GALK1

galactokinase 1

Basic information

Region (hg38): 17:75751593-75765236

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 (375 variants)
• not provided (24 variants)
• Inborn genetic diseases (15 variants)
• not specified (10 variants)
• GALK1-related condition (1 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.

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			1	161	4	166
missense	2	4	66	1	2	75
nonsense	6	18				24
start loss	1	1				2
frameshift	11	18				29
inframe indel			2			2
splice donor/acceptor (+/-2bp)	3	5				8
splice region				15		15
non coding	1	4	4	36	7	52
Total	24	50	73	198	13

Highest pathogenic variant AF is 0.0000853

Variants in GALK1

This is a list of pathogenic ClinVar variants found in the GALK1 region.

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

Position	Type	Phenotype	Significance	ClinVar
17-75751900-A-G			Likely benign (Oct 19, 2018)
17-75752027-C-T			Benign (Jul 09, 2018)
17-75752165-C-T		Junctional epidermolysis bullosa with pyloric atresia • ITGB4-related disorder	Conflicting classifications of pathogenicity (Jan 18, 2024)
17-75752168-C-T			Likely benign (Dec 18, 2022)
17-75752187-C-T			Likely benign (Oct 27, 2023)
17-75752189-T-C		Junctional epidermolysis bullosa with pyloric atresia	Uncertain significance (Jan 13, 2018)
17-75752190-G-A			Conflicting classifications of pathogenicity (Jan 30, 2024)
17-75752199-G-C			Likely benign (Dec 01, 2023)
17-75752220-C-T			Likely benign (Sep 18, 2023)
17-75752221-C-T		Junctional epidermolysis bullosa with pyloric atresia	Pathogenic (Jan 08, 2019)
17-75752238-G-A		Junctional epidermolysis bullosa with pyloric atresia	Conflicting classifications of pathogenicity (Nov 11, 2023)
17-75752241-C-T		Junctional epidermolysis bullosa with pyloric atresia	Benign/Likely benign (Jan 31, 2024)
17-75752245-C-A			Likely benign (Jun 01, 2021)
17-75752245-C-T		Inborn genetic diseases	Uncertain significance (Dec 05, 2022)
17-75752262-C-T			Likely benign (Oct 22, 2023)
17-75752263-C-T		Inborn genetic diseases	Uncertain significance (May 17, 2023)
17-75752264-G-A		Junctional epidermolysis bullosa with pyloric atresia • Inborn genetic diseases	Uncertain significance (Oct 14, 2023)
17-75752265-C-A			Likely benign (Nov 29, 2023)
17-75752265-C-T		Junctional epidermolysis bullosa with pyloric atresia;Epidermolysis bullosa, junctional 5A, intermediate	Likely benign (Sep 08, 2023)
17-75752270-C-T			Uncertain significance (Jan 16, 2022)
17-75752271-G-A			Likely benign (Dec 14, 2023)
17-75752271-G-T			Likely benign (Apr 20, 2023)
17-75752280-G-A			Likely benign (Dec 19, 2023)
17-75752281-C-T		Inborn genetic diseases	Uncertain significance (Aug 04, 2023)
17-75752282-G-A		Inborn genetic diseases	Uncertain significance (Aug 21, 2023)

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