ALDOC

Summary

ALDOC (aldolase, fructose-bisphosphate C, HGNC:418) is a protein-coding gene on chromosome 17q11.2, encoding Fructose-bisphosphate aldolase C (P09972). Catalyzes the reversible conversion of beta-D-fructose 1,6-bisphosphate (FBP) into two triose phosphate and plays a key role in glycolysis and gluconeogenesis.

This gene encodes a member of the class I fructose-biphosphate aldolase gene family. Expressed specifically in the hippocampus and Purkinje cells of the brain, the encoded protein is a glycolytic enzyme that catalyzes the reversible aldol cleavage of fructose-1,6-biphosphate and fructose 1-phosphate to dihydroxyacetone phosphate and either glyceraldehyde-3-phosphate or glyceraldehyde, respectively.

Source: NCBI Gene 230 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 55 total
• GTEx eGene: eQTL in 17 tissues, sQTL in 22 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.79 (unconstrained)
• MANE Select transcript: NM_005165
• Notable: 55 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:418
Approved symbol	ALDOC
Name	aldolase, fructose-bisphosphate C
Location	17q11.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000109107
Ensembl biotype	protein_coding
OMIM	103870
Entrez	230

Gene structure

Transcript identifiers

Ensembl transcripts: 29 — 26 protein_coding, 2 nonsense_mediated_decay, 1 retained_intron

MANE Select: ENST00000226253

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 2, TSL 3: 3, TSL 4: 1, TSL 5: 2

ENST00000226253, ENST00000395319, ENST00000395321, ENST00000435638, ENST00000460201, ENST00000578590, ENST00000581807, ENST00000582381, ENST00000584086, ENST00000854233, ENST00000854234, ENST00000854235, ENST00000854236, ENST00000918177, ENST00000918178, ENST00000918179, ENST00000949877, ENST00000949878, ENST00000949879, ENST00000976182, ENST00000976184, ENST00000976185, ENST00001016591, ENST00001016593, ENST00001092848, ENST00001092849, ENST00001092850, ENST00001092851, ENST00001139432

RefSeq mRNA: 1 — MANE Select: NM_005165 NM_005165

CCDS: CCDS11236

Canonical transcript exons

ENST00000226253 — 9 exons

Exon	Start	End
ENSE00000706694	28573735	28573934
ENSE00001656772	28574494	28574577
ENSE00001726461	28574067	28574241
ENSE00002723853	28576801	28576895
ENSE00002872258	28574952	28575006
ENSE00003529546	28575123	28575334
ENSE00003615085	28575421	28575544
ENSE00003786450	28574696	28574856
ENSE00003843474	28573120	28573621

Expression profiles

Bgee: expression breadth ubiquitous, 274 present calls, max score 99.86.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 32.8721 / max 1197.3543, expressed in 1685 samples.

Highest expression (Bgee): hemisphere of cerebellum, pons, frontal lobe, cerebellar cortex, cerebellar hemisphere.

Genetic regulation across tissues (GTEx eQTL / sQTL)

ALDOC is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 17 tissues and its splicing (sQTL) in 22 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 39 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Skin Sun Exposed Lower leg	sqtl	1.5e-19	-0.83	17:28576093:TCTC:T
Skin Not Sun Exposed Suprapubic	sqtl	3.2e-15	-0.78	17:28576093:TCTC:T
Cells EBV-transformed lymphocytes	sqtl	3.8e-12	+0.92	17:28576093:TCTC:T
Nerve Tibial	sqtl	1.6e-10	-0.57	17:28745675:G:T
Cells EBV-transformed lymphocytes	eqtl	2.4e-07	+0.53	17:28720448:A:G
Artery Tibial	sqtl	1.5e-06	-0.63	17:28780841:C:G
Skin Sun Exposed Lower leg	eqtl	1.6e-06	-0.18	17:28626854:A:G
Heart Atrial Appendage	sqtl	4.9e-06	-0.82	17:28740052:G:A
Adipose Subcutaneous	sqtl	6.9e-06	-0.60	17:28582024:T:C
Esophagus Mucosa	sqtl	3.5e-05	-0.58	17:28838164:CTGAAGCAGGAGAACTGCT:C
Muscle Skeletal	eqtl	4.4e-05	+0.42	17:28573364:C:T
Brain Caudate basal ganglia	sqtl	6.8e-05	-0.81	17:28657618:G:A
Artery Tibial	eqtl	8.8e-05	-0.69	17:28576910:C:T
Brain Frontal Cortex BA9	sqtl	3.3e-04	-1.12	17:28576093:TCTC:T
Brain Cerebellum	sqtl	4.1e-04	-0.73	17:28780841:C:G
Esophagus Muscularis	eqtl	5.1e-04	-0.90	17:28576910:C:T
Esophagus Mucosa	eqtl	6.0e-04	+0.70	17:28687610:A:G
Breast Mammary Tissue	sqtl	8.0e-04	-0.58	17:28657618:G:A
Brain Cortex	sqtl	2.0e-03	-0.87	17:28576093:TCTC:T
Adipose Visceral Omentum	sqtl	2.1e-03	-0.51	17:28567402:TA:T

FANTOM5 promoters

3 alternative TSS:

Promoter ID	TPM avg	Samples expressed
165035	25.5725	1677
165034	7.2250	625
165033	0.0747	45

Top tissues by expression

showing 100 of 297 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	99.86	gold quality
pons	UBERON:0000988	99.84	gold quality
right frontal lobe	UBERON:0002810	99.81	gold quality
cerebellar cortex	UBERON:0002129	99.73	gold quality
cerebellar hemisphere	UBERON:0002245	99.73	gold quality
cerebellum	UBERON:0002037	99.70	gold quality
lateral nuclear group of thalamus	UBERON:0002736	99.68	gold quality
amygdala	UBERON:0001876	99.65	gold quality
nucleus accumbens	UBERON:0001882	99.63	gold quality
cingulate cortex	UBERON:0003027	99.62	gold quality
superior vestibular nucleus	UBERON:0007227	99.61	gold quality
anterior cingulate cortex	UBERON:0009835	99.61	gold quality
Brodmann (1909) area 9	UBERON:0013540	99.61	gold quality
lateral globus pallidus	UBERON:0002476	99.57	gold quality
prefrontal cortex	UBERON:0000451	99.56	gold quality
putamen	UBERON:0001874	99.56	gold quality
cerebellar vermis	UBERON:0004720	99.55	gold quality
hypothalamus	UBERON:0001898	99.52	gold quality
caudate nucleus	UBERON:0001873	99.51	gold quality
postcentral gyrus	UBERON:0002581	99.50	gold quality
ventral tegmental area	UBERON:0002691	99.49	gold quality
parietal lobe	UBERON:0001872	99.48	gold quality
inferior olivary complex	UBERON:0002127	99.47	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	99.43	gold quality
substantia nigra pars compacta	UBERON:0001965	99.42	gold quality
CA1 field of hippocampus	UBERON:0003881	99.41	gold quality
temporal lobe	UBERON:0001871	99.38	gold quality
Ammon’s horn	UBERON:0001954	99.38	gold quality
medulla oblongata	UBERON:0001896	99.37	gold quality
frontal cortex	UBERON:0001870	99.32	gold quality
midbrain	UBERON:0001891	99.30	gold quality
paraflocculus	UBERON:0005351	99.30	gold quality
substantia nigra	UBERON:0002038	99.27	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	99.26	gold quality
substantia nigra pars reticulata	UBERON:0001966	99.25	gold quality
spinal cord	UBERON:0002240	99.23	gold quality
globus pallidus	UBERON:0001875	99.22	gold quality
medial globus pallidus	UBERON:0002477	99.18	gold quality
dorsal plus ventral thalamus	UBERON:0001897	99.17	gold quality
superior frontal gyrus	UBERON:0002661	99.09	gold quality
dorsal root ganglion	UBERON:0000044	99.04	gold quality
entorhinal cortex	UBERON:0002728	99.04	gold quality
apex of heart	UBERON:0002098	99.00	gold quality
telencephalon	UBERON:0001893	98.98	gold quality
subthalamic nucleus	UBERON:0001906	98.96	gold quality
inferior vagus X ganglion	UBERON:0005363	98.95	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	98.94	gold quality
orbitofrontal cortex	UBERON:0004167	98.88	gold quality
neocortex	UBERON:0001950	98.85	gold quality
cerebral cortex	UBERON:0000956	98.71	gold quality
Brodmann (1909) area 46	UBERON:0006483	98.68	gold quality
cranial nerve II	UBERON:0000941	98.62	gold quality
middle frontal gyrus	UBERON:0002702	98.55	gold quality
right atrium auricular region	UBERON:0006631	98.39	gold quality
occipital lobe	UBERON:0002021	98.33	gold quality
central nervous system	UBERON:0001017	98.31	gold quality
brain	UBERON:0000955	98.28	gold quality
frontal pole	UBERON:0002795	98.26	gold quality
trigeminal ganglion	UBERON:0001675	98.24	gold quality
cardiac atrium	UBERON:0002081	98.23	gold quality
heart left ventricle	UBERON:0002084	98.22	gold quality
cardiac ventricle	UBERON:0002082	98.19	gold quality
forebrain	UBERON:0001890	98.13	gold quality
Brodmann (1909) area 10	UBERON:0013541	98.06	gold quality
primary visual cortex	UBERON:0002436	97.99	gold quality
left ventricle myocardium	UBERON:0006566	97.75	gold quality
middle temporal gyrus	UBERON:0002771	97.68	gold quality
adult organism	UBERON:0007023	97.66	gold quality
corpus callosum	UBERON:0002336	97.64	gold quality
heart right ventricle	UBERON:0002080	97.56	gold quality
heart	UBERON:0000948	96.94	gold quality
myocardium	UBERON:0002349	96.80	gold quality
cardiac muscle of right atrium	UBERON:0003379	96.47	gold quality
tibial nerve	UBERON:0001323	95.92	gold quality
olfactory bulb	UBERON:0002264	95.35	gold quality
skin of leg	UBERON:0001511	95.22	gold quality
right lobe of liver	UBERON:0001114	94.53	gold quality
Brodmann (1909) area 23	UBERON:0013554	94.17	gold quality
skin of abdomen	UBERON:0001416	93.79	gold quality
ileal mucosa	UBERON:0000331	93.01	gold quality
zone of skin	UBERON:0000014	92.64	gold quality
ventricular zone	UBERON:0003053	92.51	gold quality
descending thoracic aorta	UBERON:0002345	92.47	gold quality
right ovary	UBERON:0002118	92.05	gold quality
ascending aorta	UBERON:0001496	92.01	gold quality
thoracic aorta	UBERON:0001515	91.98	gold quality
subcutaneous adipose tissue	UBERON:0002190	91.49	gold quality
left ovary	UBERON:0002119	91.13	gold quality
adipose tissue	UBERON:0001013	90.93	gold quality
esophagus mucosa	UBERON:0002469	90.91	gold quality
aorta	UBERON:0000947	90.76	gold quality
lower esophagus mucosa	UBERON:0035834	90.68	gold quality
vagina	UBERON:0000996	90.57	gold quality
small intestine Peyer’s patch	UBERON:0003454	90.49	gold quality
ectocervix	UBERON:0012249	90.26	gold quality
connective tissue	UBERON:0002384	90.19	gold quality
vena cava	UBERON:0004087	90.14	gold quality
liver	UBERON:0002107	90.07	gold quality
popliteal artery	UBERON:0002250	89.94	gold quality
tibial artery	UBERON:0007610	89.93	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-ENAD-21	yes	124.34
E-MTAB-7316	yes	41.81
E-GEOD-84465	yes	24.75
E-CURD-46	yes	22.21
E-MTAB-6701	yes	9.68
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Group enriched

showing 60 of 76 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Spinal cord	tissue	1766.5
Pons	tissue	1635.2
Medulla oblongata	tissue	1594.4
Cerebellum	tissue	1593.0	medium
Thalamus	tissue	1590.4
Midbrain	tissue	1540.4
Superior colliculi	tissue	1383.6
Frontal cortex	tissue	1331.3
Cerebral cortex	tissue	1331.2	medium
Somatosensory cortex	tissue	1331.2
Substantia nigra	tissue	1323.5
Periaqueductal gray	tissue	1304.7
Postcentral gyrus	tissue	1249.8
Occipital cortex	tissue	1174.6
Motor cortex	tissue	1139.9
Hippocampal formation	tissue	1123.7
Caudate putamen	tissue	1119.6
Retina	tissue	1098.1
Hypothalamus	tissue	1068.2
Temporal cortex	tissue	1053.2
Prefrontal cortex	tissue	1039.4
Entorhinal cortex	tissue	1031.5
Retrosplenial and cingulate cortex	tissue	952.1
Amygdala	tissue	922.2
Locus coeruleus	tissue	915.4
Insular cortex	tissue	913.4
Retrosplenial cortex	tissue	904.4
Hippocampus	tissue	802.6	medium
Septum	tissue	785.2
Ventral forebrain	tissue	784.1
Putamen	tissue	694.5
Basal ganglia	tissue	686.7	medium
Nucleus accumbens	tissue	648.7
Corpus callosum	tissue	496.5
Olfactory bulb	tissue	386.7
Heart muscle	tissue	167.6	not detected
Adipose tissue	tissue	81.7	not detected
Liver	tissue	74.1	not detected
Choroid plexus	tissue	73.4
Vagina	tissue	47.5	not detected
Small intestine	tissue	41.4	low
Skin 1	tissue	34.0	not detected
Ovary	tissue	28.8	not detected
Tonsil	tissue	28.5	not detected
Pituitary gland	tissue	26.8
Breast	tissue	25.5	not detected
Adrenal gland	tissue	23.0	not detected
Bone marrow	tissue	22.3	not detected
Stomach 1	tissue	22.0	not detected
Lymph node	tissue	18.1	not detected
Spleen	tissue	18.1	not detected
Esophagus	tissue	18.0	not detected
Duodenum	tissue	17.6	not detected
Seminal vesicle	tissue	14.9	not detected
Prostate	tissue	14.5	not detected
Rectum	tissue	13.8	not detected
Colon	tissue	12.8	not detected
Appendix	tissue	11.9	not detected
Smooth muscle	tissue	11.5	not detected
Parathyroid gland	tissue	11.4	not detected

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Ventral spinal cord (1766.5), Nuclei of the trapezoid body (1734.6), Principal sensory trigeminal nucleus (1561.9), Nucleus raphe magnus (1554.6), Pontine nuclei (1438.5).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): EGR1, EGR2, FOXM1, NR4A1, SP1

miRNA regulators (miRDB)

Targeting ALDOC by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 41 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548G-5P	99.78	71.12	3085
HSA-MIR-548X-5P	99.78	71.12	3085
HSA-MIR-548F-5P	99.78	71.02	3093
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-12129	99.72	67.45	1311
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-7-5P	99.67	70.53	1809
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-19A-5P	99.36	66.93	1675
HSA-MIR-19B-1-5P	99.36	67.07	1669
HSA-MIR-19B-2-5P	99.36	67.07	1669
HSA-MIR-4999-5P	99.35	69.15	926
HSA-MIR-6505-3P	99.34	67.39	1071
HSA-MIR-3194-3P	98.83	66.22	1167
HSA-MIR-6840-3P	98.68	65.95	1923
HSA-MIR-6728-3P	98.63	67.63	1534
HSA-MIR-9500	98.62	66.54	1845
HSA-MIR-3944-5P	98.50	67.55	997
HSA-MIR-4726-3P	98.49	63.89	1385
HSA-MIR-1233-5P	98.19	66.71	1201
HSA-MIR-6778-5P	98.19	66.59	1239

Functional genomics

gnomAD constraint: pLI 0.000276, LOEUF 0.785, missense Z 2.34 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000226253 — one region, missense o/e 0.74.

Literature-anchored findings (GeneRIF, showing 17)

• Diverse ALDOC promoter regions are required to direct specific LacZ expression in the hippocampus and Purkinje cells if transgenic mice. (PMID:15589842)
• This protein has been found differentially expressed in the temporal lobe from patients with schizophrenia. (PMID:19034380)
• This protein has been found differentially expressed in the dorsolateral prefrontal cortex from patients with schizophrenia. (PMID:19110265)
• This protein has been found differentially expressed in the Wernicke’s Area from patients with schizophrenia. (PMID:19405953)
• Results identified fructose bisphospate aldolase C that showed elevated levels of protein carbonyls in inferior parietal lobule (IPL) from subjects with early stage-Alzheimer’s disease. (PMID:19686046)
• This protein has been found differentially expressed in the anterior cingulate cortex in men patients with schizophrenia. (PMID:20381070)
• residues 85-102 harbor the epitope-containing region recognized by MAb 9F (PMID:24525694)
• ALDOC, Aldolase A (ALDOA) and Aldolase B (ALDOB) activate Wnt signaling. (PMID:24993527)
• NME1 enhanced ALDOC transcription, evidenced by increased expression of ALDOC pre-mRNA and activity of an ALDOC promoter-luciferase module. This is the first study to indicate that NME1 induces transcription through its direct binding to the promoter region of a target gene. (PMID:30396920)
• MUC16 C-terminal binding with ALDOC disrupts the ability of ALDOC to sense glucose and promotes gallbladder carcinoma growth. (PMID:32502493)
• EPB41 suppresses the Wnt/beta-catenin signaling in non-small cell lung cancer by sponging ALDOC. (PMID:33242559)
• The melanoma brain metastatic microenvironment: aldolase C partakes in shaping the malignant phenotype of melanoma cells - a case of inter-tumor heterogeneity. (PMID:33274599)
• BCDIN3D RNA methyltransferase stimulates Aldolase C expression and glycolysis through let-7 microRNA in breast cancer cells. (PMID:33664453)
• Identification of 4-methylation driven genes based prognostic signature in thyroid cancer: an integrative analysis based on the methylmix algorithm. (PMID:34456184)
• Overexpression of aldolase, fructose-bisphosphate C and its association with spheroid formation in colorectal cancer. (PMID:35147255)
• ALDOC- and ENO2- driven glucose metabolism sustains 3D tumor spheroids growth regardless of nutrient environmental conditions: a multi-omics analysis. (PMID:36945054)
• ALDOC regulated the biological function and immune infiltration of gastric cancer cells. (PMID:36997056)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	aldoca	ENSDARG00000057661
mus_musculus	Aldoc	ENSMUSG00000017390
rattus_norvegicus	Aldoc	ENSRNOG00000011452
drosophila_melanogaster	Ald1	FBGN0000064
drosophila_melanogaster	Ald2	FBGN0039425
caenorhabditis_elegans		WBGENE00011474
caenorhabditis_elegans		WBGENE00017166

Paralogs (2): ALDOB (ENSG00000136872), ALDOA (ENSG00000149925)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:101863) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 9 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased circulating HDL cholesterol level	1
hyperactivity	1
increased circulating triglyceride level	1
abnormal kidney morphology	1
decreased circulating triglyceride level	1
abnormal auditory brainstem response	1
decreased circulating cholesterol level	1
increased pulmonary respiratory rate	1
decreased pulmonary ventilation	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Plasmodium falciparum	P14223	100.0%	Diamond
Plasmodium falciparum 3D7	Q7KQL9	100.0%	Diamond
Plasmodium falciparum K1	Q27744	99.7%	Diamond
Pongo abelii	Q5NVR5	99.7%	Diamond
Macaca fascicularis	Q9GKW3	99.7%	Diamond
Pan troglodytes	A5A6I5	99.5%	Diamond
Xylella fastidiosa Temecula1	Q87AI0	99.4%	Diamond
Xylella fastidiosa 9a5c	Q9PF52	99.4%	Diamond
Ovis aries	P52210	99.2%	Diamond
Bos taurus	Q3T0S5	99.2%	Diamond
Oryctolagus cuniculus	P00883	98.4%	Diamond
Lathyrus oleraceus	Q01516	96.9%	Diamond
Xanthomonas campestris pv. campestris str. ATCC 33913	Q8P5Z7	96.1%	Diamond
Oryza sativa Japonica Group	P17784	94.7%	Diamond
Arabidopsis thaliana	Q9LF98	93.6%	Diamond
Carassius auratus	P53448	92.8%	Diamond
Zea mays	P08440	92.7%	Diamond
Salmo salar	B5DGM7	91.9%	Diamond
Thunnus albacares	P86979	91.9%	Diamond
Cicer arietinum	O65735	91.7%	Diamond
Gallus gallus	P53449	90.5%	Diamond
Plasmodium berghei ANKA	P49577	88.9%	Diamond
Sparus aurata	P53447	86.1%	Diamond
Spinacia oleracea	P29356	81.9%	Diamond
Lethenteron camtschaticum	P53445	78.4%	Diamond
Lymnaea stagnalis	P91759	77.6%	Diamond
Chlamydomonas reinhardtii	Q42690	75.2%	Diamond
Schistosoma mansoni	P53442	74.1%	Diamond
Echinococcus multilocularis	Q9GP32	74.1%	Diamond
Toxoplasma gondii	Q8I8I2	71.2%	Diamond
Dictyostelium discoideum	Q86A67	65.1%	Diamond
Trypanosoma brucei brucei	P07752	54.7%	Diamond
Encephalitozoon cuniculi GB-M1	Q8SSM8	46.4%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
SPAG5	protein-coding	10615
RSKR	protein-coding	124923
SDF2	protein-coding	6388
SUPT6H	protein-coding	6830
BLTP2	protein-coding	9703
SPAG5-AS1	ncRNA	100506436
PIGS	protein-coding	94005
FOXN1	protein-coding	8456
SLC13A2	protein-coding	9058
UNC119	protein-coding	9094

Protein

Protein identifiers

Fructose-bisphosphate aldolase C — P09972 (reviewed: P09972)

Alternative names: Brain-type aldolase

All UniProt accessions (8): P09972, A0A024QZ64, A8MVZ9, C9J8F3, J3KSV6, J3QKK1, J3QKP5, K7EKH5

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the reversible conversion of beta-D-fructose 1,6-bisphosphate (FBP) into two triose phosphate and plays a key role in glycolysis and gluconeogenesis.

Subunit / interactions. Homotetramer. Interacts with ATP6V1E1. May interact with PLD2.

Pathway. Carbohydrate degradation; glycolysis; D-glyceraldehyde 3-phosphate and glycerone phosphate from D-glucose: step 4/4.

Miscellaneous. In vertebrates, three forms of this ubiquitous glycolytic enzyme are found, aldolase A in muscle, aldolase B in liver and aldolase C in brain.

Similarity. Belongs to the class I fructose-bisphosphate aldolase family.

RefSeq proteins (1): NP_005156* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000741	FBA_I	Family
IPR013785	Aldolase_TIM	Homologous_superfamily
IPR029768	Aldolase_I_AS	Conserved_site

Pfam: PF00274

Enzyme classification (BRENDA)

• EC 4.1.2.13 — fructose-bisphosphate aldolase (BRENDA: 162 organisms, 156 substrates, 386 inhibitors, 299 Km, 175 kcat entries)

Substrate kinetics (BRENDA)

12 substrates with measured Km, best-characterized 12. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
D-FRUCTOSE 1,6-BISPHOSPHATE	0.0002–20	190
FRUCTOSE 1-PHOSPHATE	0.007–27	42
D-FRUCTOSE 1-PHOSPHATE	0.0017–40	20
D-FRUCTOSE-1,6-BISPHOSPHATE	0.015–0.45	16
D-GLYCERALDEHYDE 3-PHOSPHATE	0.052–1.17	9
GLYCERONE PHOSPHATE	0.065–2	8
SEDOHEPTULOSE 1,7-BISPHOSPHATE	0.008–0.19	3
FRUCTOSE 1,6-BISPHOSPHATE	0.0036–0.009	2
SEDOHEPTULOSE 1,7-DIPHOSPHATE	0.006–10	2
SEDOHEPTULOSE 7-PHOSPHATE	0.0167–0.0195	2
D-XYLULOSE 1-PHOSPHATE	0.0016	1
DIHYDROXYACETONE PHOSPHATE	0.095	1

Catalyzed reactions (Rhea)

• beta-D-fructose 1,6-bisphosphate = D-glyceraldehyde 3-phosphate + dihydroxyacetone phosphate (RHEA:14729)

UniProt features (41 total): helix 14, strand 10, modified residue 6, turn 4, active site 2, binding site 2, chain 1, sequence conflict 1, site 1

Structure

Experimental structures (PDB)

1 structures by resolution:

PDB	Title	Method	Resolution (Å)
1XFB	Human Brain Fructose 1,6-(bis)phosphate Aldolase (C isozyme)	X-RAY DIFFRACTION	3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P09972-F1	96.43	0.94

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Lyases, Metabolic proteins, Predicted intracellular proteins, Plasma proteins, Cancer-related genes, Candidate cancer biomarkers, Candidate cardiovascular disease genes, Essential proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoli fibrillar center; nucleoplasm; cytosol; vesicles

Antibody reliability (HPA): IH enhanced · IF approved

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)

Position	Role
188	proton acceptor
230	schiff-base intermediate with dihydroxyacetone-p
364	necessary for preference for fructose 1,6-bisphosphate over fructose 1-phosphate

Ligand- & substrate-binding residues (2)

Position	Role
56	substrate
147	substrate

Post-translational modifications (6)

Type	Positions
N6-acetyllysine	111
Phosphoserine	132, 36, 39, 45
Phosphotyrosine	5

Function

Pathways and Gene Ontology

Reactome pathways

3 curated (TAS) of 8; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

8 pathways:

ID	Pathway	Evidence
R-HSA-70263	Gluconeogenesis	curated
R-HSA-70171	Glycolysis	curated
R-HSA-6798695	Neutrophil degranulation	curated
R-HSA-70326	Glucose metabolism	—
R-HSA-168256	Immune System	—
R-HSA-168249	Innate Immune System	—
R-HSA-1430728	Metabolism	—
R-HSA-71387	Metabolism of carbohydrates and carbohydrate derivatives	—

MSigDB gene sets: 314 (showing top): MORF_RAGE, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_NUCLEOSIDE_DIPHOSPHATE_METABOLIC_PROCESS, REACTOME_INNATE_IMMUNE_SYSTEM, GOCC_SECRETORY_GRANULE, SP3_Q3, BOYAULT_LIVER_CANCER_SUBCLASS_G2, MENSE_HYPOXIA_UP, GOBP_CARBOHYDRATE_DERIVATIVE_CATABOLIC_PROCESS, SHAFFER_IRF4_TARGETS_IN_ACTIVATED_B_LYMPHOCYTE, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, CERVERA_SDHB_TARGETS_1_DN, KEGG_GLYCOLYSIS_GLUCONEOGENESIS, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, COLIN_PILOCYTIC_ASTROCYTOMA_VS_GLIOBLASTOMA_UP

GO Biological Process (5): fructose metabolic process (GO:0006000), gluconeogenesis (GO:0006094), glycolytic process (GO:0006096), fructose 1,6-bisphosphate metabolic process (GO:0030388), epithelial cell differentiation (GO:0030855)

GO Molecular Function (4): fructose-bisphosphate aldolase activity (GO:0004332), cytoskeletal protein binding (GO:0008092), protein binding (GO:0005515), lyase activity (GO:0016829)

GO Cellular Component (7): extracellular region (GO:0005576), cytosol (GO:0005829), cytoskeleton (GO:0005856), secretory granule lumen (GO:0034774), extracellular exosome (GO:0070062), tertiary granule lumen (GO:1904724), ficolin-1-rich granule lumen (GO:1904813)

Reactome top-level categories

5 top-level categories:

Category	Pathways
Glucose metabolism	2
Innate Immune System	1
Immune System	1
Metabolism of carbohydrates and carbohydrate derivatives	1
Metabolism	1

GO top-level categories

33 GO namespaces:

Category	Terms
cellular anatomical structure	2
intracellular organelle lumen	2
hexose metabolic process	1
glucose metabolic process	1
hexose biosynthetic process	1
phosphoglycerate kinase activity	1
phosphoglycerate mutase activity	1
phosphopyruvate hydratase activity	1
pyruvate kinase activity	1
pyruvate metabolic process	1
generation of precursor metabolites and energy	1
aerobic respiration	1
carbohydrate catabolic process	1
pyridine nucleotide catabolic process	1
glyceraldehyde-3-phosphate dehydrogenase (phosphorylating, [NAD(P)+] ) activity	1
ADP catabolic process	1
ATP metabolic process	1
nicotinamide nucleotide metabolic process	1
organophosphate metabolic process	1
carbohydrate derivative metabolic process	1
cell differentiation	1
epithelium development	1
aldehyde-lyase activity	1
protein binding	1
binding	1
catalytic activity	1
cytoplasm	1
intracellular membraneless organelle	1
secretory granule	1
cytoplasmic vesicle lumen	1
extracellular vesicle	1
tertiary granule	1
ficolin-1-rich granule	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 5 of 16 annotations. The rest are phylogenetic / computational / electronic (IEA).

5 experimentally-supported GO terms:

GO term	NS	Evidence
epithelial cell differentiation	BP	expression pattern
fructose 1,6-bisphosphate metabolic process	BP	direct assay
extracellular exosome	CC	high-throughput assay
cytoskeletal protein binding	MF	direct assay
fructose-bisphosphate aldolase activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 1,702 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ALDOC	PGK1	P00558	672
ALDOC	TPI1	P00938	663
ALDOC	PFKL	P17858	654
ALDOC	PFKP	Q01813	641
ALDOC	ENO1	P06733	635
ALDOC	ENO2	P09104	614
ALDOC	PFKM	P08237	601
ALDOC	PGAM4	Q8N0Y7	595
ALDOC	ENO3	P13929	593
ALDOC	PKM	P14618	587
ALDOC	LDHA	P00338	584
ALDOC	PGAM1	P18669	580
ALDOC	SLC1A3	P43003	547
ALDOC	FBP1	P09467	522
ALDOC	PGK2	P07205	515

IntAct

Human interaction partners of ALDOC in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

10 partners by confidence:

Partner	Interaction type	MIscore	Records
ALDOA	association	0.790	10
LNX1	physical association	0.720	6
CFTR	physical association	0.640	1
ANKS1A	physical association	0.560	3
PKM	phosphorylation reaction	0.440	1
ERBB2	physical association	0.370	1
FMR1	physical association	0.370	1
MAP2K3	physical association	0.370	1
S100A9	physical association	0.370	1
SQLE	physical association	0.370	1

BioGRID (188 interactions; top human partners by supporting records): ALDOA (Two-hybrid; 28 records), BAG3 (Affinity Capture-MS; 2 records), LNX1 (Two-hybrid; 2 records), ACO2 (Co-fractionation), ACTN4 (Co-fractionation), ADI1 (Co-fractionation), ADIPOR2 (Affinity Capture-MS), AGR2 (Proximity Label-MS), AGRN (Affinity Capture-MS), ALDOB (Affinity Capture-MS), AMBRA1 (Affinity Capture-MS), ANKRD34C (Cross-Linking-MS (XL-MS)), ANKS1A (Two-hybrid), APP (Affinity Capture-MS), ARHGAP17 (Co-fractionation)

SIGNOR signaling

3 signaling interactions:

A	Effect	B	Mechanism
ALDOC	“up-regulates quantity”	“D-glyceraldehyde 3-phosphate(2-)”	“chemical modification”
ALDOC	“up-regulates quantity”	“glycerone phosphate(2-)”	“chemical modification”
ALDOC	“down-regulates quantity”	“beta-D-fructofuranose 1,6-bisphosphate(4-)”	“chemical modification”

Disease & clinical

Genetic variants

Variant evidence for ALDOC: 55 ClinVar records (0 pathogenic / likely pathogenic).

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	46
Likely benign	3
Benign	1

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 32 predictions of 586):

Position(s)	Effect	Δscore	Sites
17:28573739	donor_gain	1.0000
17:28573935–28573936	acceptor_loss	1.0000	4
17:28573938	acceptor_gain	1.0000
17:28574065–28574066	donor_loss	1.0000	3
17:28574242	acceptor_loss	1.0000
17:28574492–28574493	donor_loss	1.0000	5
17:28574611	acceptor_gain	1.0000
17:28574694–28574695	donor_loss	1.0000	5
17:28574950–28574951	donor_loss	1.0000	5
17:28575007–28575008	acceptor_loss	1.0000	6

AlphaMissense

1,274 missense substitutions predicted likely pathogenic (of 2,350 scored), across 287 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M233	9	0.964	0.992
D34	8	0.999	1.000
D110	8	0.998	0.999
F145	8	0.989	0.999
D129	8	0.988	0.996
F270	8	0.979	0.999
H197	8	0.959	0.989
F300	8	0.948	0.999
D194	8	0.945	0.988
H220	8	0.920	0.994
N167	8	0.900	0.997
F94	8	0.842	0.973
F64	8	0.840	0.976
H81	8	0.802	0.901
D219	8	0.763	0.918
W148	7	0.998	1.000
W296	7	0.996	1.000
E35	7	0.995	0.998
E188	7	0.994	0.999
K147	7	0.991	1.000

HPA cancer prognostics

RNA cancer specificity: Cancer enriched (Glioblastoma Multiforme)

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Glioblastoma Multiforme (validation)	favorable	0.000298
Head and Neck Squamous Cell Carcinoma (TCGA)	unfavorable	0.000842

Disease associations

OMIM: gene MIM:103870 | disease phenotypes:

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295709 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression, increases expression	5
sodium arsenite	decreases expression, increases expression	4
Oxygen	increases expression	4
Cisplatin	increases expression, increases reaction, decreases expression	3
Tretinoin	increases expression, decreases expression	3
Valproic Acid	affects expression, decreases expression, decreases methylation	3
Cyclosporine	decreases expression	3
Particulate Matter	decreases expression, increases abundance, increases expression, affects cotreatment	3
cobaltous chloride	increases expression, decreases reaction	2
nickel sulfate	increases expression	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	2
bisphenol S	increases expression, affects cotreatment	2
(+)-JQ1 compound	increases expression	2
Arsenic Trioxide	affects binding, decreases reaction, decreases expression	2
Air Pollutants	decreases expression, increases abundance, increases expression	2
Doxorubicin	affects expression, decreases expression	2
Niclosamide	decreases expression, increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tetrachlorodibenzodioxin	decreases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Tunicamycin	decreases expression, increases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
aristolochic acid I	increases expression	1
GSK-J4	increases expression	1
afuresertib	increases expression	1
bisphenol F	increases expression	1
sotorasib	affects cotreatment, decreases expression	1
2,4,6-tribromophenol	decreases expression	1
alpha phellandrene	increases expression	1
triphenyl phosphate	affects expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4119012	Binding	Binding affinity to ALDOC in human NCI-H358 cells at 1 uM by mass spectrometry based pull down assay	Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. — *Bioorg Med Chem*

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.