LEMD2 (LEM domain nuclear envelope protein 2)

Gene

• Entrez ID: 221496
• Gene name: LEM domain nuclear envelope protein 2
• Gene symbol: LEMD2
• Synonyms (NCBI Gene): CTRCT42, LEM2, MARUPS, NET25, dJ482C21.1
• Chromosome: 6
• Chromosome location: 6p21.31
• Summary: This gene encodes a LEM domain-containing transmembrane protein of the inner nuclear membrane. The protein is involved in nuclear structure organization and plays a role in cell signaling and differentiation. Mutations in this gene result in Cataract 46,

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs878852983	A>C,T	Pathogenic	5 prime UTR variant, missense variant, coding sequence variant, genic upstream transcript variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT050421	hsa-miR-23a-3p	CLASH	23622248
MIRT648637	hsa-miR-8060	HITS-CLIP	23824327
MIRT648636	hsa-miR-5088-3p	HITS-CLIP	23824327
MIRT648635	hsa-miR-4769-3p	HITS-CLIP	23824327
MIRT648634	hsa-miR-6817-5p	HITS-CLIP	23824327
MIRT648633	hsa-miR-570-3p	HITS-CLIP	23824327
MIRT648632	hsa-miR-7154-5p	HITS-CLIP	23824327
MIRT648631	hsa-miR-433-3p	HITS-CLIP	23824327
MIRT648630	hsa-miR-4713-5p	HITS-CLIP	23824327
MIRT648629	hsa-miR-6867-3p	HITS-CLIP	23824327
MIRT648628	hsa-miR-4727-5p	HITS-CLIP	23824327
MIRT648627	hsa-miR-5001-3p	HITS-CLIP	23824327
MIRT648626	hsa-miR-629-3p	HITS-CLIP	23824327
MIRT648625	hsa-miR-544a	HITS-CLIP	23824327
MIRT648624	hsa-miR-6738-3p	HITS-CLIP	23824327
MIRT648637	hsa-miR-8060	HITS-CLIP	23824327
MIRT648636	hsa-miR-5088-3p	HITS-CLIP	23824327
MIRT648635	hsa-miR-4769-3p	HITS-CLIP	23824327
MIRT648634	hsa-miR-6817-5p	HITS-CLIP	23824327
MIRT648633	hsa-miR-570-3p	HITS-CLIP	23824327
MIRT648632	hsa-miR-7154-5p	HITS-CLIP	23824327
MIRT648631	hsa-miR-433-3p	HITS-CLIP	23824327
MIRT648630	hsa-miR-4713-5p	HITS-CLIP	23824327
MIRT648629	hsa-miR-6867-3p	HITS-CLIP	23824327
MIRT648628	hsa-miR-4727-5p	HITS-CLIP	23824327
MIRT648627	hsa-miR-5001-3p	HITS-CLIP	23824327
MIRT648626	hsa-miR-629-3p	HITS-CLIP	23824327
MIRT648625	hsa-miR-544a	HITS-CLIP	23824327
MIRT648624	hsa-miR-6738-3p	HITS-CLIP	23824327
MIRT1107281	hsa-miR-124	CLIP-seq
MIRT1107282	hsa-miR-128	CLIP-seq
MIRT1107283	hsa-miR-1297	CLIP-seq
MIRT1107284	hsa-miR-1539	CLIP-seq
MIRT1107285	hsa-miR-26a	CLIP-seq
MIRT1107286	hsa-miR-26b	CLIP-seq
MIRT1107287	hsa-miR-27a	CLIP-seq
MIRT1107288	hsa-miR-27b	CLIP-seq
MIRT1107289	hsa-miR-3074-5p	CLIP-seq
MIRT1107290	hsa-miR-3157-5p	CLIP-seq
MIRT1107291	hsa-miR-3193	CLIP-seq
MIRT1107292	hsa-miR-338-3p	CLIP-seq
MIRT1107293	hsa-miR-342-5p	CLIP-seq
MIRT1107294	hsa-miR-4422	CLIP-seq
MIRT1107295	hsa-miR-4465	CLIP-seq
MIRT1107296	hsa-miR-4493	CLIP-seq
MIRT1107297	hsa-miR-4508	CLIP-seq
MIRT1107298	hsa-miR-4530	CLIP-seq
MIRT1107299	hsa-miR-4537	CLIP-seq
MIRT1107300	hsa-miR-4640-3p	CLIP-seq
MIRT1107301	hsa-miR-4664-5p	CLIP-seq
MIRT1107302	hsa-miR-4675	CLIP-seq
MIRT1107303	hsa-miR-4690-3p	CLIP-seq
MIRT1107304	hsa-miR-4724-5p	CLIP-seq
MIRT1107305	hsa-miR-4741	CLIP-seq
MIRT1107306	hsa-miR-4746-3p	CLIP-seq
MIRT1107307	hsa-miR-4753-5p	CLIP-seq
MIRT1107308	hsa-miR-4786-3p	CLIP-seq
MIRT1107309	hsa-miR-506	CLIP-seq
MIRT1107310	hsa-miR-664	CLIP-seq
MIRT1107311	hsa-miR-671-5p	CLIP-seq
MIRT1107312	hsa-miR-802	CLIP-seq
MIRT1107293	hsa-miR-342-5p	CLIP-seq
MIRT1107301	hsa-miR-4664-5p	CLIP-seq
MIRT1107307	hsa-miR-4753-5p	CLIP-seq
MIRT1107281	hsa-miR-124	CLIP-seq
MIRT1107282	hsa-miR-128	CLIP-seq
MIRT1107287	hsa-miR-27a	CLIP-seq
MIRT1107288	hsa-miR-27b	CLIP-seq
MIRT2260527	hsa-miR-3194-5p	CLIP-seq
MIRT2260528	hsa-miR-3619-3p	CLIP-seq
MIRT1107296	hsa-miR-4493	CLIP-seq
MIRT2260529	hsa-miR-4717-3p	CLIP-seq
MIRT2260530	hsa-miR-4776-5p	CLIP-seq
MIRT2260531	hsa-miR-4802-3p	CLIP-seq
MIRT1107309	hsa-miR-506	CLIP-seq
MIRT2560550	hsa-miR-146a	CLIP-seq
MIRT2560551	hsa-miR-146b-5p	CLIP-seq
MIRT2560552	hsa-miR-3920	CLIP-seq
MIRT2560553	hsa-miR-4293	CLIP-seq
MIRT2560554	hsa-miR-4712-3p	CLIP-seq
MIRT2560555	hsa-miR-589	CLIP-seq
MIRT2683855	hsa-miR-1184	CLIP-seq
MIRT2560550	hsa-miR-146a	CLIP-seq
MIRT2560551	hsa-miR-146b-5p	CLIP-seq
MIRT2560552	hsa-miR-3920	CLIP-seq
MIRT2683856	hsa-miR-4252	CLIP-seq
MIRT2560553	hsa-miR-4293	CLIP-seq
MIRT2683857	hsa-miR-4691-3p	CLIP-seq
MIRT2560554	hsa-miR-4712-3p	CLIP-seq
MIRT2560555	hsa-miR-589	CLIP-seq
MIRT2683858	hsa-miR-596	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000785	Component	Chromatin	IDA	28242692
GO:0005515	Function	Protein binding	IPI	28242692, 28514442, 33961781
GO:0005634	Component	Nucleus	IEA
GO:0005635	Component	Nuclear envelope	IDA	28242692
GO:0005635	Component	Nuclear envelope	IEA
GO:0005635	Component	Nuclear envelope	TAS
GO:0005637	Component	Nuclear inner membrane	IBA
GO:0005637	Component	Nuclear inner membrane	IDA	16339967
GO:0005637	Component	Nuclear inner membrane	IEA
GO:0005637	Component	Nuclear inner membrane	TAS	28242692
GO:0005737	Component	Cytoplasm	IEA
GO:0005783	Component	Endoplasmic reticulum	IDA	28242692
GO:0005819	Component	Spindle	IEA
GO:0005856	Component	Cytoskeleton	IEA
GO:0006998	Process	Nuclear envelope organization	IMP	17097643
GO:0016020	Component	Membrane	HDA	19946888
GO:0016020	Component	Membrane	IEA
GO:0016020	Component	Membrane	TAS	28242692
GO:0022008	Process	Neurogenesis	IEA
GO:0031965	Component	Nuclear membrane	IDA
GO:0031965	Component	Nuclear membrane	IEA
GO:0034399	Component	Nuclear periphery	IBA
GO:0035914	Process	Skeletal muscle cell differentiation	IEA
GO:0035914	Process	Skeletal muscle cell differentiation	IEA
GO:0035914	Process	Skeletal muscle cell differentiation	IGI	19720741
GO:0043409	Process	Negative regulation of MAPK cascade	IEA
GO:0051898	Process	Negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	IEA
GO:0060914	Process	Heart formation	IEA
GO:0071168	Process	Protein localization to chromatin	IMP	28242692
GO:0071763	Process	Nuclear membrane organization	IBA

Other IDs

• MIM: 616312
• HGNC: 21244
• e!Ensembl: ENSG00000161904

Protein

• UniProt ID: Q8NC56
• Protein name: LEM domain-containing protein 2 (hLEM2)
• Protein function: Nuclear lamina-associated inner nuclear membrane protein that is involved in nuclear structure organization, maintenance of nuclear envelope (NE) integrity and NE reformation after mitosis (PubMed:16339967, PubMed:17097643, PubMed:28242692, PubM
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF03020	LEM	1 → 39	LEM domain	Domain
  PF09402	MSC	241 → 495	Man1-Src1p-C-terminal domain	Domain

• Tissue specificity: TISSUE SPECIFICITY: Ubiquitously expressed, including bone marrow, brain, kidney, colon, skeletal muscle, thymus, testis and uterus. {ECO:0000269|PubMed:16339967}.
• Sequence:

  MAGLSDLELRRELQALGFQPGPITDTTRDVYRNKLRRLRGEARLRDEERLREEARPRGEE
  RLREEARLREDAPLRARPAAASPRAEPWLSQPASGSAYATPGAYGDIRPSAASWVGSRGL
  AYPARPAQLRRRASVRGSSEEDEDARTPDRATQGPGLAARRWWAASPAPARLPSSLLGPD
  PRPGLRATRAGPAGAARARPEVGRRLERWLSRLLLWASLGLLLVFLGILWVKMGKPSAPQ
  EAEDNMKLLPVDCERKTDEFCQAKQKAALLELLHELYNFLAIQAGNFECGNPENLKSKCI
  PVMEAQEYIANVTSSSSAKFEAALTWILSSNKDVGIWLKGEDQSELVTTVDKVVCLESAH
  PRMGVGCRLSRALLTAVTNVLIFFWCLAFLWGLLILLKYRWRKLEEEEQAMYEMVKKIID
  VVQDHYVDWEQDMERYPYVGILHVRDSLIPPQSRRRMKRVWDRAVEFLASNESRIQTESH
  RVAGEDMLVWRWTKPSSFSDSER

• Sequence length: 503

Pathways

Reactome:

Nuclear Envelope Breakdown
Initiation of Nuclear Envelope (NE) Reformation
Depolymerisation of the Nuclear Lamina
Sealing of the nuclear envelope (NE) by ESCRT-III

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Cataract 46 juvenile-onset	Pathogenic	rs878852983	RCV000224057	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
CATARACT 46, JUVENILE-ONSET, WITH OR WITHOUT ARRHYTHMIC CARDIOMYOPATHY	—	CTD, Disgenet, HPO CTD, Disgenet, HPO CTD, Disgenet, HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CHRONIC OBSTRUCTIVE PULMONARY DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONGENITAL CATARACT	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONGENITAL HYPOPLASIA OF CLAVICLE	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONGENITAL TOTAL CATARACT	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Developmental cataract	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
EARLY-ONSET POSTERIOR SUBCAPSULAR CATARACT	—	GWAS catalog, Orphanet GWAS catalog, Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
INSOMNIA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LEMD2-related disorder	Benign; Conflicting classifications of pathogenicity; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Marbach-Rustad progeroid syndrome	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
METABOLIC SYNDROME	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MICROGNATHISM	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MICROSTOMIA	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OBESITY	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SCHIZOPHRENIA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TOTAL EARLY-ONSET CATARACT	—	GWAS catalog, Orphanet GWAS catalog, Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TYPE 2 DIABETES MELLITUS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
WORMIAN BONES-MICROGNATHIA-ABNORMAL DENTITION-PROGEROID SYNDROME	—	Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
ANOPHTHALMIA AND PULMONARY HYPOPLASIA	Syndromic microphthalmia	BEFREE	30224904		★☆☆☆☆ Found in Text Mining only
Cataract	Cataract	Pubtator	36161833	Associate	★☆☆☆☆ Found in Text Mining only
CATARACT 46, JUVENILE-ONSET	Cataract	UNIPROT_DG	26788539		★☆☆☆☆ Found in Text Mining only
CATARACT 46, JUVENILE-ONSET	Cataract	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
CATARACT 46, JUVENILE-ONSET	Cataract	CTD_human_DG			★☆☆☆☆ Found in Text Mining only
Cataract Nuclear Progressive	Congenital cataract	Pubtator	30905398	Associate	★☆☆☆☆ Found in Text Mining only
Congenital total cataract	Congenital Cataract	ORPHANET_DG	26788539		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Developmental Disabilities	Developmental disability	Pubtator	38098057	Associate	★☆☆☆☆ Found in Text Mining only
Early-onset posterior subcapsular cataract	Cataract	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Growth Disorders	Growth disorder	Pubtator	30905398	Associate	★☆☆☆☆ Found in Text Mining only
Muscular Dystrophy, Emery-Dreifuss	Emery-Dreifuss Muscular Dystrophy	BEFREE	22171324		★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	30224904		★☆☆☆☆ Found in Text Mining only
Neuroblastoma	Neuroblastoma	BEFREE	30664963		★☆☆☆☆ Found in Text Mining only
Progeria	Progeria	BEFREE	30905398		★☆☆☆☆ Found in Text Mining only
Schizophrenia	Schizophrenia	GWASCAT_DG	26198764, 30285260		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Total early-onset cataract	Cataract	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Tremor	Tremor	Pubtator	30905398	Associate	★☆☆☆☆ Found in Text Mining only