ZNHIT3

Chr 17AR

zinc finger HIT-type containing 3

Also known as: Hit1, PEHO, TRIP3

NCBI Gene: 9326ENSG00000273611UniProt: Q15649

Predicted to enable nuclear thyroid hormone receptor binding activity. Predicted to be involved in box C/D snoRNP assembly; maturation of LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA); and snoRNA localization. Located in cytoplasm and nucleus. Implicated in PEHO syndrome. [provided by Alliance of Genome Resources, Jul 2025]

Primary Disease Associations & Inheritance

PEHO syndromeMIM #260565
AR
206
ClinVar variants
114
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— ZNHIT3
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
114 Pathogenic / Likely Pathogenic· 77 VUS of 206 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.80LOEUF
pLI 0.000
Z-score -0.33
OE 1.13 (0.67–1.80)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.60Z-score
OE missense 1.19 (1.01–1.40)
98 obs / 82.5 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.1.13 (0.67–1.80)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.19 (1.01–1.40)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.10
0≤1.21.6
LoF obs/exp: 9 / 8.0Missense obs/exp: 98 / 82.5Syn Z: -0.46

ClinVar Variant Classifications

206 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic99
Likely Pathogenic15
VUS77
Likely Benign10
Benign5
99
Pathogenic
15
Likely Pathogenic
77
VUS
10
Likely Benign
5
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
99
0
99
Likely Pathogenic
0
2
13
0
15
VUS
3
68
6
0
77
Likely Benign
0
3
1
6
10
Benign
0
1
3
1
5
Total3741227206

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

View in ClinVar →

Protein Context — Lollipop Plot

ZNHIT3 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

PEHO syndrome

MIM #260565

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — ZNHIT3
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools