LMNA lamin A/C [Homo sapiens (human)] - Gene

Summary

Official Symbol: LMNAprovided by HGNC
Official Full Name: lamin A/Cprovided by HGNC
Primary source: HGNC:HGNC:6636
See related: Ensembl:ENSG00000160789 MIM:150330; AllianceGenome:HGNC:6636
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: FPL; IDC; LFP; CDDC; EMD2; FPLD; HGPS; LDP1; LMN1; LMNC; MADA; PRO1; CDCD1; CMD1A; FPLD2; LMNL1; CMT2B1; LGMD1B
Summary: The protein encoded by this gene is part of the nuclear lamina, a two-dimensional matrix of proteins located next to the inner nuclear membrane. The lamin family of proteins make up the matrix and are highly conserved in evolution. During mitosis, the lamina matrix is reversibly disassembled as the lamin proteins are phosphorylated. Lamin proteins are thought to be involved in nuclear stability, chromatin structure and gene expression. Vertebrate lamins consist of two types, A and B. Alternative splicing results in multiple transcript variants. Mutations in this gene lead to several diseases: Emery-Dreifuss muscular dystrophy, familial partial lipodystrophy, limb girdle muscular dystrophy, dilated cardiomyopathy, Charcot-Marie-Tooth disease, and Hutchinson-Gilford progeria syndrome. [provided by RefSeq, May 2022]
Expression: Ubiquitous expression in gall bladder (RPKM 77.9), skin (RPKM 65.3) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 1q22

Exon count:: 20

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	1	NC_000001.11 (156082573..156140081)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	1	NC_060925.1 (155221038..155278530)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	1	NC_000001.10 (156052364..156109872)

Chromosome 1 - NC_000001.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Deciphering the Clinical Presentations in LMNA-related Lipodystrophy: Report of 115 Cases and a Systematic Review.
Title: Deciphering the Clinical Presentations in LMNA-related Lipodystrophy: Report of 115 Cases and a Systematic Review.
Nuclear Abnormalities in LMNA p.(Glu2Lys) Variant Segregating with LMNA-Associated Cardiocutaneous Progeria Syndrome.
Title: Nuclear Abnormalities in LMNA p.(Glu2Lys) Variant Segregating with LMNA-Associated Cardiocutaneous Progeria Syndrome.
Whole-exome sequencing reveals a likely pathogenic LMNA variant causing hypertrophic cardiomyopathy.
Title: Whole-exome sequencing reveals a likely pathogenic LMNA variant causing hypertrophic cardiomyopathy.
Prelamin A and ZMPSTE24 in premature and physiological aging.
Title: Prelamin A and ZMPSTE24 in premature and physiological aging.
DNA damage induces nuclear envelope rupture through ATR-mediated phosphorylation of lamin A/C.
Title: DNA damage induces nuclear envelope rupture through ATR-mediated phosphorylation of lamin A/C.
Knockdown of LMNA inhibits Akt/beta-catenin-mediated cell invasion and migration in clear cell renal cell carcinoma cells.
Title: Knockdown of LMNA inhibits Akt/β-catenin-mediated cell invasion and migration in clear cell renal cell carcinoma cells.
An alpha-helix variant p.Arg156Pro in LMNA as a cause of hereditary dilated cardiomyopathy: genetics and bioinfomatics exploration.
Title: An alpha-helix variant p.Arg156Pro in LMNA as a cause of hereditary dilated cardiomyopathy: genetics and bioinfomatics exploration.
Somatic and germinal mosaicism in a Han Chinese family with laminopathies.
Title: Somatic and germinal mosaicism in a Han Chinese family with laminopathies.
The Clinical Characteristics and Potential Molecular Mechanism of LMNA Mutation-Related Lipodystrophy.
Title: The Clinical Characteristics and Potential Molecular Mechanism of LMNA Mutation-Related Lipodystrophy.
A recurrent homozygous LMNA missense variant p.Thr528Met causes atypical progeroid syndrome characterized by mandibuloacral dysostosis, severe muscular dystrophy, and skeletal deformities.
Title: A recurrent homozygous LMNA missense variant p.Thr528Met causes atypical progeroid syndrome characterized by mandibuloacral dysostosis, severe muscular dystrophy, and skeletal deformities.

Submit: New GeneRIF Correction See all GeneRIFs (641)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Professional guidelines

Description
Professional guideline ACMG 2013 The ACMG recommends that laboratories performing clinical sequencing seek and report mutations in LMNA that are pathogenic or expected to be pathogenic. GuidelinePubMed

Associated conditions

Description	Tests
Charcot-Marie-Tooth disease type 2B1 MedGen: C1854154 OMIM: 605588 GeneReviews: Not available	Compare labs
Congenital muscular dystrophy due to LMNA mutation MedGen: C2750785 OMIM: 613205 GeneReviews: Not available	Compare labs
Dilated cardiomyopathy 1A MedGen: C1449563 OMIM: 115200 GeneReviews: Dilated Cardiomyopathy Overview, LMNA-Related Dilated Cardiomyopathy	Compare labs
Dilated cardiomyopathy-hypergonadotropic hypogonadism syndrome MedGen: C0796031 OMIM: 212112 GeneReviews: Not available	Compare labs
Emery-Dreifuss muscular dystrophy 2, autosomal dominant MedGen: C0410190 OMIM: 181350 GeneReviews: Emery-Dreifuss Muscular Dystrophy	Compare labs
Emery-Dreifuss muscular dystrophy 3, autosomal recessive MedGen: C2750035 OMIM: 616516 GeneReviews: Not available	Compare labs
Familial partial lipodystrophy, Dunnigan type MedGen: C1720860 OMIM: 151660 GeneReviews: Not available	Compare labs
Heart-hand syndrome, Slovenian type MedGen: C1857829 OMIM: 610140 GeneReviews: Not available	Compare labs
Hutchinson-Gilford syndrome MedGen: C0033300 OMIM: 176670 GeneReviews: Hutchinson-Gilford Progeria Syndrome	Compare labs
Mandibuloacral dysplasia with type A lipodystrophy MedGen: C5399785 OMIM: 248370 GeneReviews: Not available	Compare labs
Primary dilated cardiomyopathy MedGen: C0007193 GeneReviews: Dilated Cardiomyopathy Overview	Compare labs
Restrictive dermopathy 2 MedGen: C5676942 OMIM: 619793 GeneReviews: Not available	Compare labs

Copy number response

Description
Copy number response Triplosensitivity No evidence available (Last evaluated 2023-12-14) ClinGen Genome Curation Page Haploinsufficency Sufficient evidence for dosage pathogenicity (Last evaluated 2023-12-14) ClinGen Genome Curation PagePubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Rev	rev	putative interaction based on report of Rev binding to nuclear scaffold and lamin C from mouse cells	PubMed
Tat	tat	Purified HIV-1 Tat has been shown to bind with high affinity to the nuclear matrix from H9 cells and to link viral RNAs to the nuclear matrix	PubMed
Vpr	vpr	A stable-isotope labeling by amino acids in cell culture coupled with mass spectrometry-based proteomics identifies downregulation of lamin A/C (LMNA) expression by HIV-1 Vpr in Vpr transduced macrophages	PubMed
	vpr	HIV-1 Vpr colocalizes with lamin A/C and induces localized disruptions in the normal nuclear lamin architecture, contributing to the formation of nuclear envelope herniations	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D20S1027 (e-PCR)
- UniSTS:55344

MARC_3281-3282:991936958:1 (e-PCR)
- UniSTS:231005

G15913 (e-PCR)
- UniSTS:8612

LMNA_902 (e-PCR)
- UniSTS:277454

PMC169171P1 (e-PCR)
- UniSTS:271604

PMC169171P2 (e-PCR)
- UniSTS:271605

PMC169171P3 (e-PCR)
- UniSTS:271606

PMC169171P4 (e-PCR)
- UniSTS:271607

PMC169171P5 (e-PCR)
- UniSTS:271608

PMC169171P6 (e-PCR)
- UniSTS:271609

RH69068 (e-PCR)
- UniSTS:50685

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables structural constituent of cytoskeleton	IBA Inferred from Biological aspect of Ancestor more info
enables structural constituent of cytoskeleton	IDA Inferred from Direct Assay more info	PubMed
enables structural constituent of nuclear lamina	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in DNA double-strand break attachment to nuclear envelope	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular response to hypoxia	IEP Inferred from Expression Pattern more info	PubMed
acts_upstream_of_or_within_positive_effect cellular senescence	IDA Inferred from Direct Assay more info	PubMed
involved_in establishment or maintenance of microtubule cytoskeleton polarity	ISS Inferred from Sequence or Structural Similarity more info
involved_in heterochromatin formation	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of cardiac muscle hypertrophy in response to stress	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of cell population proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of extrinsic apoptotic signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of mesenchymal cell proliferation	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of release of cytochrome c from mitochondria	IEA Inferred from Electronic Annotation more info
involved_in nuclear envelope organization	IBA Inferred from Biological aspect of Ancestor more info
involved_in nuclear envelope organization	IDA Inferred from Direct Assay more info	PubMed
involved_in nuclear migration	IBA Inferred from Biological aspect of Ancestor more info
involved_in nuclear pore localization	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of gene expression	IEA Inferred from Electronic Annotation more info
involved_in protein import into nucleus	IEA Inferred from Electronic Annotation more info
involved_in protein localization to nuclear envelope	IBA Inferred from Biological aspect of Ancestor more info
involved_in protein localization to nucleus	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of cell migration	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of protein localization to nucleus	IEA Inferred from Electronic Annotation more info
involved_in regulation of protein stability	IEA Inferred from Electronic Annotation more info
involved_in ventricular cardiac muscle cell development	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in cytosol	TAS Traceable Author Statement more info
located_in lamin filament	IEA Inferred from Electronic Annotation more info
is_active_in nuclear envelope	IBA Inferred from Biological aspect of Ancestor more info
located_in nuclear envelope	IDA Inferred from Direct Assay more info	PubMed
colocalizes_with nuclear envelope	IMP Inferred from Mutant Phenotype more info	PubMed
located_in nuclear envelope	TAS Traceable Author Statement more info
is_active_in nuclear lamina	IBA Inferred from Biological aspect of Ancestor more info
is_active_in nuclear lamina	IDA Inferred from Direct Assay more info	PubMed
located_in nuclear matrix	IDA Inferred from Direct Assay more info	PubMed
located_in nuclear membrane	HDA more info	PubMed
located_in nuclear speck	IDA Inferred from Direct Assay more info
located_in nucleoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in nucleoplasm	TAS Traceable Author Statement more info
located_in nucleus	HDA more info	PubMed
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
located_in site of double-strand break	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: lamin

Names: 70 kDa lamin; epididymis secretory sperm binding protein; lamin A/C-like 1; lamin C; mandibuloacral dysplasia type A; prelamin-A/C; progerin; renal carcinoma antigen NY-REN-32

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_008692.2 RefSeqGene

Range

4974..62517

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_254

mRNA and Protein(s)

NM_001257374.3 → NP_001244303.1 lamin isoform D

Status: REVIEWED

Description

Transcript Variant: This variant (4) represents use of an alternate promoter and uses an alternate 3' exon structure compared to variant 1. The resulting protein (isoform D) has distinct N- and C-termini and is shorter than isoform A.

Source sequence(s)

AI872233, AK295390, AL135927, BC018863

Consensus CDS

CCDS58038.1

UniProtKB/Swiss-Prot

P02545

Related

ENSP00000395597.2, ENST00000448611.6

Conserved Domains (3) summary

pfam00932
Location:321 → 429

LTD; Lamin Tail Domain

pfam09798
Location:190 → 351

LCD1; DNA damage checkpoint protein

pfam10018
Location:79 → 243

Med4; Vitamin-D-receptor interacting Mediator subunit 4
NM_001282624.2 → NP_001269553.1 lamin isoform E

See identical proteins and their annotated locations for NP_001269553.1

Status: REVIEWED

Description

Transcript Variant: This variant (5) differs in both UTRs and has multiple differences in the coding region compared to variant 1. This variant encodes isoform E, which is shorter and has distinct N- and C-termini compared to isoform prelamin A.

Source sequence(s)

AK097801, BC000511, HY027676

Consensus CDS

CCDS72942.1

UniProtKB/TrEMBL

Q5TCI8

Related

ENSP00000357280.1, ENST00000368297.5

Conserved Domains (2) summary

pfam00038
Location:48 → 305

Filament; Intermediate filament protein

pfam00932
Location:355 → 460

LTD; Lamin Tail Domain
NM_001282625.2 → NP_001269554.1 lamin isoform C

See identical proteins and their annotated locations for NP_001269554.1

Status: REVIEWED

Description

Transcript Variant: This variant (6) differs in both UTRs and has multiple differences in the coding region compared to variant 1. This results in a shorter isoform (C) with a distinct C-terminus when compared to isoform prelamin A. Both variants 2 and 6 encode the same isoform (C).

Source sequence(s)

AK056143, BC000511, DB270595

Consensus CDS

CCDS1131.1

UniProtKB/TrEMBL

W8QEH3

Related

ENSP00000357284.2, ENST00000368301.6

Conserved Domains (2) summary

pfam00038
Location:30 → 386

Filament; Intermediate filament protein

pfam00932
Location:436 → 541

LTD; Lamin Tail Domain
NM_001282626.2 → NP_001269555.1 lamin isoform A-delta50

See identical proteins and their annotated locations for NP_001269555.1

Status: REVIEWED

Description

Transcript Variant: This variant (7) uses an alternate 3' exon structure and thus differs in the 3' coding region and 3' UTR, compared to variant 1. This results in a shorter isoform (A-delta50, also known as progerin) with a distinct C-terminus when compared to isoform prelamin A. Although this isoform has been linked to Hutchinson-Gilford progeria syndrome, it is also found in unaffected individuals and thought to be linked to cellular terminal differentiation and physiological aging (see PubMed IDs: 12702809, 16645051, and 18060063).

Source sequence(s)

AI872233, AY357727, BU685425, BU732343, DA551594

Consensus CDS

CCDS72941.1

UniProtKB/TrEMBL

W8QEH3

Related

ENSP00000357282.3, ENST00000368299.7

Conserved Domains (3) summary

pfam00038
Location:30 → 386

Filament; Intermediate filament protein

pfam00932
Location:433 → 541

LTD; Lamin Tail Domain

pfam09798
Location:302 → 463

LCD1; DNA damage checkpoint protein
NM_001406983.1 → NP_001393912.1 lamin isoform A

Status: REVIEWED

Source sequence(s)

AL135927, AL355388

UniProtKB/Swiss-Prot

B4DI32, D3DVB0, D6RAQ3, E7EUI9, P02545, P02546, Q5I6Y4, Q5I6Y6, Q5TCJ2, Q5TCJ3, Q6UYC3, Q969I8, Q96JA2

UniProtKB/TrEMBL

A0A384MQX1
NM_001406984.1 → NP_001393913.1 lamin isoform C

Status: REVIEWED

Source sequence(s)

AL135927, AL355388
NM_001406985.1 → NP_001393914.1 lamin isoform F

Status: REVIEWED

Source sequence(s)

AL135927
NM_001406986.1 → NP_001393915.1 lamin isoform G

Status: REVIEWED

Source sequence(s)

AL135927
NM_001406987.1 → NP_001393916.1 lamin isoform G

Status: REVIEWED

Source sequence(s)

AL135927
NM_001406988.1 → NP_001393917.1 lamin isoform H

Status: REVIEWED

Source sequence(s)

AL135927

Related

ENSP00000421821.1, ENST00000473598.6
NM_001406989.1 → NP_001393918.1 lamin isoform I

Status: REVIEWED

Source sequence(s)

AL135927
NM_001406990.1 → NP_001393919.1 lamin isoform J

Status: REVIEWED

Source sequence(s)

AL135927
NM_001406991.1 → NP_001393920.1 lamin isoform A

Status: REVIEWED

Source sequence(s)

AL135927, AL355388

UniProtKB/Swiss-Prot

B4DI32, D3DVB0, D6RAQ3, E7EUI9, P02545, P02546, Q5I6Y4, Q5I6Y6, Q5TCJ2, Q5TCJ3, Q6UYC3, Q969I8, Q96JA2

UniProtKB/TrEMBL

A0A384MQX1

Related

ENSP00000501803.1, ENST00000675667.1
NM_001406992.1 → NP_001393921.1 lamin isoform C

Status: REVIEWED

Source sequence(s)

AL135927, AL355388
NM_001406993.1 → NP_001393922.1 lamin isoform K

Status: REVIEWED

Source sequence(s)

AL135927, AL355388

UniProtKB/TrEMBL

H0YAB0
NM_001406994.1 → NP_001393923.1 lamin isoform K

Status: REVIEWED

Source sequence(s)

AL135927
NM_001406995.1 → NP_001393924.1 lamin isoform K

Status: REVIEWED

Source sequence(s)

AL135927

UniProtKB/TrEMBL

H0YAB0
NM_001406996.1 → NP_001393925.1 lamin isoform K

Status: REVIEWED

Source sequence(s)

AL135927

UniProtKB/TrEMBL

H0YAB0
NM_001406997.1 → NP_001393926.1 lamin isoform K

Status: REVIEWED

Source sequence(s)

AL135927

UniProtKB/TrEMBL

H0YAB0

Related

ENSP00000426535.3, ENST00000504687.7
NM_001406998.1 → NP_001393927.1 lamin isoform L

Status: REVIEWED

Source sequence(s)

AL135927

Related

ENST00000675431.1
NM_001406999.1 → NP_001393928.1 lamin isoform M

Status: REVIEWED

Source sequence(s)

AL135927
NM_001407000.1 → NP_001393929.1 lamin isoform M

Status: REVIEWED

Source sequence(s)

AL135927
NM_001407001.1 → NP_001393930.1 lamin isoform M

Status: REVIEWED

Source sequence(s)

AL135927
NM_001407002.1 → NP_001393931.1 lamin isoform N

Status: REVIEWED

Source sequence(s)

AL135927, AL355388
NM_001407003.1 → NP_001393932.1 lamin isoform N

Status: REVIEWED

Source sequence(s)

AL135927, AL355388
NM_005572.4 → NP_005563.1 lamin isoform C

See identical proteins and their annotated locations for NP_005563.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate splice site in the 3' coding region, compared to variant 1. This results in a shorter isoform (C) with a distinct C-terminus when compared to isoform prelamin A. Both variants 2 and 6 encode the same isoform (C).

Source sequence(s)

AL135927

Consensus CDS

CCDS1131.1

UniProtKB/TrEMBL

W8QEH3

Related

ENSP00000503633.1, ENST00000677389.1

Conserved Domains (2) summary

pfam00038
Location:30 → 386

Filament; Intermediate filament protein

pfam00932
Location:436 → 541

LTD; Lamin Tail Domain
NM_170707.4 → NP_733821.1 lamin isoform A

See identical proteins and their annotated locations for NP_733821.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes isoform A.

Source sequence(s)

AI872233, AL135927, BC014507, BG822820

Consensus CDS

CCDS1129.1

UniProtKB/Swiss-Prot

B4DI32, D3DVB0, D6RAQ3, E7EUI9, P02545, P02546, Q5I6Y4, Q5I6Y6, Q5TCJ2, Q5TCJ3, Q6UYC3, Q969I8, Q96JA2

UniProtKB/TrEMBL

A0A384MQX1, A0A6Q8PFJ0

Related

ENSP00000357283.4, ENST00000368300.9

Conserved Domains (2) summary

pfam00038
Location:30 → 386

Filament; Intermediate filament protein

pfam00932
Location:434 → 541

LTD; Lamin Tail Domain
NM_170708.4 → NP_733822.1 lamin isoform A-delta10

See identical proteins and their annotated locations for NP_733822.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) lacks an internal segment of sequence compared to variant 1. The encoded isoform (A delta10), is shorter but has the same C-terminus when compared to isoform A.

Source sequence(s)

AF381029, AI872233, AL135927, BC000511, BC014507, BG822820

UniProtKB/TrEMBL

A0A6Q8PFJ0

Related

ENSP00000506904.1, ENST00000682650.1

Conserved Domains (5) summary

pfam00038
Location:30 → 386

Filament; Intermediate filament protein

pfam00932
Location:433 → 536

LTD; Lamin Tail Domain

pfam05384
Location:32 → 119

DegS; Sensor protein DegS

pfam09798
Location:302 → 463

LCD1; DNA damage checkpoint protein

pfam10018
Location:191 → 355

Med4; Vitamin-D-receptor interacting Mediator subunit 4