HMGA1
protein-codinghigh mobility group AT-hook 1, the group of Canonical high mobility group|MicroRNA protein coding host genes
Gene summary
This gene encodes a chromatin-associated protein involved in the regulation of gene transcription, integration of retroviruses into chromosomes, and the metastatic progression of cancer cells. The encoded protein preferentially binds to the minor groove of AT-rich regions in double-stranded DNA. Multiple transcript variants encoding different isoforms have been found for this gene. Pseudogenes of this gene have been identified on multiple chromosomes. [provided by RefSeq, Jan 2016]
- HMGIY
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~9.4 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0005148
Submitter: Labcorp Genetics (formerly Invitae)
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to HMGA1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_145899.3. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | 2 | |||
| missense | 9 | 9 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 12 | 1 | 1 | 14 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_665906.1 | 4 | MANE Select | |
| Ensembl | ENSP00000308227.4 | 4 | MANE Select | |
| RefSeq | NP_001306006.1 | 4 | Standard | |
| RefSeq | NP_001306007.1 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- miR-targeted genes in leukocytes - TarBase
- miR-targeted genes in lymphocytes - TarBase
- miR-targeted genes in muscle cell - TarBase
- miR-targeted genes in squamous cell - TarBase
- Adipogenesis
Biological Process
- DNA unwinding involved in DNA replication
- base-excision repair
- nucleosome disassembly
- regulation of transcription, DNA-templated
- negative regulation of cell population proliferation
Molecular Function
- DNA-binding transcription factor activity, RNA polymerase II-specific
- enhancer sequence-specific DNA binding
- DNA binding
- AT DNA binding
- chromatin binding
Cellular Component
- nucleus
- nucleoplasm
- transcription factor complex
- cytosol
- focal adhesion
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000447654
- Coding exons
- 4
- Length
- 9359
- Individuals with no LoFs
- 124928
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 1
- Defined
- 124929
- p
- 0.00000400
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.81 | 25 | 66.5 | 0.376 | 0.00000451 | 670 |
| Missense (PolyPhen) | 0 | 5.7641 | 0 | 31 | ||
| Synonymous | 0.0383 | 27 | 27.3 | 0.991 | 0.00000193 | 211 |
| Loss of Function | 2.25 | 0 | 5.88 | 0.00 | 3.37e-7 | 67 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.0000089 | 0.0000089 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: HMG-I/Y bind preferentially to the minor groove of A+T rich regions in double-stranded DNA. It is suggested that these proteins could function in nucleosome phasing and in the 3'-end processing of mRNA transcripts. They are also involved in the transcription regulation of genes containing, or in close proximity to A+T-rich regions.;
- Disease
- DISEASE: Note=A chromosomal aberration involving HMGA1 is found in pulmonary chondroid hamartoma. Translocation t(6;14)(p21;q23-24) with RAD51B. {ECO:0000269|PubMed:11978964}.;
Recessive Scores
- pRec
- 0.535
Intolerance Scores
- LoFtool
- 0.467
- RVIS EVS
- -0.05
- RVIS percentile EVS
- 49.39
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.959
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |