LMF2

Summary

LMF2 (lipase maturation factor 2, HGNC:25096) is a protein-coding gene on chromosome 22q13.33, encoding Lipase maturation factor 2 (Q9BU23). Involved in the maturation of specific proteins in the endoplasmic reticulum.

Predicted to be involved in protein maturation. Located in membrane.

Source: NCBI Gene 91289 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 227 total — 1 pathogenic
• MANE Select transcript: NM_033200

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25096
Approved symbol	LMF2
Name	lipase maturation factor 2
Location	22q13.33
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000100258
Ensembl biotype	protein_coding
Entrez	91289

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 23 protein_coding, 3 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000216080, ENST00000474879, ENST00000504717, ENST00000505981, ENST00000507607, ENST00000514938, ENST00000892447, ENST00000892448, ENST00000892449, ENST00000892450, ENST00000892451, ENST00000892452, ENST00000892453, ENST00000892454, ENST00000892455, ENST00000892456, ENST00000892457, ENST00000892458, ENST00000892459, ENST00000892460, ENST00000892461, ENST00000947307, ENST00000947308, ENST00000947309, ENST00000947310, ENST00000947311, ENST00000947312

RefSeq mRNA: 2 — MANE Select: NM_033200 NM_001363816, NM_033200

CCDS: CCDS14093, CCDS87035

Canonical transcript exons

ENST00000474879 — 14 exons

Exon	Start	End
ENSE00000657717	50504340	50504451
ENSE00000657719	50504559	50504727
ENSE00000657723	50505229	50505334
ENSE00000657724	50505403	50505537
ENSE00001522614	50502949	50503699
ENSE00001844900	50507582	50507702
ENSE00003549581	50506035	50506213
ENSE00003575946	50505674	50505815
ENSE00003582384	50504802	50504984
ENSE00003630339	50506638	50506666
ENSE00003651644	50506285	50506502
ENSE00003655567	50503808	50503904
ENSE00003668147	50505057	50505153
ENSE00003693305	50506782	50507035

Expression profiles

Bgee: expression breadth ubiquitous, 258 present calls, max score 98.34.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 61.7690 / max 446.8159, expressed in 1818 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
194753	60.1011	1816
194750	0.5256	314
194751	0.5225	243
194749	0.5104	282
194752	0.1096	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
body of pancreas	UBERON:0001150	98.34	gold quality
granulocyte	CL:0000094	97.56	gold quality
adenohypophysis	UBERON:0002196	96.99	gold quality
right lobe of thyroid gland	UBERON:0001119	96.47	gold quality
pituitary gland	UBERON:0000007	96.46	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.36	gold quality
left lobe of thyroid gland	UBERON:0001120	96.23	gold quality
small intestine Peyer’s patch	UBERON:0003454	96.06	gold quality
right ovary	UBERON:0002118	95.99	gold quality
left uterine tube	UBERON:0001303	95.94	gold quality
mucosa of stomach	UBERON:0001199	95.86	gold quality
endocervix	UBERON:0000458	95.85	gold quality
metanephros cortex	UBERON:0010533	95.83	gold quality
body of uterus	UBERON:0009853	95.69	gold quality
cerebellar hemisphere	UBERON:0002245	95.64	gold quality
left ovary	UBERON:0002119	95.63	gold quality
stromal cell of endometrium	CL:0002255	95.58	gold quality
apex of heart	UBERON:0002098	95.57	gold quality
minor salivary gland	UBERON:0001830	95.49	gold quality
cerebellar cortex	UBERON:0002129	95.49	gold quality
spleen	UBERON:0002106	95.42	gold quality
ectocervix	UBERON:0012249	95.35	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	95.18	gold quality
right coronary artery	UBERON:0001625	95.10	gold quality
thyroid gland	UBERON:0002046	95.06	gold quality
omental fat pad	UBERON:0010414	94.90	gold quality
lower esophagus muscularis layer	UBERON:0035833	94.89	gold quality
lower esophagus	UBERON:0013473	94.88	gold quality
peritoneum	UBERON:0002358	94.86	gold quality
ascending aorta	UBERON:0001496	94.79	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	15.36
E-MTAB-7606	no	524.70

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

23 targeting LMF2, 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-6721-5P	99.93	68.92	2981
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-5001-5P	99.05	66.76	1972
HSA-MIR-6829-5P	98.86	65.12	1480
HSA-MIR-6846-5P	98.81	65.86	1121
HSA-MIR-6848-5P	98.81	65.49	1126
HSA-MIR-4656	98.79	66.22	1306
HSA-MIR-331-3P	98.76	64.91	793
HSA-MIR-6826-3P	98.19	66.32	1153
HSA-MIR-6879-5P	97.77	65.52	1521
HSA-MIR-4675	97.69	64.82	774
HSA-MIR-4741	97.69	64.14	883
HSA-MIR-3620-5P	97.42	63.95	792
HSA-MIR-6748-3P	97.20	65.66	836
HSA-MIR-1587	96.95	64.03	932
HSA-MIR-1291	96.28	65.89	1224
HSA-MIR-4509	96.19	65.80	900

Literature-anchored findings (GeneRIF, showing 1)

• DNA methylation in the NCAPH2/LMF2 promoter region is significantly decreased in Alzheimer disease. (PMID:26742120)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	lmf2b	ENSDARG00000025859
danio_rerio	lmf2a	ENSDARG00000078094
mus_musculus	Lmf2	ENSMUSG00000022614
rattus_norvegicus	Lmf2	ENSRNOG00000030633
caenorhabditis_elegans		WBGENE00019657

Paralogs (1): LMF1 (ENSG00000103227)

Protein

Protein identifiers

Lipase maturation factor 2 — Q9BU23 (reviewed: Q9BU23)

Alternative names: Transmembrane protein 112B, Transmembrane protein 153

All UniProt accessions (1): Q9BU23

UniProt curated annotations — full annotation on UniProt →

Function. Involved in the maturation of specific proteins in the endoplasmic reticulum. May be required for maturation and transport of active lipoprotein lipase (LPL) through the secretory pathway.

Subcellular location. Endoplasmic reticulum membrane.

Similarity. Belongs to the lipase maturation factor family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9BU23-1	1	yes
Q9BU23-2	2
Q9BU23-3	3

RefSeq proteins (2): NP_001350745, NP_149977* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009613	LMF	Family
IPR057433	LMF1/2_C	Domain
IPR057434	LMF1/2_N	Domain

Pfam: PF06762, PF25179

UniProt features (21 total): transmembrane region 11, glycosylation site 2, splice variant 2, sequence variant 2, chain 1, region of interest 1, compositionally biased region 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BU23-F1	87.48	0.74

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Glycosylation sites (2): 489, 616

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-8963889	Assembly of active LPL and LIPC lipase complexes
R-HSA-174824	Plasma lipoprotein assembly, remodeling, and clearance
R-HSA-382551	Transport of small molecules
R-HSA-8963899	Plasma lipoprotein remodeling

MSigDB gene sets: 87 (showing top): GRUETZMANN_PANCREATIC_CANCER_DN, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, CAGCTG_AP4_Q5, GTGCCTT_MIR506, RICKMAN_METASTASIS_DN, GOBP_PROTEIN_MATURATION, KMCATNNWGGA_UNKNOWN, HIF1_Q3, CREB_Q3, MOOTHA_FFA_OXYDATION, TGCCTTA_MIR124A, GCCATNTTG_YY1_Q6, GCGSCMNTTT_UNKNOWN, chr22q13, GOCC_NUCLEAR_OUTER_MEMBRANE_ENDOPLASMIC_RETICULUM_MEMBRANE_NETWORK

GO Biological Process (1): protein maturation (GO:0051604)

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

GO Cellular Component (3): endoplasmic reticulum membrane (GO:0005789), membrane (GO:0016020), endoplasmic reticulum (GO:0005783)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Plasma lipoprotein remodeling	1
Transport of small molecules	1
Plasma lipoprotein assembly, remodeling, and clearance	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
gene expression	1
protein metabolic process	1
binding	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cellular anatomical structure	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

794 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LMF2	NCAPH2	Q6IBW4	668
LMF2	CIMAP1B	A8MYP8	502
LMF2	CHKB	Q9Y259	498
LMF2	SCO2	O43819	473
LMF2	REG4	Q9BYZ8	386
LMF2	TRIM44	Q96DX7	381
LMF2	MBIP	Q9NS73	360
LMF2	HMGCS1	Q01581	348
LMF2	POLH	Q9Y253	348
LMF2	SYCE3	A1L190	348
LMF2	HMGCS2	P54868	343
LMF2	VCF2	Q5XKR9	324
LMF2	MFSD1	Q9H3U5	316
LMF2	DGKZ	Q13574	314
LMF2	DENND6B	Q8NEG7	311

IntAct

87 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
ENPP6	SCAMP1	psi-mi:“MI:0914”(association)	0.640
CANX	PGRMC1	psi-mi:“MI:0914”(association)	0.570
LMF2		psi-mi:“MI:0915”(physical association)	0.560
CALCOCO2	LMF2	psi-mi:“MI:0915”(physical association)	0.560
LMF2	KRT31	psi-mi:“MI:0915”(physical association)	0.560
KRT40	LMF2	psi-mi:“MI:0915”(physical association)	0.560
KRT31	LMF2	psi-mi:“MI:0915”(physical association)	0.560
	LMF2	psi-mi:“MI:0915”(physical association)	0.560
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
PLA2G10	CHEK1	psi-mi:“MI:0914”(association)	0.530
IGFBP1	SUSD5	psi-mi:“MI:0914”(association)	0.530
GABRE	FZD6	psi-mi:“MI:0914”(association)	0.530
HMOX2	PRAF2	psi-mi:“MI:0914”(association)	0.530
FUT3	C1QL1	psi-mi:“MI:0914”(association)	0.530
SEMA7A	SGPL1	psi-mi:“MI:0914”(association)	0.530
SYT3	PGK2	psi-mi:“MI:0914”(association)	0.530
ST3GAL2	HSPA5	psi-mi:“MI:0914”(association)	0.530
STS	GJA1	psi-mi:“MI:0914”(association)	0.530
LPAR1	TMEM223	psi-mi:“MI:0914”(association)	0.530
	VAPB	psi-mi:“MI:0914”(association)	0.500

BioGRID (153): LMF2 (Two-hybrid), LMF2 (Two-hybrid), KRT40 (Two-hybrid), KRTAP10-3 (Two-hybrid), LMF2 (Affinity Capture-MS), LMF2 (Affinity Capture-MS), LMF2 (Affinity Capture-MS), LMF2 (Affinity Capture-MS), LMF2 (Affinity Capture-MS), LMF2 (Affinity Capture-MS), LMF2 (Affinity Capture-MS), LMF2 (Reconstituted Complex), LMF2 (Proximity Label-MS), LMF2 (Proximity Label-MS), LMF2 (Affinity Capture-MS)

ESM2 similar proteins: A0A8C2M425, A1L1J9, A1L504, B0BNG2, D3ZBP4, F1MH07, O08984, O75908, O77759, O88496, O88908, P38435, P70606, Q07175, Q0P4Y8, Q32LM8, Q3U9G9, Q3UDW8, Q5KR61, Q5RF50, Q5RKL5, Q5T197, Q5T1A1, Q5ZKZ9, Q643R3, Q658P3, Q68CP4, Q6NVG1, Q767L9, Q7TNJ2, Q7TPN3, Q7TQM4, Q7ZWN0, Q8BKF1, Q8C3X8, Q8CI59, Q8IUH8, Q8IZY2, Q8R1J1, Q8TDZ2

Diamond homologs: A1L1J9, A1L504, Q0P4Y8, Q5ZKZ9, Q7ZWN0, Q8C3X8, Q96S06, Q9BU23, Q0P5C0, Q3U3R4

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 111 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Neurotransmitter receptors and postsynaptic signal transmission	6	8.2×	4e-03
Transmission across Chemical Synapses	7	7.3×	4e-03

GO biological processes:

GO term	Partners	Fold	FDR
monoatomic ion transmembrane transport	8	16.5×	2e-05
regulation of membrane potential	5	11.4×	8e-03
ERAD pathway	6	10.8×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	186
Likely benign	15
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1407208	NC_000022.10:g.(?50885571)(51021210_?)del	Pathogenic

SpliceAI

1671 predictions. Top by Δscore:

Variant	Effect	Δscore
22:50503699:CCTGT:C	acceptor_loss	1.0000
22:50503700:C:CC	acceptor_gain	1.0000
22:50503802:CCTTA:C	donor_loss	1.0000
22:50503803:CTTA:C	donor_loss	1.0000
22:50503804:TTA:T	donor_loss	1.0000
22:50503805:TA:T	donor_loss	1.0000
22:50503806:ACCT:A	donor_loss	1.0000
22:50503807:C:A	donor_loss	1.0000
22:50503901:CTGG:C	acceptor_gain	1.0000
22:50504334:CCTTA:C	donor_loss	1.0000
22:50504335:CTTAC:C	donor_loss	1.0000
22:50504336:TTA:T	donor_loss	1.0000
22:50504338:A:AC	donor_gain	1.0000
22:50504338:A:T	donor_loss	1.0000
22:50504338:AC:A	donor_gain	1.0000
22:50504338:ACC:A	donor_gain	1.0000
22:50504339:C:CC	donor_gain	1.0000
22:50504339:CC:C	donor_gain	1.0000
22:50504339:CCC:C	donor_gain	1.0000
22:50504368:A:AC	donor_gain	1.0000
22:50504369:C:CC	donor_gain	1.0000
22:50504449:TCA:T	acceptor_gain	1.0000
22:50504450:CA:C	acceptor_gain	1.0000
22:50504450:CAC:C	acceptor_gain	1.0000
22:50504452:C:A	acceptor_loss	1.0000
22:50504452:C:CC	acceptor_gain	1.0000
22:50504453:T:A	acceptor_loss	1.0000
22:50504725:CTC:C	acceptor_gain	1.0000
22:50504726:TCCTG:T	acceptor_loss	1.0000
22:50504727:CCTG:C	acceptor_loss	1.0000

AlphaMissense

4466 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:50504635:A:C	F510L	0.998
22:50504635:A:T	F510L	0.998
22:50504637:A:G	F510L	0.998
22:50504874:G:C	F455L	0.997
22:50504874:G:T	F455L	0.997
22:50504876:A:G	F455L	0.997
22:50504604:A:G	W521R	0.996
22:50504604:A:T	W521R	0.996
22:50504640:A:G	W509R	0.996
22:50504640:A:T	W509R	0.996
22:50505060:G:C	S417R	0.996
22:50505060:G:T	S417R	0.996
22:50505062:T:G	S417R	0.996
22:50506322:C:A	K186N	0.996
22:50506322:C:G	K186N	0.996
22:50506639:A:G	W126R	0.996
22:50506639:A:T	W126R	0.996
22:50504649:A:G	W506R	0.995
22:50504649:A:T	W506R	0.995
22:50504876:A:T	F455I	0.995
22:50506300:A:G	W194R	0.995
22:50506300:A:T	W194R	0.995
22:50506501:C:G	D127H	0.995
22:50506502:C:A	W126C	0.995
22:50506502:C:G	W126C	0.995
22:50506652:G:C	F121L	0.995
22:50506652:G:T	F121L	0.995
22:50506654:A:G	F121L	0.995
22:50506485:T:A	E132V	0.994
22:50506500:T:A	D127V	0.994

dbSNP variants (sampled 300 via entrez): RS1000482004 (22:50508098 C>CA,CT), RS1000906384 (22:50507287 G>A,C,T), RS1001088754 (22:50508334 G>A,T), RS1001294311 (22:50508204 G>A,C), RS1001648797 (22:50507567 C>G,T), RS1001823033 (22:50509464 A>G), RS1001883107 (22:50505983 C>A), RS1002300905 (22:50502630 G>A), RS1003092213 (22:50503619 G>A), RS1003358114 (22:50506558 G>A), RS1003622142 (22:50506114 G>A,T), RS1003631943 (22:50503181 T>A,C), RS1003885280 (22:50502892 G>A), RS1003931996 (22:50507684 C>A,G,T), RS1003965769 (22:50503863 G>A,T)

Disease associations

OMIM: gene `` | disease phenotypes: MIM:602541

GenCC curated gene-disease

Mondo (1): megaconial type congenital muscular dystrophy (MONDO:0011246)

Orphanet (1): Megaconial congenital muscular dystrophy (Orphanet:280671)

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C566527	Muscular Dystrophy, Congenital, Megaconial Type (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, affects binding, increases reaction, affects cotreatment, decreases expression (+1 more)	4
Particulate Matter	decreases expression, increases abundance, affects cotreatment, increases expression	3
Air Pollutants	affects expression, increases abundance, decreases expression	2
Tobacco Smoke Pollution	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
perfluorooctanoic acid	decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
CGP 52608	affects binding, increases reaction	1
ICG 001	decreases expression	1
(+)-JQ1 compound	decreases expression	1
MT19c compound	decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Temozolomide	decreases expression	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Vehicle Emissions	increases abundance, increases expression	1
Gasoline	affects cotreatment, increases abundance, increases expression	1
Ivermectin	decreases expression	1
Manganese	affects cotreatment, decreases expression, increases abundance	1
Ozone	affects expression, increases abundance	1
Polycyclic Aromatic Hydrocarbons	affects cotreatment, increases abundance, increases expression	1
Rotenone	increases expression	1
Smoke	decreases expression	1
Valproic Acid	increases methylation	1
beta-Naphthoflavone	decreases expression	1
1-Butanol	affects cotreatment, increases abundance, increases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B1VX	Abcam HeLa LMF2 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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