EIF4H

protein-coding

eukaryotic translation initiation factor 4H, the group of RNA binding motif containing|MicroRNA protein coding host genes

Gene summary

This gene encodes one of the translation initiation factors, which functions to stimulate the initiation of protein synthesis at the level of mRNA utilization. This gene is deleted in Williams syndrome, a multisystem developmental disorder caused by the deletion of contiguous genes at 7q11.23. Alternative splicing of this gene generates 2 transcript variants. [provided by RefSeq, Jul 2008]

Previous symbols:

WBSCR1

MANE transcript

NM_022170.2

Inheritance

—

ClinVar variants

U:13B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.21

Max pathogenic AF

—

Genomic locus

chr7:74,174,231-74,197,122

External References & Databases

Ensembl (ENSG00000106682)

Transcript & Mutation Effects

hg38 • Region Span ~22.9 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 EIF4H variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 14

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_022170.2. 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			13 clinvar	1 clinvar		14
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	13	2	0	15

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 33 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_022170.2	RefSeq	NP_071496.1	7	MANE Select
ENST00000265753.13	Ensembl	ENSP00000265753.8	7	MANE Select
NM_031992.2	RefSeq	NP_114381.1	6	Standard
ENST00000353999.6	Ensembl	ENSP00000265754.8	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Translation Factors
Translation initiation complex formation
Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S
Eukaryotic Translation Initiation
Translation

Biological Process

formation of translation preinitiation complex
cytoplasmic translation
translational initiation
regulation of translational initiation
viral process

Molecular Function

RNA binding
translation initiation factor activity
protein binding
translation factor activity, RNA binding
RNA strand annealing activity

Cellular Component

cytosol
polysome
membrane
eukaryotic translation initiation factor 4F complex
perinuclear region of cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000265753
Coding exons: 7
Length: 22857
Individuals with no LoFs: 125732
Homozygous LoFs: 0
Heterozygous LoFs: 15
Defined: 125747
p: 0.0000596

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.51	69	158	0.437	0.00000972	1616
Missense (PolyPhen)		8	32.921	0.24301		372
Synonymous	-0.833	66	57.9	1.14	0.00000359	490
Loss of Function	2.74	3	14.1	0.212	9.16e-7	143

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000097	0.000097	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Stimulates the RNA helicase activity of EIF4A in the translation initiation complex. Binds weakly mRNA. {ECO:0000269|PubMed:10585411, ECO:0000269|PubMed:11418588}.;

Recessive Scores

pRec: 0.160

Intolerance Scores

LoFtool: 0.399
RVIS EVS: -0.03
RVIS percentile EVS: 51.4

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.988

Gene Damage Prediction

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