LEMD1

Summary

LEMD1 (LEM domain containing 1, HGNC:18725) is a protein-coding gene on chromosome 1q32.1, encoding LEM domain-containing protein 1 (Q68G75).

Predicted to be located in membrane.

Source: NCBI Gene 93273 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 35 total
• MANE Select transcript: NM_001199050

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18725
Approved symbol	LEMD1
Name	LEM domain containing 1
Location	1q32.1
Locus type	gene with protein product
Status	Approved
Aliases	LEMP-1, CT50
Ensembl gene	ENSG00000186007
Ensembl biotype	protein_coding
OMIM	610480
Entrez	93273

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 7 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000367149, ENST00000367151, ENST00000367152, ENST00000367153, ENST00000367154, ENST00000391936, ENST00000476884, ENST00000495594

RefSeq mRNA: 4 — MANE Select: NM_001199050 NM_001001552, NM_001199050, NM_001199051, NM_001199052

CCDS: CCDS30986, CCDS55677, CCDS55678, CCDS55679

Canonical transcript exons

ENST00000367153 — 6 exons

Exon	Start	End
ENSE00001332310	205416232	205416296
ENSE00001332313	205419230	205419352
ENSE00001855265	205421990	205422056
ENSE00003542467	205381378	205381856
ENSE00003621658	205384288	205384364
ENSE00003625561	205420455	205420574

Expression profiles

Bgee: expression breadth ubiquitous, 145 present calls, max score 96.20.

FANTOM5 (CAGE): breadth broad, TPM avg 1.4153 / max 175.8331, expressed in 475 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
16992	1.0294	412
16991	0.3268	147
16989	0.0373	3
16988	0.0145	3
16987	0.0074	3

Top tissues by expression

247 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	96.20	gold quality
sperm	CL:0000019	96.01	gold quality
right testis	UBERON:0004534	95.86	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	95.22	gold quality
testis	UBERON:0000473	94.07	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.54	gold quality
adult organism	UBERON:0007023	87.90	gold quality
ganglionic eminence	UBERON:0004023	87.50	gold quality
ventricular zone	UBERON:0003053	83.36	gold quality
cortical plate	UBERON:0005343	80.43	gold quality
corpus epididymis	UBERON:0004359	75.95	gold quality
pons	UBERON:0000988	75.09	gold quality
buccal mucosa cell	CL:0002336	73.01	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	72.95	gold quality
cerebellar cortex	UBERON:0002129	72.67	gold quality
cerebellar hemisphere	UBERON:0002245	72.55	gold quality
cerebellum	UBERON:0002037	71.94	gold quality
palpebral conjunctiva	UBERON:0001812	71.25	gold quality
right hemisphere of cerebellum	UBERON:0014890	71.10	gold quality
left ovary	UBERON:0002119	69.02	gold quality
ovary	UBERON:0000992	65.88	gold quality
ileal mucosa	UBERON:0000331	65.72	gold quality
amniotic fluid	UBERON:0000173	65.65	silver quality
right adrenal gland cortex	UBERON:0035827	65.47	gold quality
right adrenal gland	UBERON:0001233	65.28	gold quality
minor salivary gland	UBERON:0001830	64.08	gold quality
upper arm skin	UBERON:0004263	63.13	gold quality
epithelial cell of pancreas	CL:0000083	62.88	gold quality
left adrenal gland	UBERON:0001234	62.60	gold quality
left adrenal gland cortex	UBERON:0035825	62.58	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	32.18
E-MTAB-8410	yes	23.35
E-ANND-3	no	2.91

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

19 targeting LEMD1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-4525	99.94	64.38	675
HSA-MIR-5010-5P	99.94	64.11	705
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-659-3P	99.85	70.69	1620
HSA-MIR-6079	99.84	68.54	1170
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-4677-3P	99.49	67.91	1246
HSA-MIR-5009-3P	99.45	69.43	1341
HSA-MIR-372-5P	99.41	69.11	2299
HSA-MIR-1272	99.34	68.79	878
HSA-MIR-3124-3P	98.87	68.95	2123
HSA-MIR-379-5P	97.52	67.81	485
HSA-MIR-3529-5P	97.12	67.06	440
HSA-MIR-6772-3P	97.04	65.89	784
HSA-MIR-6851-3P	95.73	65.11	688

Literature-anchored findings (GeneRIF, showing 9)

• LEM domain-containing 1 is a novel testis-specific gene expressed in colorectal cancers (PMID:15254688)
• Of the prostate cancer samples, 10, 10, 23 and 40% showed ODF1, ODF2, LEMD1 and SPATA19 specific bands, respectively, but none of the BPH samples expressed any of these genes. (PMID:20682177)
• Downregulation of LEMD1 expression inhibited adhesion and transmigration of OSCCs. (PMID:27280633)
• Data show that LEM domain containing 1 (LEMD1)has five transcript splicing variants (variant 1 [V1] - variant 5 [V5]), and that LEMD1 V1, V2 and V3 is expressed in testis and CR-CSCs/CICs, whereas LEMD1 V4 and V5 is ubiquitously expressed. (PMID:28219643)
• LEM domain containing 1 promotes proliferation via activating the PI3K/Akt signaling pathway in gastric cancer. (PMID:31021450)
• Long non-coding RNA LINC00958 promotes colorectal cancer progression by enhancing the expression of LEM domain containing 1 via microRNA miR-3064-5p. (PMID:34672237)
• LEM domain containing 1 (LEMD1) transcriptionally activated by SRY-related high-mobility-group box 4 (SOX4) accelerates the progression of colon cancer by upregulating phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway. (PMID:35294319)
• Long Noncoding RNA LEMD1-AS1 Increases LEMD1 Expression and Activates PI3K-AKT Pathway to Promote Metastasis in Oral Squamous Cell Carcinoma. (PMID:35983249)
• Elevation of LEM Domain Containing 1 Predicts Poor Prognosis of NSCLC Patients and Triggers Malignant Stemness and Invasion of NSCLC Cells by Stimulating PI3K/AKT Pathway. (PMID:36967459)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	tmpoa	ENSDARG00000007315
danio_rerio	tmpob	ENSDARG00000022978
danio_rerio	lemd1	ENSDARG00000040161
mus_musculus	Lemd1	ENSMUSG00000079330
rattus_norvegicus	Lemd1	ENSRNOG00000051244
caenorhabditis_elegans	emr-1	WBGENE00001309

Paralogs (1): TMPO (ENSG00000120802)

Protein

Protein identifiers

LEM domain-containing protein 1 — Q68G75 (reviewed: Q68G75)

Alternative names: Cancer/testis antigen 50, LEM domain protein 1

All UniProt accessions (1): Q68G75

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

Tissue specificity. Testis-specific. Isoform 6 is detected in 17 of 18 colon cancer tissues examined.

Miscellaneous. Found at the nuclear membrane.

Isoforms (6)

UniProt ID	Names	Canonical?
Q68G75-1	1, LEMD1A	yes
Q68G75-2	2, LEMD1B
Q68G75-3	3, LEMD1C
Q68G75-4	4, LEMD1D
Q68G75-5	5, LEMD1E
Q68G75-6	6, LEMD1F

RefSeq proteins (4): NP_001001552, NP_001185979, NP_001185980, NP_001185981 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003887	LEM_dom	Domain
IPR011015	LEM/LEM-like_dom_sf	Homologous_superfamily
IPR051656	LEM_domain	Family

Pfam: PF03020

UniProt features (14 total): splice variant 9, chain 1, transmembrane region 1, sequence variant 1, sequence conflict 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q68G75-F1	64.36	0.18

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 69 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_DN, LHX3_01, HP1SITEFACTOR_Q6, WEBER_METHYLATED_LCP_IN_FIBROBLAST_DN, TGACATY_UNKNOWN, RICKMAN_HEAD_AND_NECK_CANCER_A, NKX25_01, HAND1E47_01, GATA1_02, FOXJ2_02, RGAGGAARY_PU1_Q6, FOXO4_02, TAATTA_CHX10_01, YKACATTT_UNKNOWN, HMGIY_Q6

GO Biological Process (0):

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (1): membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

250 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LEMD1	BANF1	O75531	801
LEMD1	LEMD2	Q8NC56	475
LEMD1	ANKLE1	Q8NAG6	445
LEMD1	LEMD3	Q9Y2U8	435
LEMD1	SPATA19	Q7Z5L4	421
LEMD1	ANKLE2	Q86XL3	411
LEMD1	CIMAP2	Q3ZCV2	399
LEMD1	SRPX2	O60687	396
LEMD1	TSGA10	Q9BZW7	396
LEMD1	MAGEC2	Q9UBF1	392
LEMD1	BANF2	Q9H503	383
LEMD1	TEX101	Q9BY14	355
LEMD1	PRSS50	Q9UI38	352
LEMD1	CCDC110	Q8TBZ0	348
LEMD1	EMD	P50402	348
LEMD1	COL25A1	Q9BXS0	348

IntAct

40 interactions, top by confidence:

A	B	Type	Score
LEMD1	SCN3B	psi-mi:“MI:0915”(physical association)	0.560
LEMD1	SLC16A7	psi-mi:“MI:0915”(physical association)	0.560
LEMD1	MEOX2	psi-mi:“MI:0915”(physical association)	0.560
LEMD1	JAGN1	psi-mi:“MI:0915”(physical association)	0.560
LEMD1	TMPPE	psi-mi:“MI:0915”(physical association)	0.560
LEMD1	REEP4	psi-mi:“MI:0915”(physical association)	0.560
LEMD1	ERMAP	psi-mi:“MI:0915”(physical association)	0.560
LEMD1	RETREG3	psi-mi:“MI:0915”(physical association)	0.560
AQP6	LEMD1	psi-mi:“MI:0915”(physical association)	0.560
LEMD1	ZDHHC15	psi-mi:“MI:0915”(physical association)	0.560
EBP	LEMD1	psi-mi:“MI:0915”(physical association)	0.560
SLC16A7	LEMD1	psi-mi:“MI:0915”(physical association)	0.560
MGST3	LEMD1	psi-mi:“MI:0915”(physical association)	0.560
BLCAP	LEMD1	psi-mi:“MI:0915”(physical association)	0.560
LEMD1	MEOX2	psi-mi:“MI:0915”(physical association)	0.000
LEMD1	TMPPE	psi-mi:“MI:0915”(physical association)	0.000
LEMD1	REEP4	psi-mi:“MI:0915”(physical association)	0.000
LEMD1	ERMAP	psi-mi:“MI:0915”(physical association)	0.000
LEMD1	RETREG3	psi-mi:“MI:0915”(physical association)	0.000
LEMD1	AQP6	psi-mi:“MI:0915”(physical association)	0.000
LEMD1	ZDHHC15	psi-mi:“MI:0915”(physical association)	0.000
LEMD1	EBP	psi-mi:“MI:0915”(physical association)	0.000
LEMD1	BLCAP	psi-mi:“MI:0915”(physical association)	0.000
LEMD1	JAGN1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (15): LEMD1 (Two-hybrid), LEMD1 (Two-hybrid), LEMD1 (Two-hybrid), LEMD1 (Two-hybrid), LEMD1 (Two-hybrid), LEMD1 (Two-hybrid), LEMD1 (Two-hybrid), LEMD1 (Two-hybrid), LEMD1 (Two-hybrid), LEMD1 (Two-hybrid), LEMD1 (Two-hybrid), LEMD1 (Two-hybrid), TMPPE (Two-hybrid), LEMD1 (Proximity Label-MS), LEMD1 (Positive Genetic)

ESM2 similar proteins: A2BDB7, A6PVY3, F6RRD7, F7BHS0, O14990, O55036, O60566, P16383, P54274, P58501, Q08B36, Q0VFF9, Q28C41, Q28GJ0, Q28GL6, Q2T9X8, Q2TBG9, Q2WG79, Q3ZCI6, Q4R6Q9, Q5BJ78, Q5M8L3, Q5NVK0, Q5R6R3, Q5R789, Q5R939, Q5RA37, Q5RBY6, Q5TID7, Q5XIG5, Q640L3, Q68G75, Q6AYN9, Q6GNQ4, Q6NTW1, Q6NZY4, Q6PCG6, Q80VH0, Q80ZU5, Q8AVX1

Diamond homologs: O01971, P42166, P42167, Q14C37, Q61029, Q61033, Q62733, Q68G75, Q9XTB5, P01249, P01250, P01251, Q9WU40, Q9Y2U8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

35 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	27
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

673 predictions. Top by Δscore:

Variant	Effect	Δscore
1:205384365:C:CC	acceptor_gain	1.0000
1:205420444:A:AC	donor_gain	1.0000
1:205420445:C:CC	donor_gain	1.0000
1:205420453:A:AC	donor_gain	1.0000
1:205420454:C:CC	donor_gain	1.0000
1:205420574:CCT:C	acceptor_gain	1.0000
1:205420576:T:C	acceptor_gain	1.0000
1:205420576:T:TC	acceptor_gain	1.0000
1:205381852:CCCAC:C	acceptor_gain	0.9900
1:205381853:CCAC:C	acceptor_gain	0.9900
1:205381853:CCACC:C	acceptor_gain	0.9900
1:205381854:CAC:C	acceptor_gain	0.9900
1:205381854:CACC:C	acceptor_gain	0.9900
1:205381856:CCTGT:C	acceptor_loss	0.9900
1:205381857:C:CC	acceptor_gain	0.9900
1:205381858:T:G	acceptor_loss	0.9900
1:205384294:C:A	donor_gain	0.9900
1:205384362:CCA:C	acceptor_gain	0.9900
1:205384363:CA:C	acceptor_gain	0.9900
1:205384363:CAC:C	acceptor_gain	0.9900
1:205384363:CACTG:C	acceptor_loss	0.9900
1:205384364:AC:A	acceptor_loss	0.9900
1:205384365:C:CA	acceptor_loss	0.9900
1:205384366:T:C	acceptor_loss	0.9900
1:205397917:AC:A	donor_gain	0.9900
1:205397918:CC:C	donor_gain	0.9900
1:205420446:TG:T	donor_gain	0.9900
1:205420449:ACAT:A	donor_loss	0.9900
1:205420450:CATA:C	donor_gain	0.9900
1:205420451:ATA:A	donor_loss	0.9900

AlphaMissense

1174 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:205420502:A:G	L12S	0.975
1:205381720:C:G	G162R	0.967
1:205419342:T:A	R31S	0.963
1:205419342:T:G	R31S	0.963
1:205420460:A:T	I26K	0.961
1:205420490:A:T	L16H	0.952
1:205381719:C:T	G162D	0.948
1:205420474:A:C	F21L	0.942
1:205420474:A:T	F21L	0.942
1:205420476:A:G	F21L	0.942
1:205420490:A:G	L16P	0.941
1:205381728:G:T	A159D	0.940
1:205420460:A:C	I26R	0.933
1:205419330:T:A	E35D	0.931
1:205419330:T:G	E35D	0.931
1:205420466:C:T	G24D	0.930
1:205419322:A:G	L38S	0.929
1:205381695:A:T	V170D	0.928
1:205381704:A:T	V167E	0.927
1:205419343:C:G	R31T	0.923
1:205420467:C:G	G24R	0.914
1:205420460:A:G	I26T	0.911
1:205381693:A:C	Y171D	0.901
1:205419343:C:A	R31I	0.898
1:205419335:A:C	Y34D	0.897
1:205419346:G:A	T30I	0.888
1:205420457:A:G	L27P	0.887
1:205381707:A:T	I166N	0.878
1:205381725:A:T	V160E	0.877
1:205419313:A:G	L41S	0.863

dbSNP variants (sampled 300 via entrez): RS1000000971 (1:205444187 C>A,G), RS1000095534 (1:205444426 G>C,T), RS1000098682 (1:205398069 G>A), RS1000105702 (1:205444381 A>C), RS1000144175 (1:205386609 G>GC), RS1000151252 (1:205397645 T>C), RS1000171642 (1:205442889 T>C), RS1000190541 (1:205428015 C>T), RS1000234224 (1:205425712 T>A), RS1000344665 (1:205432591 C>A), RS1000371276 (1:205449243 GA>G), RS1000442575 (1:205415491 G>C), RS1000496965 (1:205385290 T>C), RS1000507508 (1:205427308 G>A), RS1000532998 (1:205403625 A>T)

Disease associations

OMIM: gene MIM:610480 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST010121_2	Ceramide levels (C24:0)	5.000000e-06
GCST010122_1	Ceramide levels (C22:0)	6.000000e-06
GCST012033_4	Sleep (1/3-day periodicity)	5.000000e-08

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

37 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression	6
trichostatin A	affects cotreatment, decreases expression	3
entinostat	decreases expression, affects cotreatment	2
aristolochic acid I	increases expression	1
FR900359	decreases phosphorylation	1
sotorasib	affects cotreatment, decreases expression	1
beta-lapachone	increases expression	1
sodium arsenite	increases expression	1
perfluorooctanoic acid	decreases expression	1
hydroquinone	decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
perfluoro-n-nonanoic acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
perfluorohexanesulfonic acid	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
trametinib	decreases expression, affects cotreatment	1
(+)-JQ1 compound	increases expression	1
NVP-BKM120	affects cotreatment, decreases expression	1
Panobinostat	affects cotreatment, decreases expression	1
Glyphosate	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Carbamazepine	affects expression	1
Estradiol	affects cotreatment, decreases expression	1
Malathion	increases expression	1
Phenobarbital	increases expression	1
Phenylmercuric Acetate	affects cotreatment, decreases expression	1
Progesterone	affects cotreatment, decreases expression	1
Smoke	decreases expression, increases abundance	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.