TAF1C

protein-coding

TATA-box binding protein associated factor, RNA polymerase I subunit C

Gene summary

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. [provided by RefSeq, Jul 2011]

MANE transcript

NM_001243156.2

Inheritance

ClinVar variants

U:215B:27

Top phenotype

TAF1C-Associated Neurodevelopmental Disorder

gnomAD constraint

pLI —, LoF o/e 0.98

Max pathogenic AF

—

Genomic locus

chr16:84,177,847-84,187,070

External References & Databases

Ensembl (ENSG00000103168)

Transcript & Mutation Effects

hg38 • Region Span ~9.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

complex neurodevelopmental disorderLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0100038

Submitter: Ambry Genetics

neurodevelopmental disorderMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0700092

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TAF1C variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 216

not providedTotal: 17

TAF1C-Associated Neurodevelopmental DisorderTotal: 1

Primary ciliary dyskinesia 13Total: 1

Complex neurodevelopmental disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001243156.2. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			4 clinvar	4 clinvar	2 clinvar	10
missense			204 clinvar	20 clinvar	1 clinvar	225
nonsense			1 clinvar			1
start loss			1 clinvar			1
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	0	215	24	3	242

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 93 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001243156.2	RefSeq	NP_001230085.2	14	MANE Select
ENST00000566732.6	Ensembl	ENSP00000455933.1	14	MANE Select
NM_001243157.2	RefSeq	NP_001230086.1	7	Standard
NM_001243158.2	RefSeq	NP_001230087.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

B-WICH complex positively regulates rRNA expression
Positive epigenetic regulation of rRNA expression
SIRT1 negatively regulates rRNA expression
NoRC negatively regulates rRNA expression
Negative epigenetic regulation of rRNA expression

Biological Process

RNA polymerase I preinitiation complex assembly
regulation of transcription by RNA polymerase I
transcription by RNA polymerase I
transcription initiation from RNA polymerase I promoter
termination of RNA polymerase I transcription

Molecular Function

RNA polymerase I CORE element sequence-specific DNA binding
protein binding

Cellular Component

fibrillar center
nucleus
nucleoplasm
nucleolus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000567759
Coding exons: 13
Length: 9212
Individuals with no LoFs: 125673
Homozygous LoFs: 0
Heterozygous LoFs: 73
Defined: 125746
p: 0.000290

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-2.29	684	535	1.28	0.0000356	5397
Missense (PolyPhen)		222	202.41	1.0968		2221
Synonymous	-3.89	312	236	1.32	0.0000154	1938
Loss of Function	0.112	37	37.7	0.980	0.00000212	354

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00076	0.00074	rare
Latino/Admixed American	0.00023	0.00023	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.00017	0.00016	rare
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.00027	0.00025	rare
South Asian	0.00039	0.00039	rare
Other	0.00086	0.00081	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: 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. Recruits RNA polymerase I to the rRNA gene promoter via interaction with RRN3. {ECO:0000269|PubMed:11250903, ECO:0000269|PubMed:15970593}.;

Recessive Scores

pRec: 0.0925

Intolerance Scores

RVIS EVS: 0.59
RVIS percentile EVS: 82.46

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.656

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium