HIVEP3

Chr 1

HIVEP zinc finger 3

Also known as: KBP-1, KBP1, KRC, SHN3, Schnurri-3, ZAS3, ZNF40C

The protein functions as a transcription factor that regulates NF-kappaB-mediated transcription by binding to kappaB motifs in target genes, and also binds to recombination signal sequences involved in immunoglobulin and T-cell receptor gene rearrangement. Mutations cause autosomal dominant intellectual disability with developmental delay and seizures. The gene is highly constrained against loss-of-function variants, indicating that heterozygous mutations are likely sufficient to cause disease.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.31
Clinical SummaryHIVEP3
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.91). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
10 unique Pathogenic / Likely Pathogenic· 13 VUS of 127 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.31LOEUF
pLI 0.906
Z-score 6.34
OE 0.20 (0.140.31)
Highly constrained

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

Missense Constraint
1.17Z-score
OE missense 0.91 (0.870.95)
1274 obs / 1397.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.20 (0.140.31)
00.351.4
Missense OE0.91 (0.870.95)
00.61.4
Synonymous OE1.05
01.21.6
LoF obs/exp: 15 / 73.7Missense obs/exp: 1274 / 1397.5Syn Z: -0.87
DN
0.3991th %ile
GOF
0.3293th %ile
LOF
0.77top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.31

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

127 submitted variants in ClinVar

Classification Summary

Pathogenic7
Likely Pathogenic3
VUS13
Likely Benign42
Benign44
7
Pathogenic
3
Likely Pathogenic
13
VUS
42
Likely Benign
44
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
7
0
7
Likely Pathogenic
0
0
3
0
3
VUS
1
8
4
0
13
Likely Benign
0
11
0
31
42
Benign
0
22
1
21
44
Total1411552109

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

View in ClinVar →

Protein Context — Lollipop Plot

HIVEP3 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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