POU3F3

Summary

POU3F3 (POU class 3 homeobox 3, HGNC:9216) is a protein-coding gene on chromosome 2q12.1, encoding POU domain, class 3, transcription factor 3 (P20264). Transcription factor that acts synergistically with SOX11 and SOX4.

This gene encodes a POU-domain containing protein that functions as a transcription factor. The encoded protein recognizes an octamer sequence in the DNA of target genes. This protein may play a role in development of the nervous system.

Source: NCBI Gene 5455 — RefSeq curated summary.

At a glance

• Gene–disease (curated): complex neurodevelopmental disorder (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 10
• Clinical variants (ClinVar): 244 total — 16 pathogenic, 31 likely-pathogenic
• Phenotypes (HPO): 21
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity unscored
• MANE Select transcript: NM_006236

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9216
Approved symbol	POU3F3
Name	POU class 3 homeobox 3
Location	2q12.1
Locus type	gene with protein product
Status	Approved
Aliases	BRN1, OTF8
Ensembl gene	ENSG00000198914
Ensembl biotype	protein_coding
OMIM	602480
Entrez	5455

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000361360, ENST00000674056

RefSeq mRNA: 1 — MANE Select: NM_006236 NM_006236

CCDS: CCDS33265

Canonical transcript exons

ENST00000361360 — 1 exons

Exon	Start	End
ENSE00001435864	104854115	104858574

Expression profiles

Bgee: expression breadth ubiquitous, 143 present calls, max score 99.28.

FANTOM5 (CAGE): breadth broad, TPM avg 10.6907 / max 613.3273, expressed in 378 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
21795	5.8839	311
21794	1.8790	236
21792	1.6758	252
21797	0.4392	133
21796	0.3732	130
21798	0.3047	115
21793	0.1349	75

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	99.28	gold quality
ganglionic eminence	UBERON:0004023	99.07	gold quality
corpus epididymis	UBERON:0004359	97.69	gold quality
renal medulla	UBERON:0000362	96.99	gold quality
seminal vesicle	UBERON:0000998	96.19	gold quality
medial globus pallidus	UBERON:0002477	95.92	gold quality
caput epididymis	UBERON:0004358	95.70	gold quality
globus pallidus	UBERON:0001875	95.61	gold quality
cortical plate	UBERON:0005343	94.42	gold quality
inferior vagus X ganglion	UBERON:0005363	93.35	gold quality
postcentral gyrus	UBERON:0002581	93.14	gold quality
lateral globus pallidus	UBERON:0002476	92.97	gold quality
primary visual cortex	UBERON:0002436	92.77	gold quality
subthalamic nucleus	UBERON:0001906	92.75	gold quality
parietal lobe	UBERON:0001872	92.73	gold quality
endothelial cell	CL:0000115	92.33	gold quality
Brodmann (1909) area 23	UBERON:0013554	92.30	gold quality
occipital lobe	UBERON:0002021	91.36	gold quality
superior vestibular nucleus	UBERON:0007227	91.22	gold quality
superior frontal gyrus	UBERON:0002661	91.07	gold quality
corpus callosum	UBERON:0002336	91.00	gold quality
ventral tegmental area	UBERON:0002691	90.38	gold quality
entorhinal cortex	UBERON:0002728	90.28	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	90.11	gold quality
metanephros cortex	UBERON:0010533	89.87	gold quality
spinal cord	UBERON:0002240	89.77	gold quality
temporal lobe	UBERON:0001871	89.23	gold quality
Ammon’s horn	UBERON:0001954	89.20	gold quality
substantia nigra pars reticulata	UBERON:0001966	89.08	gold quality
adult organism	UBERON:0007023	89.08	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-11121	yes	410.13
E-HCAD-10	yes	19.31
E-ANND-3	yes	11.64

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

4 targets.

Target	Regulation
EGR2	Activation
NES
OXT
WNT1

JASPAR motifs

Motif	Name	Family
MA0788.1	POU3F3	POU domain factors

JASPAR matrix evidence (PMIDs): PMID:9852081

Upstream regulators (CollecTRI, top): DLX5

miRNA regulators (miRDB)

86 targeting POU3F3, 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-3163	100.00	77.23	8605
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-609	99.82	64.26	505

Functional genomics

ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 8)

• Long intergenic non-protein coding RNA POU3F3 contributes to the development of ESCC by interacting with EZH2 to promote methylation of POU3F3, which encodes a transcription factor. (PMID:24631494)
• linc-POU3F3 might affect glioma development via altering expression level of POU3F3, and may also have a crucial regulatory role in glioma progression (PMID:25445282)
• Data show that the long noncoding RNA encoded by a gene next to POU3F3 (linc-POU3F3) is a potential therapeutic target and novel molecular biomarker for colorectal cancer (CRC). (PMID:26510906)
• the present study showed that lncRNA POU3F3 may promote proliferation and inhibit apoptosis of cancer cells in triple-negative breast cancer by inactivating caspase 9. (PMID:30843771)
• De Novo Variants Disturbing the Transactivation Capacity of POU3F3 Cause Neurodevelopmental Disorders. (PMID:31303265)
• Long Noncoding RNA POU3F3 and alpha-Synuclein in Plasma L1CAM Exosomes Combined with beta-Glucocerebrosidase Activity: Potential Predictors of Parkinson’s Disease. (PMID:32236821)
• Coexistence of severe developmental delay, epilepsy, and hemangioma in Snijders Blok-Fisher syndrome suggests the presence of a POU3F3-related SNIBFIS endophenotype: A case report. (PMID:33645921)
• POU3F3-related disorder: Defining the phenotype and expanding the molecular spectrum. (PMID:37165752)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Pou3f3	ENSMUSG00000045515
rattus_norvegicus	Pou3f3	ENSRNOG00000074419
drosophila_melanogaster	acj6	FBGN0000028
caenorhabditis_elegans		WBGENE00006818

Paralogs (17): POU2F2 (ENSG00000028277), POU1F1 (ENSG00000064835), POU4F3 (ENSG00000091010), POU6F2 (ENSG00000106536), POU2F3 (ENSG00000137709), POU2F1 (ENSG00000143190), POU4F2 (ENSG00000151615), POU4F1 (ENSG00000152192), HDX (ENSG00000165259), POU6F1 (ENSG00000184271), POU3F2 (ENSG00000184486), POU3F1 (ENSG00000185668), POU3F4 (ENSG00000196767), CCDC160 (ENSG00000203952), POU5F1 (ENSG00000204531), POU5F1B (ENSG00000212993), POU5F2 (ENSG00000248483)

Protein

Protein identifiers

POU domain, class 3, transcription factor 3 — P20264 (reviewed: P20264)

Alternative names: Brain-specific homeobox/POU domain protein 1, Octamer-binding protein 8, Octamer-binding transcription factor 8

All UniProt accessions (1): P20264

UniProt curated annotations — full annotation on UniProt →

Function. Transcription factor that acts synergistically with SOX11 and SOX4. Plays a role in neuronal development. Is implicated in an enhancer activity at the embryonic met-mesencephalic junction; the enhancer element contains the octamer motif (5’-ATTTGCAT-3’).

Subunit / interactions. Homodimer.

Subcellular location. Nucleus.

Tissue specificity. Brain.

Disease relevance. Snijders Blok-Fisher syndrome (SNIBFIS) [MIM:618604] An autosomal dominant neurodevelopmental disorder characterized by global developmental delay, hypotonia, intellectual disability, autistic features, impairments in speech and language skills, and dysmorphic features including abnormal, cupped, or prominent ears and ocular anomalies. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the POU transcription factor family. Class-3 subfamily.

RefSeq proteins (2): NP_001420633, NP_006227* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000327	POU_dom	Domain
IPR001356	HD	Domain
IPR009057	Homeodomain-like_sf	Homologous_superfamily
IPR010982	Lambda_DNA-bd_dom_sf	Homologous_superfamily
IPR013847	POU	Domain
IPR016362	TF_POU_3	Family
IPR017970	Homeobox_CS	Conserved_site
IPR050255	POU_domain_TF	Family

Pfam: PF00046, PF00157

UniProt features (24 total): sequence variant 9, compositionally biased region 7, region of interest 4, chain 1, domain 1, DNA-binding region 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P20264-F1	58.45	0.23

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9831926	Nephron development

MSigDB gene sets: 222 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_DN, MYAATNNNNNNNGGC_UNKNOWN, GOBP_EPITHELIUM_DEVELOPMENT, FREAC2_01, MYOGENIN_Q6, GOBP_METANEPHROS_DEVELOPMENT, PAX4_01, GOBP_METANEPHRIC_EPITHELIUM_DEVELOPMENT, GOBP_LOOP_OF_HENLE_DEVELOPMENT, chr2q12, GOBP_KIDNEY_EPITHELIUM_DEVELOPMENT, GOBP_CELL_DIFFERENTIATION_INVOLVED_IN_METANEPHROS_DEVELOPMENT, GOBP_CELL_PROLIFERATION_IN_FOREBRAIN, GOBP_FOREBRAIN_DEVELOPMENT, FOXD3_01

GO Biological Process (21): regulation of transcription by RNA polymerase II (GO:0006357), central nervous system development (GO:0007417), positive regulation of cell population proliferation (GO:0008284), positive regulation of gene expression (GO:0010628), cerebral cortex radially oriented cell migration (GO:0021799), forebrain ventricular zone progenitor cell division (GO:0021869), negative regulation of apoptotic process (GO:0043066), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), chemical homeostasis (GO:0048878), urea transmembrane transport (GO:0071918), metanephric ascending thin limb development (GO:0072218), metanephric macula densa development (GO:0072227), metanephric thick ascending limb development (GO:0072233), metanephric loop of Henle development (GO:0072236), metanephric DCT cell differentiation (GO:0072240), kidney development (GO:0001822), regulation of DNA-templated transcription (GO:0006355), nervous system development (GO:0007399), brain development (GO:0007420)

GO Molecular Function (7): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription factor activity (GO:0003700), protein homodimerization activity (GO:0042803), sequence-specific DNA binding (GO:0043565), HMG box domain binding (GO:0071837), DNA binding (GO:0003677)

GO Cellular Component (3): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Kidney development	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of DNA-templated transcription	4
DNA-templated transcription	3
metanephric nephron tubule development	3
transcription by RNA polymerase II	2
system development	2
regulation of gene expression	2
regulation of transcription by RNA polymerase II	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
cellular anatomical structure	2
nervous system development	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
gene expression	1
positive regulation of macromolecule biosynthetic process	1
cerebral cortex cell migration	1
cell proliferation in forebrain	1
cell division	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
negative regulation of RNA biosynthetic process	1
positive regulation of RNA biosynthetic process	1
positive regulation of DNA-templated transcription	1
homeostatic process	1
urea transport	1
transmembrane transport	1
ascending thin limb development	1
metanephric loop of Henle development	1
macula densa development	1
metanephric juxtaglomerular apparatus development	1
metanephric nephron epithelium development	1
thick ascending limb development	1
metanephric distal tubule development	1
loop of Henle development	1
DCT cell differentiation	1
metanephric distal convoluted tubule development	1
animal organ development	1
renal system development	1
regulation of RNA biosynthetic process	1

Protein interactions and networks

STRING

1378 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
POU3F3	ASCL1	P50553	923
POU3F3	NCAPG	Q9BPX3	916
POU3F3	EZH2	Q15910	857
POU3F3	MYT1L	Q9UL68	826
POU3F3	SMC4	Q9NTJ3	811
POU3F3	NCAPH	Q15003	778
POU3F3	DLL1	O00548	740
POU3F3	SOX11	P35716	649
POU3F3	SOX2	P48431	620
POU3F3	TBXT	O15178	603
POU3F3	NKX2-2	O95096	602
POU3F3	NEUROG2	Q9H2A3	593
POU3F3	RET	P07949	586
POU3F3	DLX1	P56177	571
POU3F3	LMX1B	O60663	560

IntAct

10 interactions, top by confidence:

A	B	Type	Score
POU3F3	Dlg4	psi-mi:“MI:0407”(direct interaction)	0.440
BMI1	MEIS3P1	psi-mi:“MI:0914”(association)	0.350
RYBP	FAM186A	psi-mi:“MI:0914”(association)	0.350
GRHL1	POLRMT	psi-mi:“MI:0914”(association)	0.350
S100A2	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
POU3F3	IGKC	psi-mi:“MI:0914”(association)	0.350
CAV1	POU3F3	psi-mi:“MI:0915”(physical association)	0.000
POU3F3	PPP1R15A	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (18): POU3F3 (Synthetic Growth Defect), POU3F3 (Affinity Capture-MS), CRABP2 (Affinity Capture-MS), TYMP (Affinity Capture-MS), IVL (Affinity Capture-MS), POU3F3 (Affinity Capture-MS), POU5F1 (Affinity Capture-MS), ALDH1A3 (Affinity Capture-MS), ANXA8 (Affinity Capture-MS), EWSR1 (Affinity Capture-MS), SERPINB4 (Affinity Capture-MS), IGKC (Affinity Capture-MS), RBMXL1 (Affinity Capture-MS), POU3F3 (Proximity Label-MS), POU3F3 (Proximity Label-MS)

ESM2 similar proteins: A2TED3, O00570, O57401, O95409, P06602, P07548, P09085, P14734, P16241, P20264, P22544, P23441, P23757, P31361, P32027, P32182, P32242, P35583, P39768, P40764, P41225, P43241, P43698, P43699, P48430, P48431, P48432, P50220, P53783, P53784, P54231, P54269, P56224, P80205, Q04649, Q07687, Q24255, Q24533, Q2PG84, Q2Z1R2

Diamond homologs: A0A1L8FFY5, A1L0Z1, A7Y7W2, B3DM23, B3DM25, B7ZQA9, D3ZTL1, G3V7L5, O97552, P09086, P10036, P10037, P13528, P14859, P15143, P16143, P16241, P17208, P20263, P20264, P20265, P20266, P20267, P20268, P20912, P20913, P20914, P21952, P24350, P25425, P28069, P31360, P31361, P31362, P31363, P31364, P31365, P31367, P31368, P31369

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
POU3F4	“up-regulates activity”	POU3F3	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	16
Likely pathogenic	31
Uncertain significance	151
Likely benign	35
Benign	3

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1174106	NM_006236.3(POU3F3):c.967G>T (p.Glu323Ter)	Pathogenic
1301907	NM_006236.3(POU3F3):c.1084C>A (p.Arg362Ser)	Pathogenic
1686088	NM_006236.3(POU3F3):c.774del (p.Leu259fs)	Pathogenic
1686089	NM_006236.3(POU3F3):c.983A>C (p.Gln328Pro)	Pathogenic
1704995	NM_006236.3(POU3F3):c.655_656del (p.Leu220fs)	Pathogenic
1707602	NM_006236.3(POU3F3):c.1240G>T (p.Glu414Ter)	Pathogenic
2136171	NM_006236.3(POU3F3):c.524del (p.Pro175fs)	Pathogenic
2295035	NM_006236.3(POU3F3):c.614_620dup (p.Ser208fs)	Pathogenic
2429900	NM_006236.3(POU3F3):c.209_213delinsC (p.Val70fs)	Pathogenic
2429901	NM_006236.3(POU3F3):c.196dup (p.Asp66fs)	Pathogenic
3216927	NM_006236.3(POU3F3):c.1240_1243del (p.Ile413_Glu414insTer)	Pathogenic
3910100	NM_006236.3(POU3F3):c.559_566dup (p.Ala190fs)	Pathogenic
3936387	NM_006236.3(POU3F3):c.935C>A (p.Ser312Ter)	Pathogenic
691586	NM_006236.3(POU3F3):c.668C>A (p.Ser223Ter)	Pathogenic
691587	NM_006236.3(POU3F3):c.1284C>A (p.Cys428Ter)	Pathogenic
807662	NM_006236.3(POU3F3):c.398_407del (p.Pro133fs)	Pathogenic
1308458	NM_006236.3(POU3F3):c.1348G>A (p.Val450Met)	Likely pathogenic
1333685	NM_006236.3(POU3F3):c.1165T>G (p.Ser389Ala)	Likely pathogenic
1691852	NM_006236.3(POU3F3):c.1019A>C (p.Gln340Pro)	Likely pathogenic
1696436	NM_006236.3(POU3F3):c.998G>C (p.Arg333Pro)	Likely pathogenic
1705728	NM_006236.3(POU3F3):c.1342G>T (p.Glu448Ter)	Likely pathogenic
1707406	NM_006236.3(POU3F3):c.1147_1155del (p.Trp383_Glu385del)	Likely pathogenic
1707496	NM_006236.3(POU3F3):c.1303_1305del (p.Glu435del)	Likely pathogenic
1712272	NM_006236.3(POU3F3):c.1009G>A (p.Gly337Ser)	Likely pathogenic
1723476	NM_006236.3(POU3F3):c.246_267del (p.Met82fs)	Likely pathogenic
1801488	NM_006236.3(POU3F3):c.617_632delinsCCC (p.Leu206fs)	Likely pathogenic
2412972	NM_006236.3(POU3F3):c.366G>A (p.Trp122Ter)	Likely pathogenic
2498829	NM_006236.3(POU3F3):c.1252A>G (p.Lys418Glu)	Likely pathogenic
3027258	NM_006236.3(POU3F3):c.1358G>A (p.Trp453Ter)	Likely pathogenic
3065233	NM_006236.3(POU3F3):c.349G>T (p.Glu117Ter)	Likely pathogenic

SpliceAI

50 predictions. Top by Δscore:

Variant	Effect	Δscore
2:104857269:G:GT	donor_gain	0.6900
2:104857417:AGAAG:A	acceptor_gain	0.5900
2:104857418:GAAGG:G	acceptor_gain	0.5900
2:104857270:A:T	donor_gain	0.4700
2:104857414:TAAAG:T	acceptor_gain	0.4700
2:104857415:AAAGA:A	acceptor_gain	0.4700
2:104857416:AAGAA:A	acceptor_gain	0.4700
2:104857413:TTAAA:T	acceptor_gain	0.4600
2:104855797:A:AG	donor_gain	0.4400
2:104855798:G:GG	donor_gain	0.4400
2:104857417:AGAA:A	acceptor_gain	0.4300
2:104857418:GAAG:G	acceptor_gain	0.4300
2:104857248:G:GT	donor_gain	0.4200
2:104857418:GAA:G	acceptor_gain	0.4000
2:104857417:A:G	acceptor_gain	0.3900
2:104857416:A:C	acceptor_gain	0.3700
2:104857418:G:GG	acceptor_gain	0.3500
2:104858094:T:A	acceptor_gain	0.3400
2:104856953:G:A	donor_gain	0.3200
2:104856956:C:T	donor_gain	0.3200
2:104855583:G:GT	donor_gain	0.3000
2:104857390:G:A	acceptor_gain	0.3000
2:104855781:C:G	donor_gain	0.2900
2:104856954:G:A	donor_gain	0.2900
2:104857415:A:AG	acceptor_gain	0.2900
2:104855748:G:GT	donor_gain	0.2800
2:104857273:G:GT	donor_gain	0.2700
2:104857384:G:GA	acceptor_gain	0.2600
2:104857385:TGGTG:T	acceptor_gain	0.2500
2:104857386:GGTGG:G	acceptor_gain	0.2500

AlphaMissense

3248 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:104856475:T:A	L322Q	1.000
2:104856475:T:C	L322P	1.000
2:104856475:T:G	L322R	1.000
2:104856477:G:A	E323K	1.000
2:104856478:A:T	E323V	1.000
2:104856479:G:C	E323D	1.000
2:104856479:G:T	E323D	1.000
2:104856483:T:A	F325I	1.000
2:104856483:T:C	F325L	1.000
2:104856483:T:G	F325V	1.000
2:104856484:T:C	F325S	1.000
2:104856484:T:G	F325C	1.000
2:104856485:C:A	F325L	1.000
2:104856485:C:G	F325L	1.000
2:104856486:G:A	A326T	1.000
2:104856486:G:C	A326P	1.000
2:104856487:C:A	A326D	1.000
2:104856487:C:T	A326V	1.000
2:104856491:G:C	K327N	1.000
2:104856491:G:T	K327N	1.000
2:104856495:T:C	F329L	1.000
2:104856496:T:C	F329S	1.000
2:104856496:T:G	F329C	1.000
2:104856497:C:A	F329L	1.000
2:104856497:C:G	F329L	1.000
2:104856498:A:C	K330Q	1.000
2:104856498:A:G	K330E	1.000
2:104856499:A:C	K330T	1.000
2:104856499:A:T	K330M	1.000
2:104856500:G:C	K330N	1.000

dbSNP variants (sampled 300 via entrez): RS1000158095 (2:104854577 G>T), RS1000510406 (2:104854375 C>G), RS1001458361 (2:104853799 G>A), RS1002427502 (2:104854194 G>A,C), RS1002448633 (2:104853270 G>A,C,T), RS1002561816 (2:104855059 G>T), RS1002636155 (2:104854006 A>C), RS1002950061 (2:104858760 T>A,G), RS1003171077 (2:104855262 G>A), RS1003500186 (2:104852255 G>C), RS1003848837 (2:104853615 C>A), RS1003899434 (2:104854669 C>A), RS1005021849 (2:104858857 C>T), RS1005464275 (2:104859059 C>A), RS1005522205 (2:104854507 AT>A,ATT)

Disease associations

OMIM: gene MIM:602480 | disease phenotypes: MIM:618604

GenCC curated gene-disease

Disease	Classification	Inheritance
snijders blok-fisher syndrome	Definitive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
complex neurodevelopmental disorder	Definitive	AD

Mondo (2): snijders blok-fisher syndrome (MONDO:0032830), intellectual disability (MONDO:0001071)

Orphanet (2): Intellectual disability-cupped ears syndrome (Orphanet:656135), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

21 total (21 of 21 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000028	Cryptorchidism
HP:0000286	Epicanthus
HP:0000297	Facial hypotonia
HP:0000378	Cupped ear
HP:0000411	Protruding ear
HP:0000729	Autistic behavior
HP:0000750	Delayed speech and language development
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001257	Spasticity
HP:0001263	Global developmental delay
HP:0001266	Choreoathetosis
HP:0001290	Generalized hypotonia
HP:0002079	Hypoplasia of the corpus callosum
HP:0002172	Postural instability
HP:0002179	Opisthotonus
HP:0002188	Delayed CNS myelination
HP:0002307	Drooling
HP:0002360	Sleep disturbance
HP:0040326	Hypoplasia of the olfactory bulb

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST001692_2	Response to taxane treatment (docetaxel)	8.000000e-06
GCST005951_42	Body mass index	1.000000e-08
GCST007325_51	General risk tolerance (MTAG)	5.000000e-08
GCST010698_61	Subcortical volume (min-P)	1.000000e-09
GCST010699_84	Brain morphology (min-P)	2.000000e-14
GCST010700_44	Cortical thickness (MOSTest)	5.000000e-08
GCST010701_31	Cortical surface area (MOSTest)	6.000000e-30
GCST010702_163	Subcortical volume (MOSTest)	2.000000e-19
GCST010703_113	Brain morphology (MOSTest)	6.000000e-19
GCST010988_186	Adult body size	1.000000e-12

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0008579	risk-taking behaviour
EFO:0004346	neuroimaging measurement
EFO:0004840	cortical thickness

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: yes

ChEMBL targets (1): CHEMBL5243 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

14 total (human), top 14 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, increases methylation	3
TAK-243	increases sumoylation	1
arsenite	increases methylation	1
butyraldehyde	increases expression	1
pinostrobin	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Panobinostat	increases expression	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	decreases methylation, increases methylation	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Aflatoxin B1	decreases expression	1
Okadaic Acid	decreases expression	1
Acrylamide	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL832954	Functional	Antagonistic activity against BRN1/DNA interaction by electrophoretic mobility shift assay	Privileged scaffolds for blocking protein-protein interactions: 1,4-disubstituted naphthalene antagonists of transcription factor complex HOX-PBX/DNA. — Bioorg Med Chem Lett

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