GFOD2

Summary

GFOD2 (Gfo/Idh/MocA-like oxidoreductase domain containing 2, HGNC:28159) is a protein-coding gene on chromosome 16q22.1, encoding Glucose-fructose oxidoreductase domain-containing protein 2 (Q3B7J2). Promotes matrix assembly.

Predicted to enable nucleotide binding activity and oxidoreductase activity. Predicted to be involved in extracellular matrix organization. Predicted to be located in extracellular region. Predicted to be active in extracellular matrix.

Source: NCBI Gene 81577 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 72 total
• MANE Select transcript: NM_030819

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28159
Approved symbol	GFOD2
Name	Gfo/Idh/MocA-like oxidoreductase domain containing 2
Location	16q22.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ23802, MGC11335
Ensembl gene	ENSG00000141098
Ensembl biotype	protein_coding
OMIM	619933
Entrez	81577

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 7 protein_coding, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000268797, ENST00000602279, ENST00000602377, ENST00000602496, ENST00000602522, ENST00000602627, ENST00000602855, ENST00000868800, ENST00000929448

RefSeq mRNA: 2 — MANE Select: NM_030819 NM_001243650, NM_030819

CCDS: CCDS10845, CCDS59268

Canonical transcript exons

ENST00000268797 — 3 exons

Exon	Start	End
ENSE00000946612	67674536	67676053
ENSE00001172742	67719163	67719316
ENSE00003713182	67685457	67685802

Expression profiles

Bgee: expression breadth ubiquitous, 233 present calls, max score 96.49.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.3849 / max 77.2167, expressed in 1776 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
157814	8.3849	1776

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	96.49	gold quality
cerebellar hemisphere	UBERON:0002245	94.35	gold quality
cerebellar cortex	UBERON:0002129	94.34	gold quality
cortical plate	UBERON:0005343	94.07	gold quality
right hemisphere of cerebellum	UBERON:0014890	93.99	gold quality
cerebellum	UBERON:0002037	93.29	gold quality
right lobe of liver	UBERON:0001114	91.75	gold quality
esophagus mucosa	UBERON:0002469	90.41	gold quality
ganglionic eminence	UBERON:0004023	90.15	gold quality
prefrontal cortex	UBERON:0000451	89.22	gold quality
buccal mucosa cell	CL:0002336	88.78	gold quality
right frontal lobe	UBERON:0002810	87.60	gold quality
cerebellar vermis	UBERON:0004720	87.07	silver quality
anterior cingulate cortex	UBERON:0009835	86.60	gold quality
mucosa of transverse colon	UBERON:0004991	86.59	gold quality
cingulate cortex	UBERON:0003027	86.52	gold quality
ectocervix	UBERON:0012249	86.17	gold quality
esophagus	UBERON:0001043	86.11	gold quality
Brodmann (1909) area 9	UBERON:0013540	86.03	gold quality
spleen	UBERON:0002106	85.84	gold quality
neocortex	UBERON:0001950	85.56	gold quality
vagina	UBERON:0000996	85.51	gold quality
frontal cortex	UBERON:0001870	85.51	gold quality
skin of leg	UBERON:0001511	85.13	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	85.02	gold quality
islet of Langerhans	UBERON:0000006	84.90	gold quality
liver	UBERON:0002107	84.78	gold quality
ventricular zone	UBERON:0003053	84.74	gold quality
adenohypophysis	UBERON:0002196	84.32	gold quality
skin of abdomen	UBERON:0001416	84.31	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.10

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

26 targeting GFOD2, 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-221-5P	99.86	65.45	1052
HSA-MIR-8073	99.86	65.21	1118
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-593-3P	99.22	67.28	1327
HSA-MIR-4784	99.15	67.41	1733
HSA-MIR-4717-3P	99.06	66.34	1072
HSA-MIR-873-5P	98.84	66.90	1348
HSA-MIR-4477A	98.83	69.75	2952
HSA-MIR-3150B-3P	98.81	67.21	1728
HSA-MIR-4680-3P	98.64	68.60	2093
HSA-MIR-6728-3P	98.63	67.63	1534
HSA-MIR-4290	98.51	65.17	907
HSA-MIR-6784-3P	98.39	64.88	662
HSA-MIR-1304-3P	98.29	66.44	1207
HSA-MIR-146B-3P	97.83	65.29	782
HSA-MIR-3620-3P	97.78	64.88	772
HSA-MIR-4689	96.97	65.79	1209
HSA-MIR-339-5P	96.73	66.01	820
HSA-MIR-500B-3P	96.49	65.40	1087
HSA-MIR-6858-5P	96.05	64.59	1020
HSA-MIR-3117-3P	95.96	67.82	473
HSA-MIR-4330	95.44	66.39	993

Literature-anchored findings (GeneRIF, showing 1)

• Variation in the GFOD2 gene contributes to the genetic basis for a differential response to a cholesterol- or lipid-lowering diet. (PMID:24064143)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	gfod2	ENSDARG00000061145
mus_musculus	Gfod2	ENSMUSG00000013150
rattus_norvegicus	Gfod2	ENSRNOG00000017953
drosophila_melanogaster	CG17712	FBGN0027597

Paralogs (3): DHDH (ENSG00000104808), BLVRA (ENSG00000106605), GFOD1 (ENSG00000145990)

Protein

Protein identifiers

Glucose-fructose oxidoreductase domain-containing protein 2 — Q3B7J2 (reviewed: Q3B7J2)

All UniProt accessions (4): A0A087WT49, A0A087WTD9, A0A087X156, Q3B7J2

UniProt curated annotations — full annotation on UniProt →

Function. Promotes matrix assembly.

Subcellular location. Secreted. Extracellular space. Extracellular matrix.

Similarity. Belongs to the Gfo/Idh/MocA family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q3B7J2-1	1	yes
Q3B7J2-2	2
Q3B7J2-3	3

RefSeq proteins (2): NP_001230579, NP_110446* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000683	Gfo/Idh/MocA-like_OxRdtase_N	Domain
IPR036291	NAD(P)-bd_dom_sf	Homologous_superfamily
IPR050463	Gfo/Idh/MocA_oxidrdct_glycsds	Family
IPR055170	GFO_IDH_MocA-like_dom	Domain

Pfam: PF01408, PF22725

UniProt features (7 total): splice variant 3, signal peptide 1, chain 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q3B7J2-F1	92.08	0.82

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 111 (showing top): chr16q22, TGCGCANK_UNKNOWN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, TERAMOTO_OPN_TARGETS_CLUSTER_1, WANG_ESOPHAGUS_CANCER_VS_NORMAL_DN, MODULE_205, CP2_01, DODD_NASOPHARYNGEAL_CARCINOMA_DN, WANG_METASTASIS_OF_BREAST_CANCER_ESR1_DN, LU_EZH2_TARGETS_UP, GOBERT_OLIGODENDROCYTE_DIFFERENTIATION_UP, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY, GOCC_EXTERNAL_ENCAPSULATING_STRUCTURE, EBNA1BP2_TARGET_GENES, HOXB6_TARGET_GENES

GO Biological Process (1): extracellular matrix organization (GO:0030198)

GO Molecular Function (2): nucleotide binding (GO:0000166), oxidoreductase activity (GO:0016491)

GO Cellular Component (2): extracellular matrix (GO:0031012), extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
extracellular structure organization	1
external encapsulating structure organization	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
catalytic activity	1
external encapsulating structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1417 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GFOD2	TBCCD1	Q9NVR7	568
GFOD2	ANO8	Q9HCE9	499
GFOD2	MEP1B	Q16820	494
GFOD2	SIGLEC5	O15389	454
GFOD2	WFDC2	Q14508	453
GFOD2	BCKDHB	P21953	450
GFOD2	POPDC1	Q8NE79	449
GFOD2	TLK2	Q86UE8	448
GFOD2	GINS1	Q14691	438
GFOD2	ICMT	O60725	433
GFOD2	ENKD1	Q9H0I2	431
GFOD2	CRTAM	O95727	429
GFOD2	ZNF500	O60304	426
GFOD2	SPRYD3	Q8NCJ5	424
GFOD2	KIR3DL1	P43629	418
GFOD2	NMNAT1	Q9HAN9	418

IntAct

13 interactions, top by confidence:

A	B	Type	Score
GFOD1	PER1	psi-mi:“MI:0914”(association)	0.530
GFOD1	RALGAPA2	psi-mi:“MI:0914”(association)	0.530
NKIRAS2	RALGAPA2	psi-mi:“MI:0914”(association)	0.530
BEGAIN	GFOD2	psi-mi:“MI:0915”(physical association)	0.370
NKIRAS2	RAP1GDS1	psi-mi:“MI:0914”(association)	0.350
TXLNA	GFOD2	psi-mi:“MI:0914”(association)	0.350
GFOD1	SBF1	psi-mi:“MI:0914”(association)	0.350
GFOD1	B4GAT1	psi-mi:“MI:0914”(association)	0.350
NKIRAS2	GABARAPL2	psi-mi:“MI:0914”(association)	0.350
ORF66	RALGAPA1	psi-mi:“MI:0914”(association)	0.350

BioGRID (31): GFOD2 (Affinity Capture-MS), GFOD2 (Affinity Capture-MS), GFOD2 (Affinity Capture-MS), GFOD2 (Affinity Capture-MS), GFOD2 (Affinity Capture-RNA), GFOD2 (Affinity Capture-MS), GFOD2 (Affinity Capture-MS), GFOD2 (Proximity Label-MS), GFOD2 (Proximity Label-MS), GFOD2 (Affinity Capture-MS), GFOD2 (Proximity Label-MS), GFOD2 (Proximity Label-MS), GFOD2 (Proximity Label-MS), GFOD2 (Proximity Label-MS), GFOD2 (Proximity Label-MS)

ESM2 similar proteins: A1JPN5, A4SQW9, A4TIM4, A6KX96, A6KY05, A6KYY1, A6L1Z2, A6LB54, A7B558, A7FHH4, A8FRR2, A8GDR7, A9R093, B1JJ30, B2K5L3, B2UQL7, B4ETL7, B5XTK9, B7MXT6, C6DAW5, G3XD23, O14082, O31529, O34371, O34815, P39353, P55480, P55609, P71058, P94437, Q09745, Q1C742, Q1CIH7, Q3B7J2, Q44258, Q50EA3, Q50HM6, Q54728, Q5BIP5, Q5BKK6

Diamond homologs: Q3B7J2, Q3UHD2, Q5BIP5, Q5BKK6, Q6P4M5, Q7ZY75, Q9CYH5, Q9NXC2, O13991, Q2FSK9, O42896

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	64
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1091 predictions. Top by Δscore:

Variant	Effect	Δscore
16:67685459:AGAG:A	donor_gain	1.0000
16:67676052:ACC:A	acceptor_loss	0.9900
16:67676054:C:G	acceptor_loss	0.9900
16:67676055:T:G	acceptor_loss	0.9900
16:67719158:CTCA:C	donor_loss	0.9900
16:67719161:A:AC	donor_gain	0.9900
16:67719161:AC:A	donor_loss	0.9900
16:67719162:C:CC	donor_gain	0.9900
16:67676051:TAC:T	acceptor_gain	0.9800
16:67685451:GCGTA:G	donor_loss	0.9800
16:67685452:CGTA:C	donor_loss	0.9800
16:67685453:GTACC:G	donor_loss	0.9800
16:67685454:TAC:T	donor_loss	0.9800
16:67685455:ACCTA:A	donor_loss	0.9800
16:67685456:C:A	donor_loss	0.9800
16:67685802:CCTA:C	acceptor_loss	0.9800
16:67685803:C:CA	acceptor_loss	0.9800
16:67685804:T:A	acceptor_loss	0.9800
16:67676049:AATAC:A	acceptor_gain	0.9700
16:67676054:C:CC	acceptor_gain	0.9700
16:67676059:A:T	acceptor_gain	0.9700
16:67676050:ATAC:A	acceptor_gain	0.9600
16:67685800:CTC:C	acceptor_gain	0.9600
16:67685803:C:CC	acceptor_gain	0.9600
16:67676058:C:CT	acceptor_gain	0.9500
16:67676062:A:T	acceptor_gain	0.9500
16:67685801:TC:T	acceptor_gain	0.9500
16:67685802:CC:C	acceptor_gain	0.9500
16:67676061:C:CT	acceptor_gain	0.9400
16:67685459:AGAGC:A	donor_gain	0.9400

AlphaMissense

2504 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:67675717:C:T	G199E	0.999
16:67675265:C:G	A350P	0.998
16:67675718:C:A	G199W	0.998
16:67675778:C:A	G179W	0.998
16:67676043:C:A	K90N	0.998
16:67676043:C:G	K90N	0.998
16:67675252:G:C	S354W	0.997
16:67675534:A:T	L260H	0.997
16:67675762:T:A	D184V	0.997
16:67675777:C:T	G179E	0.997
16:67675778:C:G	G179R	0.997
16:67675778:C:T	G179R	0.997
16:67675935:G:C	F126L	0.997
16:67675935:G:T	F126L	0.997
16:67675937:A:G	F126L	0.997
16:67685513:A:G	L68P	0.997
16:67675261:A:T	I351N	0.996
16:67675593:G:C	N240K	0.996
16:67675593:G:T	N240K	0.996
16:67675718:C:G	G199R	0.996
16:67675718:C:T	G199R	0.996
16:67675940:G:T	R125S	0.996
16:67685633:A:G	F28S	0.996
16:67675253:A:G	S354P	0.995
16:67675534:A:G	L260P	0.995
16:67675644:A:C	C223W	0.995
16:67675656:G:C	S219R	0.995
16:67675656:G:T	S219R	0.995
16:67675658:T:G	S219R	0.995
16:67675759:A:G	L185P	0.995

dbSNP variants (sampled 300 via entrez): RS1000038653 (16:67676963 G>A), RS1000084362 (16:67686406 A>G), RS1000172703 (16:67683007 C>A,T), RS1000259123 (16:67693455 A>G,T), RS1000324324 (16:67706235 C>T), RS1000387703 (16:67690214 TAA>T), RS1000390804 (16:67708081 TG>T), RS1000454548 (16:67686099 G>C), RS1000596577 (16:67691686 T>A,C), RS1000608425 (16:67683341 C>T), RS1000638725 (16:67675487 G>A), RS1000678002 (16:67704643 A>G,T), RS1000720353 (16:67688536 C>A), RS1000839231 (16:67699604 C>T), RS1000840715 (16:67711042 G>A)

Disease associations

OMIM: gene MIM:619933 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST000805_12	HDL cholesterol	2.000000e-07
GCST002539_84	Schizophrenia	2.000000e-08
GCST005751_4	Empathy quotient	9.000000e-07
GCST006803_42	Schizophrenia	4.000000e-08
GCST010002_113	Refractive error	2.000000e-14
GCST90002403_679	Red blood cell count	7.000000e-13

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0009183	empathy measurement
EFO:0004305	erythrocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, increases expression, affects expression, decreases expression, affects cotreatment	3
Arsenic	affects methylation, affects cotreatment, increases abundance, increases expression	2
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Leflunomide	decreases expression	1
Atrazine	decreases expression	1
Diazinon	increases methylation	1
Estradiol	affects expression	1
Gallic Acid	decreases expression	1
Manganese	increases expression, affects cotreatment, increases abundance	1
Smoke	decreases expression	1
Urethane	increases expression	1
Vanadates	increases expression	1
Cyclosporine	decreases expression	1
Cadmium Chloride	decreases expression	1
Copper Sulfate	decreases expression	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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