ZNHIT3

protein-coding

zinc finger HIT-type containing 3, the group of Zinc fingers HIT-type

Gene summary

Predicted to enable nuclear thyroid hormone receptor binding activity. Predicted to be involved in box C/D snoRNP assembly and maturation of LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA). Located in cytoplasm and nucleus. Implicated in PEHO syndrome. [provided by Alliance of Genome Resources, Jun 2026]

Previous symbols:

TRIP3

MANE transcript

NM_004773.4

Inheritance

AD, AR

ClinVar variants

P:3U:39B:9

Top phenotype

PEHO syndrome

Max pathogenic AF

—

Genomic locus

chr17:36,486,629-36,499,310

External References & Databases

Ensembl (ENSG00000273611)

Transcript & Mutation Effects

hg38 • Region Span ~12.7 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Mayer-Rokitansky-Kuster-Hauser syndromeLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0017771

Submitter: Ambry Genetics

PEHO syndromeSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0009841

Submitter: Orphanet

PEHO syndromeMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0009841

Submitter: Ambry Genetics

PEHO syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009841

Submitter: PanelApp Australia

PEHO syndromeLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0009841

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

PEHO syndromeAR

Manifestation: Craniofacial; Dermatologic; Neurologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 28335020

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ZNHIT3 variants in ClinVar

5 Conditions Cataloged

Inborn genetic diseasesTotal: 34

not specifiedTotal: 11

not providedTotal: 9

PEHO syndromeTotal: 5

ZNHIT3-related disorderTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004773.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				6 clinvar		6
missense		2 clinvar	34 clinvar	3 clinvar		39
nonsense						0
start loss						0
frameshift		1 clinvar	4 clinvar			5
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	3	39	9	0	51

Highest pathogenic variant AF is 0.0001967253

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 23 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004773.4	RefSeq	NP_004764.1	5	MANE Select
ENST00000617429.5	Ensembl	ENSP00000484687.1	5	MANE Select
NM_001281432.2	RefSeq	NP_001268361.1	5	Standard
NM_001281433.2	RefSeq	NP_001268362.1	4	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
znhit3	Danio rerio	Structure: cerebellar granule cell Quality: decreased amount abnormal

Gene / Model

Organism

Observed Phenotype

znhit3

Danio rerio

Structure: cerebellar granule cell

Quality: decreased amount

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

maturation of LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA)
box C/D snoRNP assembly
regulation of transcription, DNA-templated
snoRNA localization

Molecular Function

protein binding
metal ion binding
thyroid hormone receptor binding

Cellular Component

nucleus
cytoplasm
pre-snoRNP complex

dbNSFP Gene Annotations

Source: dbNSFP

Disease: DISEASE: PEHO syndrome (PEHO) [MIM:260565]: An autosomal recessive syndrome characterized by progressive encephalopathy, lack of psychomotor development, severe mental retardation, early onset epileptic seizures, optic nerve/cerebellar atrophy, pedal edema, and early death. {ECO:0000269|PubMed:28335020}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.0793

Intolerance Scores

LoFtool: 0.503
RVIS EVS: -0.41
RVIS percentile EVS: 26.23

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.843

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium