TAF1D

Summary

TAF1D (TATA-box binding protein associated factor, RNA polymerase I subunit D, HGNC:28759) is a protein-coding gene on chromosome 11q21, encoding TATA box-binding protein-associated factor RNA polymerase I subunit D (Q9H5J8). Component of the transcription factor SL1/TIF-IB complex, which is involved in the assembly of the PIC (preinitiation complex) during RNA polymerase I-dependent transcription. It is a selective cancer dependency (DepMap: 58.4% of cell lines).

TAF1D is a member of the SL1 complex, which includes TBP (MIM 600075) and TAF1A (MIM 604903), TAF1B (MIM 604904), and TAF1C (MIM 604905), and plays a role in RNA polymerase I transcription (Wang et al., 2004 [PubMed 15520167]; Gorski et al., 2007 [PubMed 17318177]).

Source: NCBI Gene 79101 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 21 total
• Cancer dependency (DepMap): dependent in 58.4% of screened cell lines
• MANE Select transcript: NM_024116

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28759
Approved symbol	TAF1D
Name	TATA-box binding protein associated factor, RNA polymerase I subunit D
Location	11q21
Locus type	gene with protein product
Status	Approved
Aliases	MGC5306, TAF(I)41
Ensembl gene	ENSG00000166012
Ensembl biotype	protein_coding
OMIM	612823
Entrez	79101

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 9 retained_intron, 7 nonsense_mediated_decay, 6 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000323981, ENST00000393259, ENST00000448108, ENST00000525928, ENST00000526015, ENST00000527068, ENST00000527169, ENST00000527690, ENST00000528734, ENST00000529435, ENST00000529508, ENST00000529794, ENST00000529900, ENST00000530089, ENST00000530769, ENST00000532235, ENST00000532455, ENST00000533794, ENST00000534079, ENST00000534770, ENST00000540232, ENST00000546088, ENST00000883225, ENST00000936877, ENST00000936878

RefSeq mRNA: 1 — MANE Select: NM_024116 NM_024116

CCDS: CCDS8293

Canonical transcript exons

ENST00000448108 — 6 exons

Exon	Start	End
ENSE00001650931	93736694	93736751
ENSE00001685667	93737064	93737239
ENSE00002151697	93735567	93736304
ENSE00002169856	93741322	93741495
ENSE00003582135	93739237	93739331
ENSE00003609192	93738109	93738499

Expression profiles

Bgee: expression breadth ubiquitous, 288 present calls, max score 99.03.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0960 / max 23.6810, expressed in 13 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
121837	67.4110	1823
121834	0.5838	230
121838	0.4882	203
121833	0.0960	13
121836	0.0155	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
body of pancreas	UBERON:0001150	99.03	gold quality
visceral pleura	UBERON:0002401	98.82	gold quality
sural nerve	UBERON:0015488	98.77	gold quality
primary visual cortex	UBERON:0002436	98.46	gold quality
left ovary	UBERON:0002119	98.39	gold quality
parietal pleura	UBERON:0002400	98.31	gold quality
anterior cingulate cortex	UBERON:0009835	98.29	gold quality
cingulate cortex	UBERON:0003027	98.20	gold quality
tibial nerve	UBERON:0001323	98.19	gold quality
right frontal lobe	UBERON:0002810	98.17	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	98.17	gold quality
pylorus	UBERON:0001166	98.11	gold quality
right ovary	UBERON:0002118	98.11	gold quality
Brodmann (1909) area 23	UBERON:0013554	98.11	gold quality
pleura	UBERON:0000977	98.10	gold quality
right uterine tube	UBERON:0001302	98.09	gold quality
mucosa of stomach	UBERON:0001199	98.03	gold quality
lower esophagus mucosa	UBERON:0035834	98.02	gold quality
colonic epithelium	UBERON:0000397	97.98	gold quality
cartilage tissue	UBERON:0002418	97.95	gold quality
tibia	UBERON:0000979	97.91	gold quality
calcaneal tendon	UBERON:0003701	97.89	gold quality
ectocervix	UBERON:0012249	97.82	gold quality
peritoneum	UBERON:0002358	97.80	gold quality
omental fat pad	UBERON:0010414	97.80	gold quality
skin of abdomen	UBERON:0001416	97.79	gold quality
endocervix	UBERON:0000458	97.73	gold quality
amygdala	UBERON:0001876	97.72	gold quality
body of uterus	UBERON:0009853	97.72	gold quality
amniotic fluid	UBERON:0000173	97.67	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-7037	yes	205.69
E-MTAB-10042	yes	5.34
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

23 targeting TAF1D, 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-513A-5P	100.00	69.77	2465
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-7978	99.86	66.90	856
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-7159-3P	99.51	70.17	1920
HSA-MIR-578	99.46	68.36	1787
HSA-MIR-3191-5P	99.24	66.52	1722
HSA-MIR-664A-3P	99.22	71.08	2696
HSA-MIR-412-3P	98.86	66.89	712
HSA-MIR-6754-3P	98.84	66.60	889
HSA-MIR-6764-3P	98.44	67.64	1153
HSA-MIR-6824-3P	98.44	67.62	1154
HSA-MIR-138-1-3P	98.25	67.89	867
HSA-MIR-6782-3P	97.60	67.75	931
HSA-MIR-125B-2-3P	96.69	68.38	1210
HSA-MIR-6823-5P	96.26	65.69	919

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 58.4% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 3)

• An antigrowth activity and modulations of cell cycle events are identified in cells expressing siRNAMGC5306. (PMID:15520167)
• TAF(I)41 (MGC5306) is integral to transcriptionally active SL1 and plays a role in Pol I recruitment and, therefore, preinitiation complex formation in vivo. (PMID:17318177)
• TAF1D promotes proliferation by transcriptionally activating G2/M phase-related genes in MYCN-amplified neuroblastoma. (PMID:37094904)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Taf1d	ENSMUSG00000031939
rattus_norvegicus	Taf1d	ENSRNOG00000010921

Protein

Protein identifiers

TATA box-binding protein-associated factor RNA polymerase I subunit D — Q9H5J8 (reviewed: Q9H5J8)

Alternative names: RNA polymerase I-specific TBP-associated factor 41 kDa, TATA box-binding protein-associated factor 1D, Transcription initiation factor SL1/TIF-IB subunit D

All UniProt accessions (8): A0A1D5RMT6, E9PKU8, E9PM59, Q9H5J8, H0Y3L3, H0YCH2, H0YG36, H0YH71

UniProt curated annotations — full annotation on UniProt →

Function. Component of the transcription factor SL1/TIF-IB complex, which is involved in the assembly of the PIC (preinitiation complex) during RNA polymerase I-dependent transcription. The rate of PIC formation probably is primarily dependent on the rate of association of SL1/TIF-IB with the rDNA promoter. SL1/TIF-IB is involved in stabilization of nucleolar transcription factor 1/UBTF on rDNA. Formation of SL1/TIF-IB excludes the association of TBP with TFIID subunits.

Subunit / interactions. Component of the transcription factor SL1/TIF-IB complex, composed of TBP and at least TAF1A, TAF1B, TAF1C and TAF1D. Interacts with UBTF.

Subcellular location. Nucleus.

RefSeq proteins (1): NP_077021* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR027976	TAF1D	Family

Pfam: PF15333

UniProt features (11 total): sequence conflict 3, modified residue 3, region of interest 2, compositionally biased region 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H5J8-F1	63.46	0.11

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 (3): 23, 138, 234

Function

Pathways and Gene Ontology

Reactome pathways

12 pathways

ID	Pathway
R-HSA-427359	SIRT1 negatively regulates rRNA expression
R-HSA-427413	NoRC negatively regulates rRNA expression
R-HSA-5250924	B-WICH complex positively regulates rRNA expression
R-HSA-73762	RNA Polymerase I Transcription Initiation
R-HSA-73772	RNA Polymerase I Promoter Escape
R-HSA-73863	RNA Polymerase I Transcription Termination
R-HSA-212165	Epigenetic regulation of gene expression
R-HSA-5250913	Positive epigenetic regulation of rRNA expression
R-HSA-5250941	Negative epigenetic regulation of rRNA expression
R-HSA-73854	RNA Polymerase I Promoter Clearance
R-HSA-73864	RNA Polymerase I Transcription
R-HSA-74160	Gene expression (Transcription)

MSigDB gene sets: 181 (showing top): MODULE_97, REACTOME_RNA_POLYMERASE_I_TRANSCRIPTION_INITIATION, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, MODULE_182, ATGCAGT_MIR217, KONG_E2F3_TARGETS, CATTTCA_MIR203, DEURIG_T_CELL_PROLYMPHOCYTIC_LEUKEMIA_DN, CHIARADONNA_NEOPLASTIC_TRANSFORMATION_CDC25_UP, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM6, BILD_E2F3_ONCOGENIC_SIGNATURE, GROSS_HYPOXIA_VIA_HIF1A_UP, GNF2_FBL

GO Biological Process (2): regulation of DNA-templated transcription (GO:0006355), RNA processing (GO:0006396)

GO Molecular Function (3): DNA binding (GO:0003677), identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (7): nucleoplasm (GO:0005654), RNA polymerase transcription factor SL1 complex (GO:0005668), nucleolus (GO:0005730), cytosol (GO:0005829), centriolar satellite (GO:0034451), mitotic spindle (GO:0072686), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Negative epigenetic regulation of rRNA expression	2
RNA Polymerase I Promoter Clearance	2
RNA Polymerase I Transcription	2
Gene expression (Transcription)	2
Epigenetic regulation of gene expression	2
Positive epigenetic regulation of rRNA expression	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
nuclear lumen	2
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
gene expression	1
RNA biosynthetic process	1
primary metabolic process	1
nucleic acid binding	1
protein binding	1
binding	1
RNA polymerase I transcription regulator complex	1
intracellular membraneless organelle	1
cytoplasm	1
centrosome	1
spindle	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1082 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TAF1D	TAF1A	Q15573	996
TAF1D	TAF1B	Q53T94	992
TAF1D	TAF1C	Q15572	990
TAF1D	UBTF	P17480	725
TAF1D	TAF12	Q16514	695
TAF1D	POLB	P06746	691
TAF1D	TBP	P20226	609
TAF1D	RRN3	Q9NYV6	520
TAF1D	TAF2	Q6P1X5	493
TAF1D	DENND4A	Q7Z401	489
TAF1D	PDILT	Q8N807	476
TAF1D	POLI	Q9UNA4	469
TAF1D	SNAPC3	Q92966	465
TAF1D	RNMT	O43148	448
TAF1D	NOL8	Q76FK4	446

IntAct

95 interactions, top by confidence:

A	B	Type	Score
EAF1	ELL2	psi-mi:“MI:0914”(association)	0.840
TAF1D	CEP70	psi-mi:“MI:0915”(physical association)	0.670
CEP70	TAF1D	psi-mi:“MI:0915”(physical association)	0.670
RPL14	RRP8	psi-mi:“MI:0914”(association)	0.640
NHLH2	TAF1D	psi-mi:“MI:0915”(physical association)	0.560
TAF1D	TAF1D	psi-mi:“MI:0915”(physical association)	0.560
TAF1D	HAP1	psi-mi:“MI:0915”(physical association)	0.550
PTN	TAF1D	psi-mi:“MI:0915”(physical association)	0.550
TAF1D	POLB	psi-mi:“MI:0915”(physical association)	0.540
POLB	TAF1D	psi-mi:“MI:0915”(physical association)	0.540
TAF1D	POLB	psi-mi:“MI:0403”(colocalization)	0.540
MECP2	GTPBP10	psi-mi:“MI:0914”(association)	0.530
TRIM44	ODAD3	psi-mi:“MI:0914”(association)	0.530
RBM34	NVL	psi-mi:“MI:0914”(association)	0.530
RRP8	NVL	psi-mi:“MI:0914”(association)	0.530
ZNF2	MPHOSPH10	psi-mi:“MI:0914”(association)	0.530
RPL18A	RRP8	psi-mi:“MI:0914”(association)	0.530
EPB41L3	AP3B1	psi-mi:“MI:0914”(association)	0.530
MAGEB2	POLRMT	psi-mi:“MI:0914”(association)	0.530
SRPK2	RRP9	psi-mi:“MI:0914”(association)	0.530

BioGRID (142): CEP70 (Two-hybrid), TAF1D (Affinity Capture-MS), TAF1D (Affinity Capture-MS), TAF1D (Affinity Capture-MS), TAF1A (Affinity Capture-MS), NPM1 (Affinity Capture-MS), TAF1C (Affinity Capture-MS), TAF1D (Affinity Capture-MS), TAF1D (Affinity Capture-MS), TAF1D (Affinity Capture-MS), TAF1D (Affinity Capture-MS), TAF1A (Affinity Capture-MS), TAF1C (Affinity Capture-MS), TAF1D (Affinity Capture-MS), TAF1D (Affinity Capture-MS)

ESM2 similar proteins: A0A1B0GR13, A2AEY4, B0QZF7, B3SRR7, B3SRX3, H2KZ49, O13757, O49498, O74981, P04515, P17467, P18036, P18037, P19715, P23047, P34338, P34627, P35662, P35663, P40167, P46013, P52529, P52530, P70486, Q01030, Q03703, Q04003, Q06813, Q09280, Q09458, Q11114, Q12418, Q2YDJ5, Q32LB6, Q3ZK65, Q4QY64, Q4V7B4, Q5JRM2, Q5M948, Q5RCX3

Diamond homologs: Q32LB6, Q5M948, Q5RCX3, Q9D4V4, Q9H5J8

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
TAF1D	“form complex”	“SL1 complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 84 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Peptide chain elongation	13	25.8×	9e-14
Viral mRNA Translation	13	25.8×	9e-14
ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ribosome stalled on a no-go mRNA	14	25.8×	5e-14
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	13	25.5×	9e-14
RNA Polymerase I Transcription Termination	5	25.5×	3e-05
Formation of a pool of free 40S subunits	14	24.5×	5e-14
Selenocysteine synthesis	13	24.4×	1e-13
Eukaryotic Translation Termination	13	24.4×	1e-13

GO biological processes:

GO term	Partners	Fold	FDR
cytoplasmic translation	13	30.1×	2e-13
ribosomal large subunit biogenesis	5	27.7×	2e-04
translation	13	16.7×	2e-10
rRNA processing	7	12.4×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	15
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2604 predictions. Top by Δscore:

Variant	Effect	Δscore
11:93729961:GGGTC:G	donor_gain	1.0000
11:93729962:GGTC:G	donor_gain	1.0000
11:93729963:GTC:G	donor_gain	1.0000
11:93729964:TCT:T	donor_gain	1.0000
11:93729965:CTAAG:C	donor_loss	1.0000
11:93729967:AAGGT:A	donor_loss	1.0000
11:93729971:T:A	donor_loss	1.0000
11:93730045:A:AG	acceptor_gain	1.0000
11:93730047:A:AG	acceptor_gain	1.0000
11:93730047:AG:A	acceptor_gain	1.0000
11:93730048:G:GA	acceptor_gain	1.0000
11:93730048:GG:G	acceptor_gain	1.0000
11:93730048:GGT:G	acceptor_gain	1.0000
11:93730048:GGTT:G	acceptor_gain	1.0000
11:93730048:GGTTA:G	acceptor_gain	1.0000
11:93736300:TCCCC:T	acceptor_gain	1.0000
11:93736301:CCCC:C	acceptor_gain	1.0000
11:93736301:CCCCC:C	acceptor_gain	1.0000
11:93736302:CCC:C	acceptor_gain	1.0000
11:93736302:CCCC:C	acceptor_gain	1.0000
11:93736303:CC:C	acceptor_gain	1.0000
11:93736303:CCC:C	acceptor_gain	1.0000
11:93736304:CC:C	acceptor_gain	1.0000
11:93736687:CACTT:C	donor_loss	1.0000
11:93736688:ACTT:A	donor_loss	1.0000
11:93736689:CTT:C	donor_loss	1.0000
11:93736690:TTACT:T	donor_loss	1.0000
11:93736691:TAC:T	donor_loss	1.0000
11:93736692:A:AC	donor_gain	1.0000
11:93736692:ACTG:A	donor_gain	1.0000

AlphaMissense

1841 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:93737181:A:G	L173P	0.994
11:93737199:A:G	L167P	0.991
11:93737236:C:G	A155P	0.991
11:93738110:T:A	E153V	0.990
11:93738109:C:A	E153D	0.985
11:93738109:C:G	E153D	0.985
11:93737195:C:A	K168N	0.984
11:93737195:C:G	K168N	0.984
11:93737173:A:G	S176P	0.983
11:93737230:C:G	A157P	0.983
11:93738110:T:G	E153A	0.981
11:93737219:A:C	F160L	0.979
11:93737219:A:T	F160L	0.979
11:93737221:A:G	F160L	0.979
11:93737169:A:G	L177S	0.978
11:93737224:C:G	G159R	0.978
11:93737224:C:T	G159R	0.978
11:93737232:A:T	V156D	0.977
11:93737220:A:G	F160S	0.976
11:93738132:A:G	W146R	0.975
11:93738132:A:T	W146R	0.975
11:93738112:A:C	F152L	0.973
11:93738112:A:T	F152L	0.973
11:93738114:A:G	F152L	0.973
11:93737223:C:T	G159E	0.972
11:93737229:G:T	A157E	0.972
11:93737119:G:T	R194S	0.970
11:93736293:G:C	F235L	0.969
11:93736293:G:T	F235L	0.969
11:93736295:A:G	F235L	0.969

dbSNP variants (sampled 300 via entrez): RS1000002165 (11:93741772 A>C), RS1000096681 (11:93742040 G>T), RS1000311746 (11:93740883 G>C,T), RS1000618151 (11:93741168 G>A), RS1000687560 (11:93735293 T>C,G), RS1000823478 (11:93735035 T>G), RS1000962418 (11:93741170 G>A), RS1001122861 (11:93731096 A>G), RS1001194844 (11:93730827 G>A), RS1001352414 (11:93736934 C>A,G,T), RS1001392515 (11:93730547 A>C,G), RS1001479163 (11:93735622 T>C), RS1001507218 (11:93734591 C>T), RS1001887286 (11:93741233 G>A), RS1002539698 (11:93730250 G>A,C)

Disease associations

OMIM: gene MIM:612823 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	4
Valproic Acid	affects cotreatment, increases expression, decreases expression	4
bisphenol A	affects expression, decreases expression, increases expression	3
trichostatin A	affects cotreatment, increases expression	3
Cyclosporine	increases expression	3
Cadmium Chloride	decreases expression, increases expression	3
chromium hexavalent ion	increases expression, increases abundance	2
Air Pollutants	decreases expression, affects expression, increases abundance	2
Arsenic	affects cotreatment, increases abundance, increases expression, decreases expression	2
aristolochic acid I	decreases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
GSK-J4	increases expression	1
FR900359	decreases phosphorylation	1
TAK-243	increases sumoylation	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression, increases expression	1
alpha phellandrene	decreases expression	1
beta-lapachone	increases expression	1
methylparaben	increases expression	1
sodium bichromate	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
cobaltous chloride	increases expression	1
zinc chromate	increases abundance, increases expression	1
potassium chromate(VI)	affects cotreatment, increases expression	1
epigallocatechin gallate	affects cotreatment, increases expression	1
polyhexamethyleneguanidine	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
pentabromodiphenyl ether	increases 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

Clinical trials (associated diseases)

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