GTF3C5

protein-coding

general transcription factor IIIC subunit 5, the group of General transcription factor IIIC complex subunits|MicroRNA protein coding host genes

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_012087.4

Inheritance

ClinVar variants

U:96B:10

Top phenotype

neurodevelopmental disorder

gnomAD constraint

pLI —, LoF o/e 0.59

Max pathogenic AF

—

Genomic locus

chr9:133,030,675-133,058,503

External References & Databases

Ensembl (ENSG00000148308)

Transcript & Mutation Effects

hg38 • Region Span ~27.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurodevelopmental disorderSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0700092

Submitter: PanelApp Australia

complex neurodevelopmental disorderMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0100038

Submitter: G2P

complex neurodevelopmental disorderLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0100038

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to GTF3C5 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 95

not providedTotal: 8

Multisystem developmental disorderTotal: 2

Myopathy, myofibrillar, 12, infantile-onset, with cardiomyopathyTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_012087.4. 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			1 clinvar	5 clinvar		6
missense			93 clinvar	5 clinvar		98
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	96	10	0	106

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 38 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_012087.4	RefSeq	NP_036219.2	11	MANE Select
ENST00000372097.10	Ensembl	ENSP00000361169.5	11	MANE Select
NM_001122823.2	RefSeq	NP_001116295.1	12	Standard
NM_001286709.2	RefSeq	NP_001273638.1	9	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
skeletal muscle cell differentiation
5S class rRNA transcription by RNA polymerase III
tRNA transcription by RNA polymerase III
RNA polymerase III preinitiation complex assembly

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
RNA polymerase III transcription regulator recruiting activity
DNA binding

Cellular Component

transcription factor TFIIIC complex
nucleoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000372108
Coding exons: 12
Length: 27815
Individuals with no LoFs: 125677
Homozygous LoFs: 0
Heterozygous LoFs: 71
Defined: 125748
p: 0.000282

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.772	292	332	0.881	0.0000207	3418
Missense (PolyPhen)		78	108.23	0.7207		1053
Synonymous	-0.999	149	134	1.11	0.00000872	1014
Loss of Function	2.02	17	28.7	0.593	0.00000162	308

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00031	0.00031	rare
Latino/Admixed American	0.00039	0.00038	rare
Ashkenazi Jewish	0.00091	0.00089	rare
East Asian	0.00044	0.00044	rare
Finnish	0.00018	0.00018	rare
European (Non-Finnish)	0.00022	0.00022	rare
South Asian	0.000099	0.000098	rare
Other	0.00066	0.00065	rare

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.;

Recessive Scores

pRec: 0.109

Intolerance Scores

LoFtool: 0.744
RVIS EVS: -1.11
RVIS percentile EVS: 6.83

Essentials

Essential (CRISPR): N
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.869

Gene Damage Prediction

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