LCTL

Summary

LCTL (lactase like, HGNC:15583) is a protein-coding gene on chromosome 15q22.31, encoding Lactase-like protein (Q6UWM7). Plays a role in formation of the lens suture in the eye, which is important for normal optical properties of the lens.

This gene encodes a member of family 1 glycosidases. Glycosidases are enzymes that hydrolyze glycosidic bonds and are classified into families based on primary amino acid sequence. Most members of family 1 have two conserved glutamic acid residues, which are required for enzymatic activity. The mouse ortholog of this protein has been characterized and has a domain structure of an N-terminal signal peptide, glycosidase domain, transmembrane domain, and a short cytoplasmic tail. It lacks one of the conserved glutamic acid residues important for catalysis, and its function remains to be determined (PMID: 12084582). Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 197021 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 123 total — 1 pathogenic
• MANE Select transcript: NM_207338

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15583
Approved symbol	LCTL
Name	lactase like
Location	15q22.31
Locus type	gene with protein product
Status	Approved
Aliases	KLPH, FLJ33279, KLG
Ensembl gene	ENSG00000188501
Ensembl biotype	protein_coding
OMIM	617060
Entrez	197021

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 4 protein_coding, 2 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000341509, ENST00000537670, ENST00000562179, ENST00000563438, ENST00000565875, ENST00000695544, ENST00000695545, ENST00000695565

RefSeq mRNA: 4 — MANE Select: NM_207338 NM_001278562, NM_001394632, NM_001394633, NM_207338

CCDS: CCDS10220, CCDS61678

Canonical transcript exons

ENST00000695545 — 14 exons

Exon	Start	End
ENSE00001369307	66561006	66561101
ENSE00001373612	66550041	66550104
ENSE00001382135	66551662	66551861
ENSE00001390525	66557982	66558036
ENSE00003463942	66564676	66564839
ENSE00003524851	66552984	66553258
ENSE00003584590	66561187	66561315
ENSE00003612274	66552043	66552169
ENSE00003634823	66563516	66563625
ENSE00003646039	66557722	66557883
ENSE00003688068	66563911	66563998
ENSE00003964231	66547532	66548605
ENSE00003964234	66565857	66565998
ENSE00003964235	66565248	66565387

Expression profiles

Bgee: expression breadth ubiquitous, 123 present calls, max score 83.22.

FANTOM5 (CAGE): breadth broad, TPM avg 1.0996 / max 54.2742, expressed in 480 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
150606	0.8365	425
150605	0.1427	81
150604	0.1204	59

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	83.22	gold quality
tibial nerve	UBERON:0001323	82.28	gold quality
buccal mucosa cell	CL:0002336	80.25	silver quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	76.67	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	73.77	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	72.10	gold quality
spinal cord	UBERON:0002240	70.75	gold quality
stromal cell of endometrium	CL:0002255	61.36	gold quality
caudate nucleus	UBERON:0001873	61.16	gold quality
nucleus accumbens	UBERON:0001882	59.53	gold quality
amygdala	UBERON:0001876	59.11	gold quality
ventricular zone	UBERON:0003053	57.98	gold quality
putamen	UBERON:0001874	57.93	gold quality
substantia nigra	UBERON:0002038	57.08	gold quality
tibia	UBERON:0000979	55.59	gold quality
Brodmann (1909) area 9	UBERON:0013540	55.08	gold quality
midbrain	UBERON:0001891	55.02	gold quality
anterior cingulate cortex	UBERON:0009835	53.94	gold quality
prefrontal cortex	UBERON:0000451	53.46	gold quality
hypothalamus	UBERON:0001898	52.60	gold quality
ganglionic eminence	UBERON:0004023	52.34	gold quality
temporal lobe	UBERON:0001871	50.94	gold quality
forebrain	UBERON:0001890	50.78	gold quality
Ammon’s horn	UBERON:0001954	50.46	gold quality
neocortex	UBERON:0001950	50.42	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	49.81	gold quality
frontal cortex	UBERON:0001870	49.75	gold quality
brain	UBERON:0000955	49.73	gold quality
right frontal lobe	UBERON:0002810	49.73	gold quality
cerebral cortex	UBERON:0000956	49.40	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-MTAB-2983	no	7.96
E-ANND-3	no	3.68

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

75 targeting LCTL, 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-4262	100.00	73.26	3931
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488

Literature-anchored findings (GeneRIF, showing 1)

• The authors identified and cloned the mouse lactase-like gene (also known as Lctl, Klph). It is a member of the family 1 glycosidases but lacks one of the conserved glutamic acid residues important for catalysis. Its function remains to be determined. (PMID:12084582)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	lctlb	ENSDARG00000016337
danio_rerio	lctla	ENSDARG00000036139
mus_musculus	Lctl	ENSMUSG00000032401
rattus_norvegicus	Lctl	ENSRNOG00000009193
drosophila_melanogaster	CG9701	FBGN0036659
caenorhabditis_elegans		WBGENE00016848
caenorhabditis_elegans		WBGENE00017103

Paralogs (4): LCT (ENSG00000115850), KL (ENSG00000133116), KLB (ENSG00000134962), GBA3 (ENSG00000249948)

Protein

Protein identifiers

Lactase-like protein — Q6UWM7 (reviewed: Q6UWM7)

Alternative names: Klotho/lactase-phlorizin hydrolase-related protein

All UniProt accessions (4): A0A8Q3SI25, A0A8Q3WKK9, H3BQI3, Q6UWM7

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in formation of the lens suture in the eye, which is important for normal optical properties of the lens.

Subunit / interactions. May form dimers.

Subcellular location. Endoplasmic reticulum membrane.

Similarity. Belongs to the glycosyl hydrolase 1 family. Klotho subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q6UWM7-1	1	yes
Q6UWM7-2	2

RefSeq proteins (4): NP_001265491, NP_001381561, NP_001381562, NP_997221* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001360	Glyco_hydro_1	Family
IPR017853	GH_hydrolase_sf	Homologous_superfamily
IPR018120	Glyco_hydro_1_AS	Active_site
IPR033132	GH_1_N_CS	Conserved_site

Pfam: PF00232

UniProt features (11 total): glycosylation site 3, sequence variant 2, topological domain 2, signal peptide 1, chain 1, transmembrane region 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6UWM7-F1	92.71	0.85

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 (3): 80, 171, 245

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 66 (showing top): RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, GOBP_SENSORY_PERCEPTION_OF_LIGHT_STIMULUS, TGCTGAY_UNKNOWN, GOBP_CARBOHYDRATE_METABOLIC_PROCESS, DODD_NASOPHARYNGEAL_CARCINOMA_UP, GOBP_SENSORY_PERCEPTION, GOBP_SENSORY_ORGAN_DEVELOPMENT, GOBP_SENSORY_ORGAN_MORPHOGENESIS, GOBP_LENS_MORPHOGENESIS_IN_CAMERA_TYPE_EYE, GOBP_CAMERA_TYPE_EYE_MORPHOGENESIS, NFE2_01, GOBP_LENS_DEVELOPMENT_IN_CAMERA_TYPE_EYE, GOBP_EYE_MORPHOGENESIS, GOCC_APICAL_PART_OF_CELL

GO Biological Process (3): lens morphogenesis in camera-type eye (GO:0002089), carbohydrate metabolic process (GO:0005975), visual perception (GO:0007601)

GO Molecular Function (1): hydrolase activity, hydrolyzing O-glycosyl compounds (GO:0004553)

GO Cellular Component (4): endoplasmic reticulum membrane (GO:0005789), brush border (GO:0005903), endoplasmic reticulum (GO:0005783), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
lens development in camera-type eye	1
anatomical structure morphogenesis	1
camera-type eye morphogenesis	1
primary metabolic process	1
sensory perception of light stimulus	1
hydrolase activity, acting on glycosyl bonds	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
microvillus	1
apical part of cell	1
cluster of actin-based cell projections	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

658 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LCTL	FGF23	Q9GZV9	827
LCTL	TRPV5	Q9NQA5	739
LCTL	GINM1	Q9NU53	572
LCTL	FGFR1	P11362	520
LCTL	SNAPC5	O75971	518
LCTL	SCYL1	Q96KG9	498
LCTL	SMIM12	Q96EX1	490
LCTL	MNMIP1	A4FU49	479
LCTL	ADAM10	O14672	476
LCTL	ADAM17	P78536	460
LCTL	SLC22A4	Q9H015	439
LCTL	SHISA4	Q96DD7	438
LCTL	PIP4K2C	Q8TBX8	437
LCTL	S100A5	P33763	431
LCTL	LGSN	Q5TDP6	427

IntAct

17 interactions, top by confidence:

A	B	Type	Score
EIF4ENIF1	MCRIP1	psi-mi:“MI:0915”(physical association)	0.400
EIF4ENIF1	PABPC1	psi-mi:“MI:0915”(physical association)	0.400
ITGA8	SUSD5	psi-mi:“MI:0914”(association)	0.350
LCTL	SUSD5	psi-mi:“MI:0914”(association)	0.350
AKT1	LCTL	psi-mi:“MI:2364”(proximity)	0.270
FBXW7	LCTL	psi-mi:“MI:2364”(proximity)	0.270
SMAD4	LCTL	psi-mi:“MI:2364”(proximity)	0.270
SPOP	LCTL	psi-mi:“MI:2364”(proximity)	0.270
LCTL	SPOP	psi-mi:“MI:2364”(proximity)	0.270
LCTL	BRAF	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (25): LCTL (Affinity Capture-MS), LCTL (Affinity Capture-MS), SLC25A46 (Affinity Capture-MS), LGALS1 (Affinity Capture-MS), SFXN5 (Affinity Capture-MS), USP22 (Affinity Capture-MS), GHITM (Affinity Capture-MS), SUSD5 (Affinity Capture-MS), CYP2S1 (Affinity Capture-MS), LEMD3 (Affinity Capture-MS), FAM69A (Affinity Capture-MS), NETO2 (Affinity Capture-MS), ZDHHC17 (Affinity Capture-MS), NUS1 (Affinity Capture-MS), DHRS7 (Affinity Capture-MS)

ESM2 similar proteins: B2GUY2, O18835, O35082, P04062, P17405, P17439, P18424, P22413, P57110, P58242, P82450, Q04519, Q0VD19, Q13219, Q2KHZ8, Q3MI05, Q566E5, Q5R8E3, Q5RFU0, Q5VSG8, Q6P1J0, Q6UWM7, Q6YGZ1, Q70KH2, Q71RP1, Q86Z14, Q8BYL4, Q8K1F9, Q8K3F2, Q8N119, Q8R2R1, Q8R4K8, Q8WP17, Q90YK5, Q92485, Q96JK4, Q99N32, Q9BDT0, Q9DGD1, Q9HAT2

Diamond homologs: A2SY66, A3BMZ5, A3C053, A3RF67, B3H5Q1, B6ZKM3, B6ZKM4, B6ZKM5, B6ZKN1, B7F7K7, B7F8N7, B8AVF0, B9FHH2, B9K7M5, D5MTF8, E3W9M3, O48779, O64879, O64882, O64883, O65458, O80689, O80690, P26204, P26205, P29736, P49235, Q03506, Q08638, Q0DA21, Q0DIT2, Q0J0G1, Q0J0G2, Q0J0N4, Q1XH04, Q1XH05, Q1XIR9, Q25BW4, Q25BW5, Q2QSR8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	105
Likely benign	10
Benign	3

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
590960	GRCh37/hg19 15q22.31-22.33(chr15:66825594-67400490)	Pathogenic

SpliceAI

1808 predictions. Top by Δscore:

Variant	Effect	Δscore
15:66548335:A:AG	acceptor_gain	1.0000
15:66561182:CTTA:C	donor_loss	1.0000
15:66561183:TTAC:T	donor_loss	1.0000
15:66561184:TA:T	donor_loss	1.0000
15:66561185:A:AC	donor_gain	1.0000
15:66561185:A:C	donor_loss	1.0000
15:66561185:AC:A	donor_gain	1.0000
15:66561186:C:CC	donor_gain	1.0000
15:66561186:CC:C	donor_gain	1.0000
15:66561311:AGCAG:A	acceptor_gain	1.0000
15:66561312:GCAG:G	acceptor_gain	1.0000
15:66561313:CAG:C	acceptor_gain	1.0000
15:66561313:CAGC:C	acceptor_gain	1.0000
15:66561314:AG:A	acceptor_gain	1.0000
15:66561316:C:CC	acceptor_gain	1.0000
15:66561323:C:CT	acceptor_gain	1.0000
15:66561325:C:CT	acceptor_gain	1.0000
15:66563510:CCTCA:C	donor_loss	1.0000
15:66563511:CTCA:C	donor_loss	1.0000
15:66563512:TCA:T	donor_loss	1.0000
15:66563513:CACCT:C	donor_loss	1.0000
15:66563621:CTCGG:C	acceptor_gain	1.0000
15:66563623:CGG:C	acceptor_gain	1.0000
15:66563624:GG:G	acceptor_gain	1.0000
15:66563624:GGC:G	acceptor_loss	1.0000
15:66563625:GC:G	acceptor_loss	1.0000
15:66563626:C:CC	acceptor_gain	1.0000
15:66563629:CAGG:C	acceptor_gain	1.0000
15:66563632:G:C	acceptor_gain	1.0000
15:66563632:G:GC	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000012831 (15:66552667 C>A,T), RS1000356251 (15:66553653 G>A,T), RS1000478294 (15:66547148 T>A), RS1000815299 (15:66548784 A>C,G), RS1000831007 (15:66565477 G>A), RS1000920123 (15:66555895 T>C), RS1000981258 (15:66564992 C>G), RS1001150206 (15:66550163 A>G), RS1001223218 (15:66566596 G>A), RS1001317896 (15:66562384 C>T), RS1001333090 (15:66567431 G>A), RS1001602093 (15:66562564 G>A,C), RS1001629308 (15:66555354 G>A), RS1001721300 (15:66561437 T>C), RS1001848196 (15:66550241 G>A)

Disease associations

OMIM: gene MIM:617060 | disease phenotypes: MIM:109730

GenCC curated gene-disease

Mondo (1): aortic valve disease 1 (MONDO:0024523)

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST006957_4	Severe aortic features in Marfan syndrome	8.000000e-06
GCST009391_1596	Metabolite levels	8.000000e-06
GCST010002_173	Refractive error	2.000000e-12

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010376	phosphatidylcholine 34:2 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, increases methylation	6
trichostatin A	affects cotreatment, decreases expression	3
entinostat	decreases expression, affects cotreatment	2
belinostat	decreases expression, affects cotreatment	2
Panobinostat	affects cotreatment, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
methylmercuric chloride	decreases expression	1
sodium arsenite	decreases expression	1
butyraldehyde	decreases expression	1
tebuconazole	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
dorsomorphin	decreases expression, affects cotreatment	1
jinfukang	increases expression	1
Amiodarone	increases expression	1
Arbutin	decreases expression	1
Tretinoin	decreases expression	1
Triclosan	increases expression	1

Clinical trials (associated diseases)

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