GTF2H2

Summary

GTF2H2 (general transcription factor IIH subunit 2, HGNC:4656) is a protein-coding gene on chromosome 5q13.2, encoding General transcription factor IIH subunit 2 (Q13888). Component of the general transcription and DNA repair factor IIH (TFIIH) core complex, which is involved in general and transcription-coupled nucleotide excision repair (NER) of damaged DNA and, when complexed to CAK, in RNA transcription by RNA polymerase II.

This gene is part of a 500 kb inverted duplication on chromosome 5q13. This duplicated region contains at least four genes and repetitive elements which make it prone to rearrangements and deletions. The repetitiveness and complexity of the sequence have also caused difficulty in determining the organization of this genomic region. This gene is within the telomeric copy of the duplication. Deletion of this gene sometimes accompanies deletion of the neighboring SMN1 gene in spinal muscular atrophy (SMA) patients but it is unclear if deletion of this gene contributes to the SMA phenotype. This gene encodes the 44 kDa subunit of RNA polymerase II transcription initiation factor IIH which is involved in basal transcription and nucleotide excision repair. Transcript variants for this gene have been described, but their full length nature has not been determined. A second copy of this gene within the centromeric copy of the duplication has been described in the literature. It is reported to be different by either two or four base pairs; however, no sequence data is currently available for the centromeric copy of the gene.

Source: NCBI Gene 2966 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 64 total
• MANE Select transcript: NM_001515

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4656
Approved symbol	GTF2H2
Name	general transcription factor IIH subunit 2
Location	5q13.2
Locus type	gene with protein product
Status	Approved
Aliases	BTF2, TFIIH, BTF2P44, T-BTF2P44, p44
Ensembl gene	ENSG00000145736
Ensembl biotype	protein_coding
OMIM	601748
Entrez	2966

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 14 protein_coding, 6 retained_intron, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000274400, ENST00000330280, ENST00000508592, ENST00000517900, ENST00000518275, ENST00000518898, ENST00000519783, ENST00000521602, ENST00000521858, ENST00000521942, ENST00000522654, ENST00000523003, ENST00000523693, ENST00000873591, ENST00000873592, ENST00000873593, ENST00000873594, ENST00000916278, ENST00000916279, ENST00000916280, ENST00000916281, ENST00000916282, ENST00000953259

RefSeq mRNA: 21 — MANE Select: NM_001515 NM_001364567, NM_001364568, NM_001364569, NM_001364570, NM_001364571, NM_001364572, NM_001364573, NM_001395387, NM_001395388, NM_001395389, NM_001395390, NM_001395391, NM_001395392, NM_001395393, NM_001395394, NM_001395395, NM_001395396, NM_001395397, NM_001395398, NM_001395399, NM_001515

CCDS: CCDS34183

Canonical transcript exons

ENST00000274400 — 16 exons

Exon	Start	End
ENSE00003460072	71045444	71045507
ENSE00003499272	71049068	71049158
ENSE00003500802	71061688	71061765
ENSE00003523775	71059690	71059744
ENSE00003554243	71055352	71055457
ENSE00003559612	71048762	71048849
ENSE00003579312	71037507	71037546
ENSE00003625997	71060120	71060170
ENSE00003636072	71061272	71061308
ENSE00003659210	71041522	71041624
ENSE00003659314	71048006	71048113
ENSE00003659726	71060844	71060930
ENSE00003682425	71062708	71062796
ENSE00003689173	71042181	71042284
ENSE00003978350	71067494	71067676
ENSE00003978351	71035347	71035796

Expression profiles

Bgee: expression breadth ubiquitous, 140 present calls, max score 91.65.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endometrium	UBERON:0001295	91.65	gold quality
sural nerve	UBERON:0015488	90.65	gold quality
adrenal tissue	UBERON:0018303	90.04	gold quality
corpus callosum	UBERON:0002336	89.74	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.15	gold quality
calcaneal tendon	UBERON:0003701	88.94	gold quality
islet of Langerhans	UBERON:0000006	86.76	gold quality
monocyte	CL:0000576	85.91	gold quality
metanephros cortex	UBERON:0010533	85.57	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.50	gold quality
mucosa of transverse colon	UBERON:0004991	85.25	gold quality
smooth muscle tissue	UBERON:0001135	85.19	gold quality
vermiform appendix	UBERON:0001154	85.17	gold quality
leukocyte	CL:0000738	85.15	gold quality
pancreas	UBERON:0001264	85.05	gold quality
uterus	UBERON:0000995	84.40	gold quality
body of pancreas	UBERON:0001150	84.28	gold quality
lymph node	UBERON:0000029	84.15	gold quality
bone marrow cell	CL:0002092	83.97	gold quality
kidney	UBERON:0002113	83.97	gold quality
tonsil	UBERON:0002372	83.36	gold quality
adult mammalian kidney	UBERON:0000082	83.20	gold quality
cortex of kidney	UBERON:0001225	82.70	gold quality
right lobe of thyroid gland	UBERON:0001119	82.39	gold quality
thyroid gland	UBERON:0002046	82.16	gold quality
left lobe of thyroid gland	UBERON:0001120	82.12	gold quality
mucosa of stomach	UBERON:0001199	81.74	gold quality
adrenal gland	UBERON:0002369	81.67	gold quality
right uterine tube	UBERON:0001302	81.65	gold quality
blood	UBERON:0000178	81.48	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.10

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC

miRNA regulators (miRDB)

28 targeting GTF2H2, 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-5692A	100.00	74.40	6850
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-217-5P	99.49	69.93	1419
HSA-MIR-4735-5P	99.43	68.49	1780
HSA-MIR-183-3P	99.41	69.41	1598
HSA-MIR-888-5P	99.30	70.15	1855
HSA-MIR-6807-3P	99.15	69.23	1275
HSA-MIR-4504	99.10	69.14	1328
HSA-MIR-501-5P	98.77	68.88	1328
HSA-MIR-4680-3P	98.64	68.60	2093
HSA-MIR-5089-5P	98.45	66.06	1388
HSA-MIR-499B-5P	98.35	68.39	988
HSA-MIR-4684-3P	98.24	69.91	1075

Literature-anchored findings (GeneRIF, showing 11)

• p52 Mediates XPB function within the transcription/repair factor (PMID:12080057)
• p44 of TFIIH has a role in binding to the nonstructural protein of Rift Valley fever virus to form nuclear filamentous structures (PMID:14980221)
• solution structure of p44-(321-395) shows topology differs from other reported RING domains by a circular permutation of the extended secondary structure elements; mutagenesis suggests tight binding to p34 is mediated by hydrophobic interactions (PMID:15790571)
• Impaired transcription in IPF is associated with decreased concentrations of transcription factor II-H in alveolar macrophages and may alter the intraalveolar milieu in IPF. (PMID:17332483)
• miR-27a was identified as a key regulator of p44 mRNA. Moreover, miR-27a was shown to destabilize the p44 subunit of the TFIIH complex during the G2-M phase, thereby modulating the transcriptional shutdown observed during this transition. (PMID:21558443)
• No correlation was found for p44 and occludin gene copy number and spinal muscular atrophy (PMID:21821450)
• Together, these results suggest that p44/WDR77 expression causes the non-sensitivity of proliferating cells to TGFbeta signaling, thereby contributing to cellular proliferation during lung tumorigenesis. (PMID:24944016)
• Advanced oxidation protein products down-regulate the expression of calcium transport channels through p44/42 MAPK signaling mechanisms in the small intestinal epithelium. (PMID:25801217)
• interface variants between the p34 and p44 subunits only mildly affected the association between the full length proteins and did not impinge on TFIIH activities due to the presence of an additional interface involving the C4 domain of p34. (PMID:28977422)
• The TFIIH subunits p44/p62 act as a damage sensor during nucleotide excision repair. (PMID:33166411)
• Exosome-derived GTF2H2 from Huh7 cells can inhibit endothelial cell viability, migration, tube formation, and permeability. (PMID:36116407)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	gtf2h2	ENSDARG00000016514
mus_musculus	Gtf2h2	ENSMUSG00000021639
rattus_norvegicus	Gtf2h2	ENSRNOG00000018230
drosophila_melanogaster	Ssl1	FBGN0037202
caenorhabditis_elegans		WBGENE00011814

Paralogs (1): GTF2H2C (ENSG00000183474)

Protein

Protein identifiers

General transcription factor IIH subunit 2 — Q13888 (reviewed: Q13888)

Alternative names: Basic transcription factor 2 44 kDa subunit, General transcription factor IIH polypeptide 2, TFIIH basal transcription factor complex p44 subunit

All UniProt accessions (5): D6RAW1, D6RGC9, Q13888, R4GMS9, R4GMV2

UniProt curated annotations — full annotation on UniProt →

Function. Component of the general transcription and DNA repair factor IIH (TFIIH) core complex, which is involved in general and transcription-coupled nucleotide excision repair (NER) of damaged DNA and, when complexed to CAK, in RNA transcription by RNA polymerase II. In NER, TFIIH acts by opening DNA around the lesion to allow the excision of the damaged oligonucleotide and its replacement by a new DNA fragment. In transcription, TFIIH has an essential role in transcription initiation. When the pre-initiation complex (PIC) has been established, TFIIH is required for promoter opening and promoter escape. Phosphorylation of the C-terminal tail (CTD) of the largest subunit of RNA polymerase II by the kinase module CAK controls the initiation of transcription. The N-terminus of GTF2H2 interacts with and regulates XPD whereas an intact C-terminus is required for a successful escape of RNAP II form the promoter.

Subunit / interactions. Component of the TFIID-containing RNA polymerase II pre-initiation complex that is composed of TBP and at least GTF2A1, GTF2A2, GTF2E1, GTF2E2, GTF2F1, GTF2H2, GTF2H3, GTF2H4, GTF2H5, GTF2B, TCEA1, ERCC2 and ERCC3. Component of the 7-subunit TFIIH core complex composed of XPB/ERCC3, XPD/ERCC2, GTF2H1, GTF2H2, GTF2H3, GTF2H4 and GTF2H5, which is active in NER. The core complex associates with the 3-subunit CDK-activating kinase (CAK) module composed of CCNH/cyclin H, CDK7 and MNAT1 to form the 10-subunit holoenzyme (holo-TFIIH) active in transcription. Interacts with XPB, XPD, GTF2H1 and GTF2H3. (Microbial infection) Interacts with varicella-zoster virus IE63 protein.

Subcellular location. Nucleus.

Tissue specificity. Widely expressed, with higher expression in skeletal muscle.

Similarity. Belongs to the GTF2H2 family.

Isoforms (1)

UniProt ID	Names	Canonical?
Q13888-1	1	yes

RefSeq proteins (21): NP_001351496, NP_001351497, NP_001351498, NP_001351499, NP_001351500, NP_001351501, NP_001351502, NP_001382316, NP_001382317, NP_001382318, NP_001382319, NP_001382320, NP_001382321, NP_001382322, NP_001382323, NP_001382324, NP_001382325, NP_001382326, NP_001382327, NP_001382328, NP_001506* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002035	VWF_A	Domain
IPR004595	TFIIH_C1-like_dom	Domain
IPR007198	Ssl1-like	Domain
IPR012170	TFIIH_SSL1/p44	Family
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR013087	Znf_C2H2_type	Domain
IPR036465	vWFA_dom_sf	Homologous_superfamily
IPR046349	C1-like_sf	Homologous_superfamily

Pfam: PF04056, PF07975

UniProt features (48 total): helix 14, strand 14, mutagenesis site 8, turn 5, sequence variant 2, chain 1, domain 1, sequence conflict 1, zinc finger region 1, modified residue 1

Structure

Experimental structures (PDB)

52 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
28JM	ELECTRON MICROSCOPY	3.29
7EGB	ELECTRON MICROSCOPY	3.3
8EBU	ELECTRON MICROSCOPY	3.3
9PD3	ELECTRON MICROSCOPY	3.3
28JS	ELECTRON MICROSCOPY	3.32
5O85	X-RAY DIFFRACTION	3.4
9PD4	ELECTRON MICROSCOPY	3.4
6RO4	ELECTRON MICROSCOPY	3.5
7AD8	ELECTRON MICROSCOPY	3.5
9XYU	ELECTRON MICROSCOPY	3.5
28KE	ELECTRON MICROSCOPY	3.6
8EBX	ELECTRON MICROSCOPY	3.6
8EBY	ELECTRON MICROSCOPY	3.6
6NMI	ELECTRON MICROSCOPY	3.7
7EGC	ELECTRON MICROSCOPY	3.9
7NVX	ELECTRON MICROSCOPY	3.9
8EBT	ELECTRON MICROSCOPY	3.9
28JV	ELECTRON MICROSCOPY	3.91
8BVW	ELECTRON MICROSCOPY	4
8EBS	ELECTRON MICROSCOPY	4
7ENA	ELECTRON MICROSCOPY	4.07
8BYQ	ELECTRON MICROSCOPY	4.1
7ENC	ELECTRON MICROSCOPY	4.13
8GXS	ELECTRON MICROSCOPY	4.16
7NVW	ELECTRON MICROSCOPY	4.3
9PCP	ELECTRON MICROSCOPY	4.3
5OF4	ELECTRON MICROSCOPY	4.4
6O9M	ELECTRON MICROSCOPY	4.4
7NVR	ELECTRON MICROSCOPY	4.5
7LBM	ELECTRON MICROSCOPY	4.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13888-F1	84.29	0.53

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 95

Mutagenesis-validated functional residues (8):

Position	Phenotype
363	no effect on the transcriptional activity of the reconstituted tfiih complex.
376	no effect on the transcriptional activity of the reconstituted tfiih complex.
380	no effect on the transcriptional activity of the reconstituted tfiih complex.
382	no effect on the transcriptional activity of the reconstituted tfiih complex.
291	reconstituted tfiih complex lacks p62 and has no transcriptional activity.
308	reconstituted tfiih complex lacks p62 and has no transcriptional activity.
345	no effect on the transcriptional activity of the reconstituted tfiih complex.
360	no effect on the transcriptional activity of the reconstituted tfiih complex.

Function

Pathways and Gene Ontology

Reactome pathways

48 pathways

ID	Pathway
R-HSA-112382	Formation of RNA Pol II elongation complex
R-HSA-113418	Formation of the Early Elongation Complex
R-HSA-167152	Formation of HIV elongation complex in the absence of HIV Tat
R-HSA-167158	Formation of the HIV-1 Early Elongation Complex
R-HSA-167160	RNA Pol II CTD phosphorylation and interaction with CE during HIV infection
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-167200	Formation of HIV-1 elongation complex containing HIV-1 Tat
R-HSA-167246	Tat-mediated elongation of the HIV-1 transcript
R-HSA-427413	NoRC negatively regulates rRNA expression
R-HSA-5696395	Formation of Incision Complex in GG-NER
R-HSA-5696400	Dual Incision in GG-NER
R-HSA-674695	RNA Polymerase II Pre-transcription Events
R-HSA-6781823	Formation of TC-NER Pre-Incision Complex
R-HSA-6781827	Transcription-Coupled Nucleotide Excision Repair (TC-NER)
R-HSA-6782135	Dual incision in TC-NER
R-HSA-6782210	Gap-filling DNA repair synthesis and ligation in TC-NER
R-HSA-6796648	TP53 Regulates Transcription of DNA Repair Genes
R-HSA-72086	mRNA Capping
R-HSA-73762	RNA Polymerase I Transcription Initiation
R-HSA-73772	RNA Polymerase I Promoter Escape
R-HSA-73776	RNA Polymerase II Promoter Escape
R-HSA-73779	RNA Polymerase II Transcription Pre-Initiation And Promoter Opening
R-HSA-73863	RNA Polymerase I Transcription Termination
R-HSA-75953	RNA Polymerase II Transcription Initiation
R-HSA-75955	RNA Polymerase II Transcription Elongation
R-HSA-76042	RNA Polymerase II Transcription Initiation And Promoter Clearance
R-HSA-77075	RNA Pol II CTD phosphorylation and interaction with CE
R-HSA-162587	HIV Life Cycle

MSigDB gene sets: 185 (showing top): REACTOME_FORMATION_OF_INCISION_COMPLEX_IN_GG_NER, GOBP_G_PROTEIN_COUPLED_RECEPTOR_INTERNALIZATION, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, BROWNE_HCMV_INFECTION_6HR_DN, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, REACTOME_RNA_POLYMERASE_I_TRANSCRIPTION_INITIATION, KANNAN_TP53_TARGETS_DN, GOBP_VESICLE_MEDIATED_TRANSPORT, KAUFFMANN_DNA_REPAIR_GENES, GOBP_NUCLEOTIDE_EXCISION_REPAIR, MUELLER_PLURINET, REACTOME_HIV_INFECTION, GOBP_RESPONSE_TO_UV, GOBP_RECEPTOR_INTERNALIZATION, GOBP_DNA_DAMAGE_RESPONSE

GO Biological Process (9): G protein-coupled receptor internalization (GO:0002031), nucleotide-excision repair (GO:0006289), regulation of transcription by RNA polymerase II (GO:0006357), transcription by RNA polymerase II (GO:0006366), transcription initiation at RNA polymerase II promoter (GO:0006367), response to UV (GO:0009411), DNA repair (GO:0006281), DNA-templated transcription (GO:0006351), DNA damage response (GO:0006974)

GO Molecular Function (4): zinc ion binding (GO:0008270), RNA polymerase II general transcription initiation factor activity (GO:0016251), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (7): core TFIIH complex portion of holo TFIIH complex (GO:0000438), transcription factor TFIIH core complex (GO:0000439), nucleus (GO:0005634), nucleoplasm (GO:0005654), transcription factor TFIID complex (GO:0005669), transcription factor TFIIH holo complex (GO:0005675), nuclear speck (GO:0016607)

Reactome top-level categories

Rollup of top-12 pathways:

Category	Pathways
Transcription of the HIV genome	4
Transcription-Coupled Nucleotide Excision Repair (TC-NER)	3
RNA Polymerase II Transcription Elongation	2
HIV Transcription Elongation	2
Global Genome Nucleotide Excision Repair (GG-NER)	2
Late Phase of HIV Life Cycle	1
Tat-mediated elongation of the HIV-1 transcript	1
Negative epigenetic regulation of rRNA expression	1
RNA Polymerase II Transcription	1
Nucleotide Excision Repair	1
Transcriptional Regulation by TP53	1
Metabolism of RNA	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transcription by RNA polymerase II	3
RNA polymerase II transcription regulator complex	3
transcription factor TFIIH core complex	2
RNA polymerase II, holoenzyme	2
desensitization of G protein-coupled receptor signaling pathway	1
receptor internalization	1
DNA repair	1
regulation of DNA-templated transcription	1
DNA-templated transcription	1
DNA-templated transcription initiation	1
response to light stimulus	1
DNA metabolic process	1
DNA damage response	1
gene expression	1
RNA biosynthetic process	1
cellular response to stress	1
transition metal ion binding	1
general transcription initiation factor activity	1
binding	1
cation binding	1
transcription factor TFIIH holo complex	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1
nuclear cyclin-dependent protein kinase holoenzyme complex	1
carboxy-terminal domain protein kinase complex	1
nuclear ribonucleoprotein granule	1

Protein interactions and networks

STRING

1193 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GTF2H2	GTF2H4	Q92759	999
GTF2H2	GTF2H1	P32780	999
GTF2H2	ERCC3	P19447	998
GTF2H2	ERCC2	P18074	997
GTF2H2	GTF2H3	Q13889	997
GTF2H2	GTF2H5	Q6ZYL4	945
GTF2H2	CCNH	P51946	906
GTF2H2	CDK7	P50613	878
GTF2H2	ERCC8	Q13216	864
GTF2H2	MNAT1	P51948	808
GTF2H2	XPA	P23025	723
GTF2H2	ERCC1	P07992	722
GTF2H2	NAIP	Q13075	709
GTF2H2	GTF2B	Q00403	681
GTF2H2	SMN1	Q16637	623

IntAct

61 interactions, top by confidence:

A	B	Type	Score
GTF2H5	GTF2H2	psi-mi:“MI:0915”(physical association)	0.800
GTF2H5	GTF2H2	psi-mi:“MI:0914”(association)	0.800
CCNH	ERCC2	psi-mi:“MI:0915”(physical association)	0.750
GTF2H3	GTF2H1	psi-mi:“MI:0914”(association)	0.740
GTF2H5	GTF2H1	psi-mi:“MI:0914”(association)	0.730
ERCC2	ERCC3	psi-mi:“MI:0915”(physical association)	0.670
ERCC3	ERCC2	psi-mi:“MI:0914”(association)	0.670
GTF2H4	GTF2H1	psi-mi:“MI:0914”(association)	0.670
GTF2H1	MNAT1	psi-mi:“MI:0914”(association)	0.670
GTF2H2	GTF2H1	psi-mi:“MI:0915”(physical association)	0.660
GTF2H5	ERCC2	psi-mi:“MI:0914”(association)	0.650
GTF2H3	ERCC3	psi-mi:“MI:0914”(association)	0.640
MNAT1	ERCC2	psi-mi:“MI:0914”(association)	0.640
GTF2H3	GTF2H2	psi-mi:“MI:0914”(association)	0.640
GTF2H2	ERCC2	psi-mi:“MI:0914”(association)	0.620
GTF2H2	ERCC2	psi-mi:“MI:0915”(physical association)	0.620
GTF2H4	ERCC2	psi-mi:“MI:0914”(association)	0.530
ERCC3	BCR	psi-mi:“MI:0914”(association)	0.530
RNF135	TXLNA	psi-mi:“MI:0914”(association)	0.530
RNF135	XRCC4	psi-mi:“MI:0914”(association)	0.530
HSPB8	VWA8	psi-mi:“MI:0914”(association)	0.530
GTF2H2	ERCC8	psi-mi:“MI:0407”(direct interaction)	0.440
incE	SNX2	psi-mi:“MI:0914”(association)	0.430
KLF9	GTF2H2	psi-mi:“MI:0915”(physical association)	0.400
GTF2H2	H1-2	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (202): GTF2H2 (Affinity Capture-MS), GTF2H2C (Affinity Capture-MS), GTF2H2 (Affinity Capture-MS), GTF2H2 (Affinity Capture-MS), GTF2H2C (Co-fractionation), GTF2H2 (Co-fractionation), GTF2H2C (Co-fractionation), GTF2H2 (Co-fractionation), GTF2H2C (Co-fractionation), GTF2H2 (Co-fractionation), GTF2H4 (Co-fractionation), GTF2H4 (Co-fractionation), GTF2H2C (Affinity Capture-MS), GTF2H2 (Affinity Capture-MS), GTF2H2 (Reconstituted Complex)

ESM2 similar proteins: A0A1L8F5J9, A0JN27, F1LTR1, F1NBL0, O15294, P35438, P35439, P56558, P61201, P61202, P61203, P61599, P61600, P63138, P79101, P81436, Q03555, Q05586, Q13888, Q15303, Q27HV0, Q2PFM2, Q2TBV5, Q4L208, Q58ED9, Q5R1P0, Q5SP67, Q5ZJ75, Q61527, Q62956, Q6IQT4, Q6IR75, Q6P1K8, Q6P632, Q7ZXR3, Q8BUV3, Q8C6G8, Q8CGY8, Q8R4D1, Q91854

Diamond homologs: A0JN27, O74995, P34567, Q04673, Q13888, Q2TBV5, Q6P1K8, Q86KZ2, Q9JIB4, Q9ZVN9

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
GTF2H2	“up-regulates activity”	ESR1	phosphorylation
GTF2H2	“form complex”	TFIIH	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 53 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
RNA Pol II CTD phosphorylation and interaction with CE during HIV infection	10	116.5×	2e-17
RNA Pol II CTD phosphorylation and interaction with CE	10	116.5×	2e-17
mRNA Capping	10	108.8×	2e-17
Formation of the Early Elongation Complex	10	96.0×	4e-17
Formation of the HIV-1 Early Elongation Complex	10	96.0×	4e-17
Global Genome Nucleotide Excision Repair (GG-NER)	7	91.4×	4e-12
RNA Polymerase I Transcription Termination	9	83.9×	5e-15
Transcription-Coupled Nucleotide Excision Repair (TC-NER)	11	83.5×	2e-17

GO biological processes:

GO term	Partners	Fold	FDR
transcription initiation at RNA polymerase II promoter	9	70.2×	2e-12
nucleotide-excision repair	8	63.8×	7e-11
transcription by RNA polymerase II	9	13.2×	3e-06
DNA repair	7	9.3×	7e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	19
Likely benign	2
Benign	32

Top pathogenic / likely-pathogenic (0)

SpliceAI

2277 predictions. Top by Δscore:

Variant	Effect	Δscore
5:71037505:A:AC	donor_gain	1.0000
5:71037506:C:CC	donor_gain	1.0000
5:71048004:AC:A	donor_gain	1.0000
5:71048005:CC:C	donor_gain	1.0000
5:71048879:T:C	acceptor_gain	1.0000
5:71048879:T:TC	acceptor_gain	1.0000
5:71049160:T:C	acceptor_gain	1.0000
5:71049160:T:TC	acceptor_gain	1.0000
5:71055350:A:AC	donor_gain	1.0000
5:71055351:C:CC	donor_gain	1.0000
5:71059746:T:C	acceptor_gain	1.0000
5:71059746:T:TC	acceptor_gain	1.0000
5:71060168:CAA:C	acceptor_gain	1.0000
5:71060171:C:CC	acceptor_gain	1.0000
5:71060836:A:C	donor_gain	1.0000
5:71060838:TTTTA:T	donor_loss	1.0000
5:71060839:TTTA:T	donor_loss	1.0000
5:71060840:TTA:T	donor_loss	1.0000
5:71060841:TAC:T	donor_loss	1.0000
5:71060843:C:T	donor_loss	1.0000
5:71060926:CGCAT:C	acceptor_gain	1.0000
5:71060928:CAT:C	acceptor_gain	1.0000
5:71060929:ATCT:A	acceptor_loss	1.0000
5:71060930:TCTA:T	acceptor_loss	1.0000
5:71060931:C:CA	acceptor_loss	1.0000
5:71060931:C:CC	acceptor_gain	1.0000
5:71061762:CTCC:C	acceptor_gain	1.0000
5:71061764:CC:C	acceptor_gain	1.0000
5:71061765:CC:C	acceptor_gain	1.0000
5:71061766:C:CG	acceptor_loss	1.0000

AlphaMissense

2591 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:71041597:A:G	L318S	1.000
5:71041606:G:T	A315D	1.000
5:71041615:A:C	L312W	1.000
5:71041621:A:G	L310P	1.000
5:71042182:A:C	C308W	1.000
5:71042183:C:T	C308Y	1.000
5:71042184:A:G	C308R	1.000
5:71042191:A:C	C305W	1.000
5:71042192:C:T	C305Y	1.000
5:71042193:A:G	C305R	1.000
5:71042201:G:T	P302H	1.000
5:71042224:A:C	C294W	1.000
5:71042226:A:G	C294R	1.000
5:71042233:G:C	C291W	1.000
5:71042234:C:T	C291Y	1.000
5:71042235:A:G	C291R	1.000
5:71045503:A:C	F254L	1.000
5:71045503:A:T	F254L	1.000
5:71045504:A:C	F254C	1.000
5:71045504:A:G	F254S	1.000
5:71045505:A:C	F254V	1.000
5:71045505:A:G	F254L	1.000
5:71048006:C:G	G253R	1.000
5:71048006:C:T	G253R	1.000
5:71049113:G:C	S172R	1.000
5:71049113:G:T	S172R	1.000
5:71049115:T:G	S172R	1.000
5:71060123:A:C	S102R	1.000
5:71060123:A:T	S102R	1.000
5:71060125:T:G	S102R	1.000

dbSNP variants (sampled 300 via entrez): RS1000330265 (5:71063919 A>C), RS1000927154 (5:71056263 G>C,T), RS1002328080 (5:71061435 C>T), RS1002931893 (5:71039973 A>G), RS1004375051 (5:71050736 G>A), RS1004810720 (5:71046348 A>C,G), RS1006464156 (5:71054969 T>C), RS1006891994 (5:71056093 T>C), RS1006926714 (5:71055231 T>C), RS1008471915 (5:71036515 TG>T), RS1008565273 (5:71063822 G>A), RS1008594959 (5:71061658 CT>C,CTT), RS1010264733 (5:71059415 G>A,C), RS1010574096 (5:71051944 T>C), RS1010606648 (5:71051209 G>A)

Disease associations

OMIM: gene MIM:601748 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): primary amenorrhea (MONDO:1060208)

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

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	2
Tretinoin	decreases expression	2
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
myristicin	decreases expression	1
uranyl acetate	affects expression	1
bisphenol A	increases expression	1
beta-lapachone	increases expression	1
bromoacetate	decreases expression	1
abrine	decreases expression	1
Arecoline	decreases expression	1
Benzo(a)pyrene	increases expression	1
Cadmium	increases abundance, increases expression	1
Doxorubicin	decreases expression	1
Formaldehyde	decreases expression	1
Selenium	decreases expression, affects cotreatment, increases expression	1
Uranium	affects expression	1
Urethane	decreases expression	1
Vitamin E	affects cotreatment, increases expression, decreases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Aflatoxin B1	decreases methylation	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT07164248	Not specified	COMPLETED	Evaluation of Bone Mineral Density Indications and Outcomes in Female Adolescents: Implications for Early Detection of Osteopenia/Osteoporosis and Gynecologic Practice