GANC

Summary

GANC (glucosidase alpha, neutral C, HGNC:4139) is a protein-coding gene on chromosome 15q15.1, encoding Neutral alpha-glucosidase C (Q8TET4). Has alpha-glucosidase activity.

Glycosyl hydrolase enzymes hydrolyse the glycosidic bond between two or more carbohydrates, or between a carbohydrate and a non-carbohydrate moiety. This gene encodes a member of glycosyl hydrolases family 31. This enzyme hydrolyses terminal, non-reducing 1,4-linked alpha-D-glucose residues and releases alpha-D-glucose. This is a key enzyme in glycogen metabolism and its gene localizes to a chromosomal region (15q15) that is associated with susceptibility to diabetes. Alternative splicing results in multiple transcript variants encoding different isoforms.

Source: NCBI Gene 2595 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 157 total
• Druggable target: yes
• MANE Select transcript: NM_198141

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4139
Approved symbol	GANC
Name	glucosidase alpha, neutral C
Location	15q15.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000214013
Ensembl biotype	protein_coding
OMIM	104180
Entrez	2595

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 6 protein_coding, 3 retained_intron, 2 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000318010, ENST00000440615, ENST00000561871, ENST00000562170, ENST00000562859, ENST00000566442, ENST00000566690, ENST00000567421, ENST00000567596, ENST00000567784, ENST00000568687, ENST00000568953, ENST00000570013

RefSeq mRNA: 9 — MANE Select: NM_198141 NM_001301409, NM_001301410, NM_001393928, NM_001393929, NM_001393930, NM_001393931, NM_001393932, NM_001393933, NM_198141

CCDS: CCDS10084, CCDS76737, CCDS76738

Canonical transcript exons

ENST00000318010 — 24 exons

Exon	Start	End
ENSE00000942543	42340690	42340754
ENSE00001107564	42343078	42343154
ENSE00001149091	42339669	42339912
ENSE00001149171	42329306	42329449
ENSE00001204813	42338389	42338490
ENSE00001204816	42330576	42330672
ENSE00001204856	42276348	42276410
ENSE00001427845	42352030	42353666
ENSE00003461514	42310693	42310846
ENSE00003462815	42326298	42326424
ENSE00003471892	42345758	42345832
ENSE00003497049	42321785	42322020
ENSE00003509354	42297611	42297656
ENSE00003510695	42292735	42292917
ENSE00003543736	42310283	42310463
ENSE00003546543	42349383	42349495
ENSE00003558370	42327363	42327442
ENSE00003562185	42278482	42278590
ENSE00003575521	42348103	42348216
ENSE00003575615	42308222	42308318
ENSE00003586961	42287691	42287818
ENSE00003617343	42306546	42306612
ENSE00003623224	42351329	42351432
ENSE00003925281	42273201	42274510

Expression profiles

Bgee: expression breadth ubiquitous, 197 present calls, max score 94.11.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 16.1528 / max 307.8650, expressed in 1807 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
146232	3.8479	1610
146238	2.9850	1066
146236	2.8503	1379
146234	2.4607	1227
146243	1.6884	692
146235	1.3090	758
146237	0.4185	213
146233	0.2961	109
146242	0.1195	30
146239	0.1011	28

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	94.11	gold quality
monocyte	CL:0000576	91.16	gold quality
leukocyte	CL:0000738	90.66	gold quality
right lung	UBERON:0002167	90.25	gold quality
bone marrow cell	CL:0002092	90.17	gold quality
calcaneal tendon	UBERON:0003701	89.95	gold quality
rectum	UBERON:0001052	89.86	gold quality
upper lobe of left lung	UBERON:0008952	89.82	gold quality
right coronary artery	UBERON:0001625	89.74	gold quality
descending thoracic aorta	UBERON:0002345	89.15	gold quality
hindlimb stylopod muscle	UBERON:0004252	89.00	gold quality
upper lobe of lung	UBERON:0008948	88.90	gold quality
smooth muscle tissue	UBERON:0001135	88.63	gold quality
thoracic aorta	UBERON:0001515	88.42	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.35	gold quality
muscle of leg	UBERON:0001383	88.33	gold quality
ascending aorta	UBERON:0001496	88.31	gold quality
minor salivary gland	UBERON:0001830	88.29	gold quality
gastrocnemius	UBERON:0001388	88.20	gold quality
popliteal artery	UBERON:0002250	88.17	gold quality
tibial artery	UBERON:0007610	88.16	gold quality
aorta	UBERON:0000947	88.12	gold quality
stromal cell of endometrium	CL:0002255	87.99	gold quality
left ovary	UBERON:0002119	87.52	gold quality
right uterine tube	UBERON:0001302	87.28	gold quality
gall bladder	UBERON:0002110	87.22	gold quality
body of uterus	UBERON:0009853	87.16	gold quality
left coronary artery	UBERON:0001626	87.13	gold quality
tibial nerve	UBERON:0001323	87.11	gold quality
esophagus mucosa	UBERON:0002469	87.04	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-7008	yes	35.57
E-ANND-3	yes	17.87

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

79 targeting GANC, 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-6748-5P	100.00	65.81	1057
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-383-3P	99.85	65.84	1359
HSA-MIR-6079	99.84	68.54	1170
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-4639-5P	99.81	67.37	1028
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-5002-5P	99.76	70.84	1763
HSA-MIR-3680-3P	99.75	72.51	3095
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-494-3P	99.70	71.45	2795
HSA-MIR-6762-3P	99.66	66.94	1188
HSA-MIR-4470	99.66	69.35	1767
HSA-MIR-1290	99.59	69.90	2079
HSA-MIR-3153	99.55	67.59	2337
HSA-MIR-510-3P	99.54	70.06	2965
HSA-MIR-671-5P	99.52	67.11	1277
HSA-MIR-216A-5P	99.50	68.02	1288
HSA-MIR-4441	99.49	66.56	3216

Literature-anchored findings (GeneRIF, showing 5)

• in silico and physical cloning of two alleles of human neutral alpha-glucosidase (designated GANC on the human gene map) (PMID:12370436)
• Reports the mapping of a 2-Mb interval on human chromosome 15q15 that contains 15 genes linked to congenital dyserythropoietic anemia type 1 (CDAI). (PMID:12434312)
• Analysis of Brazilian Pompe patients showed that sometimes the nature of the mutation (alpha-Glucosidases )matched the phenotype within this group. (PMID:19588081)
• our results indicated that neutral alpha glucosidase and fructose levels are contributed to discriminating obstructive and nonobstructive azoospermia in Chinese patients based on the histological types of testes. (PMID:26610429)
• Results showed that the level of NAG in normal men was significantly higher than that in subfertile and infertile men. Meanwhile, the level of NAG in subfertile men was significantly greater than that in infertile men (PMID:29282757)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	ganc	ENSDARG00000074556
mus_musculus	Ganc	ENSMUSG00000062646
rattus_norvegicus	Ganc	ENSRNOG00000024563
drosophila_melanogaster	GCS2alpha	FBGN0027588
drosophila_melanogaster	tobi	FBGN0261575
caenorhabditis_elegans		WBGENE00018682
caenorhabditis_elegans		WBGENE00019895

Paralogs (6): GANAB (ENSG00000089597), SI (ENSG00000090402), MYORG (ENSG00000164976), GAA (ENSG00000171298), MGAM (ENSG00000257335), MGAM2 (ENSG00000257743)

Protein

Protein identifiers

Neutral alpha-glucosidase C — Q8TET4 (reviewed: Q8TET4)

All UniProt accessions (7): A0A0G2JLA2, E7EWB6, H3BMM3, H3BMW3, H3BN99, H3BRQ6, Q8TET4

UniProt curated annotations — full annotation on UniProt →

Function. Has alpha-glucosidase activity.

Similarity. Belongs to the glycosyl hydrolase 31 family.

RefSeq proteins (9): NP_001288338, NP_001288339, NP_001380857, NP_001380858, NP_001380859, NP_001380860, NP_001380861, NP_001380862, NP_937784* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000322	Glyco_hydro_31_TIM	Domain
IPR011013	Gal_mutarotase_sf_dom	Homologous_superfamily
IPR013780	Glyco_hydro_b	Homologous_superfamily
IPR017853	GH_hydrolase_sf	Homologous_superfamily
IPR025887	Glyco_hydro_31_N_dom	Domain
IPR030458	Glyco_hydro_31_AS	Active_site
IPR048395	Glyco_hydro_31_C	Domain

Pfam: PF01055, PF13802, PF21365

UniProt features (12 total): sequence variant 7, active site 3, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TET4-F1	92.63	0.87

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 (3): 511 (nucleophile); 514; 587 (proton donor)

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 154 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_UP, GOBP_N_GLYCAN_PROCESSING, GOBP_PROTEIN_N_LINKED_GLYCOSYLATION, HNF1_Q6, BEIER_GLIOMA_STEM_CELL_DN, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, GOBP_CARBOHYDRATE_METABOLIC_PROCESS, KEGG_STARCH_AND_SUCROSE_METABOLISM, AACTTT_UNKNOWN, GOBP_GLYCOPROTEIN_METABOLIC_PROCESS, AR_Q2, GOMF_GLUCOSIDASE_ACTIVITY, GOMF_HYDROLASE_ACTIVITY_ACTING_ON_GLYCOSYL_BONDS, GOMF_HYDROLASE_ACTIVITY_HYDROLYZING_O_GLYCOSYL_COMPOUNDS

GO Biological Process (2): carbohydrate metabolic process (GO:0005975), N-glycan processing (GO:0006491)

GO Molecular Function (7): alpha-1,4-glucosidase activity (GO:0004558), carbohydrate binding (GO:0030246), catalytic activity (GO:0003824), hydrolase activity, hydrolyzing O-glycosyl compounds (GO:0004553), hydrolase activity (GO:0016787), hydrolase activity, acting on glycosyl bonds (GO:0016798), alpha-glucosidase activity (GO:0090599)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
primary metabolic process	1
protein N-linked glycosylation	1
glycoprotein biosynthetic process	1
alpha-glucosidase activity	1
binding	1
molecular_function	1
hydrolase activity, acting on glycosyl bonds	1
catalytic activity	1
hydrolase activity	1
glucosidase activity	1

Protein interactions and networks

STRING

380 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GANC	DUS3L	Q96G46	354
GANC	TMEM202	A6NGA9	323
GANC	GAS2	O43903	322
GANC	NEU2	Q9Y3R4	317
GANC	DENND5A	Q6IQ26	301
GANC	ALS2CL	Q60I27	297
GANC	TMEM107	Q6UX40	297
GANC	GAS1	P54826	295
GANC	LAPTM4A	Q15012	290
GANC	MAN1C1	Q9NR34	272
GANC	NEU3	Q9UQ49	253
GANC	PFDN6	O15212	249
GANC	LRRK1	Q38SD2	248
GANC	UGGT2	Q9NYU1	248
GANC	NOS1AP	O75052	246

IntAct

4 interactions, top by confidence:

A	B	Type	Score
SMC1A	PDS5B	psi-mi:“MI:0914”(association)	0.530
GANC	TTC1	psi-mi:“MI:0915”(physical association)	0.400
FGFR1OP2	STK24	psi-mi:“MI:0914”(association)	0.350

BioGRID (7): GANC (Affinity Capture-MS), GANC (Affinity Capture-MS), TTC1 (Affinity Capture-MS), GANC (Co-fractionation), TTN (Co-fractionation), GANC (Cross-Linking-MS (XL-MS)), GANC (Affinity Capture-RNA)

ESM2 similar proteins: A1CNK4, A1D1E6, A1D1Z9, A1DJ58, A2QAN3, A2QTU5, B0XAA1, B0XMP7, B0XNL6, B0XXE7, B8MZ41, B8N6V7, B8NWY6, B8QGZ3, B9F676, D4B0X3, F4J6T7, O04893, O04931, O43451, O62653, O74254, P14410, P22861, P29064, P38138, P56526, Q0CMA7, Q0CVH2, Q12558, Q2TW69, Q2UCU3, Q2UQV7, Q4WG05, Q4WRH9, Q4WS33, Q4ZHV7, Q5AWI5, Q5BFC4, Q8BVW0

Diamond homologs: B9F676, D0KQM8, F4J6T7, O04893, O04931, O43451, P07768, P0CD66, P10253, P14410, P23739, P38138, P70699, P79403, Q12558, Q14697, Q43763, Q4R4N7, Q5R7A9, Q653V7, Q6P7A9, Q8BHN3, Q8BVW0, Q8TET4, Q92442, Q94502, Q9BE70, Q9F234, Q9FN05, Q9MYM4, Q9US55, Q09901, Q9P999, D2PPM7, Q8RQV0, Q9C0Y4, A1CNK4, A1D1E6, B0XNL6, B8MZ41

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	112
Likely benign	6
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

4887 predictions. Top by Δscore:

Variant	Effect	Δscore
15:42273252:CA:C	donor_loss	1.0000
15:42273252:CACCG:C	donor_gain	1.0000
15:42273253:A:AC	donor_gain	1.0000
15:42273253:ACCGA:A	donor_gain	1.0000
15:42273254:C:CA	donor_gain	1.0000
15:42273254:CCG:C	donor_gain	1.0000
15:42273254:CCGA:C	donor_gain	1.0000
15:42273254:CCGAC:C	donor_gain	1.0000
15:42276346:A:AG	acceptor_gain	1.0000
15:42276347:G:GG	acceptor_gain	1.0000
15:42278481:GGC:G	acceptor_gain	1.0000
15:42278586:G:GG	donor_gain	1.0000
15:42283609:A:AG	acceptor_gain	1.0000
15:42283610:G:GG	acceptor_gain	1.0000
15:42283610:GCCT:G	acceptor_gain	1.0000
15:42283690:G:GT	donor_gain	1.0000
15:42283763:A:G	donor_gain	1.0000
15:42287685:TTCCA:T	acceptor_loss	1.0000
15:42287689:A:C	acceptor_loss	1.0000
15:42287814:GTAAG:G	donor_gain	1.0000
15:42287815:TAAG:T	donor_loss	1.0000
15:42287816:AAGG:A	donor_loss	1.0000
15:42287819:G:GG	donor_gain	1.0000
15:42306607:C:G	donor_gain	1.0000
15:42310281:A:AG	acceptor_gain	1.0000
15:42310281:AGT:A	acceptor_gain	1.0000
15:42310282:G:GA	acceptor_gain	1.0000
15:42310282:GT:G	acceptor_gain	1.0000
15:42310282:GTG:G	acceptor_gain	1.0000
15:42310691:A:AG	acceptor_gain	1.0000

AlphaMissense

6037 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:42338397:T:A	W584R	0.998
15:42338397:T:C	W584R	0.998
15:42329431:C:A	N542K	0.996
15:42329431:C:G	N542K	0.996
15:42329330:T:A	W509R	0.994
15:42329330:T:C	W509R	0.994
15:42329439:G:A	G545D	0.994
15:42329344:T:A	N513K	0.993
15:42329344:T:G	N513K	0.993
15:42338399:G:C	W584C	0.993
15:42338399:G:T	W584C	0.993
15:42310759:T:A	W324R	0.992
15:42310759:T:C	W324R	0.992
15:42321913:T:A	W396R	0.992
15:42321913:T:C	W396R	0.992
15:42329438:G:C	G545R	0.992
15:42339683:T:C	F620L	0.992
15:42339685:C:A	F620L	0.992
15:42339685:C:G	F620L	0.992
15:42322016:G:C	R430P	0.990
15:42329426:C:G	H541D	0.990
15:42329341:G:A	M512I	0.989
15:42329341:G:C	M512I	0.989
15:42329341:G:T	M512I	0.989
15:42330626:A:C	R565S	0.989
15:42330626:A:T	R565S	0.989
15:42330651:T:C	F574L	0.989
15:42330653:T:A	F574L	0.989
15:42330653:T:G	F574L	0.989
15:42339752:C:A	R643S	0.989

dbSNP variants (sampled 300 via entrez): RS1000015979 (15:42334103 A>G), RS1000060913 (15:42329251 C>T), RS1000140542 (15:42352596 T>C), RS1000149584 (15:42332570 A>G), RS1000191228 (15:42286939 T>C), RS1000243138 (15:42276691 A>G), RS1000252575 (15:42282456 C>T), RS1000287071 (15:42315799 G>C), RS1000313854 (15:42338673 T>C), RS1000373151 (15:42343958 A>T), RS1000420949 (15:42317234 T>C), RS1000451750 (15:42330277 C>T), RS1000452132 (15:42316887 C>A), RS1000462454 (15:42350075 G>A), RS1000504902 (15:42327140 T>A,C)

Disease associations

OMIM: gene MIM:104180 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST010083_355	Hemoglobin levels	8.000000e-09
GCST90002379_66	Basophil count	2.000000e-12
GCST90002380_29	Basophil percentage of white cells	1.000000e-13

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004509	hemoglobin measurement
EFO:0005090	basophil count
EFO:0007992	basophil percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2520 (SINGLE PROTEIN)

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

ChEMBL bioactivities

1 potent at pChembl≥5 of 2 total, top 1 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.66	IC50	22	nM	CHEMBL320116

PubChem BioAssay actives

1 with measured affinity, of 4 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(3R,5S)-2,6-bis(hydroxymethyl)piperidine-3,4,5-triol	37119: Inhibitory activity against alpha-galactosidase from coffee bean.	ic50	0.0220	uM

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
triphenyl phosphate	affects expression	1
butyraldehyde	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
2-palmitoylglycerol	increases expression	1
abrine	decreases expression	1
Sunitinib	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Cisplatin	increases expression	1
Coal	decreases expression, increases abundance	1
Doxorubicin	decreases expression	1
Methyl Methanesulfonate	increases expression	1
Rotenone	increases expression	1
Smoke	decreases expression, increases abundance	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	affects expression	1
Cyclosporine	increases methylation	1
Okadaic Acid	decreases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL647155	Binding	Inhibitory activity against alpha-galactosidase from coffee bean.	Revised structure of a homonojirimycin isomer from Aglaonema treubii: first example of a naturally occurring alpha-homoallonojirimycin. — Bioorg Med Chem Lett

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1SP	Abcam HeLa GANC KO	Cancer cell line	Female
CVCL_SP56	HAP1 GANC (-) 1	Cancer cell line	Male
CVCL_SP57	HAP1 GANC (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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