HIVEP3

Chr 1

HIVEP zinc finger 3

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

NCBI Gene: 59269 ENSG00000127124 UniProt: Q5T1R4

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.

ResearchSummary from RefSeq, UniProt

This gene encodes a member of the human immunodeficiency virus type 1 enhancer-binding protein family. Members of this protein family contain multiple zinc finger and acid-rich (ZAS) domains and serine-threonine rich regions. This protein acts as a transcription factor and is able to regulate nuclear factor kappaB-mediated transcription by binding the kappaB motif in target genes. This protein also binds the recombination signal sequence that flanks the V, D, and J regions of immunoglobulin and T-cell receptors. Alternate splicing results in both coding and non-coding transcript variants. [provided by RefSeq, Sep 2011]

ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.31

Clinical Summary— HIVEP3

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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.

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ClinVar Variants

9 VUS of 113 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.31LOEUF

pLI 0.906

Z-score 6.34

OE 0.20 (0.14–0.31)

Highly constrained

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

Missense Constraint?

1.17Z-score

OE missense 0.91 (0.87–0.95)

1274 obs / 1397.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.20 (0.14–0.31)

0≤0.351.4

Missense OE?0.91 (0.87–0.95)

0≤0.61.4

Synonymous OE?1.05

0≤1.21.6

LoF obs/exp: 15 / 73.7Missense obs/exp: 1274 / 1397.5Syn Z: -0.87

This gene — mechanism propensity

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

113 submitted variants in ClinVar

ClinVar

Classification Summary

VUS9

Likely Benign42

Benign44

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	0	0	0	0
VUS	1	8	0	0	9
Likely Benign	0	11	0	31	42
Benign	0	22	1	21	44
Total	1	41	1	52	95

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

View in ClinVar →

10 pathogenic / likely-pathogenic (of 14) ClinVar copy-number / structural variants overlap HIVEP3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →