TAF4B

protein-coding

TATA-box binding protein associated factor 4b

Gene summary

TATA binding protein (TBP) and TBP-associated factors (TAFs) participate in the formation of the TFIID protein complex, which is involved in initiation of transcription of genes by RNA polymerase II. This gene encodes a cell type-specific TAF that may be responsible for mediating transcription by a subset of activators in B cells. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jun 2014]

Previous symbols:

TAF2C2

MANE transcript

NM_005640.3

Inheritance

AD, AR

ClinVar variants

P:1U:127B:27

Top phenotype

Spermatogenic failure 13

gnomAD constraint

pLI —, LoF o/e 0.24

Max pathogenic AF

—

Genomic locus

chr18:26,226,445-26,391,685

External References & Databases

Ensembl (ENSG00000141384)

Transcript & Mutation Effects

hg38 • Region Span ~165.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

male infertility with azoospermia or oligozoospermia due to single gene mutationSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0018393

Submitter: Orphanet

spermatogenic failure 13LIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0014365

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Spermatogenic failure 13AR

Manifestation: Genitourinary

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: 24431330

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TAF4B variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 129

not providedTotal: 17

TAF4B-related disorderTotal: 10

Spermatogenic failure 13Total: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005640.3. 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				9 clinvar	4 clinvar	13
missense			123 clinvar	9 clinvar	5 clinvar	137
nonsense	1 clinvar					1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	1	0	127	18	9	155

Highest pathogenic variant AF is 0.000005767911

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 26 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005640.3	RefSeq	NP_005631.1	15	MANE Select
ENST00000269142.10	Ensembl	ENSP00000269142.6	15	MANE Select
NM_001293725.2	RefSeq	NP_001280654.1	15	Standard
ENST00000418698.3	Ensembl	ENSP00000389365.3	10	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

transcription by RNA polymerase II
transcription initiation from RNA polymerase II promoter
spermatogenesis
positive regulation of transcription by RNA polymerase II
oogenesis

Molecular Function

DNA binding
DNA-binding transcription factor activity
transcription factor binding
protein heterodimerization activity
NF-kappaB binding

Cellular Component

fibrillar center
nucleoplasm
transcription factor TFIID complex
cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000269142
Coding exons: 15
Length: 165750
Individuals with no LoFs: 124776
Homozygous LoFs: 0
Heterozygous LoFs: 18
Defined: 124794
p: 0.0000721

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.353	417	438	0.952	0.0000210	5450
Missense (PolyPhen)		108	134.22	0.80463		1773
Synonymous	-1.26	188	167	1.12	0.00000823	1879
Loss of Function	4.37	9	38.1	0.236	0.00000205	453

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00013	0.00013	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0	0.0	absent
Finnish	0.00019	0.00019	rare
European (Non-Finnish)	0.000089	0.000088	rare
South Asian	0	0.0	absent
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Cell type-specific subunit of the general transcription factor TFIID that may function as a gene-selective coactivator in certain cells. TFIID is a multimeric protein complex that plays a central role in mediating promoter responses to various activators and repressors. TAF4B is a transcriptional coactivator of the p65/RELA NF-kappa-B subunit. Involved in the activation of a subset of antiapoptotic genes including TNFAIP3. May be involved in regulating folliculogenesis. Through interaction with OCBA/POU2AF1, acts as a coactivator of B-cell-specific transcription. Plays a role in spermiogenesis and oogenesis. {ECO:0000250|UniProtKB:G5E8Z2, ECO:0000269|PubMed:10828057, ECO:0000269|PubMed:10849440, ECO:0000269|PubMed:16088961, ECO:0000303|PubMed:24431330}.;
Disease: DISEASE: Spermatogenic failure 13 (SPGF13) [MIM:615841]: A disorder resulting in the absence (azoospermia) or reduction (oligozoospermia) of sperm in the semen, leading to male infertility. {ECO:0000269|PubMed:24431330}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.109

Intolerance Scores

LoFtool: 0.448
RVIS EVS: 0.58
RVIS percentile EVS: 82.31

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.797

Gene Damage Prediction

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