TCF20

Summary

TCF20 (transcription factor 20, HGNC:11631) is a protein-coding gene on chromosome 22q13.2, encoding Transcription factor 20 (Q9UGU0). Transcriptional activator that binds to the regulatory region of MMP3 and thereby controls stromelysin expression. It is haploinsufficient (ClinGen: sufficient evidence).

This gene encodes a transcription factor that recognizes the platelet-derived growth factor-responsive element in the matrix metalloproteinase 3 promoter. The encoded protein is thought to be a transcriptional coactivator, enhancing the activity of transcription factors such as JUN and SP1. Mutations in this gene are associated with autism spectrum disorders. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 6942 — RefSeq curated summary.

At a glance

• Gene–disease (curated): developmental delay with variable intellectual impairment and behavioral abnormalities (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 16
• Clinical variants (ClinVar): 1,311 total — 109 pathogenic, 28 likely-pathogenic
• Phenotypes (HPO): 50
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_001378418

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11631
Approved symbol	TCF20
Name	transcription factor 20
Location	22q13.2
Locus type	gene with protein product
Status	Approved
Aliases	AR1, SPBP
Ensembl gene	ENSG00000100207
Ensembl biotype	protein_coding
OMIM	603107
Entrez	6942

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 7 protein_coding

ENST00000335626, ENST00000359486, ENST00000404876, ENST00000515426, ENST00000675876, ENST00000677622, ENST00000683686

RefSeq mRNA: 3 — MANE Select: NM_001378418 NM_001378418, NM_005650, NM_181492

CCDS: CCDS14032, CCDS14033

Canonical transcript exons

ENST00000574943 — 0 exons

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 92.15.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.4009 / max 208.2473, expressed in 1788 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
194419	9.2160	1774
194418	1.9705	993
194423	0.5993	345
194422	0.2421	112
194417	0.1682	37
209491	0.1669	43
194420	0.0380	30

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	92.15	gold quality
ganglionic eminence	UBERON:0004023	86.39	gold quality
tonsil	UBERON:0002372	86.01	gold quality
bone marrow cell	CL:0002092	84.85	gold quality
islet of Langerhans	UBERON:0000006	84.65	gold quality
esophagus mucosa	UBERON:0002469	84.64	gold quality
blood	UBERON:0000178	84.60	gold quality
granulocyte	CL:0000094	84.48	gold quality
lymph node	UBERON:0000029	83.35	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	83.12	gold quality
superior frontal gyrus	UBERON:0002661	82.94	gold quality
calcaneal tendon	UBERON:0003701	82.90	gold quality
left testis	UBERON:0004533	82.83	gold quality
mucosa of transverse colon	UBERON:0004991	82.77	gold quality
bone marrow	UBERON:0002371	82.55	gold quality
zone of skin	UBERON:0000014	82.53	gold quality
testis	UBERON:0000473	82.51	gold quality
leukocyte	CL:0000738	82.50	gold quality
skin of abdomen	UBERON:0001416	82.46	gold quality
right testis	UBERON:0004534	82.43	gold quality
skin of leg	UBERON:0001511	82.38	gold quality
prefrontal cortex	UBERON:0000451	82.35	gold quality
esophagus	UBERON:0001043	82.35	gold quality
monocyte	CL:0000576	82.16	gold quality
vermiform appendix	UBERON:0001154	82.12	gold quality
uterine cervix	UBERON:0000002	82.08	gold quality
rectum	UBERON:0001052	81.88	gold quality
colonic epithelium	UBERON:0000397	81.78	gold quality
ectocervix	UBERON:0012249	81.75	gold quality
lower esophagus mucosa	UBERON:0035834	81.70	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.75

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

5 targets.

Target	Regulation
AR
DRD1
MMP3	Activation
SQSTM1
TCF20

Upstream regulators (CollecTRI, top): PAX6, TCF20

miRNA regulators (miRDB)

106 targeting TCF20, 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-574-5P	100.00	66.01	989
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-590-3P	99.96	74.34	6478
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-7153-5P	99.94	68.89	1006
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-129-5P	99.88	70.26	3273

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 12)

• SPBP behaves as a repressor of activated ERalpha (PMID:15831449)
• Interaction between SPBP and TopBP1 was found to be mediated by the ePHD domain of SPBP and the BRCT6 domain of TopBP1. (PMID:17913746)
• Study has identified SPBP as a transcriptional coactivator of AR. We also show that Pax6 inhibits SPBP-mediated enhancement of AR activity on the AR target gene probasin promoter, a repression that was partly reversed by increased expression of SPBP. (PMID:21935435)
• evolutionary conservation of chromatin binding of SPBP and RAI1 (PMID:24205348)
• SPBP is a transcriptional coactivator of NRF2 regulating expression of the autophagy receptor p62. (PMID:24416372)
• mutations in TCF20 are associated with Autism spectrum disorders (PMID:25228304)
• Nonsense and one frameshift variant of TCF20 were identified the patients with intellectual disability and postnatal overgrowth. Such de novo variants of TCF20 may represent a novel differential diagnosis in the overgrowth syndrome spectrum. (PMID:27436265)
• We provide valuable data regarding the prognosis and clinical manifestations of patients with variants in TCF20. (PMID:30739909)
• TCF20 pathogenic variants are associated with a novel syndrome manifesting clinical characteristics similar to those observed in Smith-Magenis syndrome. (PMID:30819258)
• Rare and de novo duplications containing TCF20 are associated with a neurodevelopmental disorder. (PMID:34904221)
• Diagnosis and clinical presentation of two individuals with a rare TCF20 pathogenic variant. (PMID:36593604)
• Association Between CYP2D7 and TCF20 Polymorphisms and Coronary Heart Disease. (PMID:39060884)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	tcf20	ENSDARG00000078348
mus_musculus	Tcf20	ENSMUSG00000041852
mus_musculus	Zfp957	ENSMUSG00000071262
rattus_norvegicus	Tcf20	ENSRNOG00000009585
drosophila_melanogaster	CG5098	FBGN0034300

Paralogs (1): RAI1 (ENSG00000108557)

Protein

Protein identifiers

Transcription factor 20 — Q9UGU0 (reviewed: Q9UGU0)

Alternative names: Nuclear factor SPBP, Protein AR1, Stromelysin-1 PDGF-responsive element-binding protein

All UniProt accessions (5): Q9UGU0, A0A6Q8PH68, A9JX13, I3L1M7, W5ZR30

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional activator that binds to the regulatory region of MMP3 and thereby controls stromelysin expression. It stimulates the activity of various transcriptional activators such as JUN, SP1, PAX6 and ETS1, suggesting a function as a coactivator.

Subunit / interactions. Homodimer. Interacts with RNF4 and JUN.

Subcellular location. Nucleus.

Tissue specificity. Expressed in most tissues, except in ovary and prostate. Isoform 1 is exclusively expressed in brain, heart and testis, and this form predominates in liver and kidney. Isoform 2 predominates in lung.

Disease relevance. Developmental delay with variable intellectual impairment and behavioral abnormalities (DDVIBA) [MIM:618430] An autosomal dominant disorder characterized by impaired intellectual development with speech difficulties, dysmorphic features, and behavioral abnormalities including autism spectrum disorder, attention deficit and hyperactivity. Additional variable features may include hypotonia, somatic overgrowth, macrocephaly, mild distal skeletal anomalies, sleep disturbances, movement disorders, and gastrointestinal issues, such as constipation. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The atypical PHD domain functions as a negative modulator of cofactor binding.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9UGU0-1	1	yes
Q9UGU0-2	2

RefSeq proteins (3): NP_001365347, NP_005641, NP_852469 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001965	Znf_PHD	Domain
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR034732	EPHD	Domain
IPR041972	TCF-20_ePHD	Domain
IPR052440	Trans_Reg/Chrom_Remod	Family

Pfam: PF13771

UniProt features (132 total): cross-link 32, sequence variant 28, compositionally biased region 26, modified residue 22, region of interest 13, short sequence motif 3, splice variant 2, sequence conflict 2, zinc finger region 2, chain 1, DNA-binding region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UGU0-F1	39.03	0.05

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 (54): 60, 419, 430, 538, 559, 574, 583, 602, 640, 871, 966, 1005, 1024, 1053, 1305, 1335, 1361, 1522, 1669, 1671 …

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 285 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_UP, PUJANA_CHEK2_PCC_NETWORK, MARTINEZ_RB1_TARGETS_UP, BLALOCK_ALZHEIMERS_DISEASE_UP, SCHAEFFER_PROSTATE_DEVELOPMENT_6HR_DN, ATTCTTT_MIR186, BENPORATH_ES_CORE_NINE_CORRELATED, SCHLOSSER_SERUM_RESPONSE_DN, BENPORATH_NOS_TARGETS, RASHI_RESPONSE_TO_IONIZING_RADIATION_5, GRYDER_PAX3FOXO1_ENHANCERS_IN_TADS, KAYO_AGING_MUSCLE_UP, BENPORATH_OCT4_TARGETS, GOCC_NUCLEAR_BODY, chr22q13

GO Biological Process (2): regulation of transcription by RNA polymerase II (GO:0006357), positive regulation of transcription by RNA polymerase II (GO:0045944)

GO Molecular Function (5): DNA binding (GO:0003677), RNA binding (GO:0003723), zinc ion binding (GO:0008270), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (3): nucleus (GO:0005634), nucleoplasm (GO:0005654), nuclear body (GO:0016604)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transcription by RNA polymerase II	2
nucleic acid binding	2
regulation of DNA-templated transcription	1
regulation of transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
transition metal ion binding	1
binding	1
cation binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1
nucleoplasm	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

2278 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TCF20	ALB	P02768	713
TCF20	AR	P10275	576
TCF20	HARS1	P12081	570
TCF20	MMP3	P08254	523
TCF20	SBF1	O95248	455
TCF20	BRD1	O95696	454
TCF20	CDK4	P11802	452
TCF20	TXK	P42681	451
TCF20	KCNF1	Q9H3M0	449
TCF20	ADIPOQ	Q15848	444
TCF20	THRA	P10827	441
TCF20	FOS	P01100	439
TCF20	CHKB	Q9Y259	435
TCF20	JUN	P05412	425
TCF20	SRCAP	Q6ZRS2	424

IntAct

79 interactions, top by confidence:

A	B	Type	Score
H2AZ1	ZNHIT1	psi-mi:“MI:0914”(association)	0.770
HMG20A	KDM1A	psi-mi:“MI:0914”(association)	0.730
TOPBP1	TCF20	psi-mi:“MI:0915”(physical association)	0.650
TOPBP1	TCF20	psi-mi:“MI:0914”(association)	0.650
H2BC1	PPM1G	psi-mi:“MI:0914”(association)	0.640
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
BAG2	HGS	psi-mi:“MI:0914”(association)	0.530
FKBP9	CASC3	psi-mi:“MI:0914”(association)	0.530
CLEC11A	VWA8	psi-mi:“MI:0914”(association)	0.530
DAXX	TNRC18	psi-mi:“MI:0914”(association)	0.530
TCF20	RPS7	psi-mi:“MI:0915”(physical association)	0.400
TCF20	MTA3	psi-mi:“MI:0914”(association)	0.350
TCF20		psi-mi:“MI:0914”(association)	0.350
Prdm16	ESYT2	psi-mi:“MI:0914”(association)	0.350
BMI1	HMGB1P1	psi-mi:“MI:0914”(association)	0.350
CSNK2A2	VWA8	psi-mi:“MI:0914”(association)	0.350
H2AZ1	SUPT5H	psi-mi:“MI:0914”(association)	0.350
HDAC1		psi-mi:“MI:0914”(association)	0.350
HDAC2		psi-mi:“MI:0914”(association)	0.350
H2BC21	SMCHD1	psi-mi:“MI:0914”(association)	0.350
HMGA1	SUPT5H	psi-mi:“MI:0914”(association)	0.350

BioGRID (215): TCF20 (Co-localization), TCF20 (Affinity Capture-MS), TCF20 (Affinity Capture-MS), TCF20 (Proximity Label-MS), ADARB1 (Affinity Capture-MS), CLTB (Affinity Capture-MS), COPB1 (Affinity Capture-MS), BRF1 (Affinity Capture-MS), RBBP7 (Affinity Capture-MS), TRIM27 (Affinity Capture-MS), TCF20 (Affinity Capture-MS), TCF20 (Affinity Capture-MS), TCF20 (Affinity Capture-MS), TCF20 (Affinity Capture-MS), TCF20 (Affinity Capture-MS)

ESM2 similar proteins: A0A1B0GTH6, A0A1S3C4H6, A0A338P6K9, A2RRX6, A6NCI8, B9FXV5, C7IW64, E9QAT4, O13658, O14029, O14269, O60187, O74808, P0C9Z7, P15822, P48415, P80074, P86273, Q10076, Q14207, Q196W1, Q2KHR3, Q3V0A6, Q3Y4E1, Q4JK59, Q5DTW7, Q5R782, Q5Z8V7, Q61624, Q62806, Q66IN2, Q6AYN3, Q6CM10, Q6N021, Q6YXY2, Q76E23, Q76KD6, Q8BMA5, Q8K4L6, Q8NEV8

Diamond homologs: A0A0R4I9Y1, A6H5X4, B6VQ60, F4I443, O08550, O15344, P10862, P15533, P20659, P82457, Q08DR0, Q0PF16, Q1ACD5, Q1ACD6, Q1ACD7, Q24742, Q2HJ93, Q2YEM8, Q2YEM9, Q2YEN0, Q2YEN2, Q3UWZ0, Q3ZEE5, Q587N6, Q587N7, Q5A4N5, Q5BN31, Q5C8T8, Q5C8U1, Q5C8U3, Q5C8U4, Q5D7H7, Q5D7H8, Q5D7I0, Q5D7I1, Q5D7I2, Q5D7I3, Q5D7I5, Q5D7I6, Q5D7I9

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
TCF20	“up-regulates quantity by expression”	MMP3	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 95 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
Deactivation of the beta-catenin transactivating complex	6	20.9×	8e-05
Regulation of PTEN gene transcription	7	18.6×	5e-05
ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression	6	13.6×	4e-04
Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)	6	13.1×	4e-04
NuRD complex assembly	6	12.6×	4e-04
HDACs deacetylate histones	7	12.6×	1e-04
Negative Regulation of CDH1 Gene Transcription	7	12.6×	1e-04
Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs)	7	12.3×	1e-04

GO biological processes:

GO term	Partners	Fold	FDR
chromatin remodeling	14	11.5×	1e-08
nucleosome assembly	6	9.5×	4e-03
mRNA splicing, via spliceosome	7	7.2×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

1311 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	109
Likely pathogenic	28
Uncertain significance	624
Likely benign	378
Benign	58

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1098363	NM_001378418.1(TCF20):c.1856del (p.Lys619fs)	Pathogenic
1164051	NM_001378418.1(TCF20):c.5221_5222del (p.Arg1741fs)	Pathogenic
1164052	NM_001378418.1(TCF20):c.3849_3850insTC (p.Leu1284fs)	Pathogenic
1172629	NM_001378418.1(TCF20):c.1166_1167del (p.Leu389fs)	Pathogenic
1172691	NM_001378418.1(TCF20):c.4267dup (p.Glu1423fs)	Pathogenic
1184923	NM_001378418.1(TCF20):c.4418_4419dup (p.Ser1474fs)	Pathogenic
1188821	NM_001378418.1(TCF20):c.1656dup (p.Ser553fs)	Pathogenic
1201429	NM_001378418.1(TCF20):c.5173dup (p.Tyr1725fs)	Pathogenic
1285469	NM_001378418.1(TCF20):c.3169_3170del (p.Glu1057fs)	Pathogenic
1323680	NM_001378418.1(TCF20):c.5559G>A (p.Trp1853Ter)	Pathogenic
1326918	NM_001378418.1(TCF20):c.1144dup (p.Cys382fs)	Pathogenic
1333553	NM_001378418.1(TCF20):c.2260C>T (p.Gln754Ter)	Pathogenic
1335490	NM_001378418.1(TCF20):c.2244del (p.Lys748fs)	Pathogenic
1342405	NM_001378418.1(TCF20):c.565C>T (p.Gln189Ter)	Pathogenic
1431324	NM_001378418.1(TCF20):c.830_831del (p.Val277fs)	Pathogenic
1675893	NM_001378418.1(TCF20):c.235dup (p.Tyr79fs)	Pathogenic
1679275	NM_001378418.1(TCF20):c.1411C>T (p.Gln471Ter)	Pathogenic
1679343	NM_001378418.1(TCF20):c.2748del (p.Met917fs)	Pathogenic
1686250	NM_001378418.1(TCF20):c.4988dup (p.Arg1664fs)	Pathogenic
1699206	NM_001378418.1(TCF20):c.2318_2319del (p.Gln773fs)	Pathogenic
1700131	NM_001378418.1(TCF20):c.3119C>G (p.Ser1040Ter)	Pathogenic
1708365	NM_001378418.1(TCF20):c.792C>A (p.Tyr264Ter)	Pathogenic
1805578	NM_001378418.1(TCF20):c.2380C>T (p.Gln794Ter)	Pathogenic
224102	NM_001378418.1(TCF20):c.5385_5386del (p.Cys1795fs)	Pathogenic
2429889	NM_001378418.1(TCF20):c.2803C>T (p.Gln935Ter)	Pathogenic
2575335	NM_001378418.1(TCF20):c.1198del (p.Gln400fs)	Pathogenic
2629988	NM_001378418.1(TCF20):c.853G>T (p.Gly285Ter)	Pathogenic
2664035	NM_001378418.1(TCF20):c.5006C>G (p.Ser1669Ter)	Pathogenic
2691001	NM_001378418.1(TCF20):c.2066dup (p.Gly691fs)	Pathogenic
2698068	NM_001378418.1(TCF20):c.161dup (p.Ser55fs)	Pathogenic

SpliceAI

884 predictions. Top by Δscore:

Variant	Effect	Δscore
22:42169893:CAAT:C	acceptor_gain	1.0000
22:42179603:TCTTA:T	donor_loss	1.0000
22:42179604:CTTAC:C	donor_loss	1.0000
22:42179605:TTA:T	donor_loss	1.0000
22:42179606:TACCT:T	donor_loss	1.0000
22:42179607:A:C	donor_loss	1.0000
22:42179608:C:CG	donor_loss	1.0000
22:42179698:CATTT:C	acceptor_gain	1.0000
22:42179700:TTT:T	acceptor_gain	1.0000
22:42161354:CTCAC:C	acceptor_gain	0.9900
22:42161356:CAC:C	acceptor_gain	0.9900
22:42161359:C:CC	acceptor_gain	0.9900
22:42161360:T:G	acceptor_loss	0.9900
22:42169896:TC:T	acceptor_loss	0.9900
22:42169897:C:CC	acceptor_gain	0.9900
22:42169897:CTGG:C	acceptor_loss	0.9900
22:42169898:T:A	acceptor_loss	0.9900
22:42179608:CCTG:C	donor_gain	0.9900
22:42179699:ATTT:A	acceptor_gain	0.9900
22:42179701:TT:T	acceptor_gain	0.9900
22:42179701:TTCTG:T	acceptor_loss	0.9900
22:42179703:C:CC	acceptor_gain	0.9900
22:42179704:T:A	acceptor_loss	0.9900
22:42180047:T:A	donor_gain	0.9900
22:42161355:TCAC:T	acceptor_gain	0.9800
22:42161356:CACC:C	acceptor_gain	0.9800
22:42169841:ACTC:A	donor_loss	0.9800
22:42169842:CTCA:C	donor_loss	0.9800
22:42169843:TCA:T	donor_loss	0.9800
22:42169844:CACC:C	donor_loss	0.9800

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000021261 (22:42269440 AG>A), RS1000023943 (22:42236206 A>G), RS1000029953 (22:42264480 T>C,G), RS1000032199 (22:42161727 T>C), RS1000046880 (22:42195828 T>G), RS1000063201 (22:42195780 G>A), RS1000064150 (22:42268828 C>A,G), RS1000089428 (22:42230997 A>T), RS1000095351 (22:42196199 G>T), RS1000107920 (22:42305438 C>G), RS1000113708 (22:42233190 A>C,G), RS1000138889 (22:42205574 G>A), RS1000143317 (22:42342767 G>A), RS1000159377 (22:42337415 T>C), RS1000163914 (22:42264718 A>C)

Disease associations

OMIM: gene MIM:603107 | disease phenotypes: MIM:618430, MIM:123100, MIM:169300, MIM:209850

GenCC curated gene-disease

Disease	Classification	Inheritance
developmental delay with variable intellectual impairment and behavioral abnormalities	Definitive	Autosomal dominant
syndromic intellectual disability	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
developmental delay with variable intellectual impairment and behavioral abnormalities	Definitive	AD

Mondo (9): developmental delay with variable intellectual impairment and behavioral abnormalities (MONDO:0032745), craniosynostosis (MONDO:0015469), autism spectrum disorder (MONDO:0005258), intellectual disability (MONDO:0001071), ptosis (MONDO:0000728), pectus excavatum (MONDO:0008213), autism (MONDO:0005260), attention deficit-hyperactivity disorder (MONDO:0007743), syndromic intellectual disability (MONDO:0000508)

Orphanet (3): Craniosynostosis (Orphanet:1531), NON RARE IN EUROPE: Autism (Orphanet:106), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

50 total (30 of 50 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000098	Tall stature
HP:0000194	Open mouth
HP:0000219	Thin upper lip vermilion
HP:0000248	Brachycephaly
HP:0000256	Macrocephaly
HP:0000276	Long face
HP:0000286	Epicanthus
HP:0000348	High forehead
HP:0000358	Posteriorly rotated ears
HP:0000369	Low-set ears
HP:0000414	Bulbous nose
HP:0000486	Strabismus
HP:0000490	Deeply set eye
HP:0000545	Myopia
HP:0000718	Aggressive behavior
HP:0000722	Compulsive behaviors
HP:0000729	Autistic behavior
HP:0000733	Motor stereotypy
HP:0000739	Anxiety
HP:0000750	Delayed speech and language development
HP:0000752	Hyperactivity
HP:0000771	Gynecomastia
HP:0001182	Tapered finger
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001256	Mild intellectual disability
HP:0001257	Spasticity
HP:0001263	Global developmental delay

GWAS associations

16 associations (top):

Study	Trait	p-value
GCST002539_95	Schizophrenia	2.000000e-09
GCST002774_34	Cognitive function	1.000000e-06
GCST004364_23	Intelligence	3.000000e-10
GCST004364_5	Intelligence	3.000000e-10
GCST004521_160	Autism spectrum disorder or schizophrenia	3.000000e-08
GCST004521_244	Autism spectrum disorder or schizophrenia	4.000000e-09
GCST006803_13	Schizophrenia	2.000000e-14
GCST007201_165	Schizophrenia	1.000000e-10
GCST007201_271	Schizophrenia	1.000000e-08
GCST007576_440	Chronotype	8.000000e-12
GCST007846_4	Arterial stiffness	2.000000e-07
GCST008129_35	Body mass index	3.000000e-08
GCST009212_18	Isthmus-cingulate cortex volume	4.000000e-06
GCST009312_14	Antisaccade task score	3.000000e-06
GCST009600_11	Anorexia nervosa, attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, or Tourette syndrome (pleiotropy)	1.000000e-08
GCST010002_83	Refractive error	2.000000e-27

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004337	intelligence
EFO:0008328	chronotype measurement
EFO:0004517	arterial stiffness measurement
EFO:0004340	body mass index
EFO:0007969	cognitive inhibition measurement

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D001321	Autistic Disorder	F03.625.164.113.500
D001763	Blepharoptosis	C11.338.204
D003398	Craniosynostoses	C05.116.099.370.894.232; C05.660.207.240; C05.660.906.364; C16.131.621.207.240; C16.131.621.906.364
D005660	Funnel Chest	C05.116.099.386; C05.660.386; C16.131.621.386
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)

PharmGKB variants

3 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs9306356	TCF20		0.00	0
rs5758651	TCF20		0.00	0
rs5751251	TCF20		0.00	0

CTD chemical–gene interactions

32 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
TAK-243	decreases sumoylation	1
dicrotophos	increases expression	1
2,4,6-tribromophenol	decreases expression	1
bisphenol A	decreases expression	1
decabromobiphenyl ether	decreases expression	1
beta-lapachone	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
aflatoxin B2	decreases methylation	1
beta-glycerophosphoric acid	affects cotreatment, increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
Acetaminophen	affects response to substance	1
Amiodarone	increases expression	1
Amphotericin B	increases expression	1
Ascorbic Acid	affects cotreatment, increases expression	1
Caffeine	affects phosphorylation	1
Dexamethasone	affects cotreatment, increases expression	1
Dimethyl Sulfoxide	increases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Thiram	increases expression	1
Tretinoin	decreases expression	1
Urethane	increases expression	1
Valproic Acid	increases methylation	1
Aflatoxin B1	increases methylation	1
Cadmium Chloride	decreases expression	1

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A7C8	SEES3-1V human TCF20, clone1	Embryonic stem cell	Male
CVCL_A7C9	SEES3-1V human TCF20, clone2	Embryonic stem cell	Male
CVCL_A7D0	SEES3-1V human TCF20, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00722436	PHASE4	TERMINATED	Tranexamic Acid for Craniofacial Surgery
NCT02188576	PHASE4	COMPLETED	The Efficacy and Population Pharmacokinetics of Tranexamic Acid for Craniosynostosis Surgery
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT01302964	PHASE3	COMPLETED	Mirtazapine Treatment of Anxiety in Children and Adolescents With Pervasive Developmental Disorders
NCT01706523	PHASE3	TERMINATED	Open Label Extension Study of STX209 (Arbaclofen) in Autism Spectrum Disorders
NCT01825798	PHASE3	COMPLETED	Treatment of Overweight Induced by Antipsychotic Medication in Young People With Autism Spectrum Disorders (ASD)
NCT01972074	PHASE3	COMPLETED	Behavioral and Neural Response to Memantine in Adolescents With Autism Spectrum Disorder
NCT02985749	PHASE3	COMPLETED	A Study of Oxytocin for the Treatment of Social Impairment in Individuals With High Functioning Autism Spectrum Disorder
NCT03197922	PHASE3	COMPLETED	Treatment of Encopresis in Children With Autism Spectrum Disorders
NCT03504917	PHASE3	TERMINATED	A Study of Balovaptan in Adults With Autism Spectrum Disorder With a 2-Year Open-Label Extension
NCT03553875	PHASE3	TERMINATED	Memantine for the Treatment of Social Deficits in Youth With Disorders of Impaired Social Interactions
NCT03640156	PHASE3	COMPLETED	Modulating Socially Adaptive Mirror System Functioning in Autism by Oxytocin
NCT03715153	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children Aged From 2 to Less Than 7 Years Old With Autism Spectrum Disorder.
NCT03715166	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children and Adolescents Aged From 7 to Less Than 18 Years Old With Autism Spectrum Disorder
NCT04233502	PHASE3	WITHDRAWN	Efficacy and Safety of Slenyto for Insomnia in Children With ASD
NCT04578756	PHASE3	COMPLETED	Open-Label, Flexible-dose Study to Evaluate the Long-Term Safety and Tolerability of Cariprazine in the Treatment of Pediatric Participants With Schizophrenia, Bipolar I Disorder, or Autism Spectrum Disorder
NCT04623398	PHASE3	COMPLETED	Effect of Lithium in Patients With Autism Spectrum Disorder and Phelan-McDermid Syndrome (SHANK3 Haploinsufficiency)
NCT04725383	PHASE3	TERMINATED	Amitriptyline for Repetitive Behaviors in Autism Spectrum Disorders
NCT05212493	PHASE3	COMPLETED	The Effects of Medical Cannabis in Children With Autistic Spectrum Disorder
NCT05361707	PHASE3	UNKNOWN	Evaluating the Effects of Tasimelteon in Individuals With Autism Spectrum Disorder (ASD) and Sleep Disturbances