GTF3C1

protein-coding

general transcription factor IIIC subunit 1, the group of General transcription factor IIIC complex subunits

Gene summary

Enables RNA polymerase III general transcription initiation factor activity. Involved in transcription initiation at RNA polymerase III promoter. Located in nucleoplasm. Part of transcription factor TFIIIC complex. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_001520.4

Inheritance

—

ClinVar variants

P:2U:267B:34

Top phenotype

Esophageal atresia/tracheoesophageal fistula

gnomAD constraint

pLI —, LoF o/e 0.1

Max pathogenic AF

—

Genomic locus

chr16:27,459,555-27,549,913

External References & Databases

Ensembl (ENSG00000077235)

Transcript & Mutation Effects

hg38 • Region Span ~90.4 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 GTF3C1 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 265

not providedTotal: 12

Esophageal atresia/tracheoesophageal fistulaTotal: 1

Abnormal brain morphologyTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001520.4. 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			6 clinvar	2 clinvar	6 clinvar	14
missense		2 clinvar	248 clinvar	24 clinvar	2 clinvar	276
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			12 clinvar			12
Total	0	2	267	26	8	303

Highest pathogenic variant AF is 0.000006568576

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 36 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001520.4	RefSeq	NP_001511.2	37	MANE Select
ENST00000356183.9	Ensembl	ENSP00000348510.4	37	MANE Select
NM_001286242.2	RefSeq	NP_001273171.1	37	Standard
ENST00000561623.5	Ensembl	ENSP00000455417.1	37	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Gene expression (Transcription)
rna polymerase iii 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

Biological Process

transcription by RNA polymerase III
transcription initiation from RNA polymerase III promoter
rRNA transcription
tRNA transcription
5S class rRNA transcription by RNA polymerase III

Molecular Function

RNA polymerase III general transcription initiation factor activity
RNA polymerase III type 1 promoter sequence-specific DNA binding
RNA polymerase III type 2 promoter sequence-specific DNA binding
DNA binding
protein binding

Cellular Component

transcription factor TFIIIC complex
nucleus
nucleoplasm
nucleolus
membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000356183
Coding exons: 37
Length: 90359
Individuals with no LoFs: 125726
Homozygous LoFs: 0
Heterozygous LoFs: 22
Defined: 125748
p: 0.0000875

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.26	950	1.28e+3	0.743	0.0000816	13820
Missense (PolyPhen)		252	458.97	0.54905		4694
Synonymous	-0.786	543	520	1.04	0.0000344	4153
Loss of Function	8.52	11	105	0.104	0.00000582	1157

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00021	0.00020	rare
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0	0.0	absent
Finnish	0.00019	0.00018	rare
European (Non-Finnish)	0.000072	0.000070	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Required for RNA polymerase III-mediated transcription. Component of TFIIIC that initiates transcription complex assembly on tRNA and is required for transcription of 5S rRNA and other stable nuclear and cytoplasmic RNAs. Binds to the box B promoter element.;

Recessive Scores

pRec: 0.286

Intolerance Scores

LoFtool: 0.282
RVIS EVS: -1.71
RVIS percentile EVS: 2.51

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.993

Gene Damage Prediction

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