GTF3C6

protein-coding

general transcription factor IIIC subunit 6, the group of General transcription factor IIIC complex subunits

Gene summary

RNA polymerases are unable to initiate RNA synthesis in the absence of additional proteins called general transcription factors (GTFs). GTFs assemble in a complex on the DNA promoter and recruit the RNA polymerase. GTF3C family proteins (e.g., GTF3C1, MIM 603246) are essential for RNA polymerase III to make a number of small nuclear and cytoplasmic RNAs, including 5S RNA (MIM 180420), tRNA, and adenovirus-associated (VA) RNA of both cellular and viral origin.[supplied by OMIM, Mar 2008]

Previous symbols:

C6orf51

MANE transcript

NM_138408.4

Inheritance

—

ClinVar variants

U:33B:1

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.63

Max pathogenic AF

—

Genomic locus

chr6:110,958,706-110,967,890

External References & Databases

Ensembl (ENSG00000155115)

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

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to GTF3C6 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 26

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_138408.4. 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						0
missense			28 clinvar	1 clinvar		29
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	0	33	1	0	34

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 48 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_138408.4	RefSeq	NP_612417.1	6	MANE Select
ENST00000329970.8	Ensembl	ENSP00000357863.4	6	MANE Select
ENST00000883260.1	Ensembl	ENSP00000553319.1	6	Standard
ENST00000883260.2	Ensembl	ENSP00000553319.1	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Gene expression (Transcription)
RNA Polymerase III Abortive And Retractive Initiation
RNA Polymerase III Transcription Initiation From Type 1 Promoter
RNA Polymerase III Transcription Initiation From Type 2 Promoter
RNA Polymerase III Transcription Initiation

Biological Process

transcription by RNA polymerase III
5S class rRNA transcription by RNA polymerase III
tRNA transcription by RNA polymerase III

Molecular Function

DNA binding
protein binding

Cellular Component

transcription factor TFIIIC complex
nucleoplasm
nuclear body

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000329970
Coding exons: 6
Length: 9331
Individuals with no LoFs: 125728
Homozygous LoFs: 0
Heterozygous LoFs: 16
Defined: 125744
p: 0.0000636

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.426	98	111	0.886	0.00000491	1422
Missense (PolyPhen)		20	27.405	0.72978		377
Synonymous	-1.19	47	37.7	1.25	0.00000186	362
Loss of Function	1.15	7	11.1	0.628	5.34e-7	142

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00043	0.00043	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000044	0.000044	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Involved in RNA polymerase III-mediated transcription. Integral, tightly associated component of the DNA-binding TFIIIC2 subcomplex that directly binds tRNA and virus-associated RNA promoters. {ECO:0000269|PubMed:17409385}.;

Recessive Scores

pRec: 0.0925

Intolerance Scores

LoFtool: 0.351
RVIS EVS: 0.17
RVIS percentile EVS: 65.33

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.854

Gene Damage Prediction

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