HIC1

Chr 17

HIC ZBTB transcriptional repressor 1

Also known as: ZBTB29, ZNF901, hic-1

NCBI Gene: 3090 ENSG00000177374 UniProt: Q14526 OMIM: 603825

HIC1 encodes a transcriptional repressor that regulates cell cycle genes, Wnt signaling, and developmental processes affecting the head, face, limbs, and ventral body wall. Mutations cause autosomal dominant intellectual disability with distinctive facial features, microcephaly, and developmental delays, with onset typically apparent in early childhood. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.648), and haploinsufficiency has been associated with contiguous gene deletion syndromes.

OMIM ResearchSummary from RefSeq, UniProt

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]

OMIM ResearchGenerating clinical summary…

LOEUF 0.65

Clinical Summary— HIC1

⚡

Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.28) despite low pLI — interpret in context.

📋

ClinVar Variants

98 VUS of 110 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.65LOEUF

pLI 0.130

Z-score 2.50

OE 0.28 (0.14–0.65)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

2.70Z-score

OE missense 0.60 (0.54–0.67)

222 obs / 367.9 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.28 (0.14–0.65)

0≤0.351.4

Missense OE?0.60 (0.54–0.67)

0≤0.61.4

Synonymous OE?1.05

0≤1.21.6

LoF obs/exp: 4 / 14.1Missense obs/exp: 222 / 367.9Syn Z: -0.56

ClinVar Variant Classifications

110 submitted variants in ClinVar

ClinVar

Classification Summary

VUS98

Likely Benign6

Benign4

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	98	0	98
Likely Benign	3	3	6
Benign	0	4	4
Total	101	7	108

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

View in ClinVar →

65 pathogenic / likely-pathogenic (of 76) ClinVar copy-number / structural variants overlap HIC1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →