GALT

Summary

GALT (galactose-1-phosphate uridylyltransferase, HGNC:4135) is a protein-coding gene on chromosome 9p13.3, encoding Galactose-1-phosphate uridylyltransferase (P07902). Plays an important role in galactose metabolism.

Galactose-1-phosphate uridyl transferase (GALT) catalyzes the second step of the Leloir pathway of galactose metabolism, namely the conversion of UDP-glucose + galactose-1-phosphate to glucose-1-phosphate + UDP-galactose. The absence of this enzyme results in classic galactosemia in humans and can be fatal in the newborn period if lactose is not removed from the diet. The pathophysiology of galactosemia has not been clearly defined. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 2592 — RefSeq curated summary.

At a glance

• Gene–disease (curated): galactosemia (Definitive, GenCC) — +1 more curated relationship
• Clinical variants (ClinVar): 981 total — 99 pathogenic, 148 likely-pathogenic
• Phenotypes (HPO): 77
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• MANE Select transcript: NM_000155

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4135
Approved symbol	GALT
Name	galactose-1-phosphate uridylyltransferase
Location	9p13.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000213930
Ensembl biotype	protein_coding
OMIM	606999
Entrez	2592

Gene structure

Transcript identifiers

Ensembl transcripts: 55 — 28 protein_coding, 20 retained_intron, 5 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000378842, ENST00000450095, ENST00000465543, ENST00000468099, ENST00000472111, ENST00000473506, ENST00000473529, ENST00000485531, ENST00000487381, ENST00000488412, ENST00000489643, ENST00000554085, ENST00000554139, ENST00000554330, ENST00000554550, ENST00000554638, ENST00000554897, ENST00000554944, ENST00000555020, ENST00000555086, ENST00000555214, ENST00000555754, ENST00000556157, ENST00000556244, ENST00000556403, ENST00000556494, ENST00000557541, ENST00000557706, ENST00000605275, ENST00000902330, ENST00000902331, ENST00000902332, ENST00000902333, ENST00000902334, ENST00000902335, ENST00000902336, ENST00000902337, ENST00000902338, ENST00000902339, ENST00000902340, ENST00000902341, ENST00000902342, ENST00000902343, ENST00000902344, ENST00000902345, ENST00000902346, ENST00000902347, ENST00000902348, ENST00000936127, ENST00000964991, ENST00000964992, ENST00000964993, ENST00000964994, ENST00000964995, ENST00000964996

RefSeq mRNA: 2 — MANE Select: NM_000155 NM_000155, NM_001258332

CCDS: CCDS59122, CCDS6565

Canonical transcript exons

ENST00000378842 — 11 exons

Exon	Start	End
ENSE00001876755	34650369	34651035
ENSE00003463963	34647832	34647961
ENSE00003483141	34648762	34648894
ENSE00003511392	34647492	34647567
ENSE00003533221	34648998	34649081
ENSE00003582129	34648334	34648456
ENSE00003602746	34647657	34647705
ENSE00003621373	34647089	34647258
ENSE00003673144	34648115	34648171
ENSE00003686857	34649410	34649564
ENSE00003902808	34646675	34646786

Expression profiles

Bgee: expression breadth ubiquitous, 225 present calls, max score 97.62.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.3506 / max 179.2286, expressed in 1789 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
96525	10.3370	1761
96524	4.0204	1567
96527	0.4104	162
96523	0.2611	104
96526	0.2147	101
96521	0.1071	32

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	97.62	gold quality
right adrenal gland	UBERON:0001233	96.72	gold quality
apex of heart	UBERON:0002098	96.63	gold quality
right adrenal gland cortex	UBERON:0035827	96.60	gold quality
left adrenal gland cortex	UBERON:0035825	96.19	gold quality
left adrenal gland	UBERON:0001234	96.10	gold quality
right lobe of thyroid gland	UBERON:0001119	95.80	gold quality
granulocyte	CL:0000094	95.50	gold quality
right ovary	UBERON:0002118	95.43	gold quality
adenohypophysis	UBERON:0002196	95.41	gold quality
left lobe of thyroid gland	UBERON:0001120	95.29	gold quality
right hemisphere of cerebellum	UBERON:0014890	95.06	gold quality
small intestine Peyer’s patch	UBERON:0003454	95.05	gold quality
right atrium auricular region	UBERON:0006631	94.98	gold quality
metanephros cortex	UBERON:0010533	94.96	gold quality
left ovary	UBERON:0002119	94.95	gold quality
descending thoracic aorta	UBERON:0002345	94.88	gold quality
body of uterus	UBERON:0009853	94.75	gold quality
adrenal cortex	UBERON:0001235	94.63	gold quality
mucosa of transverse colon	UBERON:0004991	94.35	gold quality
right coronary artery	UBERON:0001625	94.25	gold quality
tibial nerve	UBERON:0001323	94.20	gold quality
cerebellar hemisphere	UBERON:0002245	94.17	gold quality
adrenal gland	UBERON:0002369	94.16	gold quality
right uterine tube	UBERON:0001302	94.10	gold quality
cerebellar cortex	UBERON:0002129	94.07	gold quality
muscle layer of sigmoid colon	UBERON:0035805	94.07	gold quality
left uterine tube	UBERON:0001303	94.03	gold quality
thoracic aorta	UBERON:0001515	93.94	gold quality
spleen	UBERON:0002106	93.94	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.58
E-MTAB-6142	no	147.23
E-CURD-11	no	103.81

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTCF, ETV4, FOXO3, MYC, NR1I2, PITX2

miRNA regulators (miRDB)

14 targeting GALT, 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-570-3P	99.96	72.41	4910
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-653-5P	99.46	67.35	1300
HSA-MIR-155-5P	99.35	70.16	1509
HSA-MIR-3922-5P	98.77	66.53	1059
HSA-MIR-4501	98.72	67.19	921
HSA-MIR-3689A-5P	98.35	70.12	1049
HSA-MIR-3689B-5P	98.35	70.12	1049
HSA-MIR-3689E	98.35	70.12	1049
HSA-MIR-3689F	98.35	70.08	1052
HSA-MIR-1267	98.24	69.05	837
HSA-MIR-4708-5P	97.77	67.82	831
HSA-MIR-1291	96.28	65.89	1224
HSA-MIR-6775-3P	95.76	65.91	982

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• no effect seen of N314D GALT genotype on risk of borderline or invasive ovarian cancer (PMID:11936817)
• Data found no association between congenital absence of the uterus and vagina (CAUV) and the N314D allele of the galactose-1-phosphate uridyl transferase (GALT) gene. (PMID:12606594)
• Increased expression of Galactosyltransferase is associated with ovarian cancer (PMID:12851678)
• association of decreased galactose-1-phosphate uridyltransferase activity with idiopathic presenile cataract (PMID:14707519)
• children and adolescents with galactosemia function generally within the low average IQ range and have less well-developed executive functions. (PMID:15506833)
• No statistically significant differences were observed in the allele frequencies between the infertile women and control groups for GALT (PMID:15749517)
• Nine novel mutations in the GALT gene associated with Classical galctosemia are described. (PMID:15841485)
• No association of GALT mutations is found in 86 patients with idiopathic premature ovarian failure. (PMID:16009197)
• We postulate that molecular link between defective GALT enzyme, which result in classic galactosemia and the cerebroside galactosyl transferase, responsible for galactosylation of cerebrosides, is dependent on concentrations of UDP-galactose. (PMID:16125333)
• no relationship was found between ovarian failure and GALT polymorphisms in Indian women (PMID:16274605)
• no significant differences between women carrying at least one N314D or Q188R GALT allele and controls in IVF outcomes measured: numbers of follicles and oocytes obtained; fertilization rates and percentage of Grade A embryos; and pregnancy rates. (PMID:16595241)
• analysis of classical galactosaemia mutations in GALT1 in Spain and Portugal (PMID:17041746)
• analysis of a patient with galactose-1-phosphate uridyltransferase mutations p.Q188R and p.R333W and galactose metabolite levels during breast-feeding [case report] (PMID:17143577)
• Identified novel mutations in GALT gene using DNA testing. (PMID:17876724)
• The R204X mutation severely compromises both expression and function of human GALT;T268N is one of a very small number of naturally occurring rare but neutral missense polymorphisms in human GALT. (PMID:18210213)
• Synergistic effect of GALT and lactase mutations on cataract formation. (PMID:18454942)
• Results suggest that classical galactosaemia shows low allelic heterogeneity in Mexican patients. (PMID:18956253)
• 4 bp 5’ deletion in GALT is a causal mutation in Duarte galactosemia. (PMID:19224951)
• Galactose-1-phosphate uridyl transferase deficiency is not associated with Mullerian aplasia in Dutch patients (PMID:19646668)
• The simulated point mutations have a direct effect on the active site, or on the dimer assembly and stability, or on the monomer stability. (PMID:20008339)
• live birth incidence of classical galactosemia in Estonia is 1:19.700 (PMID:20151200)
• Congenital eye abnormalities and galactosemia were found in a family with Q188R and G1391A mutations. (PMID:20222886)
• GALT deletion mutation carrier frequency was 1 in 127 (0.79%). (PMID:21059483)
• 3 different GALT mutations viz. Q188R, N314D and S307X were found to be present in the family of a neonate diagnosed with galactosemia and having the heterozygote genotype Q188R/S307X. S307X is a novel GALT mutation linked to galactosemia. (PMID:21188552)
• Duarte1 (D1) and D2 genotypes of GALT do not appear to play a role in the association between galactose intake, possible ovarian dysfunction, and the link with ovarian cancer (PMID:22749219)
• The study determined the frequency of the two most common GALT mutations and their variants in Indian galactosemia patients. (PMID:22798028)
• Forty four novel variations in the GALT gene were identified, among them 27 nucleotide substitutions, in the French cohort of galactosemic patients. (PMID:22944367)
• Mutations of the galactose-1-phosphate uridyltranseferase gene is associated with galactosemia. (PMID:22963887)
• The novel GALT gene mutations included 6 missense mutations viz. Y89H, Q103R, P166A, S181F, K285R, R333L; one nonsense mutation, S307X and 3 silent mutations–Q103Q, K210K and H319H. (PMID:23022339)
• HGALT requires a level of flexibility to function optimally and that altered folding is the underlying reason of impairment in all the variants tested here. (PMID:23583749)
• Data suggest that in classic galactosemia residual GALT activity (predicted from activity of recombinant GALT matching patient’s mutation) correlates with reduced ovarian reserve (as indicted by biological marker, circulating anti-Mullerian hormone). (PMID:23690308)
• In this report, we present GALT gene mutations in 56 cases of galactosemia from Turkey identified using DNA microarray resequencing. (PMID:23924834)
• suggests that GALT mutations are ethnic-specific and that galactosemia is a heterogeneous disorder at the molecular level (PMID:24045215)
• Mutation activates a cryptic donor splice site, inducing an aberrant splicing of the GALT pre-mRNA, which in turn leads to a frameshift with inclusion of a premature stop codon. (PMID:25052314)
• In Korean population, novel GALT mutations were identified in the galactosemia patients different from those of other populations. (PMID:25124065)
• GALT activity in red blood cells of patients with galactosaemia (PMID:25268296)
• Novel missense mutations identified in Italian galactosemic patients. (PMID:25592817)
• A novel noncoding homozygous GALT variant associated with asymptomatic galactosemia has been described in an infant of consanguineous heterozygous parents. (PMID:25920691)
• we present the 1.9 A resolution crystal structure of human GALT (hGALT) ternary complex, revealing a homodimer arrangement that contains a covalent uridylylated intermediate and glucose-1-phosphate in the active site, as well as a structural zinc-binding site, per monomer (PMID:27005423)
• 17 VUS (37%; 7 in ACADM, 9 in GALT, and 1 in PAH) were reclassified from uncertain (6 to benign or likely benign and 11 to pathogenic or likely pathogenic). We identified common types of missing information that would have helped make a definitive classification and categorized this information by ease and cost to obtain (PMID:27308838)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	galt	ENSDARG00000069543
mus_musculus	Galt	ENSMUSG00000036073
rattus_norvegicus	Galt	ENSRNOG00000014766
drosophila_melanogaster	Galt	FBGN0263200
caenorhabditis_elegans		WBGENE00014203

Protein

Protein identifiers

Galactose-1-phosphate uridylyltransferase — P07902 (reviewed: P07902)

Alternative names: UDP-glucose–hexose-1-phosphate uridylyltransferase

All UniProt accessions (6): A0A0S2Z3Y7, P07902, F2Z2X9, G3V223, G3V3U5, H0YJL3

UniProt curated annotations — full annotation on UniProt →

Function. Plays an important role in galactose metabolism.

Subunit / interactions. Homodimer.

Disease relevance. Galactosemia 1 (GALAC1) [MIM:230400] A form of galactosemia, an inborn error of galactose metabolism typically manifesting in the neonatal period, after ingestion of galactose, with jaundice, hepatosplenomegaly, hepatocellular insufficiency, food intolerance, hypoglycemia, renal tubular dysfunction, muscle hypotonia, sepsis and cataract. GALAC1 inheritance is autosomal recessive. The disease is caused by variants affecting the gene represented in this entry.

Cofactor. Binds 2 zinc ions per subunit.

Pathway. Carbohydrate metabolism; galactose metabolism.

Similarity. Belongs to the galactose-1-phosphate uridylyltransferase type 1 family.

Isoforms (2)

UniProt ID	Names	Canonical?
P07902-1	1	yes
P07902-2	2

RefSeq proteins (2): NP_000146, NP_001245261 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001937	GalP_UDPtransf1	Family
IPR005849	GalP_Utransf_N	Domain
IPR005850	GalP_Utransf_C	Domain
IPR019779	GalP_UDPtransf1_His-AS	Active_site
IPR036265	HIT-like_sf	Homologous_superfamily

Pfam: PF01087, PF02744

Enzyme classification (BRENDA):

• EC 2.7.7.12 — UDP-glucose-hexose-1-phosphate uridylyltransferase (BRENDA: 20 organisms, 77 substrates, 60 inhibitors, 92 Km, 29 kcat entries)

Substrate kinetics (BRENDA)

8 substrates with measured Km, best-characterized 8. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ALPHA-D-GALACTOSE 1-PHOSPHATE	0.011–6.66	29
UDP-GLUCOSE	0.015–0.41	20
ALPHA-D-GLUCOSE 1-PHOSPHATE	0.092–0.5	11
UDP-GALACTOSE	0.03–0.31	8
UDP-ALPHA-D-GLUCOSE	0.0608–0.73	6
UDP-ALPHA-D-GALACTOSE	0.051–0.324	5
IMIDAZOLE	—	0
URIDINE 5’-PHOSPHOIMIDAZOLATE	—	0

Catalyzed reactions (Rhea), 1 shown:

• alpha-D-galactose 1-phosphate + UDP-alpha-D-glucose = alpha-D-glucose 1-phosphate + UDP-alpha-D-galactose (RHEA:13989)

UniProt features (183 total): sequence variant 136, strand 15, binding site 12, helix 10, sequence conflict 2, turn 2, splice variant 2, chain 1, region of interest 1, compositionally biased region 1, active site 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
6GQD	X-RAY DIFFRACTION	1.52
5IN3	X-RAY DIFFRACTION	1.73

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P07902-F1	92.08	0.81

Functional residue map

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

Catalytic / active sites (1): 186 (tele-ump-histidine intermediate)

Ligand- & substrate-binding residues (12): 202; 301; 319; 321; 334–337 (in other chain); 339–340 (in other chain); 75; 81 (in other chain); 97–98 (in other chain); 173; 184; 188 (in other chain)

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-5609978	Defective GALT can cause GALCT
R-HSA-70370	Galactose catabolism

MSigDB gene sets: 262 (showing top): MODULE_172, GRUETZMANN_PANCREATIC_CANCER_DN, RORA1_01, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GOBP_CARBOHYDRATE_DERIVATIVE_CATABOLIC_PROCESS, GOBP_MONOSACCHARIDE_CATABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, UEDA_PERIFERAL_CLOCK, chr9p13, GOBP_GALACTOSE_METABOLIC_PROCESS, GOBP_CARBOHYDRATE_METABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_CATABOLIC_PROCESS, GOBP_SMALL_MOLECULE_CATABOLIC_PROCESS

GO Biological Process (7): UDP-alpha-D-glucose metabolic process (GO:0006011), galactose metabolic process (GO:0006012), beta-D-galactose catabolic process via UDP-galactose, Leloir pathway (GO:0033499), carbohydrate metabolic process (GO:0005975), phosphate-containing compound metabolic process (GO:0006796), organophosphate metabolic process (GO:0019637), carbohydrate derivative metabolic process (GO:1901135)

GO Molecular Function (6): UDP-glucose:hexose-1-phosphate uridylyltransferase activity (GO:0008108), zinc ion binding (GO:0008270), protein binding (GO:0005515), transferase activity (GO:0016740), nucleotidyltransferase activity (GO:0016779), metal ion binding (GO:0046872)

GO Cellular Component (3): cytoplasm (GO:0005737), Golgi apparatus (GO:0005794), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Diseases associated with glycosylation precursor biosynthesis	1
Metabolism of carbohydrates and carbohydrate derivatives	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
metabolic process	2
cellular anatomical structure	2
cytoplasm	2
nucleotide-sugar metabolic process	1
hexose metabolic process	1
galactose catabolic process	1
organophosphate metabolic process	1
carbohydrate derivative metabolic process	1
primary metabolic process	1
phosphorus metabolic process	1
uridylyltransferase activity	1
transition metal ion binding	1
binding	1
catalytic activity	1
transferase activity, transferring phosphorus-containing groups	1
cation binding	1
intracellular anatomical structure	1
endomembrane system	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

622 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GALT	GALK1	P51570	969
GALT	GALE	Q14376	868
GALT	IL11RA	Q14626	803
GALT	ADCY10	Q96PN6	768
GALT	GALM	Q96C23	761
GALT	UGP2	Q16851	607
GALT	GALK2	Q01415	554
GALT	IL11	P20809	547
GALT	CNTFR	P26992	541
GALT	HINT3	Q9NQE9	531
GALT	IL6R	P08887	497
GALT	XYLB	O75191	437
GALT	IL6ST	P40189	431
GALT	HINT1	P49773	429
GALT	CNTF	P26441	424

IntAct

41 interactions, top by confidence:

A	B	Type	Score
GALT	UBTD2	psi-mi:“MI:0915”(physical association)	0.770
UBTD2	GALT	psi-mi:“MI:0915”(physical association)	0.770
GALT	TRIP13	psi-mi:“MI:0915”(physical association)	0.670
ARPC3	ARPC2	psi-mi:“MI:0914”(association)	0.640
TNK2	GALT	psi-mi:“MI:0915”(physical association)	0.560
GALT	TNK2	psi-mi:“MI:0915”(physical association)	0.560
GALT	NQO1	psi-mi:“MI:0915”(physical association)	0.560
GALT	GRPEL1	psi-mi:“MI:0915”(physical association)	0.560
GALT	KRTAP6-2	psi-mi:“MI:0915”(physical association)	0.560
UBTD2	CST4	psi-mi:“MI:0914”(association)	0.530
NRBF2	GALT	psi-mi:“MI:0914”(association)	0.530
NFE2	GALT	psi-mi:“MI:0915”(physical association)	0.400
HLA-DQA1	HLA-A	psi-mi:“MI:0914”(association)	0.350
NOTCH2NLA	IGKC	psi-mi:“MI:0914”(association)	0.350
SERTAD1	IGKC	psi-mi:“MI:0914”(association)	0.350
TIMD4	SEMG1	psi-mi:“MI:0914”(association)	0.350
NIF3L1	GALT	psi-mi:“MI:0914”(association)	0.350
MYG1	GALT	psi-mi:“MI:0914”(association)	0.350

BioGRID (45): TNK2 (Two-hybrid), GALT (Affinity Capture-MS), GALT (Affinity Capture-MS), GALT (Affinity Capture-MS), GALT (Affinity Capture-MS), TRIP13 (Two-hybrid), TNK2 (Two-hybrid), GALT (Affinity Capture-MS), GALT (Affinity Capture-MS), GALT (Affinity Capture-MS), GALT (Affinity Capture-MS), TRIP13 (Two-hybrid), VAC14 (Two-hybrid), GALT (Two-hybrid), GALT (Two-hybrid)

ESM2 similar proteins: A0R635, A5VYQ1, B3W7I7, C7Q942, E8MF11, H2K887, O84904, P07902, P08431, P09148, P09580, P0CN76, P0CN77, P0DTW0, P13212, P22714, P28629, P31764, P39575, P42238, P43424, P52095, P56192, P61405, P76092, P9WH20, P9WH21, P9WMK8, P9WMK9, Q03249, Q03BB6, Q08CA1, Q27128, Q27536, Q2T9L8, Q5LYY8, Q5M3K1, Q5RBM6, Q7RYE7, Q8DKU5

Diamond homologs: O33836, P07902, P08431, P09148, P09580, P13212, P22714, P31764, P43424, Q03249, Q27536, Q9HDU5, P0CN76, P0CN77, Q7RYE7, Q96UI1, Q9VMA2

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
GALT	“down-regulates quantity”	“alpha-D-galactose 1-phosphate”	“chemical modification”
GALT	“up-regulates quantity”	“alpha-D-glucose 1-phosphate(2-)”	“chemical modification”
GALT	“down-regulates quantity”	UDP-alpha-D-glucose(2-)	“chemical modification”
GALT	“up-regulates quantity”	UDP-alpha-D-galactose(2-)	“chemical modification”
FOXO3	“up-regulates quantity by expression”	GALT	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	99
Likely pathogenic	148
Uncertain significance	244
Likely benign	276
Benign	19

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
101049	NC_000009.11:g.(34644527_34645701)_(34650746_34653247)del	Pathogenic
1067186	NM_000155.4(GALT):c.508-2_509del	Pathogenic
1299297	NC000009.12:g.(34646588_34655077)del	Pathogenic
1332994	NM_000155.4(GALT):c.467C>A (p.Ser156Ter)	Pathogenic
1332995	NM_000155.4(GALT):c.200del (p.Arg67fs)	Pathogenic
1332996	NM_000155.4(GALT):c.708_709del (p.Ser236fs)	Pathogenic
1355405	NM_000155.4(GALT):c.40_41insT (p.Ala14fs)	Pathogenic
1360292	NM_000155.4(GALT):c.684del (p.Lys229fs)	Pathogenic
1426580	NM_000155.4(GALT):c.530T>C (p.Met177Thr)	Pathogenic
1451313	NM_000155.4(GALT):c.327del (p.Gly110fs)	Pathogenic
1454503	NM_000155.4(GALT):c.384_388del (p.Met129fs)	Pathogenic
1457073	NM_000155.4(GALT):c.558C>G (p.His186Gln)	Pathogenic
1457165	NC_000009.11:g.(?34646573)(34650446_?)del	Pathogenic
1457166	NC_000009.11:g.(?34646579)(34655067_?)del	Pathogenic
1457366	NM_000155.4(GALT):c.462G>A (p.Trp154Ter)	Pathogenic
167128	NM_000155.4(GALT):c.445dup (p.Ala149fs)	Pathogenic
1684618	NM_000155.4(GALT):c.772del (p.Arg258fs)	Pathogenic
1685839	NM_000155.4(GALT):c.142C>A (p.Arg48Ser)	Pathogenic
1687586	NM_000155.4(GALT):c.328+2T>C	Pathogenic
2004328	NM_000155.4(GALT):c.649_653dup (p.Met219fs)	Pathogenic
2030188	NM_000155.4(GALT):c.82+2T>G	Pathogenic
2034664	NM_000155.4(GALT):c.949C>T (p.Gln317Ter)	Pathogenic
203734	NM_000155.4(GALT):c.367C>T (p.Arg123Ter)	Pathogenic
2070077	NM_000155.4(GALT):c.465_474dup (p.Glu159fs)	Pathogenic
2136753	NM_000155.4(GALT):c.113A>C (p.Gln38Pro)	Pathogenic
25113	NM_000155.4(GALT):c.18del (p.Asp7fs)	Pathogenic
25142	NM_000155.4(GALT):c.253-2A>G	Pathogenic
25154	NM_000155.4(GALT):c.329-2A>C	Pathogenic
25164	NM_000155.4(GALT):c.377+1G>T	Pathogenic
25165	NM_000155.4(GALT):c.377+53_1059+87del	Pathogenic

SpliceAI

2022 predictions. Top by Δscore:

Variant	Effect	Δscore
9:34637421:C:CA	acceptor_loss	1.0000
9:34637544:CACCA:C	donor_loss	1.0000
9:34637545:A:AC	donor_gain	1.0000
9:34637546:C:CC	donor_gain	1.0000
9:34637546:C:CT	donor_loss	1.0000
9:34637546:CCAG:C	donor_gain	1.0000
9:34637553:A:AC	donor_gain	1.0000
9:34637554:C:CC	donor_gain	1.0000
9:34646949:A:T	donor_gain	1.0000
9:34647254:GAGAG:G	donor_gain	1.0000
9:34647256:GAG:G	donor_gain	1.0000
9:34647256:GAGGT:G	donor_loss	1.0000
9:34647257:AGGT:A	donor_loss	1.0000
9:34647257:AGGTA:A	donor_loss	1.0000
9:34647259:G:A	donor_loss	1.0000
9:34647259:G:GG	donor_gain	1.0000
9:34647259:GTAA:G	donor_loss	1.0000
9:34647260:T:A	donor_loss	1.0000
9:34648328:T:A	acceptor_gain	1.0000
9:34648331:CAG:C	acceptor_loss	1.0000
9:34648331:CAGG:C	acceptor_loss	1.0000
9:34648332:AGG:A	acceptor_loss	1.0000
9:34648333:G:GC	acceptor_loss	1.0000
9:34648333:GGT:G	acceptor_gain	1.0000
9:34648391:GCCTA:G	donor_gain	1.0000
9:34648426:G:GT	donor_gain	1.0000
9:34648442:GAGC:G	donor_gain	1.0000
9:34648452:GGAAG:G	donor_gain	1.0000
9:34648453:G:GT	donor_gain	1.0000
9:34648453:GAAGG:G	donor_loss	1.0000

AlphaMissense

2466 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:34649506:A:T	K334I	0.999
9:34647163:T:A	W53R	0.998
9:34647163:T:C	W53R	0.998
9:34648126:C:A	N173K	0.998
9:34648126:C:G	N173K	0.998
9:34648337:T:A	W190R	0.998
9:34648337:T:C	W190R	0.998
9:34649524:A:T	E340V	0.998
9:34647165:G:C	W53C	0.997
9:34647165:G:T	W53C	0.997
9:34648118:T:C	F171L	0.997
9:34648120:T:A	F171L	0.997
9:34648120:T:G	F171L	0.997
9:34648168:C:G	C187W	0.997
9:34648810:T:A	W246R	0.997
9:34648810:T:C	W246R	0.997
9:34649508:T:C	F335L	0.997
9:34649510:C:A	F335L	0.997
9:34649510:C:G	F335L	0.997
9:34647705:G:A	C126Y	0.996
9:34647832:T:G	C126W	0.996
9:34647844:C:G	C130W	0.996
9:34649075:T:A	W300R	0.996
9:34649075:T:C	W300R	0.996
9:34649505:A:G	K334E	0.996
9:34649507:A:C	K334N	0.996
9:34649507:A:T	K334N	0.996
9:34649547:G:C	D348H	0.996
9:34647530:C:A	N97K	0.995
9:34647530:C:G	N97K	0.995

dbSNP variants (sampled 300 via entrez): RS1000378386 (9:34650888 C>T), RS1000409519 (9:34650551 A>G), RS1002350245 (9:34648037 T>C), RS1002683828 (9:34646179 C>G), RS1003878660 (9:34646145 T>C), RS1004517257 (9:34649607 C>A,G), RS1005201242 (9:34645688 T>C), RS1005440265 (9:34645279 GAAGTC>G), RS1006449714 (9:34648383 C>A), RS1006490473 (9:34646563 T>A,G), RS1006649234 (9:34644821 G>C), RS1007418263 (9:34646903 G>A,T), RS1007618 (9:34646920 G>A,C), RS1008644205 (9:34650855 C>A,G,T), RS1009454763 (9:34645122 T>C)

Disease associations

OMIM: gene MIM:606999 | disease phenotypes: MIM:230400

GenCC curated gene-disease

Disease	Classification	Inheritance
classic galactosemia	Definitive	Autosomal recessive
galactosemia	Definitive	Autosomal recessive

Mondo (3): classic galactosemia (MONDO:0009258), galactosemia (MONDO:0018116), primary ovarian failure (MONDO:0005387)

Orphanet (3): Galactosemia (Orphanet:352), Classic galactosemia (Orphanet:79239), NON RARE IN EUROPE: Primary ovarian failure (Orphanet:619)

HPO phenotypes

77 total (30 of 77 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000518	Cataract
HP:0000707	Abnormality of the nervous system
HP:0000716	Depression
HP:0000729	Autistic behavior
HP:0000739	Anxiety
HP:0000750	Delayed speech and language development
HP:0000786	Primary amenorrhea
HP:0000815	Hypergonadotropic hypogonadism
HP:0000823	Delayed puberty
HP:0000868	Decreased fertility in females
HP:0000869	Secondary amenorrhea
HP:0000876	Oligomenorrhea
HP:0000939	Osteoporosis
HP:0000952	Jaundice
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001254	Lethargy
HP:0001256	Mild intellectual disability
HP:0001260	Dysarthria
HP:0001263	Global developmental delay
HP:0001268	Mental deterioration
HP:0001288	Gait disturbance
HP:0001290	Generalized hypotonia
HP:0001298	Encephalopathy
HP:0001328	Specific learning disability
HP:0001332	Dystonia
HP:0001394	Cirrhosis

GWAS associations

0 associations (top):

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D005693	Galactosemias	C10.228.140.163.100.320; C16.320.565.189.320; C16.320.565.202.355; C18.452.132.100.320; C18.452.648.189.320; C18.452.648.202.355
D016649	Primary Ovarian Insufficiency	C12.050.351.500.056.630.750; C12.100.250.056.630.750; C19.391.630.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

39 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	decreases expression	2
GSK-J4	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
sodium arsenite	affects cotreatment, decreases expression, increases abundance	1
cobaltous chloride	decreases expression	1
perfluorooctanoic acid	increases expression	1
manganese chloride	decreases expression, increases abundance, affects cotreatment	1
vanadyl sulfate	decreases expression	1
tamibarotene	increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorobutanesulfonic acid	decreases expression	1
jinfukang	increases expression	1
Decitabine	affects expression	1
Acetaminophen	decreases expression	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Atrazine	increases expression	1
Benzo(a)pyrene	decreases expression	1
Cisplatin	affects expression	1
Diazinon	increases methylation	1
Diuron	decreases expression	1
Doxorubicin	decreases expression	1
Lead	decreases expression	1
Manganese	affects cotreatment, decreases expression, increases abundance	1
Fenofibrate	increases expression	1
Silicon Dioxide	decreases expression	1
Smoke	decreases expression	1
Tamoxifen	affects expression	1
Thiram	decreases expression	1

Cellosaurus cell lines

50 cell lines: 26 finite cell line, 21 transformed cell line, 2 cancer cell line, 1 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_1Y19	GM00422	Finite cell line	Female
CVCL_1Y20	GM00433	Finite cell line	Female
CVCL_1Y21	GM00528	Finite cell line	Female
CVCL_1Y22	GM00727	Finite cell line	Female
CVCL_1Y23	GM01209	Finite cell line	Male
CVCL_1Y24	GM01210	Finite cell line	Male
CVCL_1Y25	GM01417	Finite cell line	Female
CVCL_1Y26	GM01418	Finite cell line	Female
CVCL_1Y27	GM01419	Finite cell line	Male
CVCL_1Y28	GM01703	Finite cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00417066	PHASE4	COMPLETED	Flexible GnRH Antagonist vs Flare up GnRH Agonist Protocol in Poor Responders
NCT00732693	PHASE4	COMPLETED	Evaluation of Physiologic and Standard Sex Steroid Replacement Regimens in Women With Premature Ovarian Failure
NCT00837616	PHASE4	COMPLETED	Estrogen Dosing in Turner Syndrome: Pharmacology and Metabolism
NCT01853501	PHASE4	UNKNOWN	Effects of ADSC Therapy in Women With POF
NCT02783937	PHASE4	COMPLETED	Filgrastim for Premature Ovarian Insufficiency
NCT03535480	PHASE4	UNKNOWN	Autologous Bone Marrow Stem Cell Ovarian Transplantation to Restore Ovarian Function in Premature Ovarian Failure
NCT05418829	PHASE3	UNKNOWN	AT-007 in Adult Subjects With Classic Galactosemia (CG)
NCT00140998	PHASE3	COMPLETED	Estrogen Treatment (Oral vs. Patches) in Turner Syndrome
NCT03580122	PHASE2	COMPLETED	The Effect of Arginine on Classic Galactosemia
NCT00001951	PHASE2	COMPLETED	Hormone Replacement in Young Women With Premature Ovarian Failure
NCT00370019	PHASE2	WITHDRAWN	Effects of an Estrogen Replacement Therapy Skin Patch on Ovulation in Women With Premature Ovarian Failure
NCT00429494	PHASE2	COMPLETED	GnRH Analogue for Ovarian Function Preservation in Hematopoietic Stem Cell Transplantation Patients
NCT03816852	PHASE2	SUSPENDED	The Safety and Efficiency Study of Mesenchymal Stem Cell (19#iSCLife®-POI) in Premature Ovarian Insufficiency
NCT04536467	PHASE2	UNKNOWN	Prevention of Chemotherapy-Induced Ovarian Failure With Goserelin in Premenopausal Lymphoma Patients
NCT06117982	PHASE2	COMPLETED	The Impact of Granulocyte Colony Stimulating Factor on Premature Ovarian Insufficiency
NCT02912104	PHASE1	COMPLETED	A Therapeutic Trial of Human Amniotic Epithelial Cells Transplantation for Primary Ovarian Failure
NCT03178695	PHASE1	COMPLETED	Inovium Ovarian Rejuvenation Trials
NCT04815213	PHASE1	ACTIVE_NOT_RECRUITING	The Use of Expandeded Mesenchymal Stromal Cells (MSC) in Premature Ovarian Failure (POF) in Adult Humans
NCT05138367	PHASE1	COMPLETED	Effects of UCA-PSCs in Women With POF
NCT06132542	PHASE1	UNKNOWN	Autologous ADMSC Transplantation in Patients With POI
NCT04902781	PHASE2/PHASE3	COMPLETED	Clinical Benefit, Safety, PK and PD Study of AT-007 in Pediatric Subjects With Classic Galactosemia
NCT04117711	PHASE1/PHASE2	COMPLETED	Safety and Pharmacokinetics of AT-007 in Healthy Subjects and in Adult Subjects With Classic Galactosemia
NCT03838016	EARLY_PHASE1	COMPLETED	Preventing Speech and Language Disorders in Children With Classic Galactosemia
NCT00309400	Not specified	COMPLETED	The Early History of Universal Screening for Metabolic Disorders
NCT00619333	Not specified	UNKNOWN	Inactive FSH in Galactosemia
NCT02091128	Not specified	COMPLETED	Pregnancy Chances in Classic Galactosemia
NCT03655223	Not specified	ENROLLING_BY_INVITATION	Early Check: Expanded Screening in Newborns
NCT04948658	Not specified	RECRUITING	Gonadal Tissue Freezing for Fertility Preservation in Individuals at Risk for Ovarian Dysfunction, Premature Ovarian Insufficiency and Clinically Indicated Gonadectomy
NCT05687474	Not specified	COMPLETED	Baby Detect : Genomic Newborn Screening
NCT07461519	Not specified	RECRUITING	Gonadic Function and Pubertal Development in Female Patients With Classic Galactosemia
NCT00948857	PHASE2/PHASE3	TERMINATED	Dehydroepiandrosterone (DHEA) Treatment and Premature Ovarian Failure (POF)
NCT04031456	PHASE2/PHASE3	RECRUITING	Autologous PRP Infusion May Restore Ovarian Function and May Promote Folliculogenesis in POI Patients
NCT02043743	PHASE1/PHASE2	UNKNOWN	Autologous Stem Cells Transplantation in Patients With Idiopathic and Drug Induced Premature Ovarian Failure
NCT02062931	PHASE1/PHASE2	UNKNOWN	Autologous Mesenchymal Stem Cells Transplantation In Women With Premature Ovarian Failure
NCT02151890	PHASE1/PHASE2	COMPLETED	Pregnancy After Stem Cell Transplantation in Premature Ovarian Failure
NCT02372474	PHASE1/PHASE2	COMPLETED	It is a Real The First Baby Of Autologous Stem Cell Therapy in Premature Ovarian Failure
NCT02603744	PHASE1/PHASE2	UNKNOWN	Autologous Adipose Derived Mesenchymal Stromal Cells Transplantation in Women With Premature Ovarian Failure (POF)
NCT02644447	PHASE1/PHASE2	COMPLETED	Transplantation of HUC-MSCs With Injectable Collagen Scaffold for POF
NCT03069209	PHASE1/PHASE2	UNKNOWN	Autologous Bone Marrow-Derived Stem Cell Transplantation in Patients With Premature Ovarian Failure (POF)
NCT03985462	PHASE1/PHASE2	WITHDRAWN	Very Small Embryonic-like Stem Cells for Ovary