TAF8

protein-coding

TATA-box binding protein associated factor 8, the group of General transcription factor IID complex subunits

Gene summary

This gene encodes one of several TATA-binding protein (TBP)-associated factors (TAFs), which are integral subunits of the general transcription factor complex TFIID. TFIID recognizes the core promoter of many genes and nucleates the assembly of a transcription preinitiation complex containing RNA polymerase II and other initiation factors. The protein encoded by this gene contains an H4-like histone fold domain, and interacts with several subunits of TFIID including TBP and the histone-fold protein TAF10. Alternatively spliced transcript variants have been described, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]

Previous symbols:

MANE transcript

NM_138572.3

Inheritance

ClinVar variants

P:7U:60B:6

Top phenotype

Neurodevelopmental disorder with severe motor impairment, absent language, cerebral hypomyelination, and brain atrophy

gnomAD constraint

pLI —, LoF o/e 1.07

Max pathogenic AF

—

Genomic locus

chr6:42,050,513-42,087,461

External References & Databases

Ensembl (ENSG00000137413)

Transcript & Mutation Effects

hg38 • Region Span ~36.9 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurodevelopmental disorder with severe motor impairment, absent language, cerebral hypomyelination, and brain atrophyMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0859266

Submitter: G2P

neurodevelopmental disorder with severe motor impairment, absent language, cerebral hypomyelination, and brain atrophySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0859266

Submitter: PanelApp Australia

neurodevelopmental disorder with severe motor impairment, absent language, cerebral hypomyelination, and brain atrophyLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0859266

Submitter: Ambry Genetics

neurodevelopmental disorder with severe motor impairment, absent language, cerebral hypomyelination, and brain atrophySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0859266

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Neurodevelopmental disorder with severe motor impairment, absent language, cerebral hypomyelination, and brain atrophyAR

Manifestation: Craniofacial; Neurologic; Ophthalmologic

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: 29648665; 35759269

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TAF8 variants in ClinVar

8 Conditions Cataloged

not specifiedTotal: 51

Neurodevelopmental disorder with severe motor impairment, absent language, cerebral hypomyelination, and brain atrophyTotal: 9

not providedTotal: 7

Neurodevelopmental disorderTotal: 2

TAF8-related disorderTotal: 1

Partial agenesis of the corpus callosumTotal: 1

MicrocephalyTotal: 1

Severe global developmental delayTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_138572.3. 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	1 clinvar		2 clinvar	3 clinvar		6
missense			52 clinvar	3 clinvar		55
nonsense	1 clinvar		2 clinvar			3
start loss						0
frameshift	2 clinvar	1 clinvar				3
splice donor/acceptor (+/-2bp)	1 clinvar	1 clinvar	4 clinvar			6
Total	5	2	60	6	0	73

Highest pathogenic variant AF is 0.00005029007

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 37 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_138572.3	RefSeq	NP_612639.2	9	MANE Select
ENST00000372977.8	Ensembl	ENSP00000362068.3	9	MANE Select
NM_001410906.1	RefSeq	NP_001397835.1	9	Standard
NM_001410907.1	RefSeq	NP_001397836.1	9	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
taf8	Danio rerio	Structure: anatomical system Quality: quality abnormal

Gene / Model

Organism

Observed Phenotype

taf8

Danio rerio

Structure: anatomical system

Quality: quality

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Basal transcription factors - Homo sapiens (human)
Gene expression (Transcription)
RNA polymerase II transcribes snRNA genes
RNA Polymerase II Transcription

Biological Process

inner cell mass cell proliferation
cell differentiation
snRNA transcription by RNA polymerase II
regulation of fat cell differentiation
positive regulation of transcription, DNA-templated

Molecular Function

protein binding
protein heterodimerization activity

Cellular Component

nucleus
nucleoplasm
transcription factor TFIID complex
perinuclear region of cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000372977
Coding exons: 9
Length: 36949
Individuals with no LoFs: 124776
Homozygous LoFs: 0
Heterozygous LoFs: 52
Defined: 124828
p: 0.000208

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.236	186	195	0.952	0.0000118	2007
Missense (PolyPhen)		53	62.098	0.85349		667
Synonymous	-1.77	98	78.1	1.25	0.00000499	631
Loss of Function	-0.253	18	16.9	1.07	9.01e-7	184

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00058	0.00058	rare
Latino/Admixed American	0.00029	0.00029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00017	0.00017	rare
Finnish	0.00019	0.00019	rare
European (Non-Finnish)	0.00019	0.00019	rare
South Asian	0.00013	0.00013	rare
Other	0	0.0	absent

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. Mediates both basal and activator-dependent transcription. Plays a role in the differentiation of preadipocyte fibroblasts to adipocytes, however, does not seem to play a role in differentiation of myoblasts. Required for the integration of TAF10 in the TAF complex. May be important for survival of cells of the inner cell mass which constitute the pluripotent cell population of the early embryo (By similarity). {ECO:0000250, ECO:0000269|PubMed:14580349}.;

Recessive Scores

pRec: 0.260

Intolerance Scores

LoFtool: 0.506
RVIS EVS: -0.38
RVIS percentile EVS: 27.69

Essentials

Essential (CRISPR): E
Essential (CRISPR2): S
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.833

Gene Damage Prediction

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