GALK1

galactokinase 1

Basic information

Region (hg38): 17:75751594-75765236

Previous symbols: [ "GALK" ]

Links

ENSG00000108479 ∙ NCBI:2584 ∙ OMIM:604313 ∙ HGNC:4118 ∙ Uniprot:P51570 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• galactokinase deficiency (Definitive), mode of inheritance: AR
• galactokinase deficiency (Definitive), mode of inheritance: AR
• galactokinase deficiency (Strong), mode of inheritance: AR
• galactokinase deficiency (Supportive), mode of inheritance: AR
• galactokinase deficiency (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Galactosemia II	AR	Biochemical	Individuals may manifest with early-onset cataracts, and dietary measures (galactose/lactose restricted diet) can be effective; The presence of pseudotumor cerebri has been described, and awareness may allow prompt recognition and management	Biochemical; Neurologic; Ophthalmologic	3043741; 5109408; 5034870; 74495; 490246; 7670469; 8908517; 10570908; 10521295; 10790206; 11139256; 11978884; 12705493; 15024738; 17517531; 20405025; 21290184; 22154682; 22632133

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GALK1 gene.

• Deficiency_of_galactokinase (493 variants)
• Inborn_genetic_diseases (55 variants)
• not_provided (19 variants)
• not_specified (15 variants)
• GALK1-related_disorder (11 variants)
• Junctional_epidermolysis_bullosa_with_pyloric_atresia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GALK1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000154.2. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous		1	6	209	4	220
missense	3	14	118	4	2	141
nonsense	9	20				29
start loss	2	2				4
frameshift	19	28				47
splice donor/acceptor (+/-2bp)	2	12				14
Total	35	77	124	213	6

Highest pathogenic variant AF is 0.000148719

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GALK1	protein_coding	protein_coding	ENST00000588479	8	14118

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000104	0.812	125692	0	18	125710	0.0000716

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.593	221	247	0.894	0.0000164	2428
Missense in Polyphen		63	81.443	0.77354		803
Synonymous	-0.00333	110	110	1.00	0.00000726	863
Loss of Function	1.30	10	15.5	0.644	6.66e-7	183

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000212	0.000209
Ashkenazi Jewish	0.0000994	0.0000992
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000635	0.0000616
Middle Eastern	0.00	0.00
South Asian	0.0000990	0.0000980
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Major enzyme for galactose metabolism.
• Disease: DISEASE: Galactosemia II (GALCT2) [MIM:230200]: Autosomal recessive deficiency characterized by congenital cataracts during infancy and presenile cataracts in the adult population. The cataracts are secondary to accumulation of galactitol in the lenses. {ECO:0000269|PubMed:10521295, ECO:0000269|PubMed:10790206, ECO:0000269|PubMed:11139256, ECO:0000269|PubMed:11231902, ECO:0000269|PubMed:12694189, ECO:0000269|PubMed:15024738}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Galactose metabolism - Homo sapiens (human);Amino sugar and nucleotide sugar metabolism - Homo sapiens (human);Galactosemia III;Galactosemia II (GALK);Galactose Metabolism;Nucleotide Sugars Metabolism;Galactosemia;Metabolism of carbohydrates;Metabolism;D-galactose degradation V (Leloir pathway);Galactose catabolism;Galactose metabolism (Consensus)

Intolerance Scores

• loftool: 0.254
• rvis_EVS: -0.84
• rvis_percentile_EVS: 11.18

Haploinsufficiency Scores

• pHI: 0.0808
• hipred: N
• hipred_score: 0.251
• ghis: 0.611

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.923

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Galk1
• Phenotype: vision/eye phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: galactose metabolic process;galactose catabolic process;galactitol metabolic process;galactose catabolic process via UDP-galactose;carbohydrate phosphorylation;glycolytic process from galactose
• Cellular component: cytoplasm;cytosol;membrane;extracellular exosome
• Molecular function: galactokinase activity;ATP binding;galactose binding