HMGA1 (High mobility group protein (non histone chromosomal) isoform I and Y)

Other names	HMG-I(Y), HMGI/Y
HGNC (Hugo)	HMGA1
LocusID (NCBI)	3159
Location	6p21.31
Location_base_pair	Starts at 34204577 and ends at 34214008 bp from pter ( according to hg19-Feb_2009)  [Mapping]
Local_order	centromeric to HLA-A, telomeric to D6S19
	Probe(s) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics

Description	10 144 bp; 8 exons, 7 introns
Transcription	HMGI and HMGY are encoded by the same gene and are generated trough alternative splicing; exons 1-4 are not transcribed, exons 5-7 encode three DNA binding domains; exon 5 contains a 33 bp segment subject to alternative splicing; exon 8 encodes the acidic carboxy-terminal end; RNA length: 1.85 kb.

Description	107 amino acids; three DNA binding domains (AT hooks)
Expression	expressed in embryonal cells; expressed in a variety of normal human adult tissues such as heart, brain, lung, skeletal muscle, kidney, pancreas, spleen, thymus, testis, ovary, small intestine, submandibular gland and leukocytes; expressed in transformed cells with a malignant phenotype and in human malignant tumors such as prostate, thyroid carcinoma and colorectal carcinomas and a subset of benign lipomas.
Localisation	nuclear
Function	architectural transcription, non histone, factor that binds to the minor groove of AT-rich DNA; alters DNA conformation by introducing bends and supercoils; HMGIY was shown to be an essential component of enhanceosome (higher order transcription enhancer complex); positive induction of several genes including IFN-b, E-selectin, interleukin-2 receptor a-chain, the chemokine MGSA/GRO, and the class II major histocompatibility complex gene HLA-DRA; negative regulation by binding the promoter regions of interleukin-4 and GP91-PHOX. the precise function remains to be elucidated; probable role in regulation of chromatin structure and gene expression, and transcriptional regulation; potential oncogenic role
Homology	member of the HMGI protein family, structural (but not expression pattern) homology with HMGIC

Entity	Pulmonary chondroid hamartoma
Disease	benign tumor of the lung
Prognosis	good
Cytogenetics	the most frequent rearrangement is a reciprocal balanced translocation t(6;14) (p21.3; q24); the rearrangement between chromosomes 6 and 14 can sometimes be complex, identifiable by FISH; molecular results also suggest that the translocations might be more complex than shown by conventional cytogenetics, with the presence of additional cryptic rearrangements; translocations involving partner chromosomes other than chromosome 14, such as chromosomes 1, 3, 4, 5, 10, 12, 17 have also been reported; inversions inv(6)(p21q21) or inv(6)(p21.3q26) have been described
Hybrid/Mutated Gene	in most cases, the breakpoint was extragenic, located within a 80 kb region 3' of HMGIY; aberrant transcripts with truncation of sequences from the 3' UTR have been described; in only one case with inversion inv(6)(p21q21), a hybrid intragenic fusion has been reported: HMGIY was fused to the LAMA4 (laminin a4 chain) gene
Abnormal Protein	the HMGIY-LAMA4 resulted from the fusion of the three HMGIY DNA-binding domains with the LAMA4 EGF-like domain
Oncogenesis	the exact role of HMGI(Y)-LAMA4 fusion is not established yet
Entity	Lipomas
Disease	benign adipocyte tumors
Prognosis	good
Cytogenetics	a small subset (5-8%) of ordinary lipomas is characterized by 6p21 rearrangements, the most frequent of which being a reciprocal translocation t(3;6)(q28;p21); in contrast to other benign mesenchymal tumors with 6p21 rearrangement, there is no evidence of HMGIY rearrangements in ordinary lipomas yet; however, to be noticed, the breakpoint on 6p21 was shown to be located whithin a 80 kb region surrounding HMGIY in one lipoma case and HMGIY expression was correlated with 6p rearrangements in two ordinary lipomas and two spindle cell lipomas
Entity	Uterine leiomyoma
Disease	benign mesenchymal tumors
Prognosis	good
Cytogenetics	approximately 40% of uterine leiomyomas present structural chromosomal rearrangements, 5% of which involve 6p abnormalities; they include t(1;6)(q23;p21), t(6;14)(p21;q24) and t(6;10)(p21;q22) as well as inversions and translocations involving other chromosomal partners; the rearrangements are sometimes complex, only identifiable by FISH analysis
Hybrid/Mutated Gene	no hybrid gene has been described yet; as for other mesenchymal tumors, the breakpoint was extragenic, located within a 80 kb region 3' of HMGIY; one case of aberrant transcript with truncation of 1295 bp from the 3' UTR has been described
Abnormal Protein	HMGIY mRNA and protein levels do not always correlate, suggesting that post-transcriptional mechanisms are involved in the regulation of HMGIY
Entity	Endometrial polyps
Disease	uterine benign tumors
Prognosis	good
Cytogenetics	several chromosomal abnormalities involving the 6p21.3 region, including translocations, deletions, inversions have been described; various chromosomal partner regions, such as 14q24, 20q13, 2q35, 10q22, 8q12, 1p32, 7p15, 15q21, have been described to be associated with 6p21.3 in reciprocal translocations.
Hybrid/Mutated Gene	no hybrid gene has been described yet; as for other mesenchymal tumors, the breakpoint is extragenic, located within a 80 kb region 3' of HMGIY
Entity	Hamartoma of the breast
Disease	benign tumor-like nodule of the breast, also called adenolipoma
Prognosis	good
Cytogenetics	one case with a t(1 ;6)(p21 ;21), involving the HMGIY gene has been described
Entity	Microfollicular adenoma of the thyroid
Disease	epithelial tumors
Prognosis	favorable
Cytogenetics	one case with a t(1;6)(p35;21) correlated with an overexpression of HMGIY has been described

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