HIC2

Chr 22

HIC ZBTB transcriptional repressor 2

Also known as: HRG22, ZBTB30, ZNF907

NCBI Gene: 23119ENSG00000169635UniProt: Q96JB3

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 and plasma membrane. [provided by Alliance of Genome Resources, Jul 2025]

252
ClinVar variants
125
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— HIC2
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
125 Pathogenic / Likely Pathogenic· 114 VUS of 252 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.18LOEUF
pLI 0.997
Z-score 3.80
OE 0.00 (0.00–0.18)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.05Z-score
OE missense 0.71 (0.64–0.78)
282 obs / 397.2 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.00 (0.00–0.18)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.71 (0.64–0.78)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.22
0≤1.21.6
LoF obs/exp: 0 / 16.8Missense obs/exp: 282 / 397.2Syn Z: -2.34

ClinVar Variant Classifications

252 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic114
Likely Pathogenic11
VUS114
Likely Benign6
Benign2
114
Pathogenic
11
Likely Pathogenic
114
VUS
6
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
114
0
114
Likely Pathogenic
0
0
11
0
11
VUS
1
97
16
0
114
Likely Benign
0
5
0
1
6
Benign
0
0
1
1
2
Total11021422247

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

HIC2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
HIC2 suppresses glioblastoma progression via transcriptional repression of SEMA3A and inhibition of TGF-β signaling.
Zhang L et al.·Free Radic Biol Med
2025
Transcriptome profiling of hiPSC-derived LSECs with nanoCAGE.
Danoy M et al.·Mol Omics
2020
HIC2 is a novel dosage-dependent regulator of cardiac development located within the distal 22q11 deletion syndrome region.
Dykes IM et al.·Circ Res
2014
[Screening and verification of key genes in T-cell acute lymphoblastic leukemia].
Jiang GJ et al.·Nan Fang Yi Ke Da Xue Xue Bao
2018
Distal deletion at 22q11.2 as differential diagnosis in Craniofacial Microsomia: Case report and literature review.
Spineli-Silva S et al.·Eur J Med Genet
2018Review
Refining the 22q11.2 deletion breakpoints in DiGeorge syndrome by aCGH.
Bittel DC et al.·Cytogenet Genome Res
2009
Shared Genetic Basis Between Systemic Lupus Erythematosus and Inflammatory Bowel Disease in East Asian Ancestry: A Genome-Wide Cross-trait Analysis.
Mo X et al.·Inflamm Bowel Dis
2026
Simultaneous capture of single cell RNA-seq, ATAC-seq, and CRISPR perturbation enables multiomic screens to identify gene regulatory relationships.
Shevade K et al.·Cell Rep Methods
2025
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools