Seroatlas · Human Serome Atlas

LEMD3

Inner nuclear membrane protein Man1

Also known as: MAN1, MAN1_HUMAN

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession: Q9Y2U8
Gene: LEMD3
Ensembl: ENSG00000174106
Chromosome: 12
Canonical length: 911 aa
Protein class: Disease related genes, Human disease related genes, Plasma proteins, Predicted membrane proteins
Subcellular location: Nuclear membrane

OverviewNCBI Gene

This locus encodes a LEM domain-containing protein. The encoded protein functions to antagonize transforming growth factor-beta signaling at the inner nuclear membrane. Two transcript variants encoding different isoforms have been found for this gene. Mutations in this gene have been associated with osteopoikilosis, Buschke-Ollendorff syndrome and melorheostosis.[provided by RefSeq, Nov 2009]

Canonical amino-acid sequenceUniProt

911 residues, UniProt reviewed canonical sequence.

>Q9Y2U8|LEMD3
     1  MAAAAASAPQ QLSDEELFSQ LRRYGLSPGP VTESTRPVYL KKLKKLREEE QQQHRSGGRG
    61  NKTRNSNNNN TAAATVAAAG PAAAAAAGMG VRPVSGDLSY LRTPGGLCRI SASGPESLLG
   121  GPGGASAAPA AGSKVLLGFS SDESDVEASP RDQAGGGGRK DRASLQYRGL KAPPAPLAAS
   181  EVTNSNSAER RKPHSWWGAR RPAGPELQTP PGKDGAVEDE EGEGEDGEER DPETEEPLWA
   241  SRTVNGSRLV PYSCRENYSD SEEEDDDDVA SSRQVLKDDS LSRHRPRRTH SKPLPPLTAK
   301  SAGGRLETSV QGGGGLAMND RAAAAGSLDR SRNLEEAAAA EQGGGCDQVD SSPVPRYRVN
   361  AKKLTPLLPP PLTDMDSTLD SSTGSLLKTN NHIGGGAFSV DSPRIYSNSL PPSAAVAASS
   421  SLRINHANHT GSNHTYLKNT YNKPKLSEPE EELLQQFKRE EVSPTGSFSA HYLSMFLLTA
   481  ACLFFLILGL TYLGMRGTGV SEDGELSIEN PFGETFGKIQ ESEKTLMMNT LYKLHDRLAQ
   541  LAGDHECGSS SQRTLSVQEA AAYLKDLGPE YEGIFNTSLQ WILENGKDVG IRCVGFGPEE
   601  ELTNITDVQF LQSTRPLMSF WCRFRRAFVT VTHRLLLLCL GVVMVCVVLR YMKYRWTKEE
   661  EETRQMYDMV VKIIDVLRSH NEACQENKDL QPYMPIPHVR DSLIQPHDRK KMKKVWDRAV
   721  DFLAANESRV RTETRRIGGA DFLVWRWIQP SASCDKILVI PSKVWQGQAF HLDRRNSPPN
   781  SLTPCLKIRN MFDPVMEIGD QWHLAIQEAI LEKCSDNDGI VHIAVDKNSR EGCVYVKCLS
   841  PEYAGKAFKA LHGSWFDGKL VTVKYLRLDR YHHRFPQALT SNTPLKPSNK HMNSMSHLRL
   901  RTGLTNSQGS S

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against LEMD3 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability: Intracellular
Secreted: No
Transmembrane segments: 2
Mean surface accessibility (rSASA): 0.53
Highest tissue expression: 20 nTPM

Expression across tissuesHPA

Tissue

bone marrow: 20 nTPM
retina: 15 nTPM
testis: 15 nTPM
parathyroid gland: 14 nTPM
thymus: 13 nTPM
lymph node: 13 nTPM

Single-cell type

neutrophil progenitors: 246 nCPM
neutrophils: 157 nCPM
somatotrophs: 116 nCPM
pituicytes/fscs: 113 nCPM
lactotrophs: 110 nCPM
thyrotrophs: 105 nCPM

Immune cell

naive CD8 T-cell: 2.1 nTPM
plasmacytoid DC: 2.1 nTPM
MAIT T-cell: 2 nTPM
memory CD4 T-cell: 2 nTPM
memory CD8 T-cell: 2 nTPM
naive B-cell: 1.9 nTPM

Brain region

cerebellum: 29 nTPM
hippocampal formation: 21 nTPM
basal ganglia: 20 nTPM
cerebral cortex: 20 nTPM
white matter: 19 nTPM
midbrain: 18 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about LEMD3.

Disease | AllUniProt

Conditions LEMD3 is implicated in, by any mechanism.

Buschke-Ollendorff syndrome (BOS) MIM:166700

Disease | GeneticClinVar

73 pathogenic / likely-pathogenic of 945 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

Dermatofibrosis lenticularis disseminata
LEMD3-related disorder
Osteopoikilosis
Melorheostosis with osteopoikilosis
Dermatofibrosis lenticularis disseminata, isolated

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance): 0.25
gnomAD pLI: 1
gnomAD missense Z: -0.26
DepMap mean gene effect: -0.22
DepMap dependency class: selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 6% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of LEMD3 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads LEMD3 as an antibody target. Whether an autoantibody or antibody against LEMD3 could matter depends on whether native LEMD3 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

LEMD3 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.

Annotation status

The present source text does not explicitly label LEMD3 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

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