ZHX1

Chr 8

zinc fingers and homeoboxes 1

ZHX1 encodes a nuclear transcriptional repressor containing zinc fingers and homeobox DNA-binding domains that forms homodimers and heterodimers with other ZHX family members and interacts with transcriptional machinery including DNMT3B. The gene is highly constrained against loss-of-function variants (pLI = 0.80, LOEUF = 0.38), suggesting intolerance to haploinsufficiency, but no specific disease associations have been established in the provided data.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
0
Pubs (1 yr)
49
P/LP submissions
0%
P/LP missense
0.38
LOEUF
LOF
Mechanism· predicted
Clinical SummaryZHX1
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.80) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
49 unique Pathogenic / Likely Pathogenic· 96 VUS of 150 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.38LOEUF
pLI 0.804
Z-score 3.96
OE 0.18 (0.090.38)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.96Z-score
OE missense 0.74 (0.680.81)
339 obs / 456.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.18 (0.090.38)
00.351.4
Missense OE0.74 (0.680.81)
00.61.4
Synonymous OE0.96
01.21.6
LoF obs/exp: 5 / 27.4Missense obs/exp: 339 / 456.7Syn Z: 0.43
DN
0.3296th %ile
GOF
0.2497th %ile
LOF
0.72top 10%

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

LOFprediction above median · LOEUF 0.38

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

150 submitted variants in ClinVar

Classification Summary

Pathogenic49
VUS96
Likely Benign2
49
Pathogenic
96
VUS
2
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
49
0
49
Likely Pathogenic
0
0
0
0
0
VUS
0
95
1
0
96
Likely Benign
0
1
0
1
2
Benign
0
0
0
0
0
Total096501147

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

View in ClinVar →

Protein Context — Lollipop Plot

ZHX1 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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