GTF2IRD2B

Summary

GTF2IRD2B (GTF2I repeat domain containing 2B, HGNC:33125) is a protein-coding gene on chromosome 7q11.23, encoding General transcription factor II-I repeat domain-containing protein 2B (Q6EKJ0).

This gene encodes a glycosylated phosphoprotein with a leucine zipper motif, two helix-loop-helix motifs (I repeats) that are similar to domains found in the TFII-I family of transcription factors, one CHARLIE8 transposable element-like sequence, and a BED zinc finger. This gene lies within a region that is deleted in Williams-Beuren syndrome. Alternatively spliced variants which encode different protein isoforms have been described; however, not all variants have been fully characterized.

Source: NCBI Gene 389524 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 33 total
• MANE Select transcript: NM_001003795

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33125
Approved symbol	GTF2IRD2B
Name	GTF2I repeat domain containing 2B
Location	7q11.23
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000174428
Ensembl biotype	protein_coding
OMIM	608900
Entrez	389524

Gene structure

Transcript identifiers

Ensembl transcripts: 31 — 26 protein_coding, 4 retained_intron, 1 nonsense_mediated_decay

ENST00000394939, ENST00000418185, ENST00000472837, ENST00000611835, ENST00000614064, ENST00000617708, ENST00000619142, ENST00000620662, ENST00000651028, ENST00000888756, ENST00000888757, ENST00000888758, ENST00000888759, ENST00000888760, ENST00000888761, ENST00000888762, ENST00000888763, ENST00000888764, ENST00000888765, ENST00000888766, ENST00000888767, ENST00000888768, ENST00000958673, ENST00000958674, ENST00000958675, ENST00000958676, ENST00000958677, ENST00000958678, ENST00000958679, ENST00000958680, ENST00000958681

RefSeq mRNA: 3 — MANE Select: NM_001003795 NM_001003795, NM_001368301, NM_001368302

CCDS: CCDS34659, CCDS94124

Canonical transcript exons

ENST00000472837 — 16 exons

Exon	Start	End
ENSE00003475622	75136785	75136850
ENSE00003520611	75126342	75126385
ENSE00003561161	75133135	75133212
ENSE00003568594	75147694	75149817
ENSE00003586698	75142482	75142665
ENSE00003619587	75141103	75141186
ENSE00003650864	75135001	75135057
ENSE00003657044	75138950	75139027
ENSE00003713555	75123488	75123516
ENSE00003721900	75123136	75123319
ENSE00003729116	75120891	75121010
ENSE00003733595	75143950	75143978
ENSE00003745919	75125916	75125970
ENSE00003751625	75108960	75109063
ENSE00003752144	75112397	75112535
ENSE00003847241	75092590	75092765

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 95.21.

FANTOM5 (CAGE): breadth broad, TPM avg 1.2489 / max 29.7496, expressed in 756 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
79111	1.2489	756

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
hindlimb stylopod muscle	UBERON:0004252	95.21	gold quality
sural nerve	UBERON:0015488	95.21	gold quality
mucosa of stomach	UBERON:0001199	94.63	gold quality
left ovary	UBERON:0002119	94.53	gold quality
ovary	UBERON:0000992	94.30	gold quality
calcaneal tendon	UBERON:0003701	94.11	gold quality
right ovary	UBERON:0002118	94.04	gold quality
right uterine tube	UBERON:0001302	94.03	gold quality
endocervix	UBERON:0000458	92.68	gold quality
muscle of leg	UBERON:0001383	92.54	gold quality
left uterine tube	UBERON:0001303	92.35	gold quality
fallopian tube	UBERON:0003889	92.31	gold quality
gastrocnemius	UBERON:0001388	92.29	gold quality
prostate gland	UBERON:0002367	92.14	gold quality
left lobe of thyroid gland	UBERON:0001120	91.77	gold quality
thyroid gland	UBERON:0002046	91.77	gold quality
body of uterus	UBERON:0009853	91.69	gold quality
muscle layer of sigmoid colon	UBERON:0035805	91.69	gold quality
right lobe of thyroid gland	UBERON:0001119	91.65	gold quality
body of pancreas	UBERON:0001150	91.62	gold quality
fundus of stomach	UBERON:0001160	91.61	gold quality
skeletal muscle tissue	UBERON:0001134	91.60	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	91.60	gold quality
lower esophagus muscularis layer	UBERON:0035833	91.52	gold quality
lower esophagus	UBERON:0013473	91.48	gold quality
cortex of kidney	UBERON:0001225	91.19	gold quality
ganglionic eminence	UBERON:0004023	91.10	gold quality
metanephros cortex	UBERON:0010533	91.09	gold quality
stomach	UBERON:0000945	91.03	gold quality
body of stomach	UBERON:0001161	91.01	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.43

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

34 targeting GTF2IRD2B, 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-371B-5P	99.99	75.34	4759
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-380-3P	99.89	70.18	1978
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-548A-3P	99.76	70.58	3524
HSA-MIR-3158-5P	99.65	67.51	1763
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-1260A	99.61	66.67	1098
HSA-MIR-1260B	99.61	66.67	1098
HSA-MIR-12117	99.50	67.57	868
HSA-MIR-5689	99.50	71.26	1154
HSA-MIR-4762-3P	99.43	69.72	2363
HSA-MIR-4316	99.37	65.75	1360
HSA-MIR-2054	99.20	68.89	1699
HSA-MIR-1294	98.91	69.26	1030
HSA-MIR-9986	98.91	69.28	1024
HSA-MIR-520G-3P	98.91	67.38	1914
HSA-MIR-520H	98.91	67.38	1914
HSA-MIR-7977	98.65	66.18	2590
HSA-MIR-4768-3P	98.16	66.02	2330
HSA-MIR-665	97.60	65.64	1781

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Gtf2ird2	ENSMUSG00000015942
rattus_norvegicus	Gtf2ird2	ENSRNOG00000001482

Paralogs (18): GTF2IRD1 (ENSG00000006704), ZMYM2 (ENSG00000121741), ZMYM5 (ENSG00000132950), THAP12 (ENSG00000137492), ZMYM4 (ENSG00000146463), ZMYM3 (ENSG00000147130), ZMYM6 (ENSG00000163867), KIAA1958 (ENSG00000165185), EPM2AIP1 (ENSG00000178567), GTF2IRD2 (ENSG00000196275), ZMYM1 (ENSG00000197056), QRICH1 (ENSG00000198218), FAM200C (ENSG00000221886), FAM200A (ENSG00000221909), SCAND3 (ENSG00000232040), ZBED5 (ENSG00000236287), FAM200B (ENSG00000237765), GTF2I (ENSG00000263001)

Protein

Protein identifiers

General transcription factor II-I repeat domain-containing protein 2B — Q6EKJ0 (reviewed: Q6EKJ0)

Alternative names: Transcription factor GTF2IRD2-beta

All UniProt accessions (3): Q6EKJ0, A0A087WW90, A0A494C1N8

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Nucleus.

Tissue specificity. Ubiquitous.

Disease relevance. GTF2IRD2B is located in the Williams-Beuren syndrome (WBS) critical region. WBS results from a hemizygous deletion of several genes on chromosome 7q11.23, thought to arise as a consequence of unequal crossing over between highly homologous low-copy repeat sequences flanking the deleted region.

Similarity. Belongs to the TFII-I family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q6EKJ0-1	1	yes
Q6EKJ0-2	2

RefSeq proteins (3): NP_001003795, NP_001355230, NP_001355231 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004212	GTF2I	Repeat
IPR012337	RNaseH-like_sf	Homologous_superfamily
IPR036647	GTF2I-like_rpt_sf	Homologous_superfamily
IPR040647	SPIN-DOC_Znf-C2H2	Domain
IPR042224	GTF2IRD2	Family

Pfam: PF02946, PF18658

UniProt features (12 total): helix 3, repeat 2, strand 2, splice variant 2, chain 1, sequence conflict 1, turn 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2E3L	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6EKJ0-F1	73.31	0.35

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 34 (showing top): TSENG_IRS1_TARGETS_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, chr7q11, ACEVEDO_LIVER_CANCER_UP, PILON_KLF1_TARGETS_UP, BRUINS_UVC_RESPONSE_VIA_TP53_GROUP_B, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, NAB2_TARGET_GENES, MIR616_5P, MIR371B_5P, MIR373_5P, MIR548AR_3P, MIR548F_3P, MIR548BC, MIR548AZ_3P

GO Biological Process (1): regulation of transcription by RNA polymerase II (GO:0006357)

GO Molecular Function (3): DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (1): nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	1
chromatin	1
RNA polymerase II transcription regulatory region sequence-specific DNA binding	1
DNA-binding transcription factor activity	1
regulation of transcription by RNA polymerase II	1
nucleic acid binding	1
binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

504 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GTF2IRD2B	NCF1	P14598	779
GTF2IRD2B	TBL2	Q9Y4P3	638
GTF2IRD2B	ELN	P15502	632
GTF2IRD2B	TRIM50	Q86XT4	607
GTF2IRD2B	NSUN5	Q96P11	579
GTF2IRD2B	BCL7B	Q9BQE9	533
GTF2IRD2B	EIF4H	Q15056	530
GTF2IRD2B	FKBP6	O75344	503
GTF2IRD2B	FKBP10	Q96AY3	483
GTF2IRD2B	CLIP2	Q9UDT6	473
GTF2IRD2B	AGT	P01019	469
GTF2IRD2B	ZNF805	Q5CZA5	434
GTF2IRD2B	DNAJC30	Q96LL9	431
GTF2IRD2B	FZD9	O00144	419
GTF2IRD2B	SRGAP2C	P0DJJ0	418

IntAct

8 interactions, top by confidence:

A	B	Type	Score
GTF2IRD2B	TRIM54	psi-mi:“MI:0915”(physical association)	0.560
GTF2IRD2B	GTF2I	psi-mi:“MI:0914”(association)	0.350
P		psi-mi:“MI:0914”(association)	0.350
GTF2IRD2B	PRMT3	psi-mi:“MI:0914”(association)	0.350
GTF2IRD2	GTF2I	psi-mi:“MI:0914”(association)	0.350
GTF2IRD2B	TRIM54	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (22): GTF2IRD2 (Affinity Capture-MS), GTF2I (Affinity Capture-MS), GTF2IRD1 (Affinity Capture-MS), GTF2IRD2 (Affinity Capture-MS), GTF2IRD1 (Affinity Capture-MS), GTF2I (Affinity Capture-MS), GTF2IRD2B (Affinity Capture-MS), GTF2IRD2B (Affinity Capture-MS), GTF2IRD2B (Affinity Capture-RNA), GTF2IRD2B (Two-hybrid), GTF2I (Affinity Capture-MS), POLR2J (Affinity Capture-MS), ACVR1C (Affinity Capture-MS), POLR2B (Affinity Capture-MS), ZMYM1 (Affinity Capture-MS)

ESM2 similar proteins: A3KMX0, A4IFA3, A4IGY9, A4Z943, A4Z944, B8QB46, D2EAC2, E1C2V1, O43422, O60290, P10911, P35125, P86452, Q13075, Q2NKX8, Q3UPF5, Q49AG3, Q5FWF4, Q5SVZ6, Q5T890, Q5TKR9, Q6DJS0, Q6EKJ0, Q6R2W3, Q6YI93, Q7Z2W4, Q80WE4, Q86UP8, Q86VD1, Q8BZ21, Q8N8K9, Q8QMP8, Q8TDB6, Q8WML3, Q92794, Q96JM7, Q96JS3, Q99388, Q99NI3, Q9CUX1

Diamond homologs: A4IFA3, A7MB80, B7ZQJ9, P78347, Q5U2Y1, Q6EKJ0, Q86UP8, Q99NI3, Q9ESZ8, Q9JI57, Q9UHL9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	27
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2407 predictions. Top by Δscore:

Variant	Effect	Δscore
7:75108956:ACAG:A	acceptor_gain	1.0000
7:75108956:ACAGG:A	acceptor_gain	1.0000
7:75108958:AGG:A	acceptor_gain	1.0000
7:75108959:GGG:G	acceptor_gain	1.0000
7:75109061:ATGG:A	donor_loss	1.0000
7:75109064:G:GG	donor_gain	1.0000
7:75109064:GT:G	donor_loss	1.0000
7:75109065:T:A	donor_loss	1.0000
7:75112392:TTCA:T	acceptor_loss	1.0000
7:75112394:CAGT:C	acceptor_loss	1.0000
7:75112395:A:AG	acceptor_gain	1.0000
7:75112395:A:C	acceptor_loss	1.0000
7:75112395:AGT:A	acceptor_gain	1.0000
7:75112396:G:GT	acceptor_gain	1.0000
7:75112396:GT:G	acceptor_gain	1.0000
7:75112396:GTG:G	acceptor_gain	1.0000
7:75112396:GTGT:G	acceptor_gain	1.0000
7:75112396:GTGTA:G	acceptor_gain	1.0000
7:75112482:G:GT	donor_gain	1.0000
7:75112504:G:GT	donor_gain	1.0000
7:75112531:ATACT:A	donor_gain	1.0000
7:75112532:TACT:T	donor_gain	1.0000
7:75112533:ACT:A	donor_gain	1.0000
7:75112534:CT:C	donor_gain	1.0000
7:75112536:G:GG	donor_gain	1.0000
7:75120976:G:GT	donor_gain	1.0000
7:75120977:A:T	donor_gain	1.0000
7:75123299:G:T	donor_gain	1.0000
7:75133122:A:AG	acceptor_gain	1.0000
7:75133123:T:G	acceptor_gain	1.0000

AlphaMissense

6292 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:75147741:T:A	W432R	1.000
7:75147741:T:C	W432R	1.000
7:75142482:G:A	G345D	0.999
7:75142487:G:C	A347P	0.999
7:75142653:T:C	F402S	0.999
7:75147729:T:C	F428L	0.999
7:75147730:T:C	F428S	0.999
7:75147731:T:A	F428L	0.999
7:75147731:T:G	F428L	0.999
7:75147743:G:C	W432C	0.999
7:75147743:G:T	W432C	0.999
7:75147786:T:C	C447R	0.999
7:75147820:A:T	K458I	0.999
7:75147821:A:C	K458N	0.999
7:75147821:A:T	K458N	0.999
7:75141171:T:C	F340L	0.998
7:75141172:T:C	F340S	0.998
7:75141173:T:A	F340L	0.998
7:75141173:T:G	F340L	0.998
7:75142584:T:C	F379S	0.998
7:75142652:T:C	F402L	0.998
7:75142654:C:A	F402L	0.998
7:75142654:C:G	F402L	0.998
7:75147702:C:A	R419S	0.998
7:75147730:T:G	F428C	0.998
7:75147788:T:G	C447W	0.998
7:75147832:T:C	L462P	0.998
7:75147838:G:C	R464P	0.998
7:75148290:A:C	S615R	0.998
7:75148292:C:A	S615R	0.998

dbSNP variants (sampled 300 via entrez): RS10260899 (7:75115014 T>C), RS10264921 (7:75121917 T>C), RS111304862 (7:75100415 C>T), RS111326735 (7:75138900 A>G), RS111428748 (7:75104310 G>A,C,T), RS111600868 (7:75113488 G>A), RS111635590 (7:75115492 T>A,C), RS111648877 (7:75109991 A>C,G,T), RS111670996 (7:75147613 A>G), RS111750385 (7:75104338 C>A,G,T), RS111951675 (7:75098137 A>T), RS112011113 (7:75122498 G>A,T), RS112113672 (7:75128641 C>T), RS112126146 (7:75121007 T>C), RS112149853 (7:75145831 T>A)

Disease associations

OMIM: gene MIM:608900 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
triphenyl phosphate	affects expression	1
propionic acid	decreases expression	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	increases reaction, affects binding	1
Resveratrol	affects cotreatment, increases expression	1
Air Pollutants, Occupational	decreases expression	1
Benzo(a)pyrene	decreases expression	1
Doxorubicin	increases expression	1
Hydrogen Peroxide	affects expression	1
Methotrexate	increases expression	1
Nickel	decreases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Smoke	decreases expression	1
Testosterone	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Asbestos, Crocidolite	increases expression	1
Okadaic Acid	decreases expression	1
Acrylamide	increases expression	1

Clinical trials (associated diseases)

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