	2024	CircDLGAP4 overexpression ameliorates neuronal injury in Parkinson's disease by binding to EIF4A3 and increasing HMGA2 expression.	0
37849332	2024	Expanding the histological spectrum of salivary gland neoplasms with HMGA2::WIF1 fusion emphasising their malignant potential: a report of eight cases.	0
38151824	2024	Exosomal circFAM63Bsuppresses bone regeneration of postmenopausal osteoporosis via regulating miR-578/HMGA2 axis.	1
38266920	2024	SOX10-Internal Tandem Duplications and PLAG1 or HMGA2 Fusions Segregate Eccrine-Type and Apocrine-Type Cutaneous Mixed Tumors.	0

Citation

Jian-Jun Wei

HMGA2 (high mobility group AT-hook 2)

Atlas Genet Cytogenet Oncol Haematol. 2015-10-01

Online version: http://atlasgeneticsoncology.org/gene/82/deep-insight-explorer/meetings/img/logo-atlas-4.svg

Historical Card

2005-12-01 HMGA2 (high mobility group AT-hook 2) by Karin Broberg Affiliation

Molecular biologist, Dep. of Occupational, Environmental Medicine, Lund University Hospital, SE-221 85 Lund, Sweden

2000-05-01 HMGA2 (high mobility group AT-hook 2) by Florence Pedeutour Affiliation

Laboratoire de Génétique des Tumeurs Solides, 5ème étage, Faculté de Médecine, 28 avenue de Valombrose, 06107 Nice cedex 2, France