PCGF2

Summary

PCGF2 (polycomb group ring finger 2, HGNC:12929) is a protein-coding gene on chromosome 17q12, encoding Polycomb group RING finger protein 2 (P35227). Transcriptional repressor.

The protein encoded by this gene contains a RING finger motif and is similar to the polycomb group (PcG) gene products. PcG gene products form complexes via protein-protein interaction and maintain the transcription repression of genes involved in embryogenesis, cell cycles, and tumorigenesis. This protein was shown to act as a negative regulator of transcription and has tumor suppressor activity. The expression of this gene was detected in various tumor cells, but is limited in neural organs in normal tissues. Knockout studies in mice suggested that this protein may negatively regulate the expression of different cytokines, chemokines, and chemokine receptors, and thus plays an important role in lymphocyte differentiation and migration, as well as in immune responses.

Source: NCBI Gene 7703 — RefSeq curated summary.

At a glance

• Gene–disease (curated): turnpenny-fry syndrome (Strong, ClinGen)
• Clinical variants (ClinVar): 228 total — 2 likely-pathogenic
• Phenotypes (HPO): 82
• MANE Select transcript: NM_007144

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12929
Approved symbol	PCGF2
Name	polycomb group ring finger 2
Location	17q12
Locus type	gene with protein product
Status	Approved
Aliases	MEL-18
Ensembl gene	ENSG00000277258
Ensembl biotype	protein_coding
OMIM	600346
Entrez	7703

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 22 protein_coding

ENST00000610747, ENST00000611883, ENST00000616129, ENST00000616199, ENST00000618506, ENST00000618941, ENST00000620225, ENST00000894201, ENST00000894202, ENST00000894203, ENST00000894204, ENST00000894205, ENST00000894206, ENST00000894207, ENST00000939014, ENST00000939015, ENST00000939016, ENST00000939017, ENST00000939018, ENST00000939019, ENST00000939020, ENST00000939021

RefSeq mRNA: 3 — MANE Select: NM_007144 NM_001369614, NM_001369615, NM_007144

CCDS: CCDS32638

Canonical transcript exons

ENST00000610440 — 0 exons

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 96.55.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 34.7508 / max 879.8990, expressed in 1625 samples.

FANTOM5 promoters (14 alternative TSS)

Promoter ID	TPM avg	Samples expressed
165550	24.4881	1570
165555	2.6683	955
165556	1.5120	808
165541	1.1751	681
165544	0.9306	581
165545	0.7985	493
165549	0.7963	473
165548	0.6954	449
165551	0.6051	352
165552	0.3455	149

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	96.55	gold quality
ganglionic eminence	UBERON:0004023	96.36	gold quality
stromal cell of endometrium	CL:0002255	95.03	gold quality
ventricular zone	UBERON:0003053	95.03	gold quality
pituitary gland	UBERON:0000007	94.17	gold quality
adenohypophysis	UBERON:0002196	93.99	gold quality
metanephros cortex	UBERON:0010533	93.98	gold quality
cortex of kidney	UBERON:0001225	93.22	gold quality
endocervix	UBERON:0000458	92.96	gold quality
adult mammalian kidney	UBERON:0000082	92.34	gold quality
body of uterus	UBERON:0009853	91.88	gold quality
left lobe of thyroid gland	UBERON:0001120	91.70	gold quality
right lobe of thyroid gland	UBERON:0001119	91.69	gold quality
thyroid gland	UBERON:0002046	91.51	gold quality
apex of heart	UBERON:0002098	91.49	gold quality
ascending aorta	UBERON:0001496	91.37	gold quality
thoracic aorta	UBERON:0001515	91.31	gold quality
ectocervix	UBERON:0012249	91.25	gold quality
uterine cervix	UBERON:0000002	91.23	gold quality
right adrenal gland cortex	UBERON:0035827	91.22	gold quality
right ovary	UBERON:0002118	91.19	gold quality
lower esophagus mucosa	UBERON:0035834	91.17	gold quality
right adrenal gland	UBERON:0001233	91.14	gold quality
left adrenal gland cortex	UBERON:0035825	91.06	gold quality
right uterine tube	UBERON:0001302	90.81	gold quality
left adrenal gland	UBERON:0001234	90.78	gold quality
myometrium	UBERON:0001296	90.73	gold quality
ovary	UBERON:0000992	90.71	gold quality
descending thoracic aorta	UBERON:0002345	90.66	gold quality
right coronary artery	UBERON:0001625	90.63	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.49

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

3 targets.

Target	Regulation
HOXA7	Activation
ZEB1	Repression
ZEB2	Repression

Upstream regulators (CollecTRI, top): HOXA7, ID1, SPI1

miRNA regulators (miRDB)

100 targeting PCGF2, 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-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-659-3P	99.85	70.69	1620
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-636	99.80	69.58	1500
HSA-MIR-6739-5P	99.80	67.87	2806

Literature-anchored findings (GeneRIF, showing 28)

• The mouse counterpart of this gene regulates the expression of Th2 cytokines, and plays a critical role in Th2 cell differentiation and Th-2 dependent immune responses. (PMID:11520462)
• The mouse counterpart of this gene regulates the expression of various chemokines and chemokine receptors, which may be important for T cell migration and differentiation. (PMID:11750047)
• The oncogenic role of MEL-18 in human primary breast carcinomas is determined by its capacity to inhibit INK4a/ARF proteins(p16INK4a, p14ARF, or h-TERT) or to induce telomerase activity. (PMID:17145810)
• Our data suggest that Mel-18 regulates Bmi-1 expression during senescence via down-regulation of c-Myc. (PMID:17151361)
• These results suggest that Bmi-1 and Mel-18 may have overlapping functions in cancer cell growth. (PMID:17452456)
• Mel-18 and Bmi-1 may regulate the Akt pathway in breast cancer cells, and that Mel-18 functions as a tumor suppressor by repressing the expression of Bmi-1 and consequently down-regulating Akt activity. (PMID:17545584)
• validated occurrence of an unusual TG 3’ splice site in intron 1 (PMID:17672918)
• Results show that a phosphorylated form of Mel-18 targets the Ring1B histone H2A ubiquitin ligase to chromatin. (PMID:17936708)
• The results of this study strengthen the conclusion that mel-18 functions as an anti-SUMO E3 factor, and extend its targets to include regulation of the sumoylation of the important cellular protein RanGAP1. (PMID:18706886)
• Loss of Mel-18 is associated with prostate cancer. (PMID:19395284)
• Single Nucleotide Polymorphism and down regulation of Mel-18 is associated with prostate cancer. (PMID:19585577)
• An association of Mel18 with emerin was observed in Hutchinson-Gilford progeria syndrome, but not in WT cells. (PMID:19727227)
• BMI1 acts as an oncogene and Mel-18 functions as a tumor suppressor via downregulation of BMI1. (PMID:20170541)
• Mel-18 may serve as a useful marker in prognostic evaluation for patients with breast cancer. (PMID:20444850)
• Our analysis showed correlation between BMI1 and PCGF2 gene’s expression and survival in children with medulloblastoma. (PMID:20717685)
• Mel-18 plays a significant role in the angiogenic function of endothelial cells by regulating endothelial gene expression. (PMID:20801102)
• Decreased Mel-18 and increased Bmi-1 mRNA expression was associated with the carcinogenesis and progression of gastric cancer (PMID:21059209)
• Bmi-1/Mel-18 ratio can be potentially used as a tool for stratifying women at risk of developing breast malignancy. (PMID:21162745)
• these findings provide that Mel-18 is a novel regulator of tumor angiogenesis through regulating HIF-1alpha and its target VEGF expressions mediated by the PTEN/PI3K/Akt pathway, suggesting a new tumor-suppressive role of Mel-18 in human breast cancer. (PMID:21602890)
• PCGF2, a PRC1 gene, played a negative role in the granulocytic differentiation of human APL cells. (PMID:22085718)
• Findings suggest that Mel-18 is a novel negative regulator of breast cancer stem cell (CSC) that inhibits the stem cell population and in vitro and in vivo self-renewal through the inactivation of Wnt-mediated Notch signaling. (PMID:22954590)
• Mel-18 functions as a tumor suppressor by its novel negative control of the epithelial-mesenchymal transition in breast cancer. (PMID:23474752)
• It was therefore concluded that the lower Mel-18 expression might contribute to colorectal cancer development/progression. (PMID:24964959)
• Mel-18 underexpression in luminal breast cancer cells caused ER-alpha downregulation.Its overexpression restored it in triple-negative breast cancer cells. MEL-18 suppressed SUMOylation of the ESR1 transactivators p53 and SP1. (PMID:25822021)
• Suggest a novel role of PCGF2 in arsenic trioxide-mediated degradation of PML-RARA that PCGF2 might act as a negative regulator of UBE2I via direct interaction. (PMID:27030546)
• Low expression of Mel-18 is correlated with gastric cancer. (PMID:27542229)
• AKT-mediated regulation of chromatin ubiquitylation and tumorigenesis through Mel18 phosphorylation. (PMID:33664452)
• SLCO4A1-AS1 triggers the malignant behaviours of melanoma cells via sponging miR-1306-5p to enhance PCGF2. (PMID:35427425)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
mus_musculus	Pcgf2	ENSMUSG00000018537
rattus_norvegicus	Pcgf2	ENSRNOG00000012705
rattus_norvegicus		ENSRNOG00000076687
rattus_norvegicus		ENSRNOG00000086586
drosophila_melanogaster	Psc	FBGN0005624
drosophila_melanogaster	Su(z)2	FBGN0265623

Paralogs (7): PCGF1 (ENSG00000115289), RNF2 (ENSG00000121481), PCGF6 (ENSG00000156374), BMI1 (ENSG00000168283), PCGF5 (ENSG00000180628), PCGF3 (ENSG00000185619), RING1 (ENSG00000204227)

Protein

Protein identifiers

Polycomb group RING finger protein 2 — P35227 (reviewed: P35227)

Alternative names: DNA-binding protein Mel-18, RING finger protein 110, Zinc finger protein 144

All UniProt accessions (4): A0A087X0Y6, A0A087X259, P35227, J3KT13

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional repressor. Binds specifically to the DNA sequence 5’-GACTNGACT-3’. Has tumor suppressor activity. May play a role in control of cell proliferation and/or neural cell development. Regulates proliferation of early T progenitor cells by maintaining expression of HES1. Also plays a role in antero-posterior specification of the axial skeleton and negative regulation of the self-renewal activity of hematopoietic stem cells. Component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development. PcG PRC1 complex acts via chromatin remodeling and modification of histones; it mediates monoubiquitination of histone H2A ‘Lys-119’, rendering chromatin heritably changed in its expressibility. Within the PRC1-like complex, regulates RNF2 ubiquitin ligase activity.

Subunit / interactions. Exists as both a monomer and homodimer. Component of a PRC1-like complex. Interacts with CBX8, RING1 and RNF2. Interacts with CBX7. Interacts with PHC2.

Subcellular location. Nucleus.

Tissue specificity. Detected in all tissues examined with high expression found in placenta lung and kidney and low expression, in liver, pancreas and skeletal muscle.

Post-translational modifications. Phosphorylated. Homodimer formation is regulated by phosphorylation with only unphosphorylated proteins forming homodimers.

Disease relevance. Turnpenny-Fry syndrome (TPFS) [MIM:618371] A syndrome characterized by facial dysmorphism, intellectual disability, feeding problems, impaired growth, and a range of brain, cardiovascular, and skeletal abnormalities. Craniofacial features include frontal bossing, sparse hair, malar hypoplasia, small palpebral fissures and oral stoma, and dysplastic ears. The disease is caused by variants affecting the gene represented in this entry.

RefSeq proteins (3): NP_001356543, NP_001356544, NP_009075* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001841	Znf_RING	Domain
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR017907	Znf_RING_CS	Conserved_site
IPR032443	RAWUL	Domain

Pfam: PF13923, PF16207

UniProt features (12 total): compositionally biased region 3, sequence variant 2, cross-link 2, chain 1, zinc finger region 1, region of interest 1, short sequence motif 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P35227-F1	75.30	0.51

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 (3): 344, 51, 88

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-3108214	SUMOylation of DNA damage response and repair proteins
R-HSA-3899300	SUMOylation of transcription cofactors
R-HSA-4551638	SUMOylation of chromatin organization proteins
R-HSA-4570464	SUMOylation of RNA binding proteins
R-HSA-4655427	SUMOylation of DNA methylation proteins
R-HSA-5617472	Activation of anterior HOX genes in hindbrain development during early embryogenesis
R-HSA-8953750	Transcriptional Regulation by E2F6

MSigDB gene sets: 389 (showing top): FLECHNER_PBL_KIDNEY_TRANSPLANT_REJECTED_VS_OK_UP, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, MIDORIKAWA_AMPLIFIED_IN_LIVER_CANCER, GOBP_EMBRYONIC_SKELETAL_SYSTEM_DEVELOPMENT, GOLDRATH_IMMUNE_MEMORY, GOBP_EMBRYONIC_SKELETAL_SYSTEM_MORPHOGENESIS, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, SP1_Q2_01, GTGCCTT_MIR506, BROWNE_HCMV_INFECTION_48HR_DN, GOBP_NEGATIVE_REGULATION_OF_GENE_EXPRESSION_EPIGENETIC

GO Biological Process (10): negative regulation of transcription by RNA polymerase II (GO:0000122), in utero embryonic development (GO:0001701), chromatin remodeling (GO:0006338), anterior/posterior pattern specification (GO:0009952), embryonic skeletal system morphogenesis (GO:0048704), cellular response to hydrogen peroxide (GO:0070301), apoptotic signaling pathway (GO:0097190), negative regulation of apoptotic signaling pathway (GO:2001234), chromatin organization (GO:0006325), embryonic skeletal system development (GO:0048706)

GO Molecular Function (6): DNA binding (GO:0003677), zinc ion binding (GO:0008270), promoter-specific chromatin binding (GO:1990841), chromatin binding (GO:0003682), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (7): chromatin (GO:0000785), sex chromatin (GO:0001739), nucleus (GO:0005634), nucleoplasm (GO:0005654), nuclear body (GO:0016604), PcG protein complex (GO:0031519), PRC1 complex (GO:0035102)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
SUMO E3 ligases SUMOylate target proteins	5
Activation of HOX genes during differentiation	1
Generic Transcription Pathway	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
chordate embryonic development	2
binding	2
cellular anatomical structure	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
chromatin organization	1
regionalization	1
embryonic organ morphogenesis	1
skeletal system morphogenesis	1
embryonic skeletal system development	1
cellular response to reactive oxygen species	1
response to hydrogen peroxide	1
apoptotic process	1
signal transduction	1
negative regulation of signal transduction	1
negative regulation of apoptotic process	1
apoptotic signaling pathway	1
regulation of apoptotic signaling pathway	1
cellular component organization	1
skeletal system development	1
nucleic acid binding	1
transition metal ion binding	1
chromatin binding	1
cation binding	1
chromosome	1
heterochromatin	1
sex chromosome	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
nucleoplasm	1
intracellular membraneless organelle	1
nuclear protein-containing complex	1
nuclear ubiquitin ligase complex	1
PcG protein complex	1

Protein interactions and networks

STRING

1125 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PCGF2	PHC1	P78364	997
PCGF2	RNF2	Q99496	991
PCGF2	RING1	Q06587	991
PCGF2	CBX2	Q14781	990
PCGF2	BMI1	P35226	987
PCGF2	R4GMX3	R4GMX3	987
PCGF2	CBX1	P23197	951
PCGF2	SCMH1	Q96GD3	937
PCGF2	RYBP	Q8N488	924
PCGF2	PHC2	Q8IXK0	918
PCGF2	SLC25A3	Q00325	907
PCGF2	TTK	P33981	902
PCGF2	YAF2	Q8IY57	897
PCGF2	CBX7	O95931	871
PCGF2	PCGF1	Q9BSM1	847

IntAct

114 interactions, top by confidence:

A	B	Type	Score
CBX8	BMI1	psi-mi:“MI:0914”(association)	0.970
PCGF2	RNF2	psi-mi:“MI:0915”(physical association)	0.950
RNF2	PCGF2	psi-mi:“MI:0915”(physical association)	0.950
PCGF2	RING1	psi-mi:“MI:0915”(physical association)	0.940
RING1	PCGF2	psi-mi:“MI:0915”(physical association)	0.940
BMI1	CBX7	psi-mi:“MI:0914”(association)	0.940
CBX7	BMI1	psi-mi:“MI:0914”(association)	0.940
PCGF2	CBX8	psi-mi:“MI:0407”(direct interaction)	0.930
PCGF2	CBX8	psi-mi:“MI:0915”(physical association)	0.930
PHC1	PCGF2	psi-mi:“MI:0915”(physical association)	0.920
PCGF2	PHC1	psi-mi:“MI:0915”(physical association)	0.920
RYBP	CSNK2A2	psi-mi:“MI:0914”(association)	0.900
PCGF2	PHC2	psi-mi:“MI:0915”(physical association)	0.890
PHC2	PCGF2	psi-mi:“MI:0915”(physical association)	0.890
PCGF2	PHC2	psi-mi:“MI:0914”(association)	0.890
PCGF2	CBX4	psi-mi:“MI:0914”(association)	0.840
CBX7	PCGF2	psi-mi:“MI:0407”(direct interaction)	0.840
CBX7	PCGF2	psi-mi:“MI:0915”(physical association)	0.840

BioGRID (241): PCGF2 (Two-hybrid), PCGF2 (Affinity Capture-MS), PCGF2 (Affinity Capture-MS), PCGF2 (Affinity Capture-MS), PCGF2 (Two-hybrid), PCGF2 (Affinity Capture-MS), RNF2 (Reconstituted Complex), PCGF2 (Biochemical Activity), UBE2D3 (Reconstituted Complex), PCGF2 (Reconstituted Complex), PCGF2 (Affinity Capture-MS), PCGF2 (Affinity Capture-MS), UBE2I (Affinity Capture-Western), PCGF2 (Affinity Capture-Western), PHC1 (Affinity Capture-MS)

ESM2 similar proteins: A0JN86, A2AHJ4, A2APV2, A2AQW0, A9JRL3, B3DK16, O08874, O35099, P0CF52, P19447, P23798, P25916, P32866, P35226, P35227, P49135, Q07139, Q1JPS1, Q1RMT1, Q21029, Q28H21, Q2YDF9, Q32KX7, Q3UK78, Q4QR06, Q5R8L2, Q5RA62, Q5SDR3, Q5ZKK7, Q640D5, Q6DD21, Q6DLV9, Q6GN16, Q6RI45, Q6ZN16, Q7T3E6, Q7Z569, Q7ZYZ7, Q86SE9, Q8BPM2

Diamond homologs: A0JN86, B3DK16, P23798, P25916, P35226, P35227, Q07G17, Q0WX00, Q14527, Q1JPS1, Q28H21, Q2KJ29, Q2YDF9, Q32KX7, Q3KNV8, Q3UK78, Q4QR06, Q5R8L2, Q5SDR3, Q5XI70, Q640D5, Q6CJM4, Q6DLV9, Q7T3E6, Q7ZYZ7, Q86SE9, Q8BTQ0, Q8JIR0, Q8R023, Q91648, Q94AY3, Q99NA9, Q9BSM1, Q9BYE7, Q9FKW0, Q9LS86, Q9M9Y4, Q9TST0, O60106, Q19336

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
PCGF2	“down-regulates activity”	HSF2	sumoylation
PCGF2	“down-regulates activity”	UBE2I	binding
PCGF2	“form complex”	“Polycomb repressive complex 1”	binding
Ub:E2	“up-regulates activity”	PCGF2	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 56 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
SUMOylation of DNA methylation proteins	9	143.9×	3e-16
RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known	13	93.0×	6e-21
SUMOylation of transcription cofactors	10	57.9×	7e-14
Transcriptional Regulation by E2F6	8	55.8×	4e-11
SUMOylation of RNA binding proteins	9	51.0×	5e-12
Regulation of PTEN gene transcription	10	42.5×	2e-12
SUMOylation of chromatin organization proteins	10	37.8×	5e-12
SUMOylation of DNA damage response and repair proteins	10	34.9×	7e-12

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	2
Uncertain significance	80
Likely benign	94
Benign	19

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
1298700	NM_007144.3(PCGF2):c.194C>G (p.Pro65Arg)	Likely pathogenic
624617	NM_007144.3(PCGF2):c.193C>T (p.Pro65Ser)	Likely pathogenic

SpliceAI

1447 predictions. Top by Δscore:

Variant	Effect	Δscore
17:38735596:CCGTT:C	acceptor_gain	1.0000
17:38735597:CGTT:C	acceptor_gain	1.0000
17:38735597:CGTTC:C	acceptor_gain	1.0000
17:38735598:GTT:G	acceptor_gain	1.0000
17:38735599:TT:T	acceptor_gain	1.0000
17:38735601:C:CC	acceptor_gain	1.0000
17:38735601:C:CG	acceptor_loss	1.0000
17:38735602:T:G	acceptor_loss	1.0000
17:38735612:G:C	acceptor_gain	1.0000
17:38735612:G:GC	acceptor_gain	1.0000
17:38736088:A:AC	donor_gain	1.0000
17:38736088:AC:A	donor_gain	1.0000
17:38736089:C:CC	donor_gain	1.0000
17:38736089:CC:C	donor_gain	1.0000
17:38736166:TCCAC:T	acceptor_gain	1.0000
17:38736167:CCAC:C	acceptor_gain	1.0000
17:38736167:CCACC:C	acceptor_gain	1.0000
17:38736168:CAC:C	acceptor_gain	1.0000
17:38736168:CACC:C	acceptor_gain	1.0000
17:38736169:AC:A	acceptor_gain	1.0000
17:38736170:CC:C	acceptor_gain	1.0000
17:38736170:CCTGG:C	acceptor_loss	1.0000
17:38736171:C:CC	acceptor_gain	1.0000
17:38736172:T:C	acceptor_loss	1.0000
17:38738539:A:AC	donor_gain	1.0000
17:38738540:C:CC	donor_gain	1.0000
17:38738540:CTTT:C	donor_gain	1.0000
17:38738857:GGGGA:G	acceptor_gain	1.0000
17:38738858:GGGA:G	acceptor_gain	1.0000
17:38738859:GGA:G	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000304779 (17:38736662 G>A,T), RS1000440255 (17:38736764 G>A), RS1000556927 (17:38747616 G>A,C), RS1000572430 (17:38736518 G>A), RS1000621822 (17:38741542 C>T), RS1000795300 (17:38747365 C>A), RS1000924349 (17:38747612 A>G), RS1000992424 (17:38741723 A>G), RS1001175740 (17:38737665 C>T), RS1001628729 (17:38742046 G>A), RS1001810963 (17:38747629 C>G,T), RS1001965546 (17:38749188 C>T), RS1002226020 (17:38733806 T>A), RS1002286801 (17:38733658 G>A), RS1002319370 (17:38734071 C>A,T)

Disease associations

OMIM: gene MIM:600346 | disease phenotypes: MIM:618371

GenCC curated gene-disease

Disease	Classification	Inheritance
turnpenny-fry syndrome	Strong	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
turnpenny-fry syndrome	Strong	AD

Mondo (2): turnpenny-fry syndrome (MONDO:0032707), intellectual disability (MONDO:0001071)

Orphanet (2): Turnpenny-Fry syndrome (Orphanet:688642), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

82 total (30 of 82 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000160	Narrow mouth
HP:0000164	Abnormality of the dentition
HP:0000218	High palate
HP:0000219	Thin upper lip vermilion
HP:0000248	Brachycephaly
HP:0000252	Microcephaly
HP:0000256	Macrocephaly
HP:0000260	Wide anterior fontanel
HP:0000272	Malar flattening
HP:0000276	Long face
HP:0000297	Facial hypotonia
HP:0000303	Mandibular prognathia
HP:0000337	Broad forehead
HP:0000369	Low-set ears
HP:0000405	Conductive hearing impairment
HP:0000473	Torticollis
HP:0000494	Downslanted palpebral fissures
HP:0000629	Periorbital fullness
HP:0000678	Dental crowding
HP:0000687	Widely spaced teeth
HP:0000689	Dental malocclusion
HP:0000691	Microdontia
HP:0000729	Autistic behavior
HP:0000767	Pectus excavatum
HP:0000768	Pectus carinatum
HP:0000774	Narrow chest
HP:0000879	Short sternum
HP:0000995	Melanocytic nevus
HP:0001054	Numerous nevi

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases methylation, affects cotreatment, decreases expression	6
Cadmium Chloride	decreases expression, increases abundance, increases expression	3
Cadmium	decreases expression, increases abundance, increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
dicrotophos	increases expression	1
trichostatin A	decreases expression	1
sodium arsenite	decreases expression	1
potassium chromate(VI)	increases expression, affects cotreatment	1
beta-methylcholine	affects expression	1
epigallocatechin gallate	affects cotreatment, increases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dimethylarsinous acid	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Vorinostat	decreases expression	1
Acetaminophen	decreases expression	1
Cannabidiol	decreases expression	1
Demecolcine	decreases expression	1
Succimer	affects cotreatment, increases expression	1
Formaldehyde	decreases expression	1
Ozone	decreases expression	1
Piroxicam	increases expression	1
Smoke	decreases expression	1
Vincristine	decreases expression	1
Chlorodiphenyl (54% Chlorine)	decreases expression	1
Magnetite Nanoparticles	affects cotreatment, increases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_1661	ZR-75-30	Cancer cell line	Female
CVCL_E2G8	HAP1 PCGF2 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT03479476	PHASE2/PHASE3	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome
NCT02616796	PHASE1/PHASE2	COMPLETED	Effects of Social Gaze Training on Brain and Behavior in Fragile X Syndrome
NCT06860672	EARLY_PHASE1	RECRUITING	Clinical Trial of the Dual Vector Base Editor for the Treatment of the CHD3-R1025W Mutation
NCT00597948	Not specified	COMPLETED	Healthy Lifestyles for People With Intellectual Disabilities
NCT01087320	Not specified	RECRUITING	Genome Medical Sequencing for Gene Discovery
NCT01652963	Not specified	UNKNOWN	Picture-based Computerised Assessment and Training of Cognitive Behaviour Therapy Skills
NCT01695395	Not specified	COMPLETED	Mental Health Care Provision for Adults With Intellectual Disability and a Mental Disorder
NCT01867554	Not specified	COMPLETED	Research and Characterization of New Genes Involved in Intellectual Disability
NCT01915381	Not specified	COMPLETED	Improving Adherence Healthy Lifestyle With a Smartphone Application Based on Adults With Intellectual Disabilities
NCT01988623	Not specified	COMPLETED	Pivotal Response Treatment for Individuals With Intellectual Disabilities
NCT02099773	Not specified	COMPLETED	Support Staff-client Interactions With Augmentative and Alternative Communication
NCT02136849	Not specified	COMPLETED	Inter-regional Project of the Great Western Exploration Approach for Exome Molecular Causes Severe Intellectual Disability Isolated or Syndromic
NCT02225041	Not specified	COMPLETED	Sedation Strategy and Cognitive Outcome After Critical Illness in Early Childhood
NCT02414438	Not specified	COMPLETED	Establishing the Clinical Utility of First StepDx PLUS and NextStepDx PLUS Study
NCT02451761	Not specified	COMPLETED	Apparently Balanced Chromosomal Translocation/ Next-generation Sequencing/ Intellectual Disability
NCT02461420	Not specified	ACTIVE_NOT_RECRUITING	Mapping the Genotype, Phenotype, and Natural History of Phelan-McDermid Syndrome
NCT02461459	Not specified	ACTIVE_NOT_RECRUITING	Autism Spectrum Disorder (ASD) and Intellectual Disability (ID) Determinants in Tuberous Sclerosis Complex (TSC)
NCT02486081	Not specified	COMPLETED	Development and Application-Smart Football for Movement Evaluation and Training in the Special Education Population
NCT02504502	Not specified	COMPLETED	Enhancing Genomic Laboratory Reports to Enhance Communication and Empower Patients
NCT02513277	Not specified	COMPLETED	Diabetes Screening & Prevention for People With Learning (Intellectual) Disabilities:STOP Diabetes Study
NCT02561754	Not specified	COMPLETED	Weight Management for Adolescents With IDD
NCT02591446	Not specified	COMPLETED	Transcranial Magnetic Stimulation Studies in Autism Spectrum Disorders
NCT02714868	Not specified	COMPLETED	Evaluation of Project TEAM (Teens Making Environmental and Activity Modifications)
NCT02721394	Not specified	UNKNOWN	FCT With Young Children With ID in the UK: A Feasibility Project V.1
NCT02746614	Not specified	COMPLETED	Psychomotor Therapy Effects in Adaptive Behavior and Motor Proficiency in Intellectual Disability
NCT02836405	Not specified	COMPLETED	TMS for the Investigation of Brain Plasticity in Autism Spectrum Disorders