HIVEP2

Chr 6AD

HIVEP zinc finger 2

Also known as: HIV-EP2, MBP-2, MIBP1, MRD43, SHN2, ZAS2, ZNF40B

This gene encodes a large zinc finger transcription factor that regulates gene expression by binding to regulatory regions of cellular and viral genes involved in growth and development. Loss-of-function mutations cause autosomal dominant intellectual developmental disorder. The gene is highly intolerant to loss-of-function variation, consistent with haploinsufficiency as the pathogenic mechanism.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismADLOEUF 0.081 OMIM phenotype
Clinical SummaryHIVEP2
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.
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.08LOEUF
pLI 1.000
Z-score 8.02
OE 0.03 (0.010.08)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint
1.83Z-score
OE missense 0.86 (0.820.90)
1129 obs / 1315.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.03 (0.010.08)
00.351.4
Missense OE0.86 (0.820.90)
00.61.4
Synonymous OE1.05
01.21.6
LoF obs/exp: 2 / 78.8Missense obs/exp: 1129 / 1315.7Syn Z: -0.94
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveHIVEP2-related syndromic developmental delay with intellectual disability with or without microcephalyLOFAD
DN
0.2698th %ile
GOF
0.2198th %ile
LOF
0.86top 5%

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

LOFprediction above median · 1 literature citation · LOEUF 0.08

Literature Evidence

LOFMutations in HIVEP2 are associated with developmental delay, intellectual disability, and dysmorphic featuresPMID:27003583

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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

HIVEP2 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗