TAF1C

Summary

TAF1C (TATA-box binding protein associated factor, RNA polymerase I subunit C, HGNC:11534) is a protein-coding gene on chromosome 16q24.1, encoding TATA box-binding protein-associated factor RNA polymerase I subunit C (Q15572). Component of the transcription factor SL1/TIF-IB complex, which is involved in the assembly of the PIC (pre-initiation complex) during RNA polymerase I-dependent transcription. It is a common-essential gene (DepMap: required in 97.7% of cancer cell lines).

Initiation of transcription by RNA polymerase I requires the formation of a complex composed of the TATA-binding protein (TBP) and three TBP-associated factors (TAFs) specific for RNA polymerase I. This complex, known as SL1, binds to the core promoter of ribosomal RNA genes to position the polymerase properly and acts as a channel for regulatory signals. This gene encodes the largest SL1-specific TAF. Multiple alternatively spliced transcript variants encoding different isoforms have been identified.

Source: NCBI Gene 9013 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder (Moderate, GenCC) — +1 more curated relationship
• GWAS associations: 4
• Clinical variants (ClinVar): 263 total — 1 pathogenic
• Cancer dependency (DepMap): dependent in 97.7% of screened cell lines (common-essential)
• MANE Select transcript: NM_001243156

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11534
Approved symbol	TAF1C
Name	TATA-box binding protein associated factor, RNA polymerase I subunit C
Location	16q24.1
Locus type	gene with protein product
Status	Approved
Aliases	TAFI110, TAFI95, SL1, MGC:39976
Ensembl gene	ENSG00000103168
Ensembl biotype	protein_coding
OMIM	604905
Entrez	9013

Gene structure

Transcript identifiers

Ensembl transcripts: 46 — 32 protein_coding, 9 retained_intron, 4 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000341690, ENST00000537450, ENST00000541676, ENST00000544090, ENST00000561955, ENST00000562330, ENST00000562445, ENST00000563428, ENST00000564208, ENST00000564345, ENST00000564454, ENST00000564774, ENST00000565279, ENST00000565544, ENST00000566183, ENST00000566732, ENST00000566903, ENST00000567759, ENST00000568265, ENST00000569505, ENST00000569609, ENST00000570117, ENST00000570270, ENST00000898178, ENST00000898179, ENST00000898180, ENST00000898181, ENST00000898182, ENST00000898183, ENST00000898184, ENST00000898185, ENST00000898186, ENST00000898187, ENST00000898188, ENST00000898189, ENST00000919615, ENST00000919616, ENST00000919617, ENST00000963848, ENST00000963849, ENST00000963850, ENST00000963851, ENST00000963852, ENST00000963853, ENST00000963854, ENST00000963855

RefSeq mRNA: 7 — MANE Select: NM_001243156 NM_001243156, NM_001243157, NM_001243158, NM_001243159, NM_001243160, NM_005679, NM_139353

CCDS: CCDS32496, CCDS45535, CCDS58488, CCDS58489

Canonical transcript exons

ENST00000566732 — 15 exons

Exon	Start	End
ENSE00002583472	84186901	84187057
ENSE00002610350	84177855	84179851
ENSE00003459534	84183697	84183778
ENSE00003471700	84184851	84185060
ENSE00003481489	84181043	84181186
ENSE00003546988	84181592	84181663
ENSE00003569454	84183076	84183149
ENSE00003569902	84179946	84180083
ENSE00003585502	84183410	84183507
ENSE00003586629	84181328	84181463
ENSE00003588945	84183244	84183333
ENSE00003603343	84182202	84182440
ENSE00003608153	84180170	84180344
ENSE00003628586	84181746	84181863
ENSE00003646263	84181942	84182058

Expression profiles

Bgee: expression breadth ubiquitous, 242 present calls, max score 96.86.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 18.9923 / max 215.4254, expressed in 1804 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
158341	15.5165	1798
158340	2.9197	1423
158339	0.5561	298

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left ovary	UBERON:0002119	96.86	gold quality
right ovary	UBERON:0002118	96.76	gold quality
body of uterus	UBERON:0009853	96.08	gold quality
metanephros cortex	UBERON:0010533	95.67	gold quality
right lobe of thyroid gland	UBERON:0001119	95.66	gold quality
endocervix	UBERON:0000458	95.53	gold quality
left lobe of thyroid gland	UBERON:0001120	95.40	gold quality
right uterine tube	UBERON:0001302	95.33	gold quality
spleen	UBERON:0002106	95.27	gold quality
mucosa of stomach	UBERON:0001199	95.04	gold quality
apex of heart	UBERON:0002098	94.99	gold quality
left uterine tube	UBERON:0001303	94.92	gold quality
sural nerve	UBERON:0015488	94.92	gold quality
granulocyte	CL:0000094	94.85	gold quality
small intestine Peyer’s patch	UBERON:0003454	94.82	gold quality
tibial nerve	UBERON:0001323	94.81	gold quality
body of stomach	UBERON:0001161	94.45	gold quality
thyroid gland	UBERON:0002046	94.39	gold quality
right hemisphere of cerebellum	UBERON:0014890	94.13	gold quality
lower esophagus mucosa	UBERON:0035834	93.90	gold quality
omental fat pad	UBERON:0010414	93.78	gold quality
minor salivary gland	UBERON:0001830	93.76	gold quality
peritoneum	UBERON:0002358	93.75	gold quality
fundus of stomach	UBERON:0001160	93.69	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	93.63	gold quality
upper lobe of left lung	UBERON:0008952	93.58	gold quality
lower esophagus	UBERON:0013473	93.54	gold quality
lower esophagus muscularis layer	UBERON:0035833	93.54	gold quality
pituitary gland	UBERON:0000007	93.53	gold quality
adenohypophysis	UBERON:0002196	93.52	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.19

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TBP

miRNA regulators (miRDB)

41 targeting TAF1C, 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-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-3913-3P	99.74	66.53	938
HSA-MIR-3679-3P	99.64	69.88	1599
HSA-MIR-1252-3P	99.55	67.71	2862
HSA-MIR-6733-3P	99.54	67.80	1281
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-513C-5P	99.50	68.42	1730
HSA-MIR-514B-5P	99.50	68.19	1766
HSA-MIR-4316	99.37	65.75	1360
HSA-MIR-324-3P	99.26	66.31	1034
HSA-MIR-6770-5P	98.97	66.76	1853
HSA-MIR-224-3P	98.91	68.42	1815
HSA-MIR-522-3P	98.91	68.56	1817
HSA-MIR-181A-2-3P	98.91	67.60	1168
HSA-MIR-7113-3P	98.75	65.71	1120

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 97.7% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 6)

• SL1 directs preinitiation complex formation, functioning in core promoter binding, RNA polymerase I recruitment, and UBF stabilization. (PMID:15970593)
• PTEN represses RNA Pol I transcription through a novel mechanism that involves disruption of the SL1 complex (PMID:16055704)
• Our results indicate that TAF1C gene harboured not only somatic frameshift mutations but also the mutational ITH, which together might play a role in tumourigenesis of gastric and colorectal cancer. (PMID:25551296)
• hCdc14B promotes reactivation of rDNA transcription by dephosphorylating TAFI110. SIRT1 becomes transiently enriched in nucleoli at the onset of mitosis. SIRT1 deacetylates TAFI68 destabilizing SL1 binding to the rDNA promoter (PMID:26023773)
• Observed significantly higher TAF1C expression in patients with type 2 diabetes mellitus (T2DM), suggesting a role for increased protein synthesis in T2DM. (PMID:31039436)
• Homozygous TAF1C variants are associated with a novel childhood-onset neurological phenotype. (PMID:32779182)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	taf1c	ENSDARG00000096310
mus_musculus	Taf1c	ENSMUSG00000031832
rattus_norvegicus	Taf1c	ENSRNOG00000015632

Protein

Protein identifiers

TATA box-binding protein-associated factor RNA polymerase I subunit C — Q15572 (reviewed: Q15572)

Alternative names: RNA polymerase I-specific TBP-associated factor 110 kDa, TATA box-binding protein-associated factor 1C, Transcription initiation factor SL1/TIF-IB subunit C

All UniProt accessions (9): Q15572, H3BMQ4, H3BNH3, H3BQH8, H3BQZ8, H3BR71, H3BR91, H3BTQ6, H3BUZ7

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 (pre-initiation 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. Recruits RNA polymerase I to the rRNA gene promoter via interaction with RRN3.

Subunit / interactions. Component of the transcription factor SL1/TIF-IB complex, composed of TBP and at least TAF1A, TAF1B, TAF1C and TAF1D. In the complex interacts directly with TBP, TAF1A and TAF1B. Interaction of the SL1/TIF-IB subunits with TBP excludes interaction of TBP with the transcription factor IID (TFIID) subunits. Interacts with MYC and RRN3. Interacts with p53/TP53; the interaction prevents the association of SL1/TIF-IB with UBTF and represses RNA polymerase I transcription. Part of Pol I pre-initiation complex (PIC), in which Pol I core assembles with RRN3 and promoter-bound UTBF and SL1/TIF-IB complex.

Subcellular location. Nucleus. Nucleolus.

Isoforms (5)

UniProt ID	Names	Canonical?
Q15572-1	1	yes
Q15572-2	2
Q15572-4	4
Q15572-5	5
Q15572-6	6

RefSeq proteins (7): NP_001230085, NP_001230086, NP_001230087, NP_001230088, NP_001230089, NP_005670, NP_647610 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR036322	WD40_repeat_dom_sf	Homologous_superfamily
IPR038801	TAF1C	Family
IPR049087	TAF1C_beta-prop	Domain
IPR049089	TAF1C_C	Domain
IPR049090	TAF1C_HB	Domain

Pfam: PF20641, PF20642, PF20643

UniProt features (28 total): sequence variant 14, splice variant 5, sequence conflict 3, region of interest 2, modified residue 2, chain 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15572-F1	64.79	0.18

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 (2): 834, 848

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: 141 (showing top): REACTOME_RNA_POLYMERASE_I_TRANSCRIPTION_INITIATION, KYNG_DNA_DAMAGE_DN, KYNG_ENVIRONMENTAL_STRESS_RESPONSE_NOT_BY_GAMMA_IN_WS, GOBP_DNA_TEMPLATED_TRANSCRIPTION_INITIATION, DEBIASI_APOPTOSIS_BY_REOVIRUS_INFECTION_UP, KYNG_ENVIRONMENTAL_STRESS_RESPONSE_UP, GNF2_DDX5, GOBP_PROTEIN_DNA_COMPLEX_ORGANIZATION, KYNG_ENVIRONMENTAL_STRESS_RESPONSE_NOT_BY_UV_IN_OLD, GINESTIER_BREAST_CANCER_ZNF217_AMPLIFIED_DN, GOCC_TRANSCRIPTION_REGULATOR_COMPLEX, GOCC_NUCLEOLUS, MALONEY_RESPONSE_TO_17AAG_UP, KYNG_ENVIRONMENTAL_STRESS_RESPONSE_NOT_BY_4NQO_IN_OLD, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING

GO Biological Process (4): transcription by RNA polymerase I (GO:0006360), transcription initiation at RNA polymerase I promoter (GO:0006361), transcription by RNA polymerase II (GO:0006366), RNA polymerase I preinitiation complex assembly (GO:0001188)

GO Molecular Function (4): RNA polymerase I core promoter sequence-specific DNA binding (GO:0001164), RNA polymerase I general transcription initiation factor activity (GO:0001181), DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (5): fibrillar center (GO:0001650), nucleoplasm (GO:0005654), RNA polymerase transcription factor SL1 complex (GO:0005668), nucleolus (GO:0005730), 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
DNA-templated transcription	2
transcription by RNA polymerase I	2
cellular anatomical structure	2
nuclear lumen	2
DNA-templated transcription initiation	1
transcription initiation at RNA polymerase I promoter	1
transcription preinitiation complex assembly	1
core promoter sequence-specific DNA binding	1
RNA polymerase I transcription regulatory region sequence-specific DNA binding	1
RNA polymerase I preinitiation complex assembly	1
general transcription initiation factor activity	1
nucleic acid binding	1
binding	1
nucleolus	1
RNA polymerase I transcription regulator complex	1
intracellular membraneless organelle	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1760 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TAF1C	TAF1B	Q53T94	999
TAF1C	TAF1A	Q15573	999
TAF1C	TAF1D	Q9H5J8	990
TAF1C	RRN3	Q9NYV6	878
TAF1C	TBP	P20226	846
TAF1C	TAF1	P21675	724
TAF1C	POLI	Q9UNA4	699
TAF1C	TAF12	Q16514	675
TAF1C	UBTF	P17480	660
TAF1C	POLR1E	Q9GZS1	642
TAF1C	POLR1A	O95602	581
TAF1C	POLR1F	Q3B726	559
TAF1C	POLR1B	Q9H9Y6	515
TAF1C	TAF3	Q5VWG9	489
TAF1C	DR1	Q01658	443

IntAct

96 interactions, top by confidence:

A	B	Type	Score
EAF1	ELL2	psi-mi:“MI:0914”(association)	0.840
TAF1A	TBP	psi-mi:“MI:0914”(association)	0.740
CCT2	TXNDC9	psi-mi:“MI:0914”(association)	0.730
TAF1B	TAF1C	psi-mi:“MI:0915”(physical association)	0.670
TAF1C	TBP	psi-mi:“MI:0915”(physical association)	0.660
TBP	TAF1C	psi-mi:“MI:0915”(physical association)	0.660
RPL14	RRP8	psi-mi:“MI:0914”(association)	0.640
CCT3	TXNDC9	psi-mi:“MI:0914”(association)	0.640
CCT5	TXNDC9	psi-mi:“MI:0914”(association)	0.640
SET	TAF1C	psi-mi:“MI:0915”(physical association)	0.630
TAF1C	SET	psi-mi:“MI:0915”(physical association)	0.630
MECP2	GTPBP10	psi-mi:“MI:0914”(association)	0.530
TRIM44	ODAD3	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
RPL37A	MPHOSPH10	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
RPL18A	RRP8	psi-mi:“MI:0914”(association)	0.530
RPL8	ZBTB24	psi-mi:“MI:0914”(association)	0.530
SRPK2	RRP9	psi-mi:“MI:0914”(association)	0.530
PDGFB	DKC1	psi-mi:“MI:0914”(association)	0.530
TAF1C	DNAJA2	psi-mi:“MI:0914”(association)	0.530
CCT7	PEX7	psi-mi:“MI:0914”(association)	0.530
IMPDH1	BCAT2	psi-mi:“MI:0914”(association)	0.530
TAF1A	TAF1C	psi-mi:“MI:0914”(association)	0.530

BioGRID (150): TAF1C (Affinity Capture-MS), TAF1C (Affinity Capture-MS), TAF1C (Affinity Capture-MS), TAF1C (Affinity Capture-MS), TAF1C (Affinity Capture-MS), TAF1C (Affinity Capture-MS), TAF1C (Affinity Capture-MS), TAF1C (Affinity Capture-MS), TAF1C (Affinity Capture-MS), TAF1C (Affinity Capture-MS), TAF1C (Affinity Capture-MS), TAF1C (Affinity Capture-MS), TAF1C (Affinity Capture-MS), TAF1C (Affinity Capture-MS), TAF1C (Affinity Capture-MS)

ESM2 similar proteins: A0JN53, A1L3T7, C9JE40, D2I4M3, G3HQ82, O43299, O75800, O94812, P58660, Q0P5G1, Q15572, Q1RMI8, Q1W1Y5, Q3T1I9, Q3U829, Q56B11, Q571B6, Q58CQ5, Q5ND34, Q5R8S0, Q66H85, Q6NZL6, Q6ZNJ1, Q6ZQA0, Q76MJ5, Q80TE0, Q80UU1, Q80UW5, Q8BGI5, Q8BMG1, Q8C3R1, Q8C3S2, Q8C7B8, Q8CE13, Q8IZL8, Q8N163, Q8VDP4, Q8WXE1, Q96HA7, Q9BQG0

Diamond homologs: Q15572, Q6P773, Q6PDZ2

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
TAF1C	“form complex”	“SL1 complex”	binding
CDC14B	“up-regulates activity”	TAF1C	dephosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 102 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	16	26.0×	6e-17
Viral mRNA Translation	16	26.0×	6e-17
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	16	25.7×	6e-17
Selenocysteine synthesis	16	24.7×	6e-17
Eukaryotic Translation Termination	16	24.7×	6e-17
Formation of a pool of free 40S subunits	17	24.4×	5e-17
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	16	24.1×	7e-17
ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ribosome stalled on a no-go mRNA	16	24.1×	7e-17

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of telomere maintenance via telomerase	5	37.4×	2e-05
cytoplasmic translation	16	30.2×	5e-17
ribosomal large subunit biogenesis	5	22.6×	2e-04
translation	16	16.8×	4e-13
rRNA processing	9	13.0×	4e-06
protein folding	7	7.4×	3e-03
protein stabilization	10	6.8×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	205
Likely benign	25
Benign	4

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
163081	NM_178452.4(DNAAF1):c.(?-181)(*77_?)del	Pathogenic

SpliceAI

2951 predictions. Top by Δscore:

Variant	Effect	Δscore
16:84181859:CAGAG:C	acceptor_gain	1.0000
16:84181861:GAG:G	acceptor_gain	1.0000
16:84181863:GC:G	acceptor_loss	1.0000
16:84181864:C:CC	acceptor_gain	1.0000
16:84181864:CT:C	acceptor_loss	1.0000
16:84182149:T:TA	donor_gain	1.0000
16:84182205:G:C	donor_gain	1.0000
16:84182210:T:TA	donor_gain	1.0000
16:84182260:T:TA	donor_gain	1.0000
16:84182438:CAC:C	acceptor_gain	1.0000
16:84183054:T:TA	donor_gain	1.0000
16:84183239:CTCA:C	donor_loss	1.0000
16:84183240:TCAC:T	donor_loss	1.0000
16:84183241:CAC:C	donor_loss	1.0000
16:84183242:A:AC	donor_gain	1.0000
16:84183242:AC:A	donor_gain	1.0000
16:84183242:ACC:A	donor_gain	1.0000
16:84183242:ACCC:A	donor_gain	1.0000
16:84183243:C:CC	donor_gain	1.0000
16:84183243:CC:C	donor_gain	1.0000
16:84183243:CCC:C	donor_gain	1.0000
16:84183243:CCCC:C	donor_gain	1.0000
16:84183251:C:CA	donor_gain	1.0000
16:84183329:CTGAT:C	acceptor_gain	1.0000
16:84183330:TGAT:T	acceptor_gain	1.0000
16:84183331:GAT:G	acceptor_gain	1.0000
16:84183332:AT:A	acceptor_gain	1.0000
16:84183332:ATC:A	acceptor_loss	1.0000
16:84183333:TCTG:T	acceptor_loss	1.0000
16:84183334:C:CC	acceptor_gain	1.0000

AlphaMissense

5346 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:84181391:G:C	F393L	0.995
16:84181391:G:T	F393L	0.995
16:84181393:A:G	F393L	0.995
16:84181663:G:C	S345R	0.994
16:84181663:G:T	S345R	0.994
16:84181747:T:G	S345R	0.994
16:84181359:T:A	D404V	0.993
16:84181392:A:G	F393S	0.990
16:84181851:A:T	V310D	0.990
16:84181977:A:T	V268D	0.990
16:84181122:T:A	E436V	0.989
16:84181360:C:G	D404H	0.989
16:84181408:A:G	W388R	0.989
16:84181408:A:T	W388R	0.989
16:84178944:G:C	F869L	0.988
16:84178944:G:T	F869L	0.988
16:84178946:A:G	F869L	0.988
16:84180325:T:A	D469V	0.988
16:84181424:G:C	F382L	0.988
16:84181424:G:T	F382L	0.988
16:84181426:A:G	F382L	0.988
16:84181359:T:G	D404A	0.987
16:84181848:C:G	R311P	0.987
16:84182234:A:T	V230D	0.987
16:84180335:A:C	Y466D	0.986
16:84181825:A:G	W319R	0.986
16:84181825:A:T	W319R	0.986
16:84179766:G:C	F595L	0.985
16:84179766:G:T	F595L	0.985
16:84179768:A:G	F595L	0.985

dbSNP variants (sampled 300 via entrez): RS1000352479 (16:84188457 T>C), RS1000404699 (16:84188267 G>A,C), RS1000546493 (16:84183636 G>A), RS1000619504 (16:84180228 G>A,T), RS1000939934 (16:84183954 C>A), RS1001861881 (16:84187988 T>G), RS1002863558 (16:84186997 G>A,C), RS1003785383 (16:84186789 G>A), RS1004301472 (16:84184144 C>T), RS1004311356 (16:84188743 G>A,C), RS1004365185 (16:84184237 G>A), RS1004573975 (16:84187109 A>C,G), RS1004664511 (16:84188119 G>A), RS1004674926 (16:84183860 T>C), RS1004695635 (16:84188336 G>A)

Disease associations

OMIM: gene MIM:604905 | disease phenotypes: MIM:244400, MIM:613193

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder	Moderate	Autosomal recessive
complex neurodevelopmental disorder	Limited	Autosomal recessive

Mondo (4): primary ciliary dyskinesia (MONDO:0016575), primary ciliary dyskinesia 13 (MONDO:0013174), complex neurodevelopmental disorder (MONDO:0100038), neurodevelopmental disorder (MONDO:0700092)

Orphanet (2): Primary ciliary dyskinesia (Orphanet:244), Non-specific syndromic intellectual disability (Orphanet:528084)

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001523_23	Visceral adipose tissue adjusted for BMI	6.000000e-06
GCST001619_4	Autism	3.000000e-07
GCST003807_10	Systolic blood pressure response to hydrochlorothiazide in hypertension	1.000000e-06
GCST004097_3	Response to platinum-based neoadjuvant chemotherapy in cervical cancer	3.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0006944	systolic blood pressure change measurement
EFO:0007943	response to platinum-based neoadjuvant chemotherapy

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D002925	Ciliary Motility Disorders	C08.200; C09.150; C16.131.077.245.500; C16.320.184.500
D007619	Kartagener Syndrome	C08.127.384.500; C08.200.531; C08.695.501; C09.150.531; C14.240.400.280.500; C14.280.400.280.500; C16.131.077.245.500.531; C16.131.240.400.280.500; C16.131.740.501; C16.131.810.250.500; C16.320.184.500.531; C16.320.480
D065886	Neurodevelopmental Disorders	F03.625
C567713	Ciliary Dyskinesia, Primary, 13 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	3
Arsenic	increases abundance, increases expression, decreases expression, affects cotreatment	2
Benzo(a)pyrene	affects methylation, increases expression	2
aristolochic acid I	increases expression	1
FR900359	increases phosphorylation	1
bisphenol A	decreases expression	1
2,5,2’,5’-tetrachlorobiphenyl	decreases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
coumarin	increases phosphorylation	1
abrine	increases expression	1
Sunitinib	increases expression	1
Atrazine	decreases expression	1
Caffeine	decreases phosphorylation	1
Cisplatin	decreases expression	1
Doxorubicin	decreases expression	1
Ellagic Acid	decreases expression	1
Ivermectin	decreases expression	1
Manganese	affects cotreatment, increases abundance, increases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	increases methylation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT02871778	PHASE2	COMPLETED	Clearing Lungs With ENaC Inhibition in Primary Ciliary Dyskinesia
NCT07318974	PHASE2	ACTIVE_NOT_RECRUITING	Melatonin Therapy for Improving ICSI Outcomes in Women With Diminished Ovarian Reserve
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT05737485	PHASE1	COMPLETED	Study Evaluating the Safety and Tolerability of RCT1100 in Healthy and PCD Subjects
NCT06600425	PHASE1	COMPLETED	A Study to Assess the Safety, Tolerability, Ciliary Rescue, and Pharmacodynamics of RCT1100 in Adults With PCD
NCT06633757	PHASE1	COMPLETED	Study of Inhaled RCT1100 in Adults With PCD Caused by Pathogenic Mutations in the DNAI1 Gene to Measure Mucociliary Clearance
NCT06310681	Not specified	COMPLETED	Pilot Testing of a Co-adapted Group Programme for Parents/Carers of Children With Complex Neurodisability
NCT07303049	Not specified	NOT_YET_RECRUITING	Cognitive Benefit of Intensive Rehabilitation Using Rhythmic Music Training in Children With Complex Neurodevelopmental Disorder
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers