VIM

protein-coding

vimentin, the group of Intermediate filaments Type III

Gene summary

This gene encodes a type III intermediate filament protein. Intermediate filaments, along with microtubules and actin microfilaments, make up the cytoskeleton. The encoded protein is responsible for maintaining cell shape and integrity of the cytoplasm, and stabilizing cytoskeletal interactions. This protein is involved in neuritogenesis and cholesterol transport and functions as an organizer of a number of other critical proteins involved in cell attachment, migration, and signaling. Bacterial and viral pathogens have been shown to attach to this protein on the host cell surface. Mutations in this gene are associated with congenital cataracts in human patients. [provided by RefSeq, Aug 2017]

MANE transcript

NM_003380.5

Inheritance

ClinVar variants

P:3U:80B:20

Top phenotype

Cataract 30, multiple types

gnomAD constraint

pLI —, LoF o/e 0.19

Max pathogenic AF

—

Genomic locus

chr10:17,228,241-17,237,593

External References & Databases

Ensembl (ENSG00000026025)

Transcript & Mutation Effects

hg38 • Region Span ~9.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

pulverulent cataractSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0011430

Submitter: Orphanet

cataract 30STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0007286

Submitter: PanelApp Australia

cataractDEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0005129

Submitter: G2P

cataract 30STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0007286

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Cataract 30, multiple typesAD

Manifestation: Ophthalmologic

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: 19126778

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to VIM variants in ClinVar

6 Conditions Cataloged

Cataract 30Total: 57

not specifiedTotal: 51

not providedTotal: 26

VIM-related disorderTotal: 6

Developmental cataractTotal: 1

syndrome with premature-agingTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003380.5. 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				13 clinvar	4 clinvar	17
missense	1 clinvar	1 clinvar	75 clinvar	2 clinvar	1 clinvar	80
nonsense			1 clinvar			1
start loss						0
frameshift		1 clinvar	1 clinvar			2
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	1	2	80	15	5	103

Highest pathogenic variant AF is 0.000011177209

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 31 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003380.5	RefSeq	NP_003371.2	9	MANE Select
ENST00000544301.7	Ensembl	ENSP00000446007.1	9	MANE Select
ENST00000224237.10	Ensembl	ENSP00000224237.5	9	Standard
ENST00000224237.9	Ensembl	ENSP00000224237.5	9	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
vim	Danio rerio	Structure: regenerating fin Quality: decreased area abnormal

Gene / Model

Organism

Observed Phenotype

vim

Danio rerio

Structure: regenerating fin

Quality: decreased area

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

MicroRNAs in cancer - Homo sapiens (human)
Epstein-Barr virus infection - Homo sapiens (human)
Allograft Rejection
Spinal Cord Injury
Primary Focal Segmental Glomerulosclerosis FSGS

Biological Process

negative regulation of neuron projection development
astrocyte development
viral process
cytokine-mediated signaling pathway
muscle filament sliding

Molecular Function

double-stranded RNA binding
structural constituent of cytoskeleton
structural constituent of eye lens
protein binding
protein C-terminus binding

Cellular Component

cytoplasm
peroxisome
cytosol
polysome
cytoskeleton

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000544301
Coding exons: 9
Length: 9335
Individuals with no LoFs: 125743
Homozygous LoFs: 0
Heterozygous LoFs: 4
Defined: 125747
p: 0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.21	213	269	0.792	0.0000153	3020
Missense (PolyPhen)		76	103.52	0.73416		1118
Synonymous	0.647	103	112	0.922	0.00000602	915
Loss of Function	3.51	4	21.6	0.185	0.00000104	246

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0.00021	0.00020	rare
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000018	0.000018	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Vimentins are class-III intermediate filaments found in various non-epithelial cells, especially mesenchymal cells. Vimentin is attached to the nucleus, endoplasmic reticulum, and mitochondria, either laterally or terminally. {ECO:0000269|PubMed:21746880}.;
Disease: DISEASE: Cataract 30, multiple types (CTRCT30) [MIM:116300]: An opacification of the crystalline lens of the eye that frequently results in visual impairment or blindness. Opacities vary in morphology, are often confined to a portion of the lens, and may be static or progressive. In general, the more posteriorly located and dense an opacity, the greater the impact on visual function. {ECO:0000269|PubMed:19126778, ECO:0000269|PubMed:26694549, ECO:0000269|PubMed:28450710}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.958

Intolerance Scores

LoFtool: 0.0455
RVIS EVS: -0.82
RVIS percentile EVS: 11.68

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: E
Indispensability score: 0.989

Gene Damage Prediction

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