THUMPD1

Summary

THUMPD1 (THUMP domain 1 NAT10 acetyltransferase adaptor , HGNC:23807) is a protein-coding gene on chromosome 16p12.3, encoding THUMP domain-containing protein 1 (Q9NXG2). Functions as a tRNA-binding adapter to mediate NAT10-dependent tRNA acetylation modifying cytidine to N4-acetylcytidine (ac4C).

Enables RNA binding activity. Predicted to be involved in tRNA modification. Predicted to be located in nucleoplasm.

Source: NCBI Gene 55623 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder with speech delay and variable ocular anomalies (Strong, GenCC)
• Clinical variants (ClinVar): 1 total — 1 pathogenic
• Phenotypes (HPO): 24
• Druggable target: yes
• MANE Select transcript: NM_017736

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23807
Approved symbol	THUMPD1
Name	THUMP domain 1 NAT10 acetyltransferase adaptor
Location	16p12.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ20274, Tan1
Ensembl gene	ENSG00000066654
Ensembl biotype	protein_coding
OMIM	616662
Entrez	55623

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 5 protein_coding, 2 nonsense_mediated_decay, 2 retained_intron

ENST00000381337, ENST00000396083, ENST00000565248, ENST00000569768, ENST00000570231, ENST00000636554, ENST00000888379, ENST00000888380, ENST00000966612

RefSeq mRNA: 2 — MANE Select: NM_017736 NM_001304550, NM_017736

CCDS: CCDS10588

Canonical transcript exons

ENST00000396083 — 4 exons

Exon	Start	End
ENSE00001141964	20738897	20739071
ENSE00001523808	20733664	20737286
ENSE00002598723	20741509	20741818
ENSE00003691886	20737708	20737956

Expression profiles

Bgee: expression breadth ubiquitous, 293 present calls, max score 99.56.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 26.8248 / max 257.0062, expressed in 1811 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
156697	26.8248	1811

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	99.56	gold quality
oocyte	CL:0000023	98.74	gold quality
mammary duct	UBERON:0001765	96.42	gold quality
epithelium of mammary gland	UBERON:0003244	96.38	gold quality
corpus epididymis	UBERON:0004359	96.20	gold quality
cauda epididymis	UBERON:0004360	96.20	gold quality
cardia of stomach	UBERON:0001162	96.14	gold quality
calcaneal tendon	UBERON:0003701	96.13	gold quality
pylorus	UBERON:0001166	96.09	gold quality
visceral pleura	UBERON:0002401	95.79	gold quality
caput epididymis	UBERON:0004358	95.65	gold quality
cerebellar vermis	UBERON:0004720	95.65	gold quality
renal medulla	UBERON:0000362	95.60	gold quality
nipple	UBERON:0002030	95.16	gold quality
urethra	UBERON:0000057	95.02	gold quality
endometrium	UBERON:0001295	94.98	gold quality
pigmented layer of retina	UBERON:0001782	94.70	gold quality
seminal vesicle	UBERON:0000998	94.66	gold quality
blood vessel layer	UBERON:0004797	94.54	gold quality
germinal epithelium of ovary	UBERON:0001304	94.52	gold quality
superior surface of tongue	UBERON:0007371	94.48	gold quality
cervix squamous epithelium	UBERON:0006922	94.14	gold quality
pleura	UBERON:0000977	94.07	gold quality
mammalian vulva	UBERON:0000997	94.06	gold quality
Brodmann (1909) area 23	UBERON:0013554	93.99	gold quality
pericardium	UBERON:0002407	93.92	gold quality
lower lobe of lung	UBERON:0008949	93.88	gold quality
penis	UBERON:0000989	93.84	gold quality
parietal pleura	UBERON:0002400	93.82	gold quality
hair follicle	UBERON:0002073	93.81	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-9801	yes	3.97
E-MTAB-2983	no	1178.35
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

144 targeting THUMPD1, 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-8485	100.00	77.57	4731
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-552-5P	99.93	68.56	1583

Literature-anchored findings (GeneRIF, showing 3)

• These results indicate that THUMPD1 promotes breast cancer cells invasion and migration via the AKT-GSK3beta-Snail pathway (PMID:28076326)
• Pan-cancer analysis of N4-acetylcytidine adaptor THUMPD1 as a predictor for prognosis and immunotherapy. (PMID:34762107)
• THUMPD1 bi-allelic variants cause loss of tRNA acetylation and a syndromic neurodevelopmental disorder. (PMID:35196516)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	thumpd1	ENSDARG00000100264
mus_musculus	Thumpd1	ENSMUSG00000030942
rattus_norvegicus	AABR07005588.1	ENSRNOG00000014946
drosophila_melanogaster	CG15014	FBGN0035532
caenorhabditis_elegans		WBGENE00020953

Protein

Protein identifiers

THUMP domain-containing protein 1 — Q9NXG2 (reviewed: Q9NXG2)

All UniProt accessions (2): Q9NXG2, H3BNW0

UniProt curated annotations — full annotation on UniProt →

Function. Functions as a tRNA-binding adapter to mediate NAT10-dependent tRNA acetylation modifying cytidine to N4-acetylcytidine (ac4C).

Subunit / interactions. Interacts with NAT10. Binds tRNA.

Disease relevance. Neurodevelopmental disorder with speech delay and variable ocular anomalies (NEDSOA) [MIM:619989] An autosomal recessive disorder characterized by global developmental delay, speech delay, moderate to severe intellectual deficiency, behavioral abnormalities such as angry outbursts, facial dysmorphism, and ophthalmological abnormalities. Brain imaging is usually normal, but abnormalities of the corpus callosum have been reported. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the THUMPD1 family.

RefSeq proteins (2): NP_001291479, NP_060206* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004114	THUMP_dom	Domain
IPR040183	THUMPD1-like	Family

Pfam: PF02926

UniProt features (32 total): sequence variant 7, modified residue 6, strand 4, compositionally biased region 4, sequence conflict 3, region of interest 3, helix 2, initiator methionine 1, chain 1, domain 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2DIR	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NXG2-F1	74.92	0.53

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 (6): 2, 79, 86, 88, 119, 270

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-6790901	rRNA modification in the nucleus and cytosol
R-HSA-72312	rRNA processing
R-HSA-8868773	rRNA processing in the nucleus and cytosol
R-HSA-8953854	Metabolism of RNA

MSigDB gene sets: 221 (showing top): GOBP_TRNA_METABOLIC_PROCESS, SENESE_HDAC1_AND_HDAC2_TARGETS_DN, GTGCCTT_MIR506, MODULE_331, GOBP_RNA_MODIFICATION, DEURIG_T_CELL_PROLYMPHOCYTIC_LEUKEMIA_DN, BYSTRYKH_HEMATOPOIESIS_STEM_CELL_AND_BRAIN_QTL_CIS, GENTILE_UV_HIGH_DOSE_DN, GCM_NUMA1, DEBIASI_APOPTOSIS_BY_REOVIRUS_INFECTION_UP, DING_LUNG_CANCER_EXPRESSION_BY_COPY_NUMBER, GENTILE_UV_RESPONSE_CLUSTER_D4, GOBP_TRNA_PROCESSING, REACTOME_METABOLISM_OF_RNA, GOBP_TRNA_MODIFICATION

GO Biological Process (1): tRNA modification (GO:0006400)

GO Molecular Function (2): RNA binding (GO:0003723), protein binding (GO:0005515)

GO Cellular Component (1): nucleoplasm (GO:0005654)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
rRNA processing in the nucleus and cytosol	1
Metabolism of RNA	1
rRNA processing	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
tRNA processing	1
RNA modification	1
nucleic acid binding	1
binding	1
nuclear lumen	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1160 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
THUMPD1	NAT10	Q9H0A0	710
THUMPD1	METTL1	Q9UBP6	444
THUMPD1	TRUB1	Q8WWH5	433
THUMPD1	TYW2	Q53H54	406
THUMPD1	TRMT61A	Q96FX7	403
THUMPD1	ICAM3	P32942	397
THUMPD1	WDR4	P57081	394
THUMPD1	EMG1	Q92979	394
THUMPD1	DIMT1	Q9UNQ2	371
THUMPD1	LDAF1	Q96B96	359
THUMPD1	PUS1	Q9Y606	353
THUMPD1	A0A3B3IRZ5	A0A3B3IRZ5	348
THUMPD1	LYRM1	O43325	334
THUMPD1	TRMT61B	Q9BVS5	325
THUMPD1	OR51A7	Q8NH64	325

IntAct

41 interactions, top by confidence:

A	B	Type	Score
TP53	MDM2	psi-mi:“MI:0914”(association)	1.000
NAT10	THUMPD1	psi-mi:“MI:0915”(physical association)	0.740
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
LIN28A	IGF2BP3	psi-mi:“MI:0914”(association)	0.640
TAS2R41	YKT6	psi-mi:“MI:0914”(association)	0.530
THUMPD1	YBX1	psi-mi:“MI:0914”(association)	0.530
ZC3H8	RSL1D1	psi-mi:“MI:0914”(association)	0.530
LIN28B	ELAVL2	psi-mi:“MI:0914”(association)	0.530
ETS1	ETS1	psi-mi:“MI:0914”(association)	0.500
gag	RNH1	psi-mi:“MI:0914”(association)	0.460
	TK2	psi-mi:“MI:0915”(physical association)	0.400
ZC3H8	RPL7	psi-mi:“MI:0914”(association)	0.350
LUM	CTH	psi-mi:“MI:0914”(association)	0.350
DDX21	GTPBP10	psi-mi:“MI:0914”(association)	0.350
LIN28A	FBLL1	psi-mi:“MI:0914”(association)	0.350
	GTPBP1	psi-mi:“MI:0914”(association)	0.350
ZNF691	FPGT	psi-mi:“MI:0914”(association)	0.350
CCL26	TBL1X	psi-mi:“MI:0914”(association)	0.350
OPTN	SMCHD1	psi-mi:“MI:0914”(association)	0.350
COL10A1	PLOD2	psi-mi:“MI:0914”(association)	0.350
ZNF691	GDF9	psi-mi:“MI:0914”(association)	0.350
THUMPD1	H2AX	psi-mi:“MI:0914”(association)	0.350
NAT10	HERC2	psi-mi:“MI:0914”(association)	0.350
LIN28A	GTPBP10	psi-mi:“MI:0914”(association)	0.350
NAT10	DIS3L2	psi-mi:“MI:0914”(association)	0.350
TCEANC2	AGRN	psi-mi:“MI:0914”(association)	0.350

BioGRID (95): THUMPD1 (Affinity Capture-MS), DDX21 (Affinity Capture-MS), NAT10 (Affinity Capture-MS), FDXACB1 (Affinity Capture-MS), PUS1 (Affinity Capture-MS), PUS7 (Affinity Capture-MS), MTO1 (Affinity Capture-MS), QTRT1 (Affinity Capture-MS), HARS (Co-fractionation), NDRG1 (Co-fractionation), SYNCRIP (Co-fractionation), THUMPD1 (Co-fractionation), THUMPD1 (Co-fractionation), THUMPD1 (Co-fractionation), THUMPD3 (Co-fractionation)

ESM2 similar proteins: A1XQU3, A1XQU5, G1SE28, G1SKF7, G1SZ12, G1TXF6, O65743, O94776, P21533, P37108, P38666, P47911, P50888, P50914, P55844, P61122, P61353, P61354, P61355, P61356, P61357, P61358, P83731, P83732, Q02878, Q2YGT9, Q3T0U2, Q42347, Q4R5C7, Q4R8Z4, Q58DQ3, Q63507, Q66WF5, Q6QMZ4, Q6Y263, Q862I1, Q8BP67, Q8ISQ3, Q8JGR4, Q90YQ0

Diamond homologs: Q24K03, Q99J36, Q9NXG2, Q9VZD8, P87151

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
2682550	NM_017736.5(THUMPD1):c.290del (p.Ala97fs)	Pathogenic

SpliceAI

1007 predictions. Top by Δscore:

Variant	Effect	Δscore
16:20737282:TATTC:T	acceptor_gain	1.0000
16:20737284:TTC:T	acceptor_gain	1.0000
16:20737284:TTCC:T	acceptor_loss	1.0000
16:20737288:T:A	acceptor_loss	1.0000
16:20737703:CATA:C	donor_loss	1.0000
16:20737705:TA:T	donor_loss	1.0000
16:20737706:A:AG	donor_loss	1.0000
16:20737707:CCT:C	donor_loss	1.0000
16:20737955:CT:C	acceptor_gain	1.0000
16:20737957:C:CC	acceptor_gain	1.0000
16:20737958:T:C	acceptor_gain	1.0000
16:20737958:T:TC	acceptor_gain	1.0000
16:20738899:AT:A	donor_gain	1.0000
16:20738899:ATC:A	donor_gain	1.0000
16:20741505:GTACC:G	donor_loss	1.0000
16:20741506:TACCT:T	donor_loss	1.0000
16:20737283:ATTC:A	acceptor_gain	0.9900
16:20737285:TC:T	acceptor_gain	0.9900
16:20737286:CC:C	acceptor_gain	0.9900
16:20737287:C:CC	acceptor_gain	0.9900
16:20737293:C:CT	acceptor_gain	0.9900
16:20737294:A:T	acceptor_gain	0.9900
16:20737706:ACCTG:A	donor_gain	0.9900
16:20737707:CCTGC:C	donor_gain	0.9900
16:20737710:G:A	donor_gain	0.9900
16:20737952:AGGCT:A	acceptor_gain	0.9900
16:20737953:GGCT:G	acceptor_gain	0.9900
16:20737956:TC:T	acceptor_loss	0.9900
16:20737957:CTTAA:C	acceptor_loss	0.9900
16:20738170:A:AC	donor_gain	0.9900

AlphaMissense

2325 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:20737187:A:T	V252D	0.999
16:20737200:A:G	C248R	0.999
16:20737775:A:C	F196L	0.999
16:20737775:A:T	F196L	0.999
16:20737777:A:G	F196L	0.999
16:20737881:C:G	R161P	0.999
16:20738937:A:C	S122R	0.999
16:20738937:A:T	S122R	0.999
16:20738939:T:G	S122R	0.999
16:20741559:C:G	A61P	0.999
16:20741600:A:G	L47P	0.999
16:20741607:C:G	G45R	0.999
16:20737160:T:A	K261I	0.998
16:20737161:T:C	K261E	0.998
16:20737189:A:C	S251R	0.998
16:20737189:A:T	S251R	0.998
16:20737191:T:G	S251R	0.998
16:20737197:A:G	C249R	0.998
16:20737247:A:G	L232P	0.998
16:20737734:C:A	R210I	0.998
16:20737755:C:G	R203P	0.998
16:20737776:A:G	F196S	0.998
16:20737872:G:C	P164R	0.998
16:20737872:G:T	P164H	0.998
16:20737929:A:G	L145P	0.998
16:20738917:A:G	F129S	0.998
16:20738953:A:G	F117S	0.998
16:20741546:A:G	L65P	0.998
16:20741549:A:G	L64P	0.998
16:20741558:G:T	A61D	0.998

dbSNP variants (sampled 300 via entrez): RS1000689950 (16:20741796 G>A,C), RS1000993929 (16:20741027 G>C), RS1001526043 (16:20740786 TAA>T), RS1001570022 (16:20741435 C>A,T), RS1001627113 (16:20734835 G>A), RS1001699275 (16:20735154 A>T), RS1001731792 (16:20735357 C>T), RS1001998001 (16:20740986 C>A), RS1002034333 (16:20733739 G>A,T), RS1002597592 (16:20742218 A>G), RS1004940325 (16:20740423 C>G,T), RS1005073997 (16:20734756 C>G,T), RS1005134882 (16:20741125 G>A), RS1005437915 (16:20740043 G>A), RS1005534659 (16:20741392 C>A,G)

Disease associations

OMIM: gene MIM:616662 | disease phenotypes: MIM:619989

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder with speech delay and variable ocular anomalies	Strong	Autosomal recessive

Mondo (1): neurodevelopmental disorder with speech delay and variable ocular anomalies (MONDO:0859272)

Orphanet (0):

HPO phenotypes

24 total (24 of 24 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000154	Wide mouth
HP:0000219	Thin upper lip vermilion
HP:0000252	Microcephaly
HP:0000286	Epicanthus
HP:0000303	Mandibular prognathia
HP:0000316	Hypertelorism
HP:0000319	Smooth philtrum
HP:0000365	Hearing impairment
HP:0000369	Low-set ears
HP:0000494	Downslanted palpebral fissures
HP:0000508	Ptosis
HP:0000750	Delayed speech and language development
HP:0001249	Intellectual disability
HP:0001263	Global developmental delay
HP:0001274	Agenesis of corpus callosum
HP:0002000	Short columella
HP:0002007	Frontal bossing
HP:0002373	Febrile seizure (within the age range of 3 months to 6 years)
HP:0003593	Infantile onset
HP:0004322	Short stature
HP:0008070	Sparse hair
HP:0030799	Scaphocephaly
HP:0045075	Sparse eyebrow

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066379 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, affects cotreatment, affects expression, increases abundance	3
aristolochic acid I	increases expression	1
FR900359	increases phosphorylation	1
ginger extract	affects cotreatment, affects expression, increases abundance	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
trichostatin A	affects expression	1
sodium arsenite	increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
bisphenol S	increases expression	1
jinfukang	decreases expression	1
LDN 193189	affects cotreatment, increases expression	1
Resveratrol	increases expression, affects cotreatment	1
Decitabine	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Azacitidine	increases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Caffeine	increases phosphorylation	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Estradiol	increases expression, affects cotreatment	1
Oils, Volatile	affects cotreatment, affects expression, increases abundance	1
Plant Extracts	increases expression, affects cotreatment	1
Progesterone	affects cotreatment, increases expression	1
Ribonucleotides	affects binding	1
Rotenone	increases expression	1
Selenium	decreases expression	1
Dihydrotestosterone	increases expression	1
Valproic Acid	decreases 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
CHEMBL5652627	Binding	Binding affinity to human THUMPD1 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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