TAF2

protein-coding

TATA-box binding protein associated factor 2, the group of General transcription factor IID complex subunits |M1 metallopeptidases

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 is stably associated with the TFIID complex. It contributes to interactions at and downstream of the transcription initiation site, interactions that help determine transcription complex response to activators. [provided by RefSeq, Jul 2008]

Previous symbols:

TAF2B

MANE transcript

NM_003184.4

Inheritance

ClinVar variants

P:6U:178B:83

Top phenotype

Neurodevelopmental disorder with feeding difficulties, thin corpus callosum, and foot deformity

gnomAD constraint

pLI —, LoF o/e 0.28

Max pathogenic AF

—

Genomic locus

chr8:119,730,774-119,832,863

External References & Databases

Ensembl (ENSG00000064313)

Transcript & Mutation Effects

hg38 • Region Span ~102.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

microcephaly-thin corpus callosum-intellectual disability syndromeLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0014273

Submitter: G2P

microcephaly-thin corpus callosum-intellectual disability syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014273

Submitter: Labcorp Genetics (formerly Invitae)

microcephaly-thin corpus callosum-intellectual disability syndromeSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0014273

Submitter: Orphanet

microcephaly-thin corpus callosum-intellectual disability syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014273

Submitter: PanelApp Australia

microcephaly-thin corpus callosum-intellectual disability syndromeMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0014273

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Neurodevelopmental disorder with feeding difficulties, thin corpus callosum, and foot deformityAR

Manifestation: 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: 21937992; 24084144

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TAF2 variants in ClinVar

6 Conditions Cataloged

not providedTotal: 222

Inborn genetic diseasesTotal: 106

Microcephaly-thin corpus callosum-intellectual disability syndromeTotal: 25

not specifiedTotal: 17

TAF2-related disorderTotal: 10

MicrocephalyTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003184.4. 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	69 clinvar	6 clinvar	76
missense	1 clinvar	2 clinvar	156 clinvar	6 clinvar	2 clinvar	167
nonsense			4 clinvar			4
start loss						0
frameshift		1 clinvar	3 clinvar			4
splice donor/acceptor (+/-2bp)		2 clinvar	14 clinvar			16
Total	1	5	178	75	8	267

Highest pathogenic variant AF is 0.000013633654

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 44 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003184.4	RefSeq	NP_003175.2	26	MANE Select
ENST00000378164.7	Ensembl	ENSP00000367406.2	26	MANE Select
NM_001437338.1	RefSeq	NP_001424267.1	27	Standard
NM_001437339.1	RefSeq	NP_001424268.1	25	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
taf2	Danio rerio	Structure: trunk Quality: necrotic abnormal

Gene / Model

Organism

Observed Phenotype

taf2

Danio rerio

Structure: trunk

Quality: necrotic

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Basal transcription factors - Homo sapiens (human)
Disease
Gene expression (Transcription)
Generic Transcription Pathway
Transcription of the HIV genome

Biological Process

G2/M transition of mitotic cell cycle
transcription by RNA polymerase II
transcription initiation from RNA polymerase II promoter
response to organic cyclic compound
positive regulation of transcription by RNA polymerase II

Molecular Function

TFIID-class transcription factor complex binding
chromatin binding
protein binding
transcription regulatory region DNA binding

Cellular Component

nucleoplasm
transcription factor TFIID complex
transcription factor TFTC complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000378164
Coding exons: 26
Length: 102089
Individuals with no LoFs: 125707
Homozygous LoFs: 0
Heterozygous LoFs: 41
Defined: 125748
p: 0.000163

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.78	427	622	0.686	0.0000300	7993
Missense (PolyPhen)		89	163.78	0.54341		2142
Synonymous	-0.0383	212	211	1.00	0.0000103	2142
Loss of Function	5.19	17	60.6	0.281	0.00000293	788

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.00020	0.00020	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.00016	0.00016	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00015	0.00015	rare
South Asian	0.00013	0.00013	rare
Other	0.0011	0.00098	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Transcription factor TFIID is one of the general factors required for accurate and regulated initiation by RNA polymerase II. TFIID is a multimeric protein complex that plays a central role in mediating promoter responses to various activators and repressors. It requires core promoter-specific cofactors for productive transcription stimulation. TAF2 stabilizes TFIID binding to core promoter. {ECO:0000269|PubMed:9418870, ECO:0000269|PubMed:9774672}.;

Recessive Scores

pRec: 0.119

Intolerance Scores

LoFtool: 0.712
RVIS EVS: -0.04
RVIS percentile EVS: 50.5

Essentials

Essential (CRISPR): N
Essential (CRISPR2): E
Essential (gene trap): H
Indispensability pred.: N
Indispensability score: 0.477

Gene Damage Prediction

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