GON7

Summary

GON7 (GON7 subunit of KEOPS complex, HGNC:20356) is a protein-coding gene on chromosome 14q32.12, encoding EKC/KEOPS complex subunit GON7 (Q9BXV9). Component of the EKC/KEOPS complex that is required for the formation of a threonylcarbamoyl group on adenosine at position 37 (t(6)A37) in tRNAs that read codons beginning with adenine.

Involved in tRNA threonylcarbamoyladenosine modification. Located in cytosol; nucleolus; and nucleoplasm. Part of EKC/KEOPS complex. Implicated in Galloway-Mowat syndrome.

Source: NCBI Gene 84520 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Galloway-Mowat syndrome 9 (Strong, GenCC)
• GWAS associations: 1
• Clinical variants (ClinVar): 10 total — 3 pathogenic
• Phenotypes (HPO): 28
• MANE Select transcript: NM_032490

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20356
Approved symbol	GON7
Name	GON7 subunit of KEOPS complex
Location	14q32.12
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000170270
Ensembl biotype	protein_coding
OMIM	617436
Entrez	84520

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000306954, ENST00000556566, ENST00000870038, ENST00000923944

RefSeq mRNA: 1 — MANE Select: NM_032490 NM_032490

CCDS: CCDS41981

Canonical transcript exons

ENST00000306954 — 2 exons

Exon	Start	End
ENSE00001176981	93202894	93203782
ENSE00001242920	93206830	93207065

Expression profiles

Bgee: expression breadth ubiquitous, 136 present calls, max score 93.88.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.4626 / max 104.1038, expressed in 1795 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
144633	13.1933	1789
144634	1.2742	668
144632	0.9951	473

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	93.88	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	93.53	gold quality
mucosa of transverse colon	UBERON:0004991	90.34	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.56	gold quality
endometrium	UBERON:0001295	87.91	gold quality
fallopian tube	UBERON:0003889	87.32	gold quality
monocyte	CL:0000576	86.54	gold quality
leukocyte	CL:0000738	86.34	gold quality
lymph node	UBERON:0000029	86.24	gold quality
rectum	UBERON:0001052	86.22	gold quality
adult mammalian kidney	UBERON:0000082	86.08	gold quality
islet of Langerhans	UBERON:0000006	85.99	gold quality
heart left ventricle	UBERON:0002084	85.71	gold quality
right adrenal gland	UBERON:0001233	85.57	gold quality
left adrenal gland	UBERON:0001234	85.43	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.41	gold quality
right adrenal gland cortex	UBERON:0035827	85.29	gold quality
duodenum	UBERON:0002114	85.05	gold quality
left adrenal gland cortex	UBERON:0035825	84.93	gold quality
adrenal gland	UBERON:0002369	84.28	gold quality
hindlimb stylopod muscle	UBERON:0004252	84.22	gold quality
gastrocnemius	UBERON:0001388	84.21	gold quality
transverse colon	UBERON:0001157	84.14	gold quality
adenohypophysis	UBERON:0002196	84.11	gold quality
muscle of leg	UBERON:0001383	84.10	gold quality
hypothalamus	UBERON:0001898	84.05	gold quality
granulocyte	CL:0000094	84.02	gold quality
heart	UBERON:0000948	84.01	gold quality
pituitary gland	UBERON:0000007	83.80	gold quality
metanephros cortex	UBERON:0010533	83.76	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.94
E-MTAB-7606	no	277.78
E-MTAB-6379	no	81.73

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

41 targeting GON7, 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-1277-5P	100.00	73.95	5056
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-651-5P	99.64	68.49	1104
HSA-MIR-1290	99.59	69.90	2079
HSA-MIR-513C-5P	99.50	68.42	1730
HSA-MIR-514B-5P	99.50	68.19	1766
HSA-MIR-365A-3P	99.43	70.02	836
HSA-MIR-365B-3P	99.43	70.02	836
HSA-MIR-1206	99.30	69.32	1016
HSA-MIR-149-5P	99.25	67.16	1315
HSA-MIR-3973	99.20	69.19	1990
HSA-MIR-3125	99.14	68.49	2269
HSA-MIR-146A-3P	99.13	68.99	1881
HSA-MIR-4504	99.10	69.14	1328
HSA-MIR-3916	98.99	68.04	2155
HSA-MIR-6859-5P	98.99	68.07	2049
HSA-MIR-138-2-3P	98.91	68.33	1643
HSA-MIR-520G-3P	98.91	67.38	1914

Literature-anchored findings (GeneRIF, showing 1)

• Mutations in GON7, encoding the fifth KEOPS subunit, lead to a milder form of Galloway-Mowat syndrome (GAMOS), an autosomal recessive disease characterized by early-onset steroid-resistant nephrotic syndrome and microcephaly. The structure and cellular characterization of GON7 suggest its involvement in the cellular stability and quaternary arrangement of the KEOPS complex. (PMID:31481669)

Cross-species orthologs

1 orthologs

Organism	Symbol	Gene ID
mus_musculus	Gon7	ENSMUSG00000091931

Protein

Protein identifiers

EKC/KEOPS complex subunit GON7 — Q9BXV9 (reviewed: Q9BXV9)

All UniProt accessions (2): Q9BXV9, H0YJA8

UniProt curated annotations — full annotation on UniProt →

Function. Component of the EKC/KEOPS complex that is required for the formation of a threonylcarbamoyl group on adenosine at position 37 (t(6)A37) in tRNAs that read codons beginning with adenine. The complex is probably involved in the transfer of the threonylcarbamoyl moiety of threonylcarbamoyl-AMP (TC-AMP) to the N6 group of A37. GON7 plays a supporting role to the catalytic subunit OSGEP in the complex.

Subunit / interactions. Component of the EKC/KEOPS complex composed of at least GON7, TP53RK, TPRKB, OSGEP and LAGE3; the whole complex dimerizes.

Subcellular location. Nucleus.

Disease relevance. Galloway-Mowat syndrome 9 (GAMOS9) [MIM:619603] A form of Galloway-Mowat syndrome, a severe renal-neurological disease characterized by early-onset nephrotic syndrome associated with microcephaly, central nervous system abnormalities, developmental delays, and a propensity for seizures. Brain anomalies include gyration defects ranging from lissencephaly to pachygyria and polymicrogyria, and cerebellar hypoplasia. Most patients show facial dysmorphism characterized by a small, narrow forehead, large/floppy ears, deep-set eyes, and micrognathia. Additional variable features are visual impairment and arachnodactyly. Most patients die in early childhood. GAMOS9 inheritance is autosomal recessive. The disease is caused by variants affecting the gene represented in this entry.

RefSeq proteins (1): NP_115879* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR027893	GON7_meta	Family

Pfam: PF15387

UniProt features (9 total): strand 3, chain 1, region of interest 1, compositionally biased region 1, modified residue 1, sequence variant 1, helix 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
6GWJ	X-RAY DIFFRACTION	1.95
9FL9	ELECTRON MICROSCOPY	3.74

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BXV9-F1	76.09	0.38

Functional residue map

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

Post-translational modifications (1): 1

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-6782315	tRNA modification in the nucleus and cytosol

MSigDB gene sets: 186 (showing top): E2F_Q4, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, E2F4DP1_01, GOBP_TRNA_METABOLIC_PROCESS, GOBP_TRANSLATION, CATRRAGC_UNKNOWN, E2F1DP1_01, E2F1DP2_01, GOBP_RNA_MODIFICATION, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, E2F1_Q3, GOBP_TRNA_THREONYLCARBAMOYLADENOSINE_METABOLIC_PROCESS, ACEVEDO_LIVER_CANCER_UP, chr14q32, GOBP_TRNA_PROCESSING

GO Biological Process (1): tRNA threonylcarbamoyladenosine modification (GO:0002949)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (5): EKC/KEOPS complex (GO:0000408), nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
tRNA processing	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
nuclear lumen	2
cellular anatomical structure	2
tRNA modification	1
binding	1
transferase complex	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1
cytoplasm	1

Protein interactions and networks

STRING

308 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GON7	LAGE3	Q14657	995
GON7	TP53RK	Q96S44	994
GON7	TPRKB	Q9Y3C4	991
GON7	OSGEP	Q9NPF4	966
GON7	OSGEPL1	Q9H4B0	885
GON7	YRDC	Q86U90	763
GON7	POLR1B	Q9H9Y6	627
GON7	WDR73	Q6P4I2	471
GON7	TMEM229B	Q8NBD8	447
GON7	TMEM131L	A2VDJ0	446
GON7	POLR1D	P0DPB6	367
GON7	SMIM21	Q3B7S5	351
GON7	ACBD7	Q8N6N7	350
GON7	SH2D2A	Q9NP31	348
GON7	OSCP1	Q8WVF1	342

IntAct

28 interactions, top by confidence:

A	B	Type	Score
LAGE3	GON7	psi-mi:“MI:0915”(physical association)	0.880
GON7	LAGE3	psi-mi:“MI:0915”(physical association)	0.880
LAGE3	GON7	psi-mi:“MI:0407”(direct interaction)	0.880
GON7	LAGE3	psi-mi:“MI:0407”(direct interaction)	0.880
GON7	LAGE3	psi-mi:“MI:0914”(association)	0.880
TP53RK	GON7	psi-mi:“MI:0914”(association)	0.820
TP53RK	NUP43	psi-mi:“MI:0914”(association)	0.730
LAGE3	CTSA	psi-mi:“MI:0914”(association)	0.530
Osgep	RPSA	psi-mi:“MI:0914”(association)	0.350
OSGEP	HYKK	psi-mi:“MI:0914”(association)	0.350
TP53RK	CLTB	psi-mi:“MI:0914”(association)	0.350
LAGE3	HYKK	psi-mi:“MI:0914”(association)	0.350
LAGE3	PPIAL4C	psi-mi:“MI:0914”(association)	0.350
OSGEP	POTEF	psi-mi:“MI:0914”(association)	0.350
TP53RK	SMS	psi-mi:“MI:0914”(association)	0.350
LAGE3	GON7	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (29): C14orf142 (Affinity Capture-MS), C14orf142 (Affinity Capture-MS), C14orf142 (Affinity Capture-MS), C14orf142 (Affinity Capture-MS), C14orf142 (Affinity Capture-MS), LAGE3 (Two-hybrid), C14orf142 (Affinity Capture-MS), C14orf142 (Affinity Capture-MS), C14orf142 (Affinity Capture-MS), C14orf142 (Affinity Capture-MS), C14orf142 (Affinity Capture-MS), C14orf142 (Affinity Capture-MS), C14orf142 (Affinity Capture-MS), C14orf142 (Affinity Capture-MS), C14orf142 (Affinity Capture-MS)

ESM2 similar proteins: A0A097I2D0, A0A1W2PP81, A0A1W2PPE2, A0A1W2PPH5, A0A1W2PPL8, A0A1W2PPW3, A0A1W2PQ09, A0A1W2PR64, A0A1W2PRV1, A6NLC8, F4HR03, O54825, O75461, P0C1H6, P0CV38, P0DMV1, P0DMV2, P0DW11, P0DW12, P0DW13, P0DW14, P40914, P49585, P49906, P81195, Q0MTC0, Q13895, Q15544, Q2N2K6, Q3SZB8, Q5DJT8, Q5RA91, Q5U1X0, Q6CER9, Q6RG77, Q6XL73, Q75DE4, Q7XHR2, Q7Z2G1, Q80WL2

Diamond homologs: P0C8B3, P0C8B4, P0C8B5, Q9BXV9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	0
Uncertain significance	3
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
1321193	NM_032490.5(GON7):c.21C>A (p.Tyr7Ter)	Pathogenic
1321194	NM_032490.5(GON7):c.19dup (p.Tyr7fs)	Pathogenic
997418	NC_000014.8:g.93660388_93690906del	Pathogenic

SpliceAI

398 predictions. Top by Δscore:

Variant	Effect	Δscore
14:93206807:TGCAG:T	donor_gain	0.9900
14:93206875:C:A	donor_gain	0.9900
14:93206874:T:TA	donor_gain	0.9800
14:93206718:T:A	donor_gain	0.9700
14:93203784:T:C	acceptor_gain	0.9600
14:93206823:AGCT:A	donor_loss	0.9600
14:93206824:GCTC:G	donor_loss	0.9600
14:93206825:CTCAC:C	donor_loss	0.9600
14:93206826:TCACC:T	donor_loss	0.9600
14:93206827:CACCG:C	donor_loss	0.9600
14:93206828:A:AC	donor_gain	0.9600
14:93206829:C:CA	donor_loss	0.9600
14:93206829:C:CC	donor_gain	0.9600
14:93207002:C:A	donor_gain	0.9600
14:93206901:T:TA	donor_gain	0.9500
14:93206828:ACCGT:A	donor_gain	0.9200
14:93206829:CCGTC:C	donor_gain	0.9200
14:93207006:T:TA	donor_gain	0.9200
14:93206822:GAGCT:G	donor_loss	0.9100
14:93203786:T:TC	acceptor_gain	0.9000
14:93206922:T:TA	acceptor_gain	0.9000
14:93203783:C:CC	acceptor_gain	0.8900
14:93206808:GCAGC:G	donor_gain	0.8900
14:93206829:CCGT:C	donor_gain	0.8900
14:93206806:CTGCA:C	donor_gain	0.8700
14:93206923:G:A	acceptor_gain	0.8700
14:93203780:CAC:C	acceptor_gain	0.8600
14:93203781:AC:A	acceptor_loss	0.8600
14:93203782:CC:C	acceptor_loss	0.8600
14:93203783:C:CA	acceptor_loss	0.8600

AlphaMissense

656 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:93206919:A:G	M40T	0.951
14:93203709:T:A	K94N	0.945
14:93203709:T:G	K94N	0.945
14:93206918:C:A	M40I	0.922
14:93206918:C:G	M40I	0.922
14:93206918:C:T	M40I	0.922
14:93207030:A:G	L3P	0.914
14:93203710:T:A	K94I	0.912
14:93207030:A:T	L3Q	0.907
14:93206919:A:C	M40R	0.900
14:93206940:A:G	L33P	0.892
14:93206907:A:T	V44E	0.889
14:93207024:C:T	G5E	0.887
14:93206940:A:T	L33Q	0.877
14:93206919:A:T	M40K	0.871
14:93203710:T:G	K94T	0.870
14:93207025:C:G	G5R	0.869
14:93207025:C:T	G5R	0.869
14:93207030:A:C	L3R	0.865
14:93207019:A:C	Y7D	0.859
14:93203711:T:C	K94E	0.844
14:93207018:T:G	Y7S	0.839
14:93207019:A:G	Y7H	0.839
14:93206940:A:C	L33R	0.837
14:93206977:A:G	C21R	0.833
14:93206928:A:T	V37E	0.825
14:93206915:C:A	K41N	0.822
14:93206915:C:G	K41N	0.822
14:93206988:A:G	L17P	0.821
14:93207019:A:T	Y7N	0.788

dbSNP variants (sampled 300 via entrez): RS1000058553 (14:93208895 T>G), RS1000334105 (14:93203707 C>T), RS1000623525 (14:93208162 C>G), RS1001680468 (14:93202483 G>C), RS1001766635 (14:93208799 CT>C,CTT), RS1002090209 (14:93207527 G>T), RS1002352237 (14:93203889 A>C), RS1002875844 (14:93207392 C>T), RS1003250334 (14:93208916 G>A), RS1003427018 (14:93207792 T>A), RS1003573341 (14:93206083 G>C), RS1003800435 (14:93206334 G>A,C,T), RS1003931358 (14:93202724 A>G), RS1003983879 (14:93203063 C>T), RS1005039394 (14:93205761 C>CTTT)

Disease associations

OMIM: gene MIM:617436 | disease phenotypes: MIM:251300, MIM:619603, MIM:619189

GenCC curated gene-disease

Disease	Classification	Inheritance
Galloway-Mowat syndrome 9	Strong	Autosomal recessive

Mondo (3): Galloway-Mowat syndrome (MONDO:0009627), Galloway-Mowat syndrome 9 (MONDO:0030471), Li-Campeau syndrome (MONDO:0030963)

Orphanet (1): Galloway-Mowat syndrome (Orphanet:2065)

HPO phenotypes

28 total (28 of 28 shown, HPO-id order):

HPO	Term
HP:0000093	Proteinuria
HP:0000100	Nephrotic syndrome
HP:0000112	Nephropathy
HP:0000164	Abnormality of the dentition
HP:0000252	Microcephaly
HP:0000316	Hypertelorism
HP:0000347	Micrognathia
HP:0000400	Macrotia
HP:0000601	Hypotelorism
HP:0001181	Adducted thumb
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001276	Hypertonia
HP:0001302	Pachygyria
HP:0001511	Intrauterine growth retardation
HP:0001622	Premature birth
HP:0002036	Hiatus hernia
HP:0002269	Abnormality of neuronal migration
HP:0002353	EEG abnormality
HP:0002410	Aqueductal stenosis
HP:0004322	Short stature
HP:0004374	Hemiplegia/hemiparesis
HP:0005108	Abnormal intervertebral disk morphology
HP:0010978	Abnormality of immune system physiology
HP:0100490	Camptodactyly of finger
HP:0100543	Cognitive impairment
HP:0100720	Hypoplasia of the ear cartilage

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST005951_7	Body mass index	4.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C537548	Galloway Mowat syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	3
Air Pollutants	decreases expression, increases abundance, increases expression	2
Smoke	decreases expression, increases abundance, increases expression	2
Tetrachlorodibenzodioxin	increases expression	2
Cyclosporine	decreases expression	2
Aflatoxin B1	decreases methylation, increases methylation	2
dicrotophos	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
aflatoxin B2	decreases methylation	1
M-VAC protocol	increases response to substance	1
di-n-butylphosphoric acid	affects expression	1
2-palmitoylglycerol	increases expression	1
K 7174	decreases expression	1
bisphenol B	increases expression	1
Sunitinib	decreases expression	1
Vorinostat	increases expression	1
Cannabidiol	increases expression	1
Cisplatin	decreases expression	1
Doxorubicin	increases expression	1
Rotenone	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	decreases expression	1
Cadmium Chloride	increases expression	1
Acrylamide	increases expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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