TAF6

protein-coding

TATA-box binding protein associated factor 6, the group of General transcription factor IID complex subunits |Armadillo like helical domain containing

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 smaller subunits of TFIID that binds weakly to TBP but strongly to TAF1, the largest subunit of TFIID. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2010]

Previous symbols:

TAF2E

MANE transcript

NM_139315.3

Inheritance

ClinVar variants

P:6U:115B:58

Top phenotype

Alazami-Yuan syndrome

gnomAD constraint

pLI —, LoF o/e 0.53

Max pathogenic AF

—

Genomic locus

chr7:100,106,876-100,119,841

External References & Databases

Ensembl (ENSG00000106290)

Transcript & Mutation Effects

hg38 • Region Span ~13.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Alazami-Yuan syndromeLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0014931

Submitter: Labcorp Genetics (formerly Invitae)

Alazami-Yuan syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014931

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Alazami-Yuan syndromeAR

Manifestation: Craniofacial; Dental; 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: 25558065; 25574841

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TAF6 variants in ClinVar

10 Conditions Cataloged

not providedTotal: 107

Inborn genetic diseasesTotal: 82

not specifiedTotal: 14

Alazami-Yuan syndromeTotal: 12

TAF6-related disorderTotal: 8

Intellectual disabilityTotal: 2

Abnormal facial shapeTotal: 1

Syndromic intellectual disabilityTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_139315.3. 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	43 clinvar	7 clinvar	52
missense	1 clinvar	1 clinvar	103 clinvar	7 clinvar	1 clinvar	113
nonsense	1 clinvar		2 clinvar			3
start loss						0
frameshift			3 clinvar			3
splice donor/acceptor (+/-2bp)		3 clinvar	5 clinvar			8
Total	2	4	115	50	8	179

Highest pathogenic variant AF is 0.00008055411

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 132 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_139315.3	RefSeq	NP_647476.1	14	MANE Select
ENST00000453269.7	Ensembl	ENSP00000389575.2	14	MANE Select
NM_001190415.2	RefSeq	NP_001177344.1	15	Standard
NM_001364998.1	RefSeq	NP_001351927.1	14	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
taf6	Danio rerio	Structure: whole organism Quality: quality abnormal

Gene / Model

Organism

Observed Phenotype

taf6

Danio rerio

Structure: whole organism

Quality: quality

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Basal transcription factors - Homo sapiens (human)
Herpes simplex infection - Homo sapiens (human)
Eukaryotic Transcription Initiation
Disease
Gene expression (Transcription)

Biological Process

chromatin organization
DNA-templated transcription, initiation
regulation of transcription by RNA polymerase II
transcription by RNA polymerase II
transcription initiation from RNA polymerase II promoter

Molecular Function

RNA polymerase II activating transcription factor binding
DNA binding
DNA-binding transcription factor activity
protein binding
aryl hydrocarbon receptor binding

Cellular Component

SAGA complex
nucleoplasm
transcription factor TFIID complex
cytosol
protein-containing complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000437822
Coding exons: 15
Length: 12772
Individuals with no LoFs: 124054
Homozygous LoFs: 50
Heterozygous LoFs: 1644
Defined: 125748
p: 0.00676

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.97	333	450	0.739	0.0000279	4554
Missense (PolyPhen)		58	123.43	0.46992		1232
Synonymous	-1.64	224	195	1.15	0.0000134	1552
Loss of Function	2.58	19	35.6	0.534	0.00000195	373

Population LoF Frequency

Population	CAF	p-value	Status
African	0.092	0.092	notable
Latino/Admixed American	0.0053	0.0053	notable
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00022	0.00022	rare
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.00032	0.00032	rare
South Asian	0.00069	0.00069	rare
Other	0.0042	0.0042	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: TAFs are components of the transcription factor IID (TFIID) complex, PCAF histone acetylase complex and TBP-free TAFII complex (TFTC). TIIFD is multimeric protein complex that plays a central role in mediating promoter responses to various activators and repressors.;
Disease: DISEASE: Alazami-Yuan syndrome (ALYUS) [MIM:617126]: An autosomal recessive syndrome reminiscent of Cornelia de Lange syndrome and characterized by delayed psychomotor development with intellectual disability, hypotonia, microcephaly, short stature, poor speech, and dysmorphic features. {ECO:0000269|PubMed:25558065, ECO:0000269|PubMed:25574841}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.138

Intolerance Scores

LoFtool: 0.827
RVIS EVS: -1.22
RVIS percentile EVS: 5.64

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.980

Gene Damage Prediction

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