HIC1

HIC ZBTB transcriptional repressor 1, the group of BTB domain containing|Zinc fingers C2H2-type

Basic information

Region (hg38): 17:2054153-2063241

Links

ENSG00000177374 ∙ NCBI:3090 ∙ OMIM:603825 ∙ HGNC:4909 ∙ Uniprot:Q14526 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the HIC1 gene.

• Inborn genetic diseases (29 variants)
• not provided (9 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HIC1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				2	5	7
missense			28	1		29
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			2			2
Total	0	0	30	3	5

Variants in HIC1

This is a list of pathogenic ClinVar variants found in the HIC1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
17-2056314-C-T		not specified	Uncertain significance (Feb 05, 2024)
17-2056344-C-G		not specified	Uncertain significance (Jun 17, 2022)
17-2056689-C-A		not specified	Uncertain significance (Jan 03, 2024)
17-2056697-G-A			Uncertain significance (Sep 01, 2023)
17-2056800-C-T		not specified	Uncertain significance (May 05, 2023)
17-2056898-G-A		not specified	Uncertain significance (Jun 18, 2021)
17-2056942-C-T			Benign (Sep 17, 2017)
17-2056946-C-T		not specified	Uncertain significance (Jan 26, 2023)
17-2056997-G-C		not specified	Uncertain significance (Feb 27, 2023)
17-2057111-G-A		not specified	Uncertain significance (May 04, 2023)
17-2057202-C-G		not specified	Uncertain significance (Jun 29, 2022)
17-2057235-C-G		not specified	Uncertain significance (Nov 17, 2022)
17-2057306-C-T		not specified	Uncertain significance (Nov 10, 2022)
17-2057441-A-G		not specified	Uncertain significance (Nov 13, 2023)
17-2057486-G-A		not specified	Uncertain significance (Oct 12, 2021)
17-2057487-C-G		not specified	Uncertain significance (Oct 12, 2021)
17-2057489-C-G		not specified	Uncertain significance (Dec 26, 2023)
17-2057495-T-C		not specified	Likely benign (Jan 04, 2024)
17-2057556-G-A		not specified	Uncertain significance (Aug 16, 2021)
17-2057556-G-T		not specified	Uncertain significance (Nov 21, 2023)
17-2057693-G-C		not specified	Uncertain significance (May 31, 2023)
17-2057696-C-T		not specified	Uncertain significance (Jan 02, 2024)
17-2057833-C-T			Benign (Jan 08, 2018)
17-2057920-C-T			Benign (Sep 07, 2017)
17-2057960-G-A		not specified	Uncertain significance (Apr 12, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HIC1	protein_coding	protein_coding	ENST00000322941	2	5534

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.130	0.866	124831	0	29	124860	0.000116

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.70	222	368	0.603	0.0000236	4553
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000524	0.000466
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000627	0.0000556
Finnish	0.00	0.00
European (Non-Finnish)	0.000106	0.000106
Middle Eastern	0.0000627	0.0000556
South Asian	0.0000980	0.0000980
Other	0.000333	0.000329

dbNSFP

Source: dbNSFP

• 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}.
• Pathway: hypoxia and p53 in the cardiovascular system;SUMOylation of transcription factors;Post-translational protein modification;SUMO E3 ligases SUMOylate target proteins;Metabolism of proteins;SUMOylation;Direct p53 effectors;E2F transcription factor network (Consensus)

Recessive Scores

• pRec: 0.198

Haploinsufficiency Scores

• pHI: 0.788
• ghis: 0.655

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.919

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Hic1
• Phenotype: growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); craniofacial phenotype; skeleton phenotype; immune system phenotype; embryo phenotype; neoplasm; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; digestive/alimentary phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hearing/vestibular/ear phenotype; limbs/digits/tail phenotype

Gene ontology

• 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;Wnt signaling pathway;negative regulation of Wnt signaling pathway;positive regulation of DNA damage response, signal transduction by p53 class mediator
• Cellular component: chromatin;nucleus;nucleoplasm;cytosol
• 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;sequence-specific DNA binding;metal ion binding