HIC1
protein-codingHIC ZBTB transcriptional repressor 1, the group of BTB domain containing|Zinc fingers C2H2-type
Gene summary
This gene functions as a growth regulatory and tumor repressor gene. Hypermethylation or deletion of the region of this gene have been associated with tumors and the contiguous-gene syndrome, Miller-Dieker syndrome. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Sep 2010]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~9.1 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to HIC1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_006497.4. 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 | 3 | 4 | 7 | |||
| missense | 88 | 2 | 90 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 88 | 5 | 4 | 97 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_006488.2 | 1 | MANE Select | |
| Ensembl | ENSP00000477858.1 | 1 | MANE Select | |
| RefSeq | NP_001091672.1 | 2 | Standard | |
| Ensembl | ENSP00000314080.3 | 2 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- hypoxia and p53 in the cardiovascular system
- SUMOylation of transcription factors
- Post-translational protein modification
- SUMO E3 ligases SUMOylate target proteins
- Metabolism of proteins
Biological Process
- negative regulation of transcription by RNA polymerase II
- regulation of transcription, DNA-templated
- cellular response to DNA damage stimulus
- multicellular organism development
- intrinsic apoptotic signaling pathway in response to DNA damage
Molecular Function
- DNA-binding transcription factor activity, RNA polymerase II-specific
- DNA-binding transcription repressor activity, RNA polymerase II-specific
- DNA-binding transcription factor activity
- protein binding
- histone deacetylase binding
Cellular Component
- chromatin
- nucleus
- nucleoplasm
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000322941
- Coding exons
- 2
- Length
- 5534
- Individuals with no LoFs
- 124831
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 29
- Defined
- 124860
- p
- 0.000116
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.70 | 222 | 368 | 0.603 | 0.0000236 | 4553 |
| Missense (PolyPhen) | 44 | 119.11 | 0.36941 | 1230 | ||
| Synonymous | -0.564 | 190 | 180 | 1.05 | 0.0000136 | 1584 |
| Loss of Function | 2.50 | 4 | 14.1 | 0.283 | 6.07e-7 | 197 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00031 | 0.00025 | rare |
| Latino/Admixed American | 0.00021 | 0.00020 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000063 | 0.000056 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00011 | 0.00011 | rare |
| South Asian | 0.000098 | 0.000098 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Transcriptional repressor. Recognizes and binds to the consensus sequence '5-[CG]NG[CG]GGGCA[CA]CC-3'. May act as a tumor suppressor. May be involved in development of head, face, limbs and ventral body wall. Involved in down-regulation of SIRT1 and thereby is involved in regulation of p53/TP53-dependent apoptotic DNA-damage responses. The specific target gene promoter association seems to be depend on corepressors, such as CTBP1 or CTBP2 and MTA1. The regulation of SIRT1 transcription in response to nutrient deprivation seems to involve CTBP1. In cooperation with MTA1 (indicative for an association with the NuRD complex) represses transcription from CCND1/cyclin-D1 and CDKN1C/p57Kip2 specifically in quiescent cells. Involved in regulation of the Wnt signaling pathway probably by association with TCF7L2 and preventing TCF7L2 and CTNNB1 association with promoters of TCF- responsive genes. Seems to repress transcription from E2F1 and ATOH1 which involves ARID1A, indicative for the participation of a distinct SWI/SNF-type chromatin-remodeling complex. Probably represses transcription from ACKR3, FGFBP1 and EFNA1. {ECO:0000269|PubMed:12052894, ECO:0000269|PubMed:15231840, ECO:0000269|PubMed:16269335, ECO:0000269|PubMed:16690027, ECO:0000269|PubMed:16724116, ECO:0000269|PubMed:17213307, ECO:0000269|PubMed:18347096, ECO:0000269|PubMed:19486893, ECO:0000269|PubMed:19525223, ECO:0000269|PubMed:20154726, ECO:0000269|PubMed:20547755}.;
Recessive Scores
- pRec
- 0.198
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.919
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |