TAF4

protein-coding

TATA-box binding protein associated factor 4, the group of General transcription factor IID complex subunits

Gene summary

Initiation of transcription by RNA polymerase II requires the activities of more than 70 polypeptides. The protein that coordinates these activities is transcription factor IID (TFIID), which binds to the core promoter to position the polymerase properly, serves as the scaffold for assembly of the remainder of the transcription complex, and acts as a channel for regulatory signals. TFIID is composed of the TATA-binding protein (TBP) and a group of evolutionarily conserved proteins known as TBP-associated factors or TAFs. TAFs may participate in basal transcription, serve as coactivators, function in promoter recognition or modify general transcription factors (GTFs) to facilitate complex assembly and transcription initiation. This gene encodes one of the larger subunits of TFIID that has been shown to potentiate transcriptional activation by retinoic acid, thyroid hormone and vitamin D3 receptors. In addition, this subunit interacts with the transcription factor CREB, which has a glutamine-rich activation domain, and binds to other proteins containing glutamine-rich regions. Aberrant binding to this subunit by proteins with expanded polyglutamine regions has been suggested as one of the pathogenetic mechanisms underlying a group of neurodegenerative disorders referred to as polyglutamine diseases. [provided by RefSeq, Jul 2008]

Previous symbols:

TAF4A
TAF2C1
TAF2C

MANE transcript

NM_003185.4

Inheritance

ClinVar variants

P:31U:253B:47

Top phenotype

Intellectual developmental disorder, autosomal dominant 73

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr20:61,953,469-62,065,881

External References & Databases

Ensembl (ENSG00000130699)

Transcript & Mutation Effects

hg38 • Region Span ~112.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

intellectual developmental disorder, autosomal dominant 73LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0957536

Submitter: G2P

intellectual developmental disorder, autosomal dominant 73STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0957536

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Intellectual developmental disorder, autosomal dominant 73AD

Manifestation: Craniofacial; Musculoskeletal; Neurologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 33875846; 35904126

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TAF4 variants in ClinVar

7 Conditions Cataloged

Inborn genetic diseasesTotal: 192

not providedTotal: 94

Intellectual developmental disorder, autosomal dominant 73Total: 35

not specifiedTotal: 26

TAF4-related disordersTotal: 4

Neurodevelopmental disorderTotal: 3

TAF4-related conditionTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003185.4. 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	27 clinvar	1 clinvar	31
missense		1 clinvar	236 clinvar	18 clinvar	1 clinvar	256
nonsense	5 clinvar	3 clinvar	2 clinvar			10
start loss						0
frameshift	7 clinvar	15 clinvar	7 clinvar			29
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	12	19	253	45	2	331

Highest pathogenic variant AF is 0.000007360771

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 7 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003185.4	RefSeq	NP_003176.2	15	MANE Select
ENST00000252996.9	Ensembl	ENSP00000252996.3	15	MANE Select
ENST00000474089.5	Ensembl	ENSP00000476270.1	3	Standard
ENST00000488539.1	Ensembl	ENSP00000476294.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Huntington,s disease - Homo sapiens (human)
Basal transcription factors - Homo sapiens (human)
Herpes simplex infection - Homo sapiens (human)
Disease
Gene expression (Transcription)

Biological Process

ovarian follicle development
DNA-templated transcription, initiation
transcription by RNA polymerase II
transcription initiation from RNA polymerase II promoter
viral process

Molecular Function

DNA binding
DNA-binding transcription factor activity
transcription coactivator activity
protein binding
transcription factor binding

Cellular Component

nuclear chromatin
nucleoplasm
transcription factor TFIID complex
cytosol
protein-containing complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000252996
Coding exons: 15
Length: 112342
Individuals with no LoFs: 108127
Homozygous LoFs: 0
Heterozygous LoFs: 1
Defined: 108128
p: 0.00000462

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.68	287	447	0.643	0.0000281	6715
Missense (PolyPhen)		95	214.62	0.44263		2374
Synonymous	-1.82	236	203	1.16	0.0000147	2473
Loss of Function	5.61	0	36.7	0.00	0.00000182	436

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000010	0.000010	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Part of the TFIID complex, a multimeric protein complex that plays a central role in mediating promoter responses to various activators and repressors. Potentiates transcriptional activation by the AF-2S of the retinoic acid, vitamin D3 and thyroid hormone.;

Recessive Scores

pRec: 0.185

Essentials

Essential (CRISPR): N
Essential (CRISPR2): E
Essential (gene trap): K
Indispensability pred.: N
Indispensability score: 0.309

Gene Damage Prediction

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