TTF1

protein-coding

transcription termination factor 1, the group of Myb/SANT domain containing

Gene summary

This gene encodes a transcription termination factor that is localized to the nucleolus and plays a critical role in ribosomal gene transcription. The encoded protein mediates the termination of RNA polymerase I transcription by binding to Sal box terminator elements downstream of pre-rRNA coding regions. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. This gene shares the symbol/alias 'TFF1' with another gene, NK2 homeobox 1, also known as thyroid transcription factor 1, which plays a role in the regulation of thyroid-specific gene expression. [provided by RefSeq, Apr 2011]

MANE transcript

NM_007344.4

Inheritance

ClinVar variants

U:133B:26

Top phenotype

Hypothyroidism, congenital, nongoitrous, 2

gnomAD constraint

pLI —, LoF o/e 0.67

Max pathogenic AF

—

Genomic locus

chr9:132,375,548-132,406,851

External References & Databases

Ensembl (ENSG00000125482)

Transcript & Mutation Effects

hg38 • Region Span ~31.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

congenital hypothyroidismMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0018612

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TTF1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 146

not providedTotal: 10

Hypothyroidism, congenital, nongoitrous, 2Total: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_007344.4. 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				2 clinvar	2 clinvar	4
missense			128 clinvar	19 clinvar	3 clinvar	150
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	0	133	21	5	159

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 18 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_007344.4	RefSeq	NP_031370.2	10	MANE Select
ENST00000334270.3	Ensembl	ENSP00000333920.2	10	MANE Select
NM_001205296.2	RefSeq	NP_001192225.1	9	Standard
ENST00000612514.4	Ensembl	ENSP00000481441.1	9	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Thyroid hormone synthesis - Homo sapiens (human)
Human Thyroid Stimulating Hormone (TSH) signaling pathway
ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression
Positive epigenetic regulation of rRNA expression
NoRC negatively regulates rRNA expression

Biological Process

DNA-templated transcription, termination
termination of RNA polymerase I transcription
negative regulation of DNA replication
cellular protein metabolic process

Molecular Function

DNA binding
chromatin binding

Cellular Component

nucleus
nucleoplasm
nucleolus
cytosol
plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000334270
Coding exons: 10
Length: 31202
Individuals with no LoFs: 125691
Homozygous LoFs: 0
Heterozygous LoFs: 57
Defined: 125748
p: 0.000227

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.107	476	483	0.986	0.0000257	5987
Missense (PolyPhen)		61	78.088	0.78117		996
Synonymous	-0.548	189	180	1.05	0.0000104	1654
Loss of Function	1.85	25	37.2	0.673	0.00000208	469

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00055	0.00055	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00021	0.00021	rare
South Asian	0.00024	0.00023	rare
Other	0.00081	0.00081	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Multifunctional nucleolar protein that terminates ribosomal gene transcription, mediates replication fork arrest and regulates RNA polymerase I transcription on chromatin. Plays a dual role in rDNA regulation, being involved in both activation and silencing of rDNA transcription. Interaction with BAZ2A/TIP5 recovers DNA-binding activity. {ECO:0000269|PubMed:7597036}.;

Recessive Scores

pRec: 0.0867

Intolerance Scores

LoFtool: 0.944
RVIS EVS: 1.27
RVIS percentile EVS: 93.67

Essentials

Essential (CRISPR): N
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.866

Gene Damage Prediction

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