LIM2

protein-coding

lens intrinsic membrane protein 2

Gene summary

This gene encodes an eye lens-specific protein found at the junctions of lens fiber cells, where it may contribute to cell junctional organization. It acts as a receptor for calmodulin, and may play an important role in both lens development and cataractogenesis. Mutations in this gene have been associated with cataract formation. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Sep 2009]

MANE transcript

NM_001161748.2

Inheritance

AR, AD

ClinVar variants

P:3U:60B:12

Top phenotype

Cataract 19. multiple types

gnomAD constraint

pLI —, LoF o/e 0.65

Max pathogenic AF

—

Genomic locus

chr19:51,379,909-51,387,974

External References & Databases

Ensembl (ENSG00000105370)

Transcript & Mutation Effects

hg38 • Region Span ~8.1 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

cataract 19 multiple typesLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0014111

Submitter: Ambry Genetics

total early-onset cataractSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0021548

Submitter: Orphanet

cataract 19 multiple typesDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0014111

Submitter: G2P

cataract 19 multiple typesSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0014111

Submitter: PanelApp Australia

cataract 19 multiple typesSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014111

Submitter: PanelApp Australia

cataract 19 multiple typesSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014111

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Cataract 19. multiple typesAD/AR

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: 11917274; 32202185; 33708862; 35736209

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to LIM2 variants in ClinVar

6 Conditions Cataloged

Cataract 19 multiple typesTotal: 59

Inborn genetic diseasesTotal: 51

not providedTotal: 18

LIM2-related disorderTotal: 10

not specifiedTotal: 2

CataractTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001161748.2. 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			6 clinvar	8 clinvar		14
missense	2 clinvar	1 clinvar	49 clinvar	4 clinvar		56
nonsense			2 clinvar			2
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	2	1	60	12	0	75

Highest pathogenic variant AF is 0.000002478582

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 8 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001161748.2	RefSeq	NP_001155220.1	4	MANE Select
ENST00000596399.2	Ensembl	ENSP00000472090.2	4	MANE Select
NM_030657.4	RefSeq	NP_085915.2	4	Standard
ENST00000221973.7	Ensembl	ENSP00000221973.2	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

lens development in camera-type eye
cell-cell junction assembly

Molecular Function

structural constituent of eye lens

Cellular Component

plasma membrane
integral component of membrane
cell junction
vesicle

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000221973
Coding exons: 4
Length: 8052
Individuals with no LoFs: 125736
Homozygous LoFs: 0
Heterozygous LoFs: 11
Defined: 125747
p: 0.0000437

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.667	158	136	1.16	0.0000101	1382
Missense (PolyPhen)		67	64	1.0469		624
Synonymous	-0.308	55	52.2	1.05	0.00000345	450
Loss of Function	0.985	6	9.23	0.650	4.06e-7	97

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000044	0.000044	rare
South Asian	0.000098	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Present in the thicker 16-17 nm junctions of mammalian lens fiber cells, where it may contribute to cell junctional organization. Acts as a receptor for calmodulin. May play an important role in both lens development and cataractogenesis.;

Recessive Scores

pRec: 0.210

Intolerance Scores

LoFtool: 0.181
RVIS EVS: -0.54
RVIS percentile EVS: 20.54

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.148

Gene Damage Prediction

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