POLR1D

Summary

POLR1D (RNA polymerase I and III subunit D, HGNC:20422) is a protein-coding gene on chromosome 13q12.2, encoding Protein POLR1D, isoform 2 (P0DPB5). It is haploinsufficient (ClinGen: sufficient evidence).

The protein encoded by this gene is a component of the RNA polymerase I and RNA polymerase III complexes, which function in the synthesis of ribosomal RNA precursors and small RNAs, respectively. Mutations in this gene are a cause of Treacher Collins syndrome (TCS), a craniofacial development disorder. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 51082 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Treacher Collins syndrome 2 (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 1
• Clinical variants (ClinVar): 112 total — 11 pathogenic, 10 likely-pathogenic
• Phenotypes (HPO): 78
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_015972

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20422
Approved symbol	POLR1D
Name	RNA polymerase I and III subunit D
Location	13q12.2
Locus type	gene with protein product
Status	Approved
Aliases	RPAC2, RPA16, RPO1-3, RPA9, MGC9850, AC19
Ensembl gene	ENSG00000186184
Ensembl biotype	protein_coding
OMIM	613715
Entrez	51082

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 15 protein_coding, 8 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay, 2 retained_intron

ENST00000302979, ENST00000399696, ENST00000399697, ENST00000465887, ENST00000472179, ENST00000489647, ENST00000621089, ENST00000626064, ENST00000626929, ENST00000627604, ENST00000630281, ENST00000630983, ENST00000636117, ENST00000636226, ENST00000636411, ENST00000636618, ENST00000636679, ENST00000636817, ENST00000636952, ENST00000637071, ENST00000637180, ENST00000637389, ENST00000685267, ENST00000692944, ENST00000693488, ENST00000869873, ENST00000927204

RefSeq mRNA: 4 — MANE Select: NM_015972 NM_001206559, NM_001374407, NM_015972, NM_152705

CCDS: CCDS73555, CCDS9324, CCDS9325

Canonical transcript exons

ENST00000302979 — 2 exons

Exon	Start	End
ENSE00001157702	27622875	27623449
ENSE00003899880	27621892	27622009

Expression profiles

Bgee: expression breadth ubiquitous, 288 present calls, max score 99.33.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 135.6251 / max 734.8202, expressed in 1827 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
134535	128.0538	1826
134528	6.2748	1540
134531	0.3119	161
134529	0.3027	149
134532	0.2913	131
134534	0.1557	66
134530	0.1526	74
134533	0.0824	35

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	99.33	gold quality
lower esophagus mucosa	UBERON:0035834	99.17	gold quality
secondary oocyte	CL:0000655	98.96	gold quality
skin of abdomen	UBERON:0001416	98.85	gold quality
body of stomach	UBERON:0001161	98.80	gold quality
cerebellar hemisphere	UBERON:0002245	98.75	gold quality
right adrenal gland cortex	UBERON:0035827	98.74	gold quality
right adrenal gland	UBERON:0001233	98.73	gold quality
right hemisphere of cerebellum	UBERON:0014890	98.73	gold quality
left ovary	UBERON:0002119	98.72	gold quality
cerebellar cortex	UBERON:0002129	98.69	gold quality
left adrenal gland cortex	UBERON:0035825	98.67	gold quality
right testis	UBERON:0004534	98.66	gold quality
skin of leg	UBERON:0001511	98.65	gold quality
left testis	UBERON:0004533	98.65	gold quality
left adrenal gland	UBERON:0001234	98.64	gold quality
esophagus mucosa	UBERON:0002469	98.61	gold quality
cortical plate	UBERON:0005343	98.61	gold quality
adrenal cortex	UBERON:0001235	98.57	gold quality
right uterine tube	UBERON:0001302	98.53	gold quality
cerebellum	UBERON:0002037	98.49	gold quality
pancreas	UBERON:0001264	98.48	gold quality
stomach	UBERON:0000945	98.47	gold quality
parotid gland	UBERON:0001831	98.47	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	98.46	gold quality
saliva-secreting gland	UBERON:0001044	98.45	gold quality
granulocyte	CL:0000094	98.43	gold quality
minor salivary gland	UBERON:0001830	98.43	gold quality
mucosa of stomach	UBERON:0001199	98.42	gold quality
monocyte	CL:0000576	98.39	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

71 targeting POLR1D, 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-5193	100.00	67.26	1744
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-767-5P	99.95	70.85	993
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-1200	99.71	70.42	1838
HSA-MIR-3934-5P	99.67	64.04	846
HSA-MIR-26A-1-3P	99.64	66.81	788
HSA-MIR-26A-2-3P	99.64	66.82	786
HSA-MIR-3685	99.62	68.83	1621
HSA-MIR-488-3P	99.61	68.79	1731
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-1252-3P	99.55	67.71	2862
HSA-MIR-510-3P	99.54	70.06	2965
HSA-MIR-4441	99.49	66.56	3216

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 13)

• analyzed the kinetics of assembly and elongation of the RNA polymerase I complex on endogenous ribosomal genes in the nuclei of living cells with the use of in vivo microscopy (PMID:12446911)
• heterozygous mutations of POLR1D in 252 individuals with Treacher Collins syndrome (PMID:21131976)
• Autosomal recessive POLR1D mutation with decrease of TCOF1 mRNA is responsible for Treacher Collins syndrome. (PMID:24603435)
• Mutations in TCOF1, POLR1C and POLR1D have all been implicated in causing TCS (PMID:24690222)
• Whole exome sequencing identified a nonsynonymous mutation in POLR1D (subunit of RNA polymerase I and II): exon2:c.T332C:p.L111P. (PMID:25348728)
• We report a clinical and extensive molecular study, including TCOF1, POLR1D, POLR1C, and EFTUD2 genes, in a series of 146 patients with TCS. (PMID:25790162)
• High POLR1D expression is associated with colorectal cancer progression. (PMID:30582221)
• POLR1B and neural crest cell anomalies in Treacher Collins syndrome type 4. (PMID:31649276)
• High POLR1D expression is an independent prognostic factor for poor overall survival in colorectal cancer. (PMID:31722331)
• Cell-free DNA analysis reveals POLR1D-mediated resistance to bevacizumab in colorectal cancer. (PMID:32087735)
• A clinically-relevant residue of POLR1D is required for Drosophila development. (PMID:35656583)
• POLR1D silencing suppresses lung cancer cells proliferation and migration via inhibition of PI3K-Akt pathway. (PMID:38844975)
• Characterization of the homologous mouse protein. (PMID:8955128)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	polr1d	ENSDARG00000037570
mus_musculus	Polr1d	ENSMUSG00000029642
rattus_norvegicus	Polr1d	ENSRNOG00000079294
drosophila_melanogaster	Polr1D	FBGN0086447
caenorhabditis_elegans		WBGENE00010230

Paralogs (3): POLR2J (ENSG00000005075), POLR2J2 (ENSG00000228049), POLR2J3 (ENSG00000285437)

Protein

Protein identifiers

Protein POLR1D, isoform 2 — P0DPB5 (reviewed: P0DPB5, P0DPB6)

All UniProt accessions (9): A0A087WTY1, A0A087X0U2, A0A0R4J2F3, A0A1B0GUZ5, A0A8I5KX40, A0A8I5QL02, P0DPB5, P0DPB6, Q7Z776

UniProt curated annotations — full annotation on UniProt →

Isoforms (2)

UniProt ID	Names	Canonical?
P0DPB5-1	2	yes
P0DPB6-1	1

RefSeq proteins (4): NP_001193488, NP_001361336, NP_057056, NP_689918 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR038948	POLR1D-like	Family
IPR008193	RNA_pol_Rpb11_13-16kDa_CS	Conserved_site
IPR009025	RBP11-like_dimer	Domain
IPR022905	Rpo11-like	Family
IPR033898	RNAP_AC19	Family
IPR036603	RBP11-like	Homologous_superfamily

Pfam: PF13656

UniProt features (24 total): sequence variant 7, strand 6, compositionally biased region 3, modified residue 3, chain 2, helix 2, region of interest 1

Structure

Experimental structures (PDB)

36 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
7OB9	ELECTRON MICROSCOPY	2.7
7AE1	ELECTRON MICROSCOPY	2.8
9K39	ELECTRON MICROSCOPY	2.8
7VBB	ELECTRON MICROSCOPY	2.81
7VBA	ELECTRON MICROSCOPY	2.89
7D58	ELECTRON MICROSCOPY	2.9
9K36	ELECTRON MICROSCOPY	2.9
9K2G	ELECTRON MICROSCOPY	3
9K3U	ELECTRON MICROSCOPY	3
7VBC	ELECTRON MICROSCOPY	3.01
7AE3	ELECTRON MICROSCOPY	3.1
7D59	ELECTRON MICROSCOPY	3.1
7OBA	ELECTRON MICROSCOPY	3.1
9K38	ELECTRON MICROSCOPY	3.1
9FSO	ELECTRON MICROSCOPY	3.28
7A6H	ELECTRON MICROSCOPY	3.3
7OBB	ELECTRON MICROSCOPY	3.3
9LXN	ELECTRON MICROSCOPY	3.3
7DU2	ELECTRON MICROSCOPY	3.35
9FSP	ELECTRON MICROSCOPY	3.39
7AEA	ELECTRON MICROSCOPY	3.4
8IUH	ELECTRON MICROSCOPY	3.4
7DN3	ELECTRON MICROSCOPY	3.5
9K3V	ELECTRON MICROSCOPY	3.5
9LKT	ELECTRON MICROSCOPY	3.5
9FSQ	ELECTRON MICROSCOPY	3.51
7FJI	ELECTRON MICROSCOPY	3.6
7FJJ	ELECTRON MICROSCOPY	3.6
9LXO	ELECTRON MICROSCOPY	3.6
9FSR	ELECTRON MICROSCOPY	3.76

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P0DPB5-F1	70.27	0.41
AF-P0DPB6-F1	86.77	0.71

Functional residue map

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

P0DPB5 (canonical)

Post-translational modifications (2): 1, 104

P0DPB6

Post-translational modifications (1): 1

Function

Pathways and Gene Ontology

Reactome pathways

22 pathways

ID	Pathway
R-HSA-1834949	Cytosolic sensors of pathogen-associated DNA
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-73780	RNA Polymerase III Chain Elongation
R-HSA-73863	RNA Polymerase I Transcription Termination
R-HSA-73980	RNA Polymerase III Transcription Termination
R-HSA-749476	RNA Polymerase III Abortive And Retractive Initiation
R-HSA-76061	RNA Polymerase III Transcription Initiation From Type 1 Promoter
R-HSA-76066	RNA Polymerase III Transcription Initiation From Type 2 Promoter
R-HSA-76071	RNA Polymerase III Transcription Initiation From Type 3 Promoter
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
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-74158	RNA Polymerase III Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-76046	RNA Polymerase III Transcription Initiation

MSigDB gene sets: 402 (showing top): REACTOME_RNA_POLYMERASE_III_TRANSCRIPTION_INITIATION_FROM_TYPE_3_PROMOTER, REACTOME_RNA_POLYMERASE_III_TRANSCRIPTION_TERMINATION, REACTOME_INNATE_IMMUNE_SYSTEM, REACTOME_RNA_POLYMERASE_III_CHAIN_ELONGATION, GOBP_DNA_TEMPLATED_TRANSCRIPTION_TERMINATION, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, REACTOME_RNA_POLYMERASE_I_TRANSCRIPTION_INITIATION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_TRANSCRIPTION_BY_RNA_POLYMERASE_III, AREB6_01, BIOCARTA_ARF_PATHWAY, CAGCTG_AP4_Q5, GOBP_RRNA_TRANSCRIPTION, KEGG_CYTOSOLIC_DNA_SENSING_PATHWAY, MUELLER_PLURINET

GO Biological Process (3): transcription elongation by RNA polymerase I (GO:0006362), transcription by RNA polymerase III (GO:0006383), DNA-templated transcription (GO:0006351)

GO Molecular Function (4): DNA binding (GO:0003677), DNA-directed RNA polymerase activity (GO:0003899), protein dimerization activity (GO:0046983), protein binding (GO:0005515)

GO Cellular Component (8): nucleoplasm (GO:0005654), cytosol (GO:0005829), RNA polymerase III complex (GO:0005666), RNA polymerase I complex (GO:0005736), nuclear DNA-directed RNA polymerase complex (GO:0055029), DNA-directed RNA polymerase complex (GO:0000428), nucleus (GO:0005634), nucleolus (GO:0005730)

Reactome top-level categories

Rollup of top-10 pathways:

Category	Pathways
RNA Polymerase III Transcription	3
RNA Polymerase III Transcription Initiation	3
Gene expression (Transcription)	3
RNA Polymerase I Promoter Clearance	2
RNA Polymerase I Transcription	2
Epigenetic regulation of gene expression	2
Innate Immune System	1
Negative epigenetic regulation of rRNA expression	1
Positive epigenetic regulation of rRNA expression	1
Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA-directed RNA polymerase complex	3
nuclear protein-containing complex	3
RNA biosynthetic process	2
nuclear lumen	2
cellular anatomical structure	2
DNA-templated transcription elongation	1
transcription by RNA polymerase I	1
DNA-templated transcription	1
gene expression	1
nucleic acid binding	1
5’-3’ RNA polymerase activity	1
protein binding	1
binding	1
cytoplasm	1
nucleolus	1
nucleoplasm	1
RNA polymerase complex	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

11 interactions, top by confidence:

A	B	Type	Score
POLR2L	RCCD1	psi-mi:“MI:0914”(association)	0.640
POLR3K	POLR3A	psi-mi:“MI:0914”(association)	0.640
POLR2F	POLR3A	psi-mi:“MI:0914”(association)	0.640
POLR3H	POLR3A	psi-mi:“MI:0914”(association)	0.530
CDC42	BBX	psi-mi:“MI:0914”(association)	0.350
CDK8	CCNC	psi-mi:“MI:0914”(association)	0.350
POLR1D	POLR3A	psi-mi:“MI:0914”(association)	0.350
POLR1H	POLR1C	psi-mi:“MI:0914”(association)	0.350
POLR1D	RPSA2	psi-mi:“MI:0914”(association)	0.350

ESM2 similar proteins: A5DFI4, A6ZVE9, B3LTX4, B5VKI1, C5DMI3, C7GWJ7, G2TRQ9, O14076, O14113, O14279, O16207, O36018, O43031, O74517, O94693, P0DPB5, P34656, P38326, P40470, P46947, P53277, P53317, P53854, P53913, Q03772, Q06152, Q12334, Q12420, Q28IC1, Q59LQ5, Q6BWZ7, Q6CIS0, Q6CJ08, Q6CKH1, Q6CLA4, Q6CUQ5, Q6FML0, Q6FNC2, Q6FSQ0, Q6FVL2

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
POLR1D	“form complex”	“RNA Polymerase I”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 13 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
RNA Polymerase III Chain Elongation	6	346.1×	5e-13
RNA Polymerase III Transcription Termination	6	270.8×	1e-12
RNA Polymerase III Transcription Initiation From Type 2 Promoter	6	230.7×	2e-12
RNA Polymerase III Transcription Initiation From Type 1 Promoter	6	222.5×	2e-12
RNA Polymerase III Transcription Initiation From Type 3 Promoter	6	222.5×	2e-12
RNA Polymerase III Transcription Initiation	6	183.2×	6e-12
RNA Polymerase III Transcription	6	178.0×	6e-12
Cytosolic sensors of pathogen-associated DNA	6	155.7×	1e-11

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	11
Likely pathogenic	10
Uncertain significance	54
Likely benign	17
Benign	14

Top pathogenic / likely-pathogenic (21)

Variant ID	HGVS	Classification
1458945	NM_015972.4(POLR1D):c.109dup (p.Arg37fs)	Pathogenic
156464	NM_015972.4(POLR1D):c.163C>G (p.Leu55Val)	Pathogenic
1697855	NM_015972.4(POLR1D):c.261del (p.Gly88fs)	Pathogenic
31051	NM_015972.4(POLR1D):c.152T>G (p.Leu51Arg)	Pathogenic
31052	NM_015972.4(POLR1D):c.326_327del (p.His109fs)	Pathogenic
31053	NM_015972.4(POLR1D):c.262_263dup (p.Thr89fs)	Pathogenic
31054	NM_015972.4(POLR1D):c.88_89dup (p.Gln31fs)	Pathogenic
4683085	NM_015972.4(POLR1D):c.232_233del (p.Ser78fs)	Pathogenic
546551	NM_015972.4(POLR1D):c.170dup (p.Tyr57Ter)	Pathogenic
563999	GRCh37/hg19 13q12.2(chr13:28147818-28258950)x1	Pathogenic
815578	GRCh37/hg19 13q12.2(chr13:28159780-28289790)x1	Pathogenic
1705417	NM_015972.4(POLR1D):c.89_117del (p.Val30fs)	Likely pathogenic
1806833	NM_015972.4(POLR1D):c.60dup (p.Gly21fs)	Likely pathogenic
2630776	NM_015972.4(POLR1D):c.265_268delinsTCTGAA (p.Thr89fs)	Likely pathogenic
3032749	NM_015972.4(POLR1D):c.128dup (p.Leu44fs)	Likely pathogenic
31049	NM_015972.4(POLR1D):c.259C>T (p.Arg87Ter)	Likely pathogenic
31050	NM_015972.4(POLR1D):c.139G>A (p.Glu47Lys)	Likely pathogenic
3899327	NM_015972.4(POLR1D):c.220dup (p.His74fs)	Likely pathogenic
451304	NM_015972.4(POLR1D):c.99_144del (p.Gly34fs)	Likely pathogenic
4526615	NM_015972.4(POLR1D):c.31del (p.Ile11fs)	Likely pathogenic
4814197	NM_015972.4(POLR1D):c.227C>A (p.Ser76Ter)	Likely pathogenic

SpliceAI

235 predictions. Top by Δscore:

Variant	Effect	Δscore
13:27622874:GAAAA:G	acceptor_gain	0.9900
13:27621575:G:T	donor_gain	0.9800
13:27622866:T:G	acceptor_gain	0.9800
13:27622873:A:AG	acceptor_gain	0.9800
13:27622874:G:GG	acceptor_gain	0.9800
13:27622006:AGAGG:A	donor_loss	0.9600
13:27622008:AG:A	donor_loss	0.9600
13:27622009:GGTAA:G	donor_loss	0.9600
13:27622010:GTAA:G	donor_loss	0.9600
13:27622011:T:A	donor_loss	0.9600
13:27622874:GA:G	acceptor_gain	0.9600
13:27622983:C:G	acceptor_gain	0.9600
13:27622007:GAG:G	donor_gain	0.9500
13:27622874:GAA:G	acceptor_gain	0.9500
13:27622874:GAAA:G	acceptor_gain	0.9500
13:27621987:G:GT	donor_gain	0.9300
13:27622857:T:G	acceptor_gain	0.9300
13:27622859:A:G	acceptor_gain	0.9200
13:27622870:TGTA:T	acceptor_loss	0.9200
13:27622872:TA:T	acceptor_loss	0.9200
13:27622873:A:T	acceptor_loss	0.9200
13:27622981:CACG:C	acceptor_gain	0.9200
13:27622982:ACGA:A	acceptor_gain	0.9200
13:27621575:G:GT	donor_gain	0.9100
13:27621884:C:A	acceptor_gain	0.9100
13:27622869:GTGTA:G	acceptor_loss	0.9100
13:27621539:G:GT	donor_gain	0.9000
13:27621539:G:T	donor_gain	0.8900
13:27622007:G:GT	donor_gain	0.8900
13:27622025:G:GT	donor_gain	0.8900

AlphaMissense

882 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
13:27623070:T:A	H74Q	0.998
13:27623070:T:G	H74Q	0.998
13:27623003:G:A	G52E	0.997
13:27623003:G:T	G52V	0.997
13:27623002:G:A	G52R	0.996
13:27623002:G:C	G52R	0.996
13:27623068:C:G	H74D	0.996
13:27623069:A:G	H74R	0.996
13:27623047:T:C	F67L	0.995
13:27623049:T:A	F67L	0.995
13:27623049:T:G	F67L	0.995
13:27623051:G:A	C68Y	0.995
13:27623156:T:C	L103P	0.995
13:27623147:T:C	L100P	0.994
13:27622995:T:A	H49Q	0.993
13:27622995:T:G	H49Q	0.993
13:27623012:T:C	L55P	0.993
13:27623050:T:C	C68R	0.993
13:27623052:T:G	C68W	0.993
13:27623099:T:A	I84N	0.993
13:27623007:T:A	N53K	0.992
13:27623007:T:G	N53K	0.992
13:27623054:G:A	G69D	0.992
13:27623056:T:C	Y70H	0.992
13:27623096:G:C	R83P	0.992
13:27622973:T:C	F42S	0.991
13:27622972:T:C	F42L	0.990
13:27622974:T:A	F42L	0.990
13:27622974:T:G	F42L	0.990
13:27622979:T:C	L44S	0.990

dbSNP variants (sampled 300 via entrez): RS1000028248 (13:27629858 C>T), RS1000054820 (13:27624030 A>C), RS1000226669 (13:27636204 G>C), RS1000252201 (13:27624283 C>T), RS1000286357 (13:27624490 G>A,T), RS1000493045 (13:27647930 A>G), RS1000593858 (13:27634445 C>G), RS1000617408 (13:27640912 C>T), RS1000662268 (13:27635828 A>C,T), RS1000775628 (13:27648333 C>A,T), RS1000808623 (13:27654416 T>C), RS1000832366 (13:27647626 G>A), RS1000959045 (13:27654814 T>C), RS1000964635 (13:27634757 C>G,T), RS1001157787 (13:27661694 C>T)

Disease associations

OMIM: gene MIM:613715 | disease phenotypes: MIM:613717, MIM:154500

GenCC curated gene-disease

Disease	Classification	Inheritance
Treacher Collins syndrome 2	Definitive	Autosomal dominant
Treacher-Collins syndrome	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
Treacher Collins syndrome 2	Definitive	AD

Mondo (3): Treacher Collins syndrome 2 (MONDO:0013385), hearing loss disorder (MONDO:0005365), Treacher-Collins syndrome (MONDO:0002457)

Orphanet (1): Treacher-Collins syndrome (Orphanet:861)

HPO phenotypes

78 total (30 of 78 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000046	Small scrotum
HP:0000143	Rectovaginal fistula
HP:0000154	Wide mouth
HP:0000160	Narrow mouth
HP:0000162	Glossoptosis
HP:0000164	Abnormality of the dentition
HP:0000175	Cleft palate
HP:0000204	Cleft upper lip
HP:0000218	High palate
HP:0000248	Brachycephaly
HP:0000272	Malar flattening
HP:0000278	Retrognathia
HP:0000294	Low anterior hairline
HP:0000308	Microretrognathia
HP:0000316	Hypertelorism
HP:0000327	Hypoplasia of the maxilla
HP:0000347	Micrognathia
HP:0000356	Abnormality of the outer ear
HP:0000358	Posteriorly rotated ears
HP:0000370	Abnormality of the middle ear
HP:0000384	Preauricular skin tag
HP:0000405	Conductive hearing impairment
HP:0000413	Atresia of the external auditory canal
HP:0000431	Wide nasal bridge
HP:0000452	Choanal stenosis
HP:0000453	Choanal atresia
HP:0000486	Strabismus

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST005951_4	Body mass index	2.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D034381	Hearing Loss	C09.218.458.341; C10.597.751.418.341; C23.888.592.763.393.341

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	increases abundance, increases oxidation, decreases expression, affects cotreatment	3
methylmercuric chloride	decreases expression	2
Particulate Matter	increases abundance, decreases expression	2
GSK-J4	increases expression	1
FR900359	increases phosphorylation	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
beta-lapachone	decreases expression, increases expression	1
sodium arsenite	decreases expression	1
cobaltous chloride	increases expression	1
butyraldehyde	decreases expression	1
potassium chromate(VI)	increases expression, affects cotreatment	1
methacrylaldehyde	increases oxidation, increases abundance, affects cotreatment	1
beta-methylcholine	affects expression	1
epigallocatechin gallate	affects cotreatment, increases expression	1
chloropicrin	decreases expression	1
(+)-JQ1 compound	decreases expression	1
Temozolomide	increases expression	1
Sunitinib	increases expression	1
Acetaminophen	increases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Arsenic	affects methylation	1
Atrazine	increases expression	1
Benzo(a)pyrene	affects methylation	1
Carbamazepine	affects expression	1
Diethylstilbestrol	decreases expression	1
Ketoconazole	decreases expression	1
Methyl Methanesulfonate	increases expression	1
Ozone	affects cotreatment, increases oxidation, increases abundance	1
Quercetin	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B2BI	Abcam HeLa POLR1D KO	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00205881	PHASE4	COMPLETED	Bilateral Benefit in Adult Users of the HiRes 90K Bionic Ear System
NCT00331539	PHASE4	UNKNOWN	Relationship Between Auto NRT and Behavioural T & C Levels With the Nucleus Freedom Cochlear Implant
NCT00424307	PHASE4	UNKNOWN	Bilateral Cochlear Implant Benefit in Young Children
NCT00765635	PHASE4	COMPLETED	Chlorobutanol, Potassium Carbonate, and Irrigation in Cerumen Removal
NCT03321006	PHASE4	COMPLETED	Treating Hearing Loss to Improve Mood and Cognition in Older Adults
NCT01499901	PHASE3	WITHDRAWN	Comparison of the Bilateral Sequential and Simultaneous Cochlear Implantation in the Deaf Children
NCT02561091	PHASE3	COMPLETED	AM-111 in the Treatment of Acute Inner Ear Hearing Loss
NCT03331627	PHASE3	COMPLETED	Safety and Efficacy of STR001-IT and STR001-ER in Patients With SSHL
NCT05532657	PHASE3	ACTIVE_NOT_RECRUITING	ACHIEVE Brain Health Follow-Up Study
NCT00013455	PHASE2	COMPLETED	Quantifying Auditory Perceptual Learning Following Hearing Aid Fitting
NCT00323427	PHASE2	COMPLETED	Clinical Trial of the Living Well With Hearing Loss Workshop
NCT00552786	PHASE2	COMPLETED	Antioxidation Medication for Noise-induced Hearing Loss
NCT00802425	PHASE2	COMPLETED	Efficacy of AM-111 in Patients With Acute Sensorineural Hearing Loss
NCT01139281	PHASE2	COMPLETED	The Protective Effect of Ginkgo Biloba Extract on Cisplatin-induced Ototoxicity in Humans
NCT01451853	PHASE2	UNKNOWN	SPI-1005 for Prevention and Treatment of Chemotherapy Induced Hearing Loss
NCT01588925	PHASE2	COMPLETED	Hearing Preservation Using Dexamethasone and Hyaluronic Acid for Cochlear Implantation
NCT01773278	PHASE2	RECRUITING	Cholesterol and Antioxidant Treatment in Patients With Smith-Lemli-Opitz Syndrome (SLOS)
NCT02832128	PHASE2	COMPLETED	Evaluating Possible Improvement in Speech and Hearing Tests After 28 Days of Dosing of the Study Drug AUT00063 Compared to Placebo (QuicKfire)
NCT04915183	PHASE2	RECRUITING	Atorvastatin to Reduce Cisplatin-Induced Hearing Loss Among Individuals With Head and Neck Cancer
NCT05258773	PHASE2	COMPLETED	Evaluation of the Presence of SENS-401 in the Perilymph
NCT06340633	PHASE2	RECRUITING	SPI-1005 in Adults Receiving Cochlear Implant
NCT00582946	PHASE1	COMPLETED	Wide-Bandwidth Open Canal Hearing Aid For Better Multitalker Speech Understanding
NCT00584155	PHASE1	WITHDRAWN	Protection From Cisplatin Ototoxicity by Lactated Ringers
NCT01206829	PHASE1	UNKNOWN	Hearing Impairment, Cognitive Therapy and Coping
NCT01256229	PHASE1	COMPLETED	Outcomes In Children With Developmental Delay And Deafness
NCT01343394	PHASE1	WITHDRAWN	Safety of Autologous Human Umbilical Cord Blood Mononuclear Fraction to Treat Acquired Hearing Loss in Children
NCT01452607	PHASE1	COMPLETED	Study to Evaluate the Safety and Pharmacokinetics of SPI-1005
NCT02259595	PHASE1	COMPLETED	Study to Determine the Safety, Tolerability, and Pharmacokinetic Profile of HPN-07 and HPN-07 Plus NAC
NCT04041440	PHASE1	COMPLETED	Speech Recognition Training in Children With Hearing Loss
NCT07218913	PHASE1	RECRUITING	Testing the Addition of Pedmark to Cisplatin Chemotherapy for Reducing Drug-Induced Ear Damage in Men With Stage II-III Metastatic Testicular Germ Cell Tumors
NCT04931056	Not specified	COMPLETED	A Post Market Clinical Follow-up Study on Biomet Microfixation HTR PEKK (Midface), Facial & Mandibular Plates.
NCT00486577	PHASE2/PHASE3	COMPLETED	Chronic Electrical Stimulation of the Auditory Cortex for Intractable Tinnitus
NCT00789061	PHASE2/PHASE3	UNKNOWN	Applying Proton Pump Inhibitor to Prevent and Treat Acute Fluctuating Hearing Loss in Patients With SLC26A4 Mutation
NCT01423409	PHASE2/PHASE3	COMPLETED	Multicenter Trial Assessing an Innovative VAS of Pain Among Deaf People
NCT05786378	PHASE2/PHASE3	UNKNOWN	Assessment of The Efficacy of Intratympanic Platelet Rich Plasma for Treatment of Sensorineural Hearing Loss.
NCT01108601	PHASE1/PHASE2	UNKNOWN	Transtympanic Ringer’s Lactate for the Prevention of Cisplatin Ototoxicity
NCT01621256	PHASE1/PHASE2	COMPLETED	Efficacy, Safety, and Tolerability of Ancrod in Patients With Sudden Hearing Loss
NCT06370351	PHASE1/PHASE2	RECRUITING	A Phase I/II Clinical Trial with SENS-501 in Children Suffering from Severe to Profound Hearing Loss Due to Otoferlin (OTOF) Mutations
NCT06545175	PHASE1/PHASE2	RECRUITING	Intracochlear Application of VSF1.01 for the Reduction of Cochlear Implant Surgery Related Trauma
NCT07304024	PHASE1/PHASE2	RECRUITING	A Treatment for a Form of Age-Related Central Auditory Processing Disorder Consisting of Clemastine Fumarate Plus Engineered Sound