GTF2A1L

Summary

GTF2A1L (general transcription factor IIA subunit 1 like, HGNC:30727) is a protein-coding gene on chromosome 2p16.3, encoding TFIIA-alpha and beta-like factor (Q9UNN4). May function as a testis specific transcription factor.

The assembly and stability of the RNA polymerase II transcription pre-initiation complex on a eukaryotic core promoter involve the effects of transcription factor IIA (TFIIA) on the interaction between TATA-binding protein (TBP) and DNA. This gene encodes a germ cell-specific counterpart of the large (alpha/beta) subunit of general transcription factor TFIIA that is able to stabilize the binding of TBP to DNA and may be uniquely important to testis biology. Alternative splicing for this locus has been observed and two variants, encoding distinct isoforms, have been identified. Co-transcription of this gene and the neighboring upstream gene generates a rare transcript (SALF), which encodes a fusion protein comprised of sequence sharing identity with each individual gene product.

Source: NCBI Gene 11036 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 41 total — 1 pathogenic
• MANE Select transcript: NM_006872

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30727
Approved symbol	GTF2A1L
Name	general transcription factor IIA subunit 1 like
Location	2p16.3
Locus type	gene with protein product
Status	Approved
Aliases	ALF
Ensembl gene	ENSG00000242441
Ensembl biotype	protein_coding
OMIM	605358
Entrez	11036

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 5 protein_coding, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000403751, ENST00000423675, ENST00000430487, ENST00000437125, ENST00000448460, ENST00000468326, ENST00000508440

RefSeq mRNA: 2 — MANE Select: NM_006872 NM_001193487, NM_006872

CCDS: CCDS46281, CCDS54359

Canonical transcript exons

ENST00000403751 — 9 exons

Exon	Start	End
ENSE00001519447	48679335	48679604
ENSE00001939761	48617856	48617895
ENSE00003486372	48642402	48642457
ENSE00003504545	48621167	48621290
ENSE00003516662	48620851	48620952
ENSE00003576343	48671591	48671680
ENSE00003601040	48645033	48645117
ENSE00003666476	48669722	48669982
ENSE00003791421	48646453	48647042

Expression profiles

Bgee: expression breadth ubiquitous, 156 present calls, max score 91.64.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0781 / max 70.2217, expressed in 4 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
20206	0.0690	4
20204	0.0052	3
20205	0.0039	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	91.64	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	91.63	gold quality
right testis	UBERON:0004534	91.13	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.29	gold quality
testis	UBERON:0000473	88.19	gold quality
muscle layer of sigmoid colon	UBERON:0035805	79.49	gold quality
lower esophagus muscularis layer	UBERON:0035833	78.84	gold quality
lower esophagus	UBERON:0013473	78.75	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	77.85	gold quality
lower esophagus mucosa	UBERON:0035834	75.51	gold quality
stromal cell of endometrium	CL:0002255	73.15	gold quality
left uterine tube	UBERON:0001303	71.18	gold quality
calcaneal tendon	UBERON:0003701	71.01	gold quality
descending thoracic aorta	UBERON:0002345	70.87	gold quality
endocervix	UBERON:0000458	68.18	gold quality
body of uterus	UBERON:0009853	67.14	gold quality
esophagus	UBERON:0001043	66.93	gold quality
right lung	UBERON:0002167	66.25	gold quality
thoracic aorta	UBERON:0001515	65.93	gold quality
popliteal artery	UBERON:0002250	65.92	gold quality
tibial artery	UBERON:0007610	65.89	gold quality
ectocervix	UBERON:0012249	65.82	gold quality
aorta	UBERON:0000947	65.78	gold quality
myometrium	UBERON:0001296	65.78	gold quality
ascending aorta	UBERON:0001496	65.55	gold quality
left coronary artery	UBERON:0001626	65.47	gold quality
ventricular zone	UBERON:0003053	65.47	gold quality
mucosa of stomach	UBERON:0001199	65.45	gold quality
left ovary	UBERON:0002119	65.34	gold quality
omental fat pad	UBERON:0010414	65.15	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.97

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

21 targeting GTF2A1L, 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-513B-5P	99.99	69.96	2150
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-587	99.64	70.86	2611
HSA-MIR-4452	99.50	68.45	1493
HSA-MIR-422A	99.18	65.83	550
HSA-MIR-6737-3P	98.95	68.56	1577
HSA-MIR-7157-3P	98.95	68.70	1582
HSA-MIR-6074	98.89	69.64	2187
HSA-MIR-5008-3P	98.73	67.50	1433
HSA-MIR-4680-3P	98.64	68.60	2093
HSA-MIR-7158-3P	98.46	66.45	728
HSA-MIR-378A-3P	98.43	66.10	548
HSA-MIR-378B	98.43	65.36	573
HSA-MIR-378C	98.43	66.10	548
HSA-MIR-378D	98.43	66.10	548
HSA-MIR-378E	98.43	65.99	551
HSA-MIR-378F	98.43	65.66	554
HSA-MIR-378H	98.43	66.16	545
HSA-MIR-378I	98.43	66.10	548

Literature-anchored findings (GeneRIF, showing 4)

• A unique CpG-specific methylation pattern at the ALF promoter precedes expression in pachytene spermatocytes. (PMID:11889132)
• Results identified ALF as a human spermatogenesis related gene, the abnormal expression of ALF might be the partial cause for human infertility. (PMID:16525715)
• TFIIA tau is associated with undifferentiated cells during development, yet is down-regulated at the chromatin level upon cellular differentiation. (PMID:16646664)
• Our results provided a new insight into susceptibility of USF1 variant with male infertility. rs11204546 of OR2W3 and rs11677854 of GTF2A1L might be additional valuable molecular predictive markers (PMID:25374392)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	gtf2a1l	ENSDARG00000063670
mus_musculus	Gtf2a1l	ENSMUSG00000024154
rattus_norvegicus	Gtf2a1l	ENSRNOG00000016703
drosophila_melanogaster	TfIIA-L	FBGN0011289
caenorhabditis_elegans		WBGENE00004136

Paralogs (1): GTF2A1 (ENSG00000165417)

Protein

Protein identifiers

TFIIA-alpha and beta-like factor — Q9UNN4 (reviewed: Q9UNN4)

Alternative names: General transcription factor II A, 1-like factor

All UniProt accessions (6): A0A140VKA3, C9J2C1, C9JJY0, F8WE56, H0Y8M0, Q9UNN4

UniProt curated annotations — full annotation on UniProt →

Function. May function as a testis specific transcription factor. Binds DNA in conjunction with GTF2A2 and TBP (the TATA-binding protein) and together with GTF2A2, allows mRNA transcription.

Subcellular location. Nucleus.

Tissue specificity. Testis specific. Detected in adult testis mostly in round and elongating spermatids (at protein level). Detected in testis.

Induction. Down-regulated in Sertoli cell-only syndrome (SCOS) patients.

Similarity. Belongs to the TFIIA subunit 1 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9UNN4-1	1	yes
Q9UNN4-2	2

RefSeq proteins (2): NP_001180416, NP_006863* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004855	TFIIA_asu/bsu	Family
IPR009088	TFIIA_b-brl	Homologous_superfamily

Pfam: PF03153

UniProt features (7 total): compositionally biased region 2, sequence conflict 2, chain 1, region of interest 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UNN4-F1	53.77	0.18

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 63 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_UP, GOBP_COGNITION, NKX61_01, MODULE_205, GOBP_DNA_TEMPLATED_TRANSCRIPTION_INITIATION, GOBP_TRANSCRIPTION_INITIATION_AT_RNA_POLYMERASE_II_PROMOTER, TATA_C, GOCC_RNA_POLYMERASE_COMPLEX, CDPCR3HD_01, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, IVANOVA_HEMATOPOIESIS_EARLY_PROGENITOR, TAL1BETAE47_01, FOXO4_02, WEBER_METHYLATED_HCP_IN_FIBROBLAST_DN, GOCC_TRANSFERASE_COMPLEX_TRANSFERRING_PHOSPHORUS_CONTAINING_GROUPS

GO Biological Process (4): transcription by RNA polymerase II (GO:0006366), transcription initiation at RNA polymerase II promoter (GO:0006367), cognition (GO:0050890), positive regulation of DNA-templated transcription (GO:0045893)

GO Molecular Function (3): DNA binding (GO:0003677), transcription coactivator activity (GO:0003713), protein binding (GO:0005515)

GO Cellular Component (4): male germ cell nucleus (GO:0001673), transcription factor TFIIA complex (GO:0005672), cytoplasm (GO:0005737), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA-templated transcription	2
DNA-templated transcription initiation	1
transcription by RNA polymerase II	1
nervous system process	1
regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
nucleic acid binding	1
transcription coregulator activity	1
positive regulation of DNA-templated transcription	1
binding	1
germ cell nucleus	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

580 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GTF2A1L	STON1	Q9Y6Q2	932
GTF2A1L	GTF2A2	P52657	891
GTF2A1L	TBP	P20226	713
GTF2A1L	TBPL1	P62380	557
GTF2A1L	TASP1	Q9H6P5	539
GTF2A1L	STPG4	Q8N801	472
GTF2A1L	PPP1R27	Q86WC6	445
GTF2A1L	LHCGR	P22888	429
GTF2A1L	CSNK2A1	P19138	424
GTF2A1L	RNASEH2A	O75792	419
GTF2A1L	TAF10	Q12962	417
GTF2A1L	DENND1A	Q8TEH3	406
GTF2A1L	PPP1R21	Q6ZMI0	402
GTF2A1L	TMEM247	A6NEH6	400
GTF2A1L	TAF4	O00268	399

IntAct

21 interactions, top by confidence:

A	B	Type	Score
GAB1	GTF2A1L	psi-mi:“MI:0915”(physical association)	0.560
GTF2A1L	GAB1	psi-mi:“MI:0915”(physical association)	0.560
HMG20A	GTF2A1L	psi-mi:“MI:0915”(physical association)	0.370
CEBPE	GTF2A1L	psi-mi:“MI:0915”(physical association)	0.370
EMX1	GTF2A1L	psi-mi:“MI:0915”(physical association)	0.370
EMX2	GTF2A1L	psi-mi:“MI:0915”(physical association)	0.370
TLX2	GTF2A1L	psi-mi:“MI:0915”(physical association)	0.370
HOXA5	GTF2A1L	psi-mi:“MI:0915”(physical association)	0.370
HOXC9	GTF2A1L	psi-mi:“MI:0915”(physical association)	0.370
HOXC11	GTF2A1L	psi-mi:“MI:0915”(physical association)	0.370
MAFG	GTF2A1L	psi-mi:“MI:0915”(physical association)	0.370
ATF4	GTF2A1L	psi-mi:“MI:0915”(physical association)	0.370
SIX6	GTF2A1L	psi-mi:“MI:0915”(physical association)	0.370
PAX9	GTF2A1L	psi-mi:“MI:0915”(physical association)	0.370
GTF2A1L	NKX2-3	psi-mi:“MI:0915”(physical association)	0.370
GTF2A1L	RBFOX2	psi-mi:“MI:0915”(physical association)	0.370
GTF2A1L	MAFF	psi-mi:“MI:0915”(physical association)	0.370
GTF2A1L	TLX3	psi-mi:“MI:0915”(physical association)	0.370
GTF2A1L	ZBTB3	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (25): GTF2A1L (Two-hybrid), GTF2A1L (Synthetic Lethality), GTF2A1L (Reconstituted Complex), GTF2A1L (Co-fractionation), GTF2A1L (Co-fractionation), GTF2A1L (Co-fractionation), GTF2A1L (Co-fractionation), GTF2A1L (Co-fractionation), GTF2A1L (Two-hybrid), GTF2A1L (Two-hybrid), GTF2A1L (Two-hybrid), GTF2A1L (Two-hybrid), GTF2A1L (Two-hybrid), GTF2A1L (Two-hybrid), GTF2A1L (Two-hybrid)

ESM2 similar proteins: A0A1L8GSA2, A0A1L8H0H2, A0JP82, A0MS83, A2AWL7, A2RRX6, A6NCI8, B2RRF6, F8VPJ6, K9JHZ4, O43303, P15822, P16128, P48552, P52551, P59759, Q03172, Q14207, Q28DZ0, Q2KHR2, Q3V0A6, Q3Y4E1, Q499M7, Q4V7H1, Q4V7J0, Q5DTW7, Q5R782, Q5R9I1, Q60988, Q61624, Q62806, Q68DE3, Q7SZL5, Q7TSH4, Q8BMA5, Q8CBD1, Q8CDD9, Q8IWI9, Q8NFU7, Q90ZS6

Diamond homologs: O08949, P32773, P52654, P52655, Q54G80, Q5RCU0, Q8R4I4, Q8SW23, Q99PM3, Q9UNN4, Q9USU9

SIGNOR signaling

8 interactions.

A	Effect	B	Mechanism
CSNK2A1	“up-regulates activity”	GTF2A1L	phosphorylation
CSNK2A2	“up-regulates activity”	GTF2A1L	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	38
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
151770	GRCh38/hg38 2p16.3(chr2:48634764-48761441)x0	Pathogenic

SpliceAI

4534 predictions. Top by Δscore:

Variant	Effect	Δscore
2:48618086:G:GT	donor_gain	1.0000
2:48621163:GCA:G	acceptor_loss	1.0000
2:48621165:A:AG	acceptor_gain	1.0000
2:48621165:AGC:A	acceptor_loss	1.0000
2:48621166:G:GA	acceptor_gain	1.0000
2:48621166:GCTCT:G	acceptor_gain	1.0000
2:48621309:A:AG	donor_gain	1.0000
2:48642397:T:G	acceptor_gain	1.0000
2:48642400:A:AG	acceptor_gain	1.0000
2:48642401:G:GG	acceptor_gain	1.0000
2:48645121:A:T	donor_gain	1.0000
2:48669720:A:AG	acceptor_gain	1.0000
2:48669720:AG:A	acceptor_gain	1.0000
2:48669721:G:A	acceptor_gain	1.0000
2:48669721:G:GA	acceptor_gain	1.0000
2:48669721:G:GG	acceptor_gain	1.0000
2:48669721:GG:G	acceptor_gain	1.0000
2:48669721:GGA:G	acceptor_gain	1.0000
2:48669721:GGAT:G	acceptor_gain	1.0000
2:48669721:GGATT:G	acceptor_gain	1.0000
2:48669828:G:GT	donor_gain	1.0000
2:48669943:T:TA	donor_gain	1.0000
2:48669944:A:AA	donor_gain	1.0000
2:48669980:GAG:G	donor_gain	1.0000
2:48669980:GAGG:G	donor_loss	1.0000
2:48669981:AGG:A	donor_loss	1.0000
2:48669983:GTGAG:G	donor_loss	1.0000
2:48670001:C:G	donor_gain	1.0000
2:48725674:A:AC	donor_gain	1.0000
2:48725675:C:CC	donor_gain	1.0000

AlphaMissense

3168 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:48679356:T:A	W451R	0.999
2:48679356:T:C	W451R	0.999
2:48679437:T:A	W478R	0.998
2:48679437:T:C	W478R	0.998
2:48671666:T:C	C439R	0.996
2:48679358:G:C	W451C	0.996
2:48679358:G:T	W451C	0.996
2:48621170:T:A	W43R	0.995
2:48621170:T:C	W43R	0.995
2:48671668:T:G	C439W	0.995
2:48679363:T:C	F453S	0.995
2:48679369:T:C	L455S	0.995
2:48679410:T:C	F469L	0.995
2:48679411:T:C	F469S	0.995
2:48679412:T:A	F469L	0.995
2:48679412:T:G	F469L	0.995
2:48679357:G:C	W451S	0.994
2:48679419:G:C	A472P	0.994
2:48679439:G:C	W478C	0.994
2:48679439:G:T	W478C	0.994
2:48671672:T:G	Y441D	0.992
2:48679431:G:C	A476P	0.992
2:48679378:G:A	G458D	0.991
2:48671664:T:A	V438D	0.990
2:48621172:G:C	W43C	0.989
2:48621172:G:T	W43C	0.989
2:48671667:G:A	C439Y	0.989
2:48679411:T:G	F469C	0.989
2:48671673:A:C	Y441S	0.988
2:48679426:G:A	G474D	0.987

dbSNP variants (sampled 300 via entrez): RS1000018638 (2:48654031 T>C), RS1000049705 (2:48636847 A>G), RS1000059048 (2:48617142 C>G,T), RS1000105533 (2:48659086 A>G), RS1000114949 (2:48621766 T>A), RS1000121269 (2:48617516 C>A), RS1000184041 (2:48652467 T>C), RS1000223362 (2:48649183 A>G), RS1000239399 (2:48654257 A>T), RS1000311711 (2:48622045 C>T), RS1000334999 (2:48630373 T>C), RS1000345714 (2:48644443 T>A,C), RS1000386038 (2:48617698 C>A,T), RS1000400462 (2:48671994 G>A), RS1000459479 (2:48616495 T>A)

Disease associations

OMIM: gene MIM:605358 | disease phenotypes: MIM:614325

GenCC curated gene-disease

Mondo (1): Pitt-Hopkins-like syndrome 2 (MONDO:0013690)

Orphanet (2): OBSOLETE: Pitt-Hopkins-like syndrome (Orphanet:221150), NRXN1-related severe neurodevelopmental disorder-motor stereotypies-chronic constipation-sleep-wake cycle disturbance (Orphanet:600663)

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST000914_4	Polycystic ovary syndrome	8.000000e-21
GCST003944_26	Hepcidin/ferritin ratio	5.000000e-06
GCST003998_16	Joint mobility (Beighton score)	1.000000e-07
GCST004813_1	Laterality in neovascular age-related macular degeneration	3.000000e-08
GCST010988_283	Adult body size	2.000000e-08
GCST012100_7	Hypertrophic cardiomyopathy (sarcomere positive)	7.000000e-07

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007901	hepcidin:ferritin ratio
EFO:0007905	joint hypermobility measurement
EFO:0008372	laterality measurement

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
Benzo(a)pyrene	affects methylation, decreases expression, decreases methylation	2
benzo(e)pyrene	increases methylation	1
Butyrates	decreases expression	1
Methapyrilene	increases methylation	1
Tretinoin	decreases expression	1
Valproic Acid	increases expression	1

Clinical trials (associated diseases)

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