TTF2

protein-coding

transcription termination factor 2, the group of Zinc fingers GRF-type|MicroRNA protein coding host genes

Gene summary

This gene encodes a member of the SWI2/SNF2 family of proteins, which play a critical role in altering protein-DNA interactions. The encoded protein has been shown to have dsDNA-dependent ATPase activity and RNA polymerase II termination activity. This protein interacts with cell division cycle 5-like, associates with human splicing complexes, and plays a role in pre-mRNA splicing. [provided by RefSeq, Jul 2008]

MANE transcript

NM_003594.4

Inheritance

ClinVar variants

U:162B:34

Top phenotype

KBG syndrome

gnomAD constraint

pLI —, LoF o/e 0.69

Max pathogenic AF

—

Genomic locus

chr1:117,060,326-117,107,453

External References & Databases

Ensembl (ENSG00000116830)

Transcript & Mutation Effects

hg38 • Region Span ~47.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

congenital hypothyroidismLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0018612

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TTF2 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 164

not providedTotal: 20

KBG syndromeTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003594.4. 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				3 clinvar	4 clinvar	7
missense			155 clinvar	19 clinvar	8 clinvar	182
nonsense			2 clinvar			2
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	0	162	22	12	196

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 46 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003594.4	RefSeq	NP_003585.3	23	MANE Select
ENST00000369466.9	Ensembl	ENSP00000358478.3	23	MANE Select
ENST00000427271.1	Ensembl	ENSP00000408111.1	4	Standard
ENST00000931120.1	Ensembl	ENSP00000601179.1	23	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

Biological Process

DNA-templated transcription, termination
termination of RNA polymerase II transcription
mRNA processing
RNA splicing

Molecular Function

DNA binding
helicase activity
protein binding
ATP binding
DNA-dependent ATPase activity

Cellular Component

spliceosomal complex
cytosol
transcription elongation factor complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000369466
Coding exons: 23
Length: 47151
Individuals with no LoFs: 125620
Homozygous LoFs: 0
Heterozygous LoFs: 128
Defined: 125748
p: 0.000509

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.807	561	617	0.909	0.0000320	7548
Missense (PolyPhen)		175	191.47	0.91396		2366
Synonymous	-0.275	237	232	1.02	0.0000120	2273
Loss of Function	2.32	45	65.2	0.690	0.00000355	746

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00055	0.00055	rare
Latino/Admixed American	0.00073	0.00072	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00077	0.00076	rare
Finnish	0.00019	0.00018	rare
European (Non-Finnish)	0.00057	0.00057	rare
South Asian	0.00020	0.00020	rare
Other	0.00082	0.00081	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: DsDNA-dependent ATPase which acts as a transcription termination factor by coupling ATP hydrolysis with removal of RNA polymerase II from the DNA template. May contribute to mitotic transcription repression. May also be involved in pre-mRNA splicing. {ECO:0000269|PubMed:10455150, ECO:0000269|PubMed:12927788, ECO:0000269|PubMed:15125840, ECO:0000269|PubMed:9748214}.;

Recessive Scores

pRec: 0.0955

Intolerance Scores

LoFtool: 0.155
RVIS EVS: 1.43
RVIS percentile EVS: 95.03

Essentials

Essential (CRISPR): N
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.861

Gene Damage Prediction

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