ZHX1

Chr 8

zinc fingers and homeoboxes 1

NCBI Gene: 11244 ENSG00000165156 UniProt: Q9UKY1 OMIM: 604764

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.

OMIM ResearchSummary from RefSeq, UniProt

The members of the zinc fingers and homeoboxes gene family are nuclear homodimeric transcriptional repressors that interact with the A subunit of nuclear factor-Y (NF-YA) and contain two C2H2-type zinc fingers and five homeobox DNA-binding domains. This gene encodes member 1 of this gene family. In addition to forming homodimers, this protein heterodimerizes with members 2 and 3 of the zinc fingers and homeoboxes family. Alternative splicing results in multiple transcript variants. Read-through transcription also exists between this gene and the downstream chromosome 8 open reading frame 76 (C8orf76) gene. [provided by RefSeq, Feb 2011]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.38

Clinical Summary— ZHX1

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.80) — some intolerance to loss-of-function variants.

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ClinVar Variants

96 VUS of 101 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.38LOEUF

pLI 0.804

Z-score 3.96

OE 0.18 (0.09–0.38)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.96Z-score

OE missense 0.74 (0.68–0.81)

339 obs / 456.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.18 (0.09–0.38)

0≤0.351.4

Missense OE?0.74 (0.68–0.81)

0≤0.61.4

Synonymous OE?0.96

0≤1.21.6

LoF obs/exp: 5 / 27.4Missense obs/exp: 339 / 456.7Syn Z: 0.43

This gene — mechanism propensity

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

101 submitted variants in ClinVar

ClinVar

Classification Summary

VUS96

Likely Benign2

VUS

Likely 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	96	0	96
Likely Benign	1	1	2
Benign	0	0	0
Total	97	1	98

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

View in ClinVar →

49 pathogenic / likely-pathogenic (of 50) ClinVar copy-number / structural variants overlap ZHX1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →