HIC2

protein-coding

HIC ZBTB transcriptional repressor 2, the group of BTB domain containing|Zinc fingers C2H2-type

Gene summary

Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II; regulation of cytokine production; and regulation of immune system process. Located in nucleoplasm. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_015094.3

Inheritance

—

ClinVar variants

U:100B:7

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr22:21,417,371-21,451,463

External References & Databases

Ensembl (ENSG00000169635)

Transcript & Mutation Effects

hg38 • Region Span ~34.1 kb

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GenCC 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 HIC2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 100

not providedTotal: 6

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_015094.3. 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 clinvar	1 clinvar	2
missense			99 clinvar	5 clinvar		104
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)						0
Total	0	0	100	6	1	107

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 11 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_015094.3	RefSeq	NP_055909.2	2	MANE Select
ENST00000407464.7	Ensembl	ENSP00000385319.2	2	MANE Select
ENST00000407598.2	Ensembl	ENSP00000384889.2	2	Standard
ENST00000407598.3	Ensembl	ENSP00000384889.2	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

negative regulation of transcription by RNA polymerase II
negative regulation of transcription, DNA-templated

Molecular Function

RNA polymerase II regulatory region sequence-specific DNA binding
DNA-binding transcription factor activity, RNA polymerase II-specific
DNA-binding transcription repressor activity, RNA polymerase II-specific
DNA binding
protein C-terminus binding

Cellular Component

nucleus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000443632
Coding exons: 2
Length: 34060
Individuals with no LoFs: 123229
Homozygous LoFs: 0
Heterozygous LoFs: 2
Defined: 123231
p: 0.00000811

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.05	282	397	0.710	0.0000268	3974
Missense (PolyPhen)		32	80.536	0.39734		643
Synonymous	-2.34	217	177	1.22	0.0000133	1265
Loss of Function	3.80	0	16.8	0.00	7.98e-7	193

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)	0.0000090	0.0000090	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Transcriptional repressor.;

Recessive Scores

pRec: 0.125

Intolerance Scores

LoFtool: 0.0150
RVIS EVS: -0.4
RVIS percentile EVS: 26.85

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.327

Gene Damage Prediction

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