POU4F1

Summary

POU4F1 (POU class 4 homeobox 1, HGNC:9218) is a protein-coding gene on chromosome 13q31.1, encoding POU domain, class 4, transcription factor 1 (Q01851). Multifunctional transcription factor with different regions mediating its different effects.

This gene encodes a member of the POU-IV class of neural transcription factors. This protein is expressed in a subset of retinal ganglion cells and may be involved in the developing sensory nervous system. This protein may also promote the growth of cervical tumors. A translocation of this gene is associated with some adult acute myeloid leukemias.

Source: NCBI Gene 5457 — RefSeq curated summary.

At a glance

• Gene–disease (curated): ataxia, intention tremor, and hypotonia syndrome, childhood-onset (Strong, GenCC)
• GWAS associations: 3
• Clinical variants (ClinVar): 7 total
• Phenotypes (HPO): 46
• Transcription factor: yes — 35 downstream targets (CollecTRI)
• MANE Select transcript: NM_006237

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9218
Approved symbol	POU4F1
Name	POU class 4 homeobox 1
Location	13q31.1
Locus type	gene with protein product
Status	Approved
Aliases	RDC-1
Ensembl gene	ENSG00000152192
Ensembl biotype	protein_coding
OMIM	601632
Entrez	5457

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000377208

RefSeq mRNA: 1 — MANE Select: NM_006237 NM_006237

CCDS: CCDS31996

Canonical transcript exons

ENST00000377208 — 2 exons

Exon	Start	End
ENSE00001473105	78598362	78602551
ENSE00001473106	78603204	78603552

Expression profiles

Bgee: expression breadth broad, 61 present calls, max score 88.85.

FANTOM5 (CAGE): breadth broad, TPM avg 2.6400 / max 882.9193, expressed in 439 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
137711	1.6396	270
137712	0.9154	330
137710	0.0850	39

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	88.85	gold quality
dorsal root ganglion	UBERON:0000044	83.14	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.78	gold quality
oocyte	CL:0000023	79.24	gold quality
trigeminal ganglion	UBERON:0001675	77.51	gold quality
buccal mucosa cell	CL:0002336	68.94	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	62.25	gold quality
ileal mucosa	UBERON:0000331	62.20	silver quality
tibialis anterior	UBERON:0001385	61.74	silver quality
pancreatic ductal cell	CL:0002079	59.96	silver quality
medulla oblongata	UBERON:0001896	59.01	silver quality
decidua	UBERON:0002450	56.55	gold quality
endometrium epithelium	UBERON:0004811	54.95	gold quality
deltoid	UBERON:0001476	54.90	silver quality
hair follicle	UBERON:0002073	53.06	gold quality
bone marrow cell	CL:0002092	52.81	gold quality
medial globus pallidus	UBERON:0002477	52.66	silver quality
cranial nerve II	UBERON:0000941	52.25	silver quality
quadriceps femoris	UBERON:0001377	51.34	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	50.96	gold quality
lymph node	UBERON:0000029	50.79	gold quality
skeletal muscle tissue	UBERON:0001134	50.42	gold quality
frontal pole	UBERON:0002795	50.41	gold quality
oviduct epithelium	UBERON:0004804	50.32	gold quality
middle frontal gyrus	UBERON:0002702	50.30	gold quality
muscle tissue	UBERON:0002385	50.26	gold quality
choroid plexus epithelium	UBERON:0003911	50.26	gold quality
paraflocculus	UBERON:0005351	50.18	gold quality
Brodmann (1909) area 10	UBERON:0013541	50.18	gold quality
vastus lateralis	UBERON:0001379	50.08	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-HCAD-56	yes	818.63
E-ANND-3	no	0.80

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

35 targets.

Target	Regulation
BAX	Repression
BCL2	Activation
BCL2L1
BRCA1	Activation
CCND1	Repression
CDKN1A	Activation
EGR1	Activation
GAL	Activation
GNAS
HIPK2
HPSE	Unknown
HSP90AA1	Activation
HSPB1
IL2
INA	Activation
JUP
NGF
NOS2
NTRK1	Activation
NTRK2
PMAIP1	Repression
POMC
POU4F1
POU4F2	Repression
POU4F3	Unknown
PRND
PRPH2
RIT2	Activation
SCN9A	Activation
SGPL1

JASPAR motifs

Motif	Name	Family
MA0790.1	POU4F1	POU domain factors
MA0790.2	POU4F1	POU domain factors

JASPAR matrix evidence (PMIDs): PMID:18077589

Upstream regulators (CollecTRI, top): EWSR1, POU4F1, POU4F2, TFAP2D

miRNA regulators (miRDB)

158 targeting POU4F1, 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-4692	100.00	67.32	2066
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-301A-3P	99.90	73.15	1839
HSA-MIR-301B-3P	99.90	73.19	1836

Literature-anchored findings (GeneRIF, showing 22)

• genomic organization of the Brn-3a locus and the mechanisms that control the expression of two different proteins from one genomic locus (PMID:12427558)
• Measurement of Brn-3a levels in smears can be used to detect a significant proportion of cervical lesions that were missed by Pap smear. (PMID:12893201)
• These results indicate that Brn-3a could play an important role in the near future in improving cervical cancer screening. (PMID:12911730)
• oncogenic rearrangement of EWS to produce EWS/Fli-1 may enhance the antiapoptotic effect of Brn-3a and inhibit its ability to promote neuronal differentiation. (PMID:15021903)
• Hsp27 expression and cell survival are regulated by the POU transcription factor Brn3a (PMID:15272315)
• Brn-3a has a role in differential regulation of different human papilloma virus variants (PMID:16247485)
• Upregulation of Brn-3a is associated with prostate cancer (PMID:16276351)
• Ewing sarcoma induce expression of neuronal markers such as BRN3A showing that the function of those same markers may be restricted or controlled in an sarcoma-dependent manner. (PMID:20348952)
• Dysregulation of POU4F1 is associated with t(8;21) acute myeloid leukemia. (PMID:20376082)
• BRN3A possesses anti-apoptotic property, and considering the above results, it may be regarded as the key component in promoting tumorigenic growth in the uterine cervical cells. (PMID:21928122)
• PoU4F1 is highly expressed in t(8;21) samples, with AML/ETO appearning to promote some BRN3A expression (PMID:22064348)
• Data indicate that median methylation levels of BCAN, HOXD1, KCTD8, KLF11, NXPH1, POU4F1, SIM1, and TCF7L1 were >/=30% higher than in normal samples, representing potential biomarkers for tumor diagnosis. (PMID:22930747)
• Brn3a cooperates with activated RAS/RAF signalling by reducing oncogene-induced senescence in melanocytic tumourigenesis. (PMID:23666755)
• We report a case of a nine-year-old male who presented with facial nerve stimulation four years after cochlear implantation. A dilated internal auditory meatus was revealed. Genetic analysis demonstrated X-linked deafness type 2 (DFNX2) caused by a novel c.769C T nucleotide change in the POU domain, class 3, transcription factor 4 gene (PMID:27863625)
• Papillary thyroid carcinoma was characterized by high expression of ESR2 and AR, which was associated with expression and content of nuclear factors Brn-3A and TRIM16. (PMID:30488195)
• Brn3a/Pou4f1 Functions as a Tumor Suppressor by Targeting c-MET/STAT3 Signaling in Thyroid Cancer. (PMID:32474599)
• POU4F1 promotes the resistance of melanoma to BRAF inhibitors through MEK/ERK pathway activation and MITF up-regulation. (PMID:32532957)
• No association between POU4F1, POU4F2, ISL1 polymorphisms and normal-tension glaucoma. (PMID:32597291)
• POU4F1 confers trastuzumab resistance in HER2-positive breast cancer through regulating ERK1/2 signaling pathway. (PMID:32988584)
• Haploinsufficiency of POU4F1 causes an ataxia syndrome with hypotonia and intention tremor. (PMID:33783914)
• HDAC2 Is Involved in the Regulation of BRN3A in Melanocytes and Melanoma. (PMID:35055045)
• Activation of Bivalent Gene POU4F1 Promotes and Maintains Basal-like Breast Cancer. (PMID:38491910)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	pou4f1	ENSDARG00000005559
mus_musculus	Pou4f1	ENSMUSG00000048349
rattus_norvegicus	Pou4f1	ENSRNOG00000089245
drosophila_melanogaster	acj6	FBGN0000028
caenorhabditis_elegans		WBGENE00006818

Paralogs (17): POU2F2 (ENSG00000028277), POU1F1 (ENSG00000064835), POU4F3 (ENSG00000091010), POU6F2 (ENSG00000106536), POU2F3 (ENSG00000137709), POU2F1 (ENSG00000143190), POU4F2 (ENSG00000151615), HDX (ENSG00000165259), POU6F1 (ENSG00000184271), POU3F2 (ENSG00000184486), POU3F1 (ENSG00000185668), POU3F4 (ENSG00000196767), POU3F3 (ENSG00000198914), CCDC160 (ENSG00000203952), POU5F1 (ENSG00000204531), POU5F1B (ENSG00000212993), POU5F2 (ENSG00000248483)

Protein

Protein identifiers

POU domain, class 4, transcription factor 1 — Q01851 (reviewed: Q01851)

Alternative names: Brain-specific homeobox/POU domain protein 3A, Homeobox/POU domain protein RDC-1, Oct-T1

All UniProt accessions (1): Q01851

UniProt curated annotations — full annotation on UniProt →

Function. Multifunctional transcription factor with different regions mediating its different effects. Acts by binding (via its C-terminal domain) to sequences related to the consensus octamer motif 5’-ATGCAAAT-3’ in the regulatory regions of its target genes. Regulates the expression of specific genes involved in differentiation and survival within a subset of neuronal lineages. It has been shown that activation of some of these genes requires its N-terminal domain, maybe through a neuronal-specific cofactor. Activates BCL2 expression and protects neuronal cells from apoptosis (via the N-terminal domain). Induces neuronal process outgrowth and the coordinate expression of genes encoding synaptic proteins. Exerts its major developmental effects in somatosensory neurons and in brainstem nuclei involved in motor control. Stimulates the binding affinity of the nuclear estrogene receptor ESR1 to DNA estrogen response element (ERE), and hence modulates ESR1-induced transcriptional activity. May positively regulate POU4F2 and POU4F3. Regulates dorsal root ganglion sensory neuron specification and axonal projection into the spinal cord. Plays a role in TNFSF11-mediated terminal osteoclast differentiation. Negatively regulates its own expression interacting directly with a highly conserved autoregulatory domain surrounding the transcription initiation site. Able to act as transcription factor, cannot regulate the expression of the same subset of genes than isoform 1. Does not have antiapoptotic effect on neuronal cells.

Subunit / interactions. Interacts (via N-terminus) with RIT2; the interaction controls POU4F1 transactivation activity on some neuronal target genes. Isoform 1 interacts with POU4F2; this interaction inhibits both POU4F1 DNA-binding and transcriptional activities. Isoform 1 interacts (C-terminus) with ESR1 (via DNA-binding domain); this interaction decreases the estrogen receptor ESR1 transcriptional activity in a DNA- and ligand 17-beta-estradiol-independent manner.

Subcellular location. Nucleus. Cytoplasm.

Tissue specificity. Expressed in the brain and the retina. Present in the developing brain, spinal cord and eye.

Disease relevance. Ataxia, intention tremor, and hypotonia syndrome, childhood-onset (ATITHS) [MIM:619352] An autosomal dominant neurodevelopmental disorder characterized by global developmental delay, mildly impaired intellectual development with speech delay or learning disabilities, delayed walking due to ataxia, intention tremor, and hypotonia apparent from early childhood. Brain imaging shows cerebellar atrophy in some patients. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The C-terminal domain is able to act as both DNA-binding domain and a transcriptional activator. The N-terminal domain is also required for transactivation activity on some target genes acting as a discrete activation domain. Neurite outgrowth and expression of genes required for synapse formation are primarily dependent on the C-terminal domain, however the N-terminal domain is required for maximal induction.

Similarity. Belongs to the POU transcription factor family. Class-4 subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q01851-1	1, Brn-3A-Long	yes
Q01851-2	2, Brn-3A-Short

RefSeq proteins (1): NP_006228* (*=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
IPR017970	Homeobox_CS	Conserved_site
IPR050255	POU_domain_TF	Family

Pfam: PF00046, PF00157

UniProt features (23 total): sequence conflict 12, sequence variant 2, region of interest 2, compositionally biased region 2, chain 1, domain 1, DNA-binding region 1, short sequence motif 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q01851-F1	62.61	0.26

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-6804759	Regulation of TP53 Activity through Association with Co-factors

MSigDB gene sets: 460 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_UP, GSE45365_NK_CELL_VS_CD8A_DC_UP, GOBP_CARDIAC_CHAMBER_DEVELOPMENT, GGGACCA_MIR133A_MIR133B, VERHAAK_AML_WITH_NPM1_MUTATED_DN, GOBP_HINDBRAIN_DEVELOPMENT, MODULE_52, GOBP_NEGATIVE_REGULATION_OF_NEURON_APOPTOTIC_PROCESS, TAATAAT_MIR126, CAR_TNFRSF25, GOBP_MUSCLE_TISSUE_DEVELOPMENT, GOBP_REGULATION_OF_OSTEOCLAST_DIFFERENTIATION, BENPORATH_ES_WITH_H3K27ME3, GOBP_BEHAVIOR

GO Biological Process (39): negative regulation of transcription by RNA polymerase II (GO:0000122), neuron migration (GO:0001764), suckling behavior (GO:0001967), ventricular compact myocardium morphogenesis (GO:0003223), regulation of transcription by RNA polymerase II (GO:0006357), axonogenesis (GO:0007409), synapse assembly (GO:0007416), mesoderm development (GO:0007498), heart development (GO:0007507), positive regulation of gene expression (GO:0010628), negative regulation of gene expression (GO:0010629), cell migration in hindbrain (GO:0021535), trigeminal nerve development (GO:0021559), central nervous system neuron differentiation (GO:0021953), habenula development (GO:0021986), neuron projection development (GO:0031175), negative regulation of apoptotic process (GO:0043066), negative regulation of programmed cell death (GO:0043069), negative regulation of neuron apoptotic process (GO:0043524), positive regulation of neuron apoptotic process (GO:0043525), positive regulation of osteoclast differentiation (GO:0045672), positive regulation of transcription by RNA polymerase II (GO:0045944), neuron fate specification (GO:0048665), sensory system development (GO:0048880), peripheral nervous system neuron development (GO:0048935), regulation of neurogenesis (GO:0050767), obsolete regulation of DNA-binding transcription factor activity (GO:0051090), proprioception involved in equilibrioception (GO:0051355), neuron apoptotic process (GO:0051402), regulation of cell cycle (GO:0051726), innervation (GO:0060384), cellular response to cytokine stimulus (GO:0071345), cellular response to estradiol stimulus (GO:0071392), intrinsic apoptotic signaling pathway by p53 class mediator (GO:0072332), positive regulation of transcription regulatory region DNA binding (GO:2000679), regulation of DNA-templated transcription (GO:0006355), nervous system development (GO:0007399), neuron differentiation (GO:0030182), peripheral nervous system neuron differentiation (GO:0048934)

GO Molecular Function (13): 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 repressor activity, RNA polymerase II-specific (GO:0001227), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), chromatin binding (GO:0003682), single-stranded DNA binding (GO:0003697), sequence-specific DNA binding (GO:0043565), GTPase binding (GO:0051020), RNA polymerase II-specific DNA-binding transcription factor binding (GO:0061629), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700), protein binding (GO:0005515)

GO Cellular Component (6): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), neuron projection (GO:0043005), RNA polymerase II transcription regulator complex (GO:0090575)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Regulation of TP53 Activity	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA polymerase II transcription regulatory region sequence-specific DNA binding	4
cellular anatomical structure	3
regulation of transcription by RNA polymerase II	2
transcription by RNA polymerase II	2
cell migration	2
regulation of DNA-templated transcription	2
gene expression	2
regulation of gene expression	2
regulation of neuron apoptotic process	2
neuron apoptotic process	2
DNA-binding transcription factor activity, RNA polymerase II-specific	2
binding	2
DNA binding	2
negative regulation of DNA-templated transcription	1
generation of neurons	1
feeding behavior	1
ventricular cardiac muscle tissue morphogenesis	1
cell morphogenesis involved in neuron differentiation	1
neuron projection morphogenesis	1
axon development	1
nervous system development	1
cell junction assembly	1
synapse organization	1
tissue development	1
animal organ development	1
circulatory system development	1
positive regulation of macromolecule biosynthetic process	1
negative regulation of macromolecule biosynthetic process	1
hindbrain development	1
cranial nerve development	1
central nervous system development	1
neuron differentiation	1
epithalamus development	1
anatomical structure development	1
neuron development	1
plasma membrane bounded cell projection organization	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
programmed cell death	1

Protein interactions and networks

STRING

1244 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
POU4F1	NEUROG1	Q92886	910
POU4F1	NEUROG2	Q9H2A3	827
POU4F1	ATOH1	Q92858	820
POU4F1	LHX9	Q9NQ69	793
POU4F1	RIT2	Q99578	775
POU4F1	ASCL1	P50553	756
POU4F1	ISL1	P20663	732
POU4F1	VSX2	P58304	727
POU4F1	RBPMS	Q93062	712
POU4F1	OPN4	Q9UHM6	694
POU4F1	ATOH7	Q8N100	647
POU4F1	NEFL	P07196	635
POU4F1	PAX6	P26367	629
POU4F1	CALB1	P05937	605
POU4F1	RCVRN	P35243	599

IntAct

7 interactions, top by confidence:

A	B	Type	Score
POU4F1	MAPRE3	psi-mi:“MI:0915”(physical association)	0.560
POU4F1	NTHL1	psi-mi:“MI:0915”(physical association)	0.400
Mecom	ESYT2	psi-mi:“MI:0914”(association)	0.350
S100A2	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
MAPRE3	POU4F1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (10): RIT2 (Two-hybrid), RIT2 (Reconstituted Complex), POU4F1 (Two-hybrid), ESR1 (Reconstituted Complex), ESR1 (Two-hybrid), POU4F1 (Affinity Capture-RNA), POU4F1 (Affinity Capture-MS), NTHL1 (Affinity Capture-MS), EWSR1 (Two-hybrid), EWSR1 (Reconstituted Complex)

ESM2 similar proteins: A2WY46, A6BLW4, B8A9B2, G0SB31, G4MRQ6, G4N3L5, M2TF54, O54772, O65001, O70132, P17208, P20264, P20265, P20266, P20267, P21952, P25209, P31360, P31361, P53784, P56222, Q01851, Q02516, Q03052, Q0JGS5, Q13164, Q60764, Q60EQ4, Q63262, Q655V5, Q69J40, Q69TW5, Q6EU10, Q75IZ7, Q8L4B2, Q8LCG7, Q8LH59, Q8QZW2, Q92925, Q960X8

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

3 interactions.

A	Effect	B	Mechanism
RIT2	“up-regulates activity”	POU4F1	binding
POU4F1	“up-regulates activity”	ESR1	binding
POU4F1	“up-regulates quantity by expression”	SCN9A	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	3
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

156 predictions. Top by Δscore:

Variant	Effect	Δscore
13:78603198:GCTTA:G	donor_loss	1.0000
13:78603199:CTTAC:C	donor_loss	1.0000
13:78603200:TTA:T	donor_loss	1.0000
13:78603201:TACCG:T	donor_loss	1.0000
13:78603203:CCGG:C	donor_gain	1.0000
13:78603197:CGCTT:C	donor_loss	0.9900
13:78603202:A:AC	donor_gain	0.9900
13:78603203:C:CC	donor_gain	0.9900
13:78602547:TGCAG:T	acceptor_gain	0.9700
13:78602549:CAG:C	acceptor_gain	0.9700
13:78602552:C:CC	acceptor_gain	0.9700
13:78602569:C:CT	acceptor_gain	0.9700
13:78602550:AG:A	acceptor_gain	0.9600
13:78602560:G:T	acceptor_gain	0.9600
13:78602574:C:CT	acceptor_gain	0.9600
13:78602575:A:T	acceptor_gain	0.9600
13:78602551:GCT:G	acceptor_loss	0.9500
13:78602552:CTGCA:C	acceptor_loss	0.9500
13:78602570:A:T	acceptor_gain	0.9500
13:78602548:GCAG:G	acceptor_gain	0.9400
13:78602549:CAGC:C	acceptor_gain	0.9400
13:78602559:C:CT	acceptor_gain	0.9400
13:78602562:C:CT	acceptor_gain	0.9400
13:78603203:CCG:C	donor_gain	0.9400
13:78602556:A:T	acceptor_gain	0.9200
13:78602564:C:CT	acceptor_gain	0.9200
13:78602583:C:CT	acceptor_gain	0.9200
13:78603202:ACCGG:A	donor_gain	0.9200
13:78603203:CCGGC:C	donor_gain	0.9200
13:78602555:C:CT	acceptor_gain	0.9000

AlphaMissense

2710 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
13:78601430:G:C	F415L	1.000
13:78601430:G:T	F415L	1.000
13:78601432:A:G	F415L	1.000
13:78601441:G:A	R412W	1.000
13:78601442:C:A	K411N	1.000
13:78601442:C:G	K411N	1.000
13:78601443:T:A	K411M	1.000
13:78601444:T:C	K411E	1.000
13:78601446:T:G	Q410P	1.000
13:78601448:C:A	K409N	1.000
13:78601448:C:G	K409N	1.000
13:78601449:T:A	K409M	1.000
13:78601450:T:C	K409E	1.000
13:78601451:C:A	Q408H	1.000
13:78601451:C:G	Q408H	1.000
13:78601452:T:C	Q408R	1.000
13:78601452:T:G	Q408P	1.000
13:78601453:G:T	Q408K	1.000
13:78601454:T:A	R407S	1.000
13:78601454:T:G	R407S	1.000
13:78601455:C:A	R407I	1.000
13:78601455:C:G	R407T	1.000
13:78601456:T:C	R407G	1.000
13:78601457:C:A	Q406H	1.000
13:78601457:C:G	Q406H	1.000
13:78601458:T:G	Q406P	1.000
13:78601460:G:C	N405K	1.000
13:78601460:G:T	N405K	1.000
13:78601461:T:A	N405I	1.000
13:78601461:T:G	N405T	1.000

dbSNP variants (sampled 300 via entrez): RS1000118146 (13:78603591 G>C), RS1000511431 (13:78601953 G>A), RS1001511765 (13:78600712 G>C), RS1001542977 (13:78600399 A>C), RS1002416212 (13:78604352 T>C), RS1002518006 (13:78599238 G>A,T), RS1002554040 (13:78598952 A>C), RS1002640078 (13:78605235 A>C), RS1002704822 (13:78603849 C>T), RS1002857226 (13:78604029 A>T), RS1003145796 (13:78598360 G>A,C), RS1003242336 (13:78600207 G>C), RS1003481488 (13:78599929 A>G), RS1003526641 (13:78597947 A>G), RS1004422908 (13:78602273 C>G,T)

Disease associations

OMIM: gene MIM:601632 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
ataxia, intention tremor, and hypotonia syndrome, childhood-onset	Strong	Autosomal dominant

Mondo (1): ataxia, intention tremor, and hypotonia syndrome, childhood-onset (MONDO:0859158)

Orphanet (0):

HPO phenotypes

46 total (30 of 46 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000160	Narrow mouth
HP:0000179	Thick lower lip vermilion
HP:0000256	Macrocephaly
HP:0000276	Long face
HP:0000307	Pointed chin
HP:0000343	Long philtrum
HP:0000414	Bulbous nose
HP:0000445	Wide nose
HP:0000463	Anteverted nares
HP:0000486	Strabismus
HP:0000490	Deeply set eye
HP:0000565	Esotropia
HP:0000639	Nystagmus
HP:0000718	Aggressive behavior
HP:0000729	Autistic behavior
HP:0000750	Delayed speech and language development
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001256	Mild intellectual disability
HP:0001260	Dysarthria
HP:0001263	Global developmental delay
HP:0001310	Dysmetria
HP:0001319	Neonatal hypotonia
HP:0001321	Cerebellar hypoplasia
HP:0001348	Brisk reflexes
HP:0002003	Large forehead
HP:0002019	Constipation
HP:0002080	Intention tremor
HP:0002120	Cerebral cortical atrophy

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST000892_9	Total ventricular volume (Alzheimer’s disease interaction)	7.000000e-06
GCST009302_17	Antipsychotic drug-induced weight gain in schizophrenia	6.000000e-06
GCST009302_2	Antipsychotic drug-induced weight gain in schizophrenia	2.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004567	antipsychotic drug related weight gain

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression, decreases methylation, increases expression	9
Benzo(a)pyrene	increases expression, increases methylation	3
mercuric bromide	decreases expression, affects cotreatment	2
Rotenone	decreases expression, increases expression	2
Cyclosporine	decreases expression, increases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
methylmercuric chloride	decreases expression	1
bisphenol A	decreases expression	1
trichostatin A	decreases expression, increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
azoxystrobin	decreases expression	1
CGP 52608	increases reaction, affects binding	1
deguelin	decreases expression	1
2-palmitoylglycerol	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	decreases expression	1
pyrachlostrobin	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
picoxystrobin	decreases expression	1
Arsenic Trioxide	increases expression	1
Vorinostat	increases expression	1
Leflunomide	decreases expression	1
Antimycin A	decreases expression	1
Arsenic	increases methylation	1
Carbamazepine	affects expression	1
Diethylhexyl Phthalate	decreases expression	1
Methotrexate	decreases expression	1
Silicon Dioxide	increases expression	1
Dronabinol	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_A5M5	SEES3-1V human POU4F1, clone1	Embryonic stem cell	Male
CVCL_A5M6	SEES3-1V human POU4F1, clone2	Embryonic stem cell	Male
CVCL_A5M7	SEES3-1V human POU4F1, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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