LCT

lactase, the group of Glycoside hydrolase family 1

Basic information

Region (hg38): 2:135787850-135837184

Links

ENSG00000115850 ∙ NCBI:3938 ∙ OMIM:603202 ∙ HGNC:6530 ∙ Uniprot:P09848 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• congenital lactase deficiency (Strong), mode of inheritance: AR
• congenital lactase deficiency (Moderate), mode of inheritance: AR
• congenital lactase deficiency (Strong), mode of inheritance: AR
• congenital lactase deficiency (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Lactase deficiency, congenital	AR	Gastrointestinal	Breast-feeding or lactose-containing formulas leads to severe osmotic diarrhea, which can be treated effectively with lactose-free diet	Gastrointestinal	5419986; 6847226; 9758622; 11788828; 16400612; 17345962; 19161632; 19432082; 22688420; 23445879
Upstream/noncoding variants may also result in adult-onset lactose intolerance

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the LCT gene.

• not provided (17 variants)
• Congenital lactase deficiency (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the LCT gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			10	223	7	240
missense		2	310	7	6	325
nonsense	7					7
start loss						0
frameshift	9	3	2			14
inframe indel			1			1
splice donor/acceptor (+/-2bp)		5				5
splice region			5	13		18
non coding	1		7	54	39	101
Total	17	10	330	284	52

Highest pathogenic variant AF is 0.0000263

Variants in LCT

This is a list of pathogenic ClinVar variants found in the LCT region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
2-135787878-AAC-A		Congenital lactase deficiency • Lactose intolerance	Likely benign (Jun 14, 2016)
2-135787895-T-G		Congenital lactase deficiency • Lactose intolerance	Likely benign (Jun 14, 2016)
2-135787999-C-G		Congenital lactase deficiency • Lactose intolerance	Conflicting classifications of pathogenicity (Jan 13, 2018)
2-135788049-T-C		Congenital lactase deficiency	Uncertain significance (Jan 12, 2018)
2-135788073-C-T		Lactose intolerance • Congenital lactase deficiency	Uncertain significance (Jun 14, 2016)
2-135788085-G-A		Congenital lactase deficiency	Uncertain significance (Jan 12, 2018)
2-135788089-G-A		Congenital lactase deficiency	Likely benign (Jan 13, 2018)
2-135788094-A-G		Lactose intolerance • Congenital lactase deficiency	Uncertain significance (Jan 12, 2018)
2-135788131-G-A		Congenital lactase deficiency	Uncertain significance (Jan 13, 2018)
2-135788274-C-G		Lactose intolerance • Congenital lactase deficiency	Benign (Nov 12, 2018)
2-135788314-T-G		Lactose intolerance • Congenital lactase deficiency	Uncertain significance (Jun 14, 2016)
2-135788337-A-G		Lactose intolerance • Congenital lactase deficiency	Uncertain significance (Jan 13, 2018)
2-135788339-C-T			Likely benign (Nov 08, 2023)
2-135788340-G-A		Inborn genetic diseases	Uncertain significance (Aug 09, 2021)
2-135788340-G-T		Lactose intolerance • Congenital lactase deficiency • LCT-related disorder	Benign/Likely benign (Jan 29, 2024)
2-135788342-G-C			Uncertain significance (Mar 16, 2022)
2-135788347-A-C			Uncertain significance (Dec 06, 2022)
2-135788360-T-G			Likely benign (Jun 04, 2023)
2-135788369-T-C			Benign (Mar 01, 2023)
2-135788380-T-G			Uncertain significance (Feb 27, 2022)
2-135788382-G-C			Uncertain significance (Nov 13, 2023)
2-135788384-G-T			Likely benign (Dec 23, 2022)
2-135788385-C-T		Congenital lactase deficiency	Uncertain significance (Sep 24, 2018)
2-135788386-G-A		Congenital lactase deficiency	Conflicting classifications of pathogenicity (Sep 20, 2024)
2-135788386-G-T			Uncertain significance (Jul 21, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
LCT	protein_coding	protein_coding	ENST00000264162	17	49341

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0598	0.940	125462	1	285	125748	0.00114

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.16	771	1.06e+3	0.727	0.0000644	12719
Missense in Polyphen		160	376.37	0.42511		4669
Synonymous	0.313	437	445	0.981	0.0000307	3800
Loss of Function	6.19	19	78.0	0.244	0.00000415	851

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000579	0.000579
Ashkenazi Jewish	0.000198	0.000198
East Asian	0.000163	0.000163
Finnish	0.0104	0.0104
European (Non-Finnish)	0.000308	0.000308
Middle Eastern	0.000163	0.000163
South Asian	0.000196	0.000196
Other	0.000815	0.000815

dbNSFP

Source: dbNSFP

• Function: FUNCTION: LPH splits lactose in the small intestine.
• Disease: DISEASE: Congenital lactase deficiency (COLACD) [MIM:223000]: Autosomal recessive, rare and severe gastrointestinal disorder. It is characterized by watery diarrhea in infants fed with breast milk or other lactose-containing formulas. An almost total lack of LCT activity is found in jejunal biopsy material of patients with congenital lactase deficiency. Opposite to congenital lactase deficiency, also known as lactose intolerance, is the most common enzyme deficiency worldwide. It is caused by developmental down- regulation of lactase activity during childhood or early adulthood. The decline of lactase activity is a normal physiological phenomenon; however, the majority of Northern Europeans have the ability to maintain lactase activity and digest lactose throughout life (lactase persistence). The down-regulation of lactase activity operates at the transcriptional level and it is associated with a noncoding variation in the MCM6 gene, located in the upstream vicinity of LCT. {ECO:0000269|PubMed:16400612}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Carbohydrate digestion and absorption - Homo sapiens (human);Galactose metabolism - Homo sapiens (human);Galactose Metabolism;Galactosemia;Lactose Degradation;Lactose Intolerance;Digestion of dietary carbohydrate;Glycosphingolipid biosynthesis - ganglioseries;Glycosphingolipid metabolism;Galactose metabolism;Glycerophospholipid metabolism;Digestion;Digestion and absorption (Consensus)

Recessive Scores

• pRec: 0.666

Intolerance Scores

• loftool: 0.571
• rvis_EVS: -1.34
• rvis_percentile_EVS: 4.66

Haploinsufficiency Scores

• pHI: 0.106
• hipred: Y
• hipred_score: 0.685

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.837

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	High
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Lct

Gene ontology

• Biological process: carbohydrate metabolic process;polysaccharide digestion
• Cellular component: plasma membrane;integral component of plasma membrane;membrane;apical plasma membrane
• Molecular function: lactase activity;beta-glucosidase activity;glycosylceramidase activity