EIF3H

protein-coding

eukaryotic translation initiation factor 3 subunit H, the group of Eukaryotic translation initiation factor 3|JAMM/MPN+ metallopeptidase family

Gene summary

Enables metal-dependent deubiquitinase activity. Contributes to translation initiation factor activity. Involved in negative regulation of proteasomal ubiquitin-dependent protein catabolic process and translational initiation. Located in extracellular exosome and membrane. Part of eukaryotic translation initiation factor 3 complex. Implicated in breast cancer; prostate cancer; and prostate carcinoma. Biomarker of prostate cancer. [provided by Alliance of Genome Resources, Jul 2025]

Previous symbols:

EIF3S3

MANE transcript

NM_003756.3

Inheritance

—

ClinVar variants

U:55

Top phenotype

Autism

gnomAD constraint

pLI —, LoF o/e 0.3

Max pathogenic AF

—

Genomic locus

chr8:116,642,130-116,766,925

External References & Databases

Ensembl (ENSG00000147677)

Transcript & Mutation Effects

hg38 • Region Span ~124.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to EIF3H variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 42

AutismTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003756.3. 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			1 clinvar			1
missense			43 clinvar			43
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			10 clinvar			10
Total	0	0	55	0	0	55

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 42 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003756.3	RefSeq	NP_003747.1	8	MANE Select
ENST00000521861.6	Ensembl	ENSP00000429931.1	8	MANE Select
ENST00000276682.8	Ensembl	ENSP00000276682.4	9	Standard
ENST00000276682.9	Ensembl	ENSP00000276682.4	9	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
eif3hb	Danio rerio	Structure: trunk Quality: bent abnormal

Gene / Model

Organism

Observed Phenotype

eif3hb

Danio rerio

Structure: trunk

Quality: bent

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

RNA transport - Homo sapiens (human)
Measles - Homo sapiens (human)
Translation Factors
Formation of the ternary complex, and subsequently, the 43S complex
Translation initiation complex formation

Biological Process

formation of cytoplasmic translation initiation complex
translational initiation
regulation of translational initiation
proteolysis

Molecular Function

RNA binding
translation initiation factor activity
protein binding
metallopeptidase activity

Cellular Component

cytosol
eukaryotic translation initiation factor 3 complex
membrane
eukaryotic 43S preinitiation complex
eukaryotic 48S preinitiation complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000521861
Coding exons: 8
Length: 124796
Individuals with no LoFs: 125737
Homozygous LoFs: 0
Heterozygous LoFs: 10
Defined: 125747
p: 0.0000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.638	174	199	0.873	0.0000104	2331
Missense (PolyPhen)		27	58.843	0.45885		731
Synonymous	-0.496	77	71.7	1.07	0.00000365	644
Loss of Function	2.90	6	20.0	0.300	0.00000103	228

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.000054	0.000054	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000035	0.000035	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is required for several steps in the initiation of protein synthesis (PubMed:17581632, PubMed:25849773, PubMed:27462815). The eIF-3 complex associates with the 40S ribosome and facilitates the recruitment of eIF-1, eIF-1A, eIF-2:GTP:methionyl-tRNAi and eIF-5 to form the 43S pre- initiation complex (43S PIC). The eIF-3 complex stimulates mRNA recruitment to the 43S PIC and scanning of the mRNA for AUG recognition. The eIF-3 complex is also required for disassembly and recycling of post-termination ribosomal complexes and subsequently prevents premature joining of the 40S and 60S ribosomal subunits prior to initiation (PubMed:17581632). The eIF- 3 complex specifically targets and initiates translation of a subset of mRNAs involved in cell proliferation, including cell cycling, differentiation and apoptosis, and uses different modes of RNA stem-loop binding to exert either translational activation or repression (PubMed:25849773). {ECO:0000255|HAMAP-Rule:MF_03007, ECO:0000269|PubMed:17581632, ECO:0000269|PubMed:25849773, ECO:0000269|PubMed:27462815}.;

Recessive Scores

pRec: 0.234

Intolerance Scores

LoFtool: 0.497
RVIS EVS: -0.38
RVIS percentile EVS: 27.42

Essentials

Essential (CRISPR): N
Essential (CRISPR2): E
Essential (gene trap): H
Indispensability pred.: E
Indispensability score: 0.881

Gene Damage Prediction

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