ZNHIT3

Chr 17AR

zinc finger HIT-type containing 3

Also known as: Hit1, PEHO, TRIP3

The protein enables nuclear thyroid hormone receptor binding and is involved in ribosomal RNA processing and small nucleolar RNA assembly. Mutations cause PEHO syndrome (progressive encephalopathy with edema, hypsarrhythmia, and optic atrophy), a severe early-onset neurodevelopmental disorder with characteristic brain imaging findings, seizures, and visual impairment. Inheritance is autosomal recessive.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM
ARLOEUF 1.801 OMIM phenotype
Clinical SummaryZNHIT3
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
116 unique Pathogenic / Likely Pathogenic· 77 VUS of 226 total submissions
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GeneReview available — ZNHIT3
Authoritative clinical overview · Recommended first read
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.80LOEUF
pLI 0.000
Z-score -0.33
OE 1.13 (0.671.80)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.60Z-score
OE missense 1.19 (1.011.40)
98 obs / 82.5 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.13 (0.671.80)
00.351.4
Missense OE1.19 (1.011.40)
00.61.4
Synonymous OE1.10
01.21.6
LoF obs/exp: 9 / 8.0Missense obs/exp: 98 / 82.5Syn Z: -0.46

ClinVar Variant Classifications

226 submitted variants in ClinVar

Classification Summary

Pathogenic101
Likely Pathogenic15
VUS77
Likely Benign11
Benign5
101
Pathogenic
15
Likely Pathogenic
77
VUS
11
Likely Benign
5
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
101
0
101
Likely Pathogenic
0
2
13
0
15
VUS
3
68
6
0
77
Likely Benign
0
3
1
7
11
Benign
1
1
2
1
5
Total4741238209

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.

3D Protein StructureAlphaFold

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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