TAF7L

Summary

TAF7L (TATA-box binding protein associated factor 7 like, HGNC:11548) is a protein-coding gene on chromosome Xq22.1, encoding Transcription initiation factor TFIID subunit 7-like (Q5H9L4). Probably functions as a spermatogenesis-specific component of the DNA-binding general transcription factor complex TFIID, a multimeric protein complex that plays a central role in mediating promoter responses to various activators and repressors.

This gene is similar to a mouse gene that encodes a TATA box binding protein-associated factor, and shows testis-specific expression. The encoded protein could be a spermatogenesis-specific component of the DNA-binding general transcription factor complex TFIID. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 54457 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 95 total — 1 pathogenic, 1 likely-pathogenic
• MANE Select transcript: NM_001168474

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11548
Approved symbol	TAF7L
Name	TATA-box binding protein associated factor 7 like
Location	Xq22.1
Locus type	gene with protein product
Status	Approved
Aliases	CT40
Ensembl gene	ENSG00000102387
Ensembl biotype	protein_coding
OMIM	300314
Entrez	54457

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000324762, ENST00000356784, ENST00000372907

RefSeq mRNA: 3 — MANE Select: NM_001168474 NM_001168474, NM_001410720, NM_024885

CCDS: CCDS35347, CCDS55466, CCDS94640

Canonical transcript exons

ENST00000356784 — 13 exons

Exon	Start	End
ENSE00000673943	101278049	101278121
ENSE00000673944	101281720	101281775
ENSE00000868931	101276307	101276528
ENSE00000868932	101277606	101277719
ENSE00000868935	101278994	101279035
ENSE00000868937	101282327	101282453
ENSE00000868938	101283450	101283583
ENSE00000868940	101286575	101286653
ENSE00001295538	101276000	101276112
ENSE00001319364	101275222	101275281
ENSE00001428283	101291224	101291334
ENSE00001435623	101268257	101269237
ENSE00003545475	101287478	101287545

Expression profiles

Bgee: expression breadth ubiquitous, 136 present calls, max score 91.50.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2556 / max 84.3570, expressed in 55 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
199944	0.1044	27
199943	0.1010	26
199945	0.0259	2
199946	0.0243	3

Top tissues by expression

266 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right testis	UBERON:0004534	91.50	gold quality
left testis	UBERON:0004533	91.09	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.83	gold quality
testis	UBERON:0000473	88.80	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.36	gold quality
adult organism	UBERON:0007023	69.02	gold quality
stromal cell of endometrium	CL:0002255	65.67	gold quality
endocervix	UBERON:0000458	62.33	gold quality
nucleus accumbens	UBERON:0001882	61.64	gold quality
endometrium	UBERON:0001295	59.47	gold quality
skin of leg	UBERON:0001511	58.79	gold quality
right lobe of liver	UBERON:0001114	57.12	gold quality
seminal vesicle	UBERON:0000998	57.05	silver quality
Brodmann (1909) area 9	UBERON:0013540	56.96	gold quality
ectocervix	UBERON:0012249	56.86	gold quality
anterior cingulate cortex	UBERON:0009835	56.34	gold quality
cingulate cortex	UBERON:0003027	56.33	gold quality
ventricular zone	UBERON:0003053	56.15	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	56.06	gold quality
right frontal lobe	UBERON:0002810	55.98	gold quality
amygdala	UBERON:0001876	55.88	gold quality
zone of skin	UBERON:0000014	55.03	gold quality
uterine cervix	UBERON:0000002	54.04	gold quality
caudate nucleus	UBERON:0001873	53.81	gold quality
skin of abdomen	UBERON:0001416	53.63	gold quality
prefrontal cortex	UBERON:0000451	53.44	gold quality
lateral globus pallidus	UBERON:0002476	53.26	gold quality
telencephalon	UBERON:0001893	52.89	gold quality
Ammon’s horn	UBERON:0001954	52.64	gold quality
neocortex	UBERON:0001950	52.63	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.59

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TBPL1

miRNA regulators (miRDB)

33 targeting TAF7L, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-520F-3P	99.82	71.32	1216
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-12124	99.68	69.17	2700
HSA-MIR-24-3P	99.59	69.97	1934
HSA-MIR-17-3P	99.55	66.77	1311
HSA-MIR-3176	99.25	64.35	954
HSA-MIR-3922-3P	99.25	64.96	1136
HSA-MIR-1264	99.25	66.81	1317
HSA-MIR-548AS-3P	99.12	69.12	2294
HSA-MIR-193A-3P	98.59	66.36	769
HSA-MIR-193B-3P	98.59	66.62	748
HSA-MIR-4266	98.53	67.29	1035
HSA-MIR-3144-3P	98.15	67.34	677
HSA-MIR-6502-3P	97.86	65.43	569
HSA-MIR-562	97.66	65.63	698
HSA-MIR-645	97.28	66.30	486

Literature-anchored findings (GeneRIF, showing 9)

• TAF7L gene polymorphisms were found in male infertility patients and normal controls. (PMID:16597641)
• The sequence variant in exon 13 of the TAF7L gene located on the X chromosome may represent a risk factor for spermatogenic failure. (PMID:17714218)
• expression of AURKC, OIP5, PIWIL2 and TAF7L differed between patients with Acute myeloid leukemia, myelodysplastic syndrome and healthy controls in a gender-dependent manner (PMID:23292864)
• Frameshift mutations of TAF7L gene is associated with stomach and colorectal cancers. (PMID:25098277)
• Over-expression of TAF7L was observed in breast tumor cell lines. (PMID:26107214)
• these findings support a putative role of TAF7L in tumor suppression (PMID:29307603)
• Identification of a missense mutation (D136G) in the X-linked TAF7L gene as a potential cause of oligozoospermia in men. (PMID:35554494)
• The association of testis-specific hTAF7L gene variants with idiopathic azoospermic and severe oligozoospermic male infertility. (PMID:36068176)
• Deleterious variants in TAF7L cause human oligoasthenoteratozoospermia and its impairing histone to protamine exchange inducing reduced in vitro fertilization. (PMID:36714566)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
mus_musculus	Taf7l	ENSMUSG00000009596
mus_musculus	Taf7l2	ENSMUSG00000121803
rattus_norvegicus	Taf7l-ps1	ENSRNOG00000022632
rattus_norvegicus	Taf7l	ENSRNOG00000026315
drosophila_melanogaster	Taf7	FBGN0024909
caenorhabditis_elegans		WBGENE00006388
caenorhabditis_elegans		WBGENE00006389

Paralogs (1): TAF7 (ENSG00000178913)

Protein

Protein identifiers

Transcription initiation factor TFIID subunit 7-like — Q5H9L4 (reviewed: Q5H9L4)

Alternative names: Cancer/testis antigen 40, RNA polymerase II TBP-associated factor subunit Q, TATA box-binding protein-associated factor 50 kDa, Transcription initiation factor TFIID 50 kDa subunit

All UniProt accessions (1): Q5H9L4

UniProt curated annotations — full annotation on UniProt →

Function. Probably functions as a spermatogenesis-specific component of the DNA-binding general transcription factor complex TFIID, a multimeric protein complex that plays a central role in mediating promoter responses to various activators and repressors. May play a role in spermatogenesis.

Subunit / interactions. TFIID is composed of TATA binding protein (TBP) and a number of TBP-associated factors (TAFs). TAF7L may replace TAF7 in a spermatogenesis-specific form of TFIID. Interacts with TBP; the interaction occurs in a sub-population of cells (pachytene and haploid round spermatids) and is developmentally regulated through differential intracellular localization of the two proteins. Interacts with TAF1.

Subcellular location. Nucleus. Cytoplasm.

Tissue specificity. Testis-specific.

Similarity. Belongs to the TAF7 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q5H9L4-1	1	yes
Q5H9L4-2	2
Q5H9L4-3	3

RefSeq proteins (3): NP_001161946, NP_001397649, NP_079161 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006751	TAFII55_prot_cons_reg	Domain
IPR037817	TAF7	Family

Pfam: PF04658

UniProt features (15 total): sequence variant 6, compositionally biased region 3, region of interest 2, splice variant 2, chain 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5H9L4-F1	68.14	0.33

Function

Pathways and Gene Ontology

Reactome pathways

20 pathways

ID	Pathway
R-HSA-167161	HIV Transcription Initiation
R-HSA-167162	RNA Polymerase II HIV Promoter Escape
R-HSA-167172	Transcription of the HIV genome
R-HSA-674695	RNA Polymerase II Pre-transcription Events
R-HSA-6804756	Regulation of TP53 Activity through Phosphorylation
R-HSA-73776	RNA Polymerase II Promoter Escape
R-HSA-73779	RNA Polymerase II Transcription Pre-Initiation And Promoter Opening
R-HSA-75953	RNA Polymerase II Transcription Initiation
R-HSA-76042	RNA Polymerase II Transcription Initiation And Promoter Clearance
R-HSA-162587	HIV Life Cycle
R-HSA-162599	Late Phase of HIV Life Cycle
R-HSA-162906	HIV Infection
R-HSA-1643685	Disease
R-HSA-212436	Generic Transcription Pathway
R-HSA-3700989	Transcriptional Regulation by TP53
R-HSA-5633007	Regulation of TP53 Activity
R-HSA-5663205	Infectious disease
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-9824446	Viral Infection Pathways

MSigDB gene sets: 79 (showing top): SCHWAB_TARGETS_OF_BMYB_POLYMORPHIC_VARIANTS_DN, GOBP_MALE_GAMETE_GENERATION, REACTOME_HIV_INFECTION, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM5, GOBP_DNA_TEMPLATED_TRANSCRIPTION_INITIATION, GOBP_TRANSCRIPTION_INITIATION_AT_RNA_POLYMERASE_II_PROMOTER, SLEBOS_HEAD_AND_NECK_CANCER_WITH_HPV_UP, TATA_C, GOCC_RNA_POLYMERASE_COMPLEX, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, GOBP_PROTEIN_DNA_COMPLEX_ORGANIZATION, GOCC_TRANSCRIPTION_FACTOR_TFIID_COMPLEX, GOCC_TRANSFERASE_COMPLEX_TRANSFERRING_PHOSPHORUS_CONTAINING_GROUPS, GOCC_RNA_POLYMERASE_II_TRANSCRIPTION_REGULATOR_COMPLEX, GOCC_TRANSFERASE_COMPLEX

GO Biological Process (4): spermatogenesis (GO:0007283), cell differentiation (GO:0030154), RNA polymerase II preinitiation complex assembly (GO:0051123), transcription initiation at RNA polymerase II promoter (GO:0006367)

GO Molecular Function (2): protein binding (GO:0005515), RNA polymerase II general transcription initiation factor activity (GO:0016251)

GO Cellular Component (3): transcription factor TFIID complex (GO:0005669), cytoplasm (GO:0005737), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-13 pathways:

Category	Pathways
RNA Polymerase II Transcription	4
Transcription of the HIV genome	2
RNA Polymerase II Transcription Initiation And Promoter Clearance	2
Late Phase of HIV Life Cycle	1
Regulation of TP53 Activity	1
HIV Infection	1
HIV Life Cycle	1
Viral Infection Pathways	1
Generic Transcription Pathway	1
Transcriptional Regulation by TP53	1
Disease	1
Gene expression (Transcription)	1
Infectious disease	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transcription by RNA polymerase II	2
developmental process involved in reproduction	1
male gamete generation	1
cellular developmental process	1
transcription initiation at RNA polymerase II promoter	1
transcription preinitiation complex assembly	1
DNA-templated transcription initiation	1
binding	1
general transcription initiation factor activity	1
RNA polymerase II, holoenzyme	1
RNA polymerase II transcription regulator complex	1
intracellular anatomical structure	1
cellular anatomical structure	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

926 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TAF7L	TBP	P20226	914
TAF7L	TBPL1	P62380	751
TAF7L	TAF4	O00268	658
TAF7L	TEX11	Q8IYF3	649
TAF7L	TAF8	Q7Z7C8	644
TAF7L	TAF9B	Q9HBM6	640
TAF7L	TAF5	Q15542	634
TAF7L	TBPL2	Q6SJ96	628
TAF7L	TAF6	P49848	625
TAF7L	NXF2B	Q9GZY0	618
TAF7L	TAF3	Q5VWG9	616
TAF7L	TAF10	Q12962	578
TAF7L	TAF12	Q16514	571
TAF7L	TAF9	Q16594	548
TAF7L	TAF1	P21675	544

IntAct

12 interactions, top by confidence:

A	B	Type	Score
NAA10	TAF7L	psi-mi:“MI:0915”(physical association)	0.560
TAF7L	TAF4	psi-mi:“MI:0914”(association)	0.530
SRPK2	TAF7L	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
LRRK2	TAF7L	psi-mi:“MI:0407”(direct interaction)	0.440
TAF7L	TUFM	psi-mi:“MI:0915”(physical association)	0.400
NEK4	E2F8	psi-mi:“MI:0914”(association)	0.350
TAF7L	KLRG2	psi-mi:“MI:0914”(association)	0.350
NAA10	TAF7L	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (46): TAF1 (Affinity Capture-MS), TAF3 (Affinity Capture-MS), TAF9B (Affinity Capture-MS), TAF2 (Affinity Capture-MS), TAF11 (Affinity Capture-MS), TAF6 (Affinity Capture-MS), TAF5 (Affinity Capture-MS), TAF4B (Affinity Capture-MS), TAF9 (Affinity Capture-MS), TAF8 (Affinity Capture-MS), TAF4 (Affinity Capture-MS), TAF12 (Affinity Capture-MS), TAF13 (Affinity Capture-MS), TAF10 (Affinity Capture-MS), UTP6 (Affinity Capture-MS)

ESM2 similar proteins: A2AU37, A5LFW4, A6QNM3, A6QPC8, A9SV60, A9SY64, B0BN28, C0SV12, C6KIE6, F4JET1, O15013, O60566, O65312, O82504, P43124, Q0V7M7, Q10SU5, Q24168, Q28GV1, Q2RBJ4, Q2TBI1, Q3V124, Q4V3E2, Q4V8G2, Q5H9L4, Q5RH01, Q60862, Q641G4, Q6AUQ7, Q75PQ8, Q86VD1, Q8C5W4, Q8H1E8, Q8N140, Q91628, Q96BD8, Q9C689, Q9CPV1, Q9FJX9, Q9LUR0

Diamond homologs: B9DG24, Q15545, Q2HJG8, Q4R5A5, Q5H9L4, Q5R7L9, Q6R1L1, Q9D3R9, Q9R1C0, Q9VHY5, O13701, Q05021

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

95 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	41
Likely benign	7
Benign	3

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
3246507	NC_000023.10:g.(?100486637)(100662891_?)del	Pathogenic
4086106	NM_001168474.2(TAF7L):c.145+1G>A	Likely pathogenic

SpliceAI

1462 predictions. Top by Δscore:

Variant	Effect	Δscore
X:101275216:TCTTA:T	donor_loss	1.0000
X:101275217:CTTAC:C	donor_loss	1.0000
X:101275218:TTA:T	donor_loss	1.0000
X:101275219:TA:T	donor_loss	1.0000
X:101275221:CCTT:C	donor_gain	1.0000
X:101275279:ATTC:A	acceptor_loss	1.0000
X:101275280:TT:T	acceptor_gain	1.0000
X:101275281:TCT:T	acceptor_loss	1.0000
X:101275282:C:CA	acceptor_loss	1.0000
X:101275282:C:CC	acceptor_gain	1.0000
X:101275283:T:G	acceptor_loss	1.0000
X:101275995:TTTAC:T	donor_loss	1.0000
X:101275996:TTACC:T	donor_loss	1.0000
X:101275997:TA:T	donor_loss	1.0000
X:101275998:A:C	donor_loss	1.0000
X:101275999:C:CT	donor_loss	1.0000
X:101276108:CATGA:C	acceptor_gain	1.0000
X:101276109:ATGA:A	acceptor_gain	1.0000
X:101276110:TGA:T	acceptor_gain	1.0000
X:101276111:GA:G	acceptor_gain	1.0000
X:101276113:C:CC	acceptor_gain	1.0000
X:101276527:TTCTA:T	acceptor_gain	1.0000
X:101276529:CTA:C	acceptor_gain	1.0000
X:101276532:C:CC	acceptor_gain	1.0000
X:101278057:A:AC	donor_gain	1.0000
X:101278058:C:CA	donor_gain	1.0000
X:101278058:CG:C	donor_gain	1.0000
X:101278058:CGG:C	donor_gain	1.0000
X:101278122:C:CC	acceptor_gain	1.0000
X:101278140:T:TC	acceptor_gain	1.0000

AlphaMissense

2543 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:101277717:A:G	W280R	0.988
X:101277717:A:T	W280R	0.988
X:101283501:G:C	S162R	0.987
X:101283501:G:T	S162R	0.987
X:101283503:T:G	S162R	0.987
X:101283562:A:T	V142D	0.987
X:101287494:A:T	I103K	0.986
X:101283535:G:T	A151D	0.984
X:101278061:C:G	A275P	0.982
X:101278081:A:G	L268P	0.981
X:101283464:C:G	A175P	0.980
X:101287488:C:G	R105P	0.980
X:101287491:A:G	L104S	0.979
X:101282329:C:T	G221D	0.978
X:101281738:G:C	F234L	0.976
X:101281738:G:T	F234L	0.976
X:101281740:A:G	F234L	0.976
X:101282442:G:C	C183W	0.975
X:101282444:A:G	C183R	0.974
X:101286637:A:T	V114D	0.974
X:101282449:A:T	L181H	0.973
X:101282452:A:G	M180T	0.973
X:101287489:G:T	R105S	0.972
X:101287494:A:C	I103R	0.972
X:101277715:C:A	W280C	0.968
X:101277715:C:G	W280C	0.968
X:101283499:A:G	L163P	0.968
X:101283520:A:G	L156S	0.968
X:101287485:A:G	L106P	0.968
X:101276031:A:G	L418P	0.965

dbSNP variants (sampled 300 via entrez): RS1000270309 (X:101284148 G>A), RS1000292111 (X:101288435 G>A), RS1000582636 (X:101290057 A>T), RS1000664021 (X:101288172 C>T), RS1000759115 (X:101280480 A>C), RS1000791768 (X:101280919 C>G,T), RS1000870154 (X:101270107 C>T), RS1000877026 (X:101271537 CTT>C), RS1000953236 (X:101267947 C>T), RS1000972144 (X:101280724 T>C), RS1001059443 (X:101290380 T>C), RS1001525325 (X:101294495 A>G), RS1001699481 (X:101286778 G>A), RS1001764718 (X:101287214 T>C), RS1001902227 (X:101276970 C>A)

Disease associations

OMIM: gene MIM:300314 | disease phenotypes: MIM:300643, MIM:301106

GenCC curated gene-disease

Mondo (3): rolandic epilepsy, intellectual disability, and speech dyspraxia, X-linked (MONDO:0010388), spermatogenic failure, X-linked, 7 (MONDO:0957202), congenital portosystemic shunt (MONDO:0018811)

Orphanet (1): Congenital portosystemic shunt (Orphanet:480531)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C564467	Rolandic Epilepsy, Mental Retardation, and Speech Dyspraxia, X-Linked (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

6 total (human), top 6 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
arsenite	increases methylation	1
cupric chloride	increases expression	1
CGP 52608	increases reaction, affects binding	1
Decitabine	decreases expression, decreases reaction	1
Benzo(a)pyrene	decreases methylation	1
Smoke	decreases expression, decreases reaction	1

Clinical trials (associated diseases)

2 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT06041906	Not specified	ENROLLING_BY_INVITATION	International Registry of Congenital Portosystemic Shunt (IRCPSS)
NCT07314814	Not specified	NOT_YET_RECRUITING	Genetic Hallmarks of Patients With Congenital Portosystemic Shunts and Portopulmonary Hypertension