AMY1C

Summary

AMY1C (amylase alpha 1C, HGNC:476) is a protein-coding gene on chromosome 1p21.1, encoding Alpha-amylase 1C (P0DTE8). Calcium-binding enzyme that initiates starch digestion in the oral cavity.

Amylases are secreted proteins that hydrolyze 1,4-alpha-glucoside bonds in oligosaccharides and polysaccharides, and thus catalyze the first step in digestion of dietary starch and glycogen. The human genome has a cluster of several amylase genes that are expressed at high levels in either salivary gland or pancreas. This gene encodes an amylase isoenzyme produced by the salivary gland.

Source: NCBI Gene 278 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 9 total
• MANE Select transcript: NM_001008219

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:476
Approved symbol	AMY1C
Name	amylase alpha 1C
Location	1p21.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000187733
Ensembl biotype	protein_coding
OMIM	104702
Entrez	278

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 8 protein_coding

ENST00000370079, ENST00000622339, ENST00000683532, ENST00000684141, ENST00000908426, ENST00000908427, ENST00000908428, ENST00000969756

RefSeq mRNA: 6 — MANE Select: NM_001008219 NM_001008219, NM_001346780, NM_001422120, NM_001422123, NM_001422127, NM_001422129

CCDS: CCDS30784

Canonical transcript exons

ENST00000622339 — 11 exons

Exon	Start	End
ENSE00001671242	103758469	103758692
ENSE00001722772	103757024	103757149
ENSE00001727559	103754499	103754621
ENSE00001729478	103751933	103752130
ENSE00001760462	103756795	103756913
ENSE00001783842	103754715	103754814
ENSE00001784866	103753549	103753682
ENSE00001803691	103750983	103751129
ENSE00002220507	103752579	103752809
ENSE00003731007	103750424	103750637
ENSE00003749528	103749898	103750066

Expression profiles

Bgee: expression breadth broad, 53 present calls, max score 97.62.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	97.62	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	93.04	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	91.20	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.87	gold quality
right lobe of thyroid gland	UBERON:0001119	81.62	gold quality
fallopian tube	UBERON:0003889	79.46	gold quality
left lobe of thyroid gland	UBERON:0001120	76.15	gold quality
thyroid gland	UBERON:0002046	75.22	gold quality
body of pancreas	UBERON:0001150	73.60	gold quality
right lung	UBERON:0002167	71.71	gold quality
upper lobe of left lung	UBERON:0008952	71.04	gold quality
lung	UBERON:0002048	69.02	gold quality
left testis	UBERON:0004533	68.13	gold quality
saliva-secreting gland	UBERON:0001044	67.74	gold quality
testis	UBERON:0000473	67.19	gold quality
minor salivary gland	UBERON:0001830	64.77	gold quality
right testis	UBERON:0004534	61.84	gold quality
pancreas	UBERON:0001264	60.04	gold quality
left uterine tube	UBERON:0001303	58.07	gold quality
endocervix	UBERON:0000458	55.17	gold quality
tonsil	UBERON:0002372	54.94	gold quality
uterine cervix	UBERON:0000002	42.56	gold quality
placenta	UBERON:0001987	41.93	gold quality
bone marrow	UBERON:0002371	39.12	silver quality
apex of heart	UBERON:0002098	38.27	silver quality
endometrium	UBERON:0001295	38.15	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
bone marrow cell	CL:0002092	36.16	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-9841	yes	68.18
E-ANND-3	no	2.79

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 5)

• These findings confirm that sAA is sensitive to the effects of potentially stressful stimuli (state variance) and at the same time demonstrate its relative robustness and stability across time and conditions (trait variance). (PMID:21827821)
• results show a strong association between acute physical stressor-induced elevations in sAA levels and patients with MDD. (PMID:22063648)
• Diurnal and stress-response salivary alpha amylase patterns were related to child adiposity: decreased morning alpha amylase was associated with increased BMI. (PMID:25588701)
• At baseline, a modest association between AMY1 gene copy number and BMI (P = 0.04) was observed but AMY1 gene copy was not associated with baseline glycemic variables. (PMID:30982860)
• AMY1 Gene Copy Number Correlates With Glucose Absorption and Visceral Fat Volume, but Not with Insulin Resistance. (PMID:32697825)

Cross-species orthologs

12 orthologs

Organism	Symbol	Gene ID
drosophila_melanogaster	Amy-d	FBGN0000078
drosophila_melanogaster	Amy-p	FBGN0000079
drosophila_melanogaster	Mal-A2	FBGN0002569
drosophila_melanogaster	Mal-A3	FBGN0002571
drosophila_melanogaster	Amyrel	FBGN0020506
drosophila_melanogaster	Mal-B1	FBGN0032381
drosophila_melanogaster	Mal-B2	FBGN0032382
drosophila_melanogaster	Mal-A4	FBGN0033294
drosophila_melanogaster	Mal-A7	FBGN0033296
drosophila_melanogaster	Mal-A8	FBGN0033297
drosophila_melanogaster	Mal-A6	FBGN0050360
caenorhabditis_elegans		WBGENE00008220

Paralogs (7): GBE1 (ENSG00000114480), SLC3A1 (ENSG00000138079), SLC3A2 (ENSG00000168003), AMY1B (ENSG00000174876), AMY1A (ENSG00000237763), AMY2B (ENSG00000240038), AMY2A (ENSG00000243480)

Protein

Protein identifiers

Alpha-amylase 1C — P0DTE8 (reviewed: P0DTE8)

All UniProt accessions (2): A0A804HHZ3, P0DTE8

UniProt curated annotations — full annotation on UniProt →

Function. Calcium-binding enzyme that initiates starch digestion in the oral cavity. Catalyzes the hydrolysis of internal (1->4)-alpha-D-glucosidic bonds, yielding a mixture of maltose, isomaltose, small amounts of glucose as well as small linear and branched oligosaccharides called dextrins.

Subunit / interactions. Monomer.

Subcellular location. Secreted.

Cofactor. Binds 1 Ca(2+) ion per subunit. Binds 1 Cl(-) ion per subunit.

Similarity. Belongs to the glycosyl hydrolase 13 family.

RefSeq proteins (6): NP_001008220, NP_001333709, NP_001409049, NP_001409052, NP_001409056, NP_001409058 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006046	Alpha_amylase	Family
IPR006047	GH13_cat_dom	Domain
IPR006048	A-amylase/branching_C	Domain
IPR013780	Glyco_hydro_b	Homologous_superfamily
IPR017853	GH_hydrolase_sf	Homologous_superfamily
IPR031319	A-amylase_C	Domain

Pfam: PF00128, PF02806

UniProt features (23 total): binding site 7, disulfide bond 5, modified residue 4, glycosylation site 2, active site 2, signal peptide 1, chain 1, site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P0DTE8-F1	96.58	0.96

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): 315 (transition state stabilizer); 212 (nucleophile); 248 (proton donor)

Ligand- & substrate-binding residues (7): 352; 115; 173; 182; 210; 216; 313

Post-translational modifications (4): 16, 365, 427, 474

Disulfide bonds (5): 43–101, 85–130, 156–175, 393–399, 465–477

Glycosylation sites (2): 427, 476

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-189085	Digestion of dietary carbohydrate
R-HSA-8935690	Digestion
R-HSA-8963743	Digestion and absorption

MSigDB gene sets: 18 (showing top): GOBP_OLIGOSACCHARIDE_METABOLIC_PROCESS, REACTOME_DIGESTION_OF_DIETARY_CARBOHYDRATE, GOBP_CARBOHYDRATE_METABOLIC_PROCESS, KEGG_STARCH_AND_SUCROSE_METABOLISM, chr1p21, GOMF_HYDROLASE_ACTIVITY_ACTING_ON_GLYCOSYL_BONDS, GOMF_HYDROLASE_ACTIVITY_HYDROLYZING_O_GLYCOSYL_COMPOUNDS, GOMF_AMYLASE_ACTIVITY, GOMF_CHLORIDE_ION_BINDING, REACTOME_DIGESTION, REACTOME_DIGESTION_AND_ABSORPTION, NAKAYA_PLASMACYTOID_DENDRITIC_CELL_FLUMIST_AGE_18_50YO_7DY_UP, NAKAYA_PBMC_FLUMIST_AGE_18_50YO_7DY_UP, NAKAYA_PBMC_FLUARIX_FLUVIRIN_AGE_18_50YO_3DY_DN, NAKAYA_MYELOID_DENDRITIC_CELL_FLUARIX_FLUVIRIN_AGE_18_50YO_7DY_UP

GO Biological Process (2): carbohydrate metabolic process (GO:0005975), oligosaccharide metabolic process (GO:0009311)

GO Molecular Function (9): alpha-amylase activity (GO:0004556), calcium ion binding (GO:0005509), chloride ion binding (GO:0031404), catalytic activity (GO:0003824), amylase activity (GO:0016160), hydrolase activity (GO:0016787), hydrolase activity, acting on glycosyl bonds (GO:0016798), cation binding (GO:0043169), metal ion binding (GO:0046872)

GO Cellular Component (3): obsolete extracellular space (GO:0005615), extracellular exosome (GO:0070062), extracellular region (GO:0005576)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Digestion	1
Digestion and absorption	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
primary metabolic process	1
carbohydrate metabolic process	1
amylase activity	1
metal ion binding	1
anion binding	1
molecular_function	1
hydrolase activity, hydrolyzing O-glycosyl compounds	1
catalytic activity	1
hydrolase activity	1
ion binding	1
cation binding	1
extracellular vesicle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: H2N0D4, O18344, O18345, O18408, O18420, O18552, O76260, O76261, O76262, O76263, O76264, O76265, O76284, O76459, O77011, O77012, O77013, O77014, O77015, O77016, O77018, O77019, O77020, O77021, O77022, O97396, P00687, P00688, P00689, P00690, P04063, P04746, P04750, P08144, P09107, P0DTE7, P0DTE8, P0DUB6, P19961, P54215

Diamond homologs: A0A096XJN4, B0KZK1, H2N0D4, O18344, O18345, O18408, O18420, O18552, O76260, O76261, O76262, O76263, O76264, O76265, O76284, O76459, O77011, O77012, O77013, O77014, O77015, O77016, O77018, O77019, O77020, O77021, O77022, O97396, P00687, P00688, P00689, P00690, P04746, P08144, P08486, P09107, P09794, P0DTE7, P0DTE8, P0DUB6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	9
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1206 predictions. Top by Δscore:

Variant	Effect	Δscore
1:103751126:TGGGG:T	donor_loss	1.0000
1:103751127:GGG:G	donor_gain	1.0000
1:103751127:GGGGT:G	donor_loss	1.0000
1:103751128:GG:G	donor_gain	1.0000
1:103751128:GGG:G	donor_gain	1.0000
1:103751129:GG:G	donor_gain	1.0000
1:103751129:GGTA:G	donor_loss	1.0000
1:103751130:G:GG	donor_gain	1.0000
1:103751130:GTAA:G	donor_loss	1.0000
1:103751131:TAAG:T	donor_loss	1.0000
1:103751932:GGTTC:G	acceptor_gain	1.0000
1:103752770:C:G	donor_gain	1.0000
1:103752806:GGAG:G	donor_gain	1.0000
1:103752807:G:GT	donor_gain	1.0000
1:103753536:A:AG	acceptor_gain	1.0000
1:103753537:A:G	acceptor_gain	1.0000
1:103753544:TCTAG:T	acceptor_loss	1.0000
1:103753545:CTAGG:C	acceptor_loss	1.0000
1:103753546:TAG:T	acceptor_loss	1.0000
1:103753548:GGT:G	acceptor_gain	1.0000
1:103753548:GGTA:G	acceptor_gain	1.0000
1:103753662:A:T	donor_gain	1.0000
1:103753681:AA:A	donor_gain	1.0000
1:103753683:G:GG	donor_gain	1.0000
1:103754614:GATGC:G	donor_gain	1.0000
1:103754618:C:G	donor_gain	1.0000
1:103754713:A:AG	acceptor_gain	1.0000
1:103754714:G:GG	acceptor_gain	1.0000
1:103754714:GGCT:G	acceptor_gain	1.0000
1:103754810:GAAAA:G	donor_gain	1.0000

AlphaMissense

3415 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:103618086:T:A	C101S	0.999
1:103618087:G:C	C101S	0.999
1:103618940:T:A	N115K	0.999
1:103618940:T:G	N115K	0.999
1:103619685:G:C	K215N	0.999
1:103619685:G:T	K215N	0.999
1:103620617:T:C	F271L	0.999
1:103620619:C:A	F271L	0.999
1:103620619:C:G	F271L	0.999
1:103621637:C:A	N313K	0.999
1:103621637:C:G	N313K	0.999
1:103617540:T:A	W34R	0.998
1:103617540:T:C	W34R	0.998
1:103617542:G:C	W34C	0.998
1:103617542:G:T	W34C	0.998
1:103617567:T:A	C43S	0.998
1:103617568:G:A	C43Y	0.998
1:103617568:G:C	C43S	0.998
1:103617569:T:G	C43W	0.998
1:103618002:T:A	W73R	0.998
1:103618002:T:C	W73R	0.998
1:103618004:G:C	W73C	0.998
1:103618004:G:T	W73C	0.998
1:103618087:G:A	C101Y	0.998
1:103618087:G:T	C101F	0.998
1:103618088:T:G	C101W	0.998
1:103619563:T:A	C175S	0.998
1:103619564:G:C	C175S	0.998
1:103619565:T:G	C175W	0.998
1:103619663:G:A	G208E	0.998

dbSNP variants (sampled 300 via entrez): RS1002302238 (1:103755603 C>G,T), RS1008774139 (1:103749414 G>A,T), RS1010980411 (1:103754772 A>G), RS1015105309 (1:103756018 T>C), RS1022351148 (1:103755422 A>C,G), RS1028863617 (1:103749323 C>T), RS1030593966 (1:103749526 C>G), RS1030857893 (1:103754689 T>C), RS1034756666 (1:103755617 A>G), RS1037742710 (1:103754464 G>T), RS1052252499 (1:103755300 T>C), RS11266912 (1:103750694 T>C), RS112861460 (1:103755245 A>G), RS1156299918 (1:103750347 T>C), RS1156500728 (1:103755687 T>A)

Disease associations

OMIM: gene MIM:104702 | 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
GCST008295_18	Number of decayed, missing and filled tooth surfaces or use of dentures	2.000000e-10
GCST008306_1	Dentures	4.000000e-09
GCST009391_374	Metabolite levels	8.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0010078	dentures
EFO:0010436	triacylglycerol 56:9 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PubChem BioAssay actives

30 with measured affinity, of 327 total; 6 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
(2S)-N-[(2S)-1-amino-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]-5-(diaminomethylideneamino)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[(3S,10S,13S,16S)-10-(hydroxymethyl)-3,13-bis[(4-hydroxyphenyl)methyl]-2,5,9,12,15-pentaoxo-7-thia-1,4,8,11,14-pentazabicyclo[14.3.0]nonadecan-8-yl]-3-sulfanylpropanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-3-methylbutanoyl]amino]pentanamide	1802659: Inhibition Assay (piHA-Dm) from Article 10.1016/j.chembiol.2017.02.001: “Rapid Discovery of Potent and Selective Glycosidase-Inhibiting De Novo Peptides.”	ic50	0.0340	uM
(7R,8S,9S,10R)-7-[[(2S,3R,4R,5S,6R)-5-[(2R,3R,4S,5S,6R)-3,4-dihydroxy-6-methyl-5-[[(1S,4R,5S,6S)-4,5,6-trihydroxy-3-(hydroxymethyl)cyclohex-2-en-1-yl]amino]oxan-2-yl]oxy-3,4-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxymethyl]-8,9,10-trihydroxy-2-sulfanylidene-6-oxa-1,3-diazaspiro[4.5]decan-4-one	1248395: Non-competitive inhibition of human salivary alpha-amylase using GalG2CNP as substrate assessed as CNP liberation by Lineweaver-Burk plot analysis	ki	0.1900	uM
(3R,4R,5S,6R)-5-[(2R,3R,4R,5S,6R)-5-[(2R,3R,4S,5S,6R)-3,4-dihydroxy-6-methyl-5-[[(1S,4R,5S,6S)-4,5,6-trihydroxy-3-(hydroxymethyl)cyclohex-2-en-1-yl]amino]oxan-2-yl]oxy-3,4-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-6-(hydroxymethyl)oxane-2,3,4-triol	1248385: Inhibition of human salivary alpha-amylase using GalG2CNP as substrate by UV-Vis spectrophotometric analysis	ic50	0.5000	uM
5-[5-[[4-[5-[3,4-dihydroxy-6-methyl-5-[[4,5,6-trihydroxy-3-(hydroxymethyl)cyclohex-2-en-1-yl]amino]oxan-2-yl]oxy-3,4-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-5,6-dihydroxy-3-(hydroxymethyl)cyclohex-2-en-1-yl]amino]-3,4-dihydroxy-6-methyloxan-2-yl]oxy-6-(hydroxymethyl)oxane-2,3,4-triol	1248392: Inhibition of human salivary alpha-amylase using GalG2CNP as substrate	ki	0.7000	uM
[(2R,3R,4S,5R,6S)-3,4,5,6-tetrakis[(3,4,5-trihydroxybenzoyl)oxy]oxan-2-yl]methyl 3,4,5-trihydroxybenzoate	1248394: Inhibition of human salivary alpha-amylase using GalG2CNP as substrate assessed as CNP liberation by spectrophotometric analysis	ic50	2.3500	uM
5,6,7-trihydroxy-2-(4-hydroxyphenyl)chromen-4-one	1798320: In Vitro alpha-Amylase Activity Assay from Article 10.1021/jm800115x: “Flavonoids for controlling starch digestion: structural requirements for inhibiting human alpha-amylase.”	ic50	9.6400	uM

CTD chemical–gene interactions

9 total (human), top 9 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, decreases expression	1
beta-methylcholine	affects expression	1
chloropicrin	increases expression	1
bisphenol S	affects cotreatment, decreases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Indomethacin	affects cotreatment, decreases expression	1
Tunicamycin	decreases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, decreases expression	1
Thapsigargin	decreases expression	1

Clinical trials (associated diseases)

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