POU1F1

Summary

POU1F1 (POU class 1 homeobox 1, HGNC:9210) is a protein-coding gene on chromosome 3p11.2, encoding Pituitary-specific positive transcription factor 1 (P28069). Transcription factor involved in the specification of the lactotrope, somatotrope, and thyrotrope phenotypes in the developing anterior pituitary.

This gene encodes a member of the POU family of transcription factors that regulate mammalian development. The protein regulates expression of several genes involved in pituitary development and hormone expression. Mutations in this genes result in combined pituitary hormone deficiency. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 5449 — RefSeq curated summary.

At a glance

• Gene–disease (curated): pituitary hormone deficiency, combined, 1 (Definitive, GenCC) — +3 more curated relationships
• GWAS associations: 2
• Clinical variants (ClinVar): 244 total — 27 pathogenic, 12 likely-pathogenic
• Phenotypes (HPO): 98
• Transcription factor: yes — 73 downstream targets (CollecTRI)
• MANE Select transcript: NM_000306

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9210
Approved symbol	POU1F1
Name	POU class 1 homeobox 1
Location	3p11.2
Locus type	gene with protein product
Status	Approved
Aliases	GHF-1, POU1F1a, PIT-1
Ensembl gene	ENSG00000064835
Ensembl biotype	protein_coding
OMIM	173110
Entrez	5449

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000344265, ENST00000350375, ENST00000560656, ENST00000561167

RefSeq mRNA: 2 — MANE Select: NM_000306 NM_000306, NM_001122757

CCDS: CCDS2919, CCDS46873

Canonical transcript exons

ENST00000350375 — 6 exons

Exon	Start	End
ENSE00000774302	87261273	87261333
ENSE00000774345	87262071	87262235
ENSE00000995625	87273347	87273418
ENSE00000995626	87264288	87264512
ENSE00001167453	87276321	87276584
ENSE00001220764	87259404	87260104

Expression profiles

Bgee: expression breadth broad, 73 present calls, max score 93.10.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.0395 / max 933.4326, expressed in 6 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
43287	0.9146	6
43286	0.1249	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pituitary gland	UBERON:0000007	93.10	gold quality
adenohypophysis	UBERON:0002196	91.08	gold quality
decidua	UBERON:0002450	56.55	gold quality
frontal pole	UBERON:0002795	50.41	gold quality
middle frontal gyrus	UBERON:0002702	50.30	gold quality
Brodmann (1909) area 10	UBERON:0013541	50.18	gold quality
quadriceps femoris	UBERON:0001377	50.01	gold quality
metanephric glomerulus	UBERON:0004736	49.61	gold quality
vastus lateralis	UBERON:0001379	49.45	gold quality
thymus	UBERON:0002370	49.30	gold quality
Brodmann (1909) area 46	UBERON:0006483	49.30	gold quality
cerebellar vermis	UBERON:0004720	49.25	gold quality
cervix squamous epithelium	UBERON:0006922	49.20	gold quality
olfactory bulb	UBERON:0002264	48.92	gold quality
myocardium	UBERON:0002349	48.87	gold quality
type B pancreatic cell	CL:0000169	48.83	gold quality
cardiac muscle of right atrium	UBERON:0003379	48.55	gold quality
CA1 field of hippocampus	UBERON:0003881	48.50	gold quality
hindlimb stylopod muscle	UBERON:0004252	48.38	silver quality
epithelial cell of pancreas	CL:0000083	48.25	gold quality
left ventricle myocardium	UBERON:0006566	48.24	gold quality
oviduct epithelium	UBERON:0004804	48.21	gold quality
orbitofrontal cortex	UBERON:0004167	48.20	gold quality
kidney epithelium	UBERON:0004819	48.11	gold quality
upper arm skin	UBERON:0004263	48.06	gold quality
cervix epithelium	UBERON:0004801	48.04	gold quality
tongue squamous epithelium	UBERON:0006919	47.92	gold quality
mucosa of urinary bladder	UBERON:0001259	47.80	gold quality
layer of synovial tissue	UBERON:0007616	47.54	gold quality
nephron tubule	UBERON:0001231	47.30	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.95

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

73 targets.

Target	Regulation
ADAM2
BDKRB1	Unknown
C1QTNF3	Activation
CASP3	Unknown
CCND1	Activation
CD74
CDKN2A	Unknown
CEL
CGA	Unknown
CNTF
CREBBP
CS
CSH1	Activation
CYC1
EGF
ESR1
FGF23
FGFR4	Activation
FOS	Unknown
FSHB
GH1	Activation
GH2	Activation
GHR	Activation
GHRHR	Activation
GHRL
GNRH1
GNRHR
HESX1
HSPA9
IBSP

JASPAR motifs

Motif	Name	Family
MA0784.1	POU1F1	POU domain factors
MA0784.2	POU1F1	POU domain factors
MA0784.3	POU1F1	POU domain factors

JASPAR matrix evidence (PMIDs): PMID:2350782

Upstream regulators (CollecTRI, top): AP1, CREB1, CTCF, HESX1, HMGA1, HMGA2, JUN, LEF1, LHX2, LHX4, NCOR1, OTX2, PHF20, PITX1, PITX2, POU1F1, POU2F1, PREB, PROP1, SP1, SP3, VDR, ZFHX3

miRNA regulators (miRDB)

30 targeting POU1F1, 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-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-1277-5P	100.00	73.95	5056
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-29B-2-5P	99.67	68.98	1726
HSA-MIR-12117	99.50	67.57	868
HSA-MIR-12132	99.47	68.90	1341
HSA-MIR-3915	99.45	68.49	1905
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-3182	99.40	68.15	2454
HSA-MIR-4652-3P	99.33	70.02	2742
HSA-MIR-580-5P	99.28	70.94	1776
HSA-MIR-6815-3P	99.13	68.98	1530
HSA-MIR-4796-3P	99.08	68.38	1681
HSA-MIR-6878-5P	98.49	67.91	2142
HSA-MIR-4474-3P	96.97	65.87	870
HSA-MIR-6746-5P	92.37	63.66	103

Literature-anchored findings (GeneRIF, showing 40)

• severe hypothyroidism and combined pituitary hormone deficiency due to a new mutation in the PIT-1 gene. the newly described mutation is inherited in an autosomal-recessive way. (PMID:11847467)
• the clinical presentation of the PIT1 mutation involves intrauterine growth retardation (PMID:11924936)
• silence in silent thyrotroph adenomas seems to be downstream to transcription of Pit-1 gene in the pathway leading to hormone secretion (PMID:12165656)
• specification of unique Pit-1 activity in the hGH locus control region (PMID:12189206)
• found that codon 24 proline in the transactivation domain as well as the POU domain of Pit-1 was crucial to recruit coactivator CREB-binding protein (CBP) for the expression of Pit-1-targeted genes. (PMID:12200420)
• full responsiveness to several signaling pathways regulating the hPRL promoter requires the B2 Pitx binding site and that Pitx factors may be part of the proteic complex involved in these regulations (PMID:12223489)
• phosphorylation of Pit-1 affects binding to transcription factor Ets-1 (PMID:12242337)
• Pit-1 which is required for generation of hormone producing cells in the anterior pituitary gland, have proved to be important in the cause of hypopituitarism in humans–REVIEW (PMID:12717343)
• that phenotypically normal cases have been reported with this mutation, our results deny the relationship between R271W and combined pituitary hormone deficiency. (PMID:12773133)
• New mutation located in the N-terminal (Q-4ter) of PIT-1 gene causing recessive combined pitutary hormone deficiency. (PMID:12932747)
• “PIT1 mutations in man are associated with …thyroid stimulating hormone and growth hormone deficiency…” p. 278 (PMID:14646405)
• “Mutations within POUF1 or P1T1 are associated with growth hormone, thyroid stimulating hormone and prolactin deficiency…” p. 207 (PMID:14714741)
• the smad pathway and the tumor suppressor menin are key regulators of activin effects on PRL and Pit-1 expression, as well as on cell growth inhibition (PMID:15031321)
• the phenotype associated with POU1F1 mutations may be more variable, with the occasional preservation of TSH secretion in pituitary deficiency disease (PMID:15928241)
• Findings are consistent with the existence of LHX4-driven pathway leading to expression of GH through transcriptional activation of POU1F1. They argue against dominant-negative effect of mutant LHX4 proteins over normal LHX4. (PMID:15998782)
• The redistribution of co-repressor complexes by Pit-1 might represent an important mechanism by which transcription factors direct changes in cell-specific gene expression. (PMID:16030140)
• depending on its level of expression, Pit-1 may be involved in normal mammary development, breast disorders, or both (PMID:16061841)
• Data suggest that the expression of Pit-1 in cells of the alpha SU-based gonadotropin cell lineage might also lead to the expression of growth hormone, prolactin, and thyroid-stimulating hormone beta subunit. (PMID:16133148)
• CBP/p300 recruitment and Pit-1 dimerization are necessary for Pit-1 target gene activation and are important in the pathogenesis of combined pituitary hormone deficiency (PMID:16263824)
• direct interaction between the vitamin D receptor (VDR) as homodimer (without the retinoid X receptor), and the Pit-1 promoter, supporting the view that Pit-1 is a direct transcriptional target of VDR (PMID:16322098)
• findings show that activin negatively regulates the human Pit-1 gene promoter; activin effects on Pit-1 gene regulation are Smad independent and require the p38 MAPK pathway (PMID:16740974)
• Review article uses Pit-1 as an example while exploring the role of transcription factors in pituitary hormone secretion, and examining mutations involved in human anterior pituitary pathologies. (PMID:16879162)
• The growth-promoting effects of Pit-1 are at least partly due to the fact that this transcription factor prevents apoptotic cell death. (PMID:16901973)
• the Pit-1/Pit-1beta TADs are composed of multiple, modular, and transferable subdomains, including a regulatory R1 domain, a basal activation region, a selective inhibitory-Ras-responsive segment, and a beta-specific repressor domain (PMID:17021049)
• Review discusses the possibility that Pit-1-driven remodeling at nuclease-hypersensitive site (HS) III may precede that at HS I/II in the pituitary. (PMID:17047377)
• up-regulation of VDR transcription by Pit-1 is dependent on the presence of VDR protein (PMID:17456792)
• Phosphate uptake via Pit-1 is required for osteochondrogenic phenotypic change and calcification of vascular smooth muscle cells in vitro.[review] (PMID:17565274)
• novel POU1F1 splice site mutation, IVS4+1G>A, the first of its kind, in a Thai patient with combined pituitary hormone deficiency (PMID:18059085)
• The novel functioning binding elements of Prop1 in human Pit-1 gene. (PMID:18653712)
• Our results suggested that there is a coordinated interrelationship between 2 key participants of Pi and PPi metabolism, ANKH and PiT-1. (PMID:19369455)
• These findings are consistent with a role for Pit-1 as an initiating factor in human growth hormone (hGH) locus activation during somatotrope ontogeny, acting through binding sites at the locus control region. (PMID:19427323)
• analysis of a Pit-1beta 26-amino acid dominant and independent repressor domain (PMID:19556346)
• Activation of Syt1 gene expression is part of a mechanism mediating POU1F-induced differentiation of pituitary cells. (PMID:19608642)
• Novel association of two rare conditions Pit-1 mutation and lipoedema in a family that has not been described before. (PMID:19609847)
• Pit-1 regulates mammary PRL transcription by binding to the proximal PRL promoter. Pit-1 raises cyclin D1 expression before increasing PRL levels. There was a significant correlation between Pit-1 & PRL expression in 94 invasive ductal breast carcinomas. (PMID:19808898)
• Data suggest phosphorylation of Pit-1 (POU1F1) at T220 serves as a mechanism to modulate Pit-1 target genes by regulating binding of Pit-1 to monomeric (Pit-1) versus dimeric (Ets-1/Pit-1) sites on DNA (PMID:19887646)
• These results support the inference that W194XProp1 is unable to increase POU1F1 gene expression by the defect of transactivating domain and that S156insTProp1 is unable to increase due to the loss of DNA-binding activity. (PMID:20381582)
• Data are consistent with recruitment and an early role for Pit-1 in remodeling of the growth hormone locus control region at the constitutively open hypersensitive site III through protein-protein interaction. (PMID:20395397)
• Pit-1 overexpression or knockdown in human breast cancer cell lines induced profound phenotypic changes in the expression of proteins involved in cell proliferation, apoptosis, and invasion. (PMID:21060149)
• study, which identifies a novel loss-of-function mutation in POU1F1, describes the phenotype of a rare condition in a patient followed from the first weeks of life to adulthood (PMID:21521297)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	pou1f1	ENSDARG00000058924
mus_musculus	Pou1f1	ENSMUSG00000004842
rattus_norvegicus	Pou1f1	ENSRNOG00000000715
drosophila_melanogaster	acj6	FBGN0000028
caenorhabditis_elegans		WBGENE00006818

Paralogs (17): POU2F2 (ENSG00000028277), POU4F3 (ENSG00000091010), POU6F2 (ENSG00000106536), POU2F3 (ENSG00000137709), POU2F1 (ENSG00000143190), POU4F2 (ENSG00000151615), POU4F1 (ENSG00000152192), HDX (ENSG00000165259), POU6F1 (ENSG00000184271), POU3F2 (ENSG00000184486), POU3F1 (ENSG00000185668), POU3F4 (ENSG00000196767), POU3F3 (ENSG00000198914), CCDC160 (ENSG00000203952), POU5F1 (ENSG00000204531), POU5F1B (ENSG00000212993), POU5F2 (ENSG00000248483)

Protein

Protein identifiers

Pituitary-specific positive transcription factor 1 — P28069 (reviewed: P28069)

Alternative names: Growth hormone factor 1

All UniProt accessions (3): P28069, H0YK06, H0YNM5

UniProt curated annotations — full annotation on UniProt →

Function. Transcription factor involved in the specification of the lactotrope, somatotrope, and thyrotrope phenotypes in the developing anterior pituitary. Specifically binds to the consensus sequence 5’-TAAAT-3’. Activates growth hormone and prolactin genes.

Subunit / interactions. Interacts with PITX1. Interacts with LHX3. Interacts with ELK1.

Subcellular location. Nucleus.

Disease relevance. Pituitary hormone deficiency, combined, 1 (CPHD1) [MIM:613038] Combined pituitary hormone deficiency is defined as the impaired production of growth hormone and one or more of the other five anterior pituitary hormones. CPHD1 is characterized by pleiotropic deficiencies of growth hormone, prolactin and thyroid-stimulating hormone, while the production of adrenocorticotropic hormone, luteinizing hormone, and follicle-stimulating hormone are preserved. In infancy severe growth deficiency from birth as well as distinctive facial features with prominent forehead, marked midfacial hypoplasia with depressed nasal bridge, deep-set eyes, and a short nose with anteverted nostrils and hypoplastic pituitary gland by MRI examination can be seen. Some cases present with severe intellectual disability along with short stature. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors.

Miscellaneous. Altered in its ability to trans-activate compared to isoform B.

Similarity. Belongs to the POU transcription factor family. Class-1 subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
P28069-1	B, Pit-1B, GHF-1	yes
P28069-2	A, Pit-1A, GHF-2

RefSeq proteins (2): NP_000297, NP_001116229 (=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 (34 total): sequence variant 16, helix 8, mutagenesis site 5, chain 1, domain 1, DNA-binding region 1, short sequence motif 1, splice variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
5WC9	X-RAY DIFFRACTION	3.15

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P28069-F1	68.43	0.38

Functional residue map

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

Mutagenesis-validated functional residues (5):

Position	Phenotype
74	no effect on the interaction with elk1, lhx3 and pitx1.
75	increases the interaction with lhx3. no effect on the interaction with elk1.
76	increases the interaction with lhx3 and pitx1. no effect on the interaction with elk1.
77	increases the interaction with lhx3 and pitx1. no effect on the interaction with elk1.
78	increases the interaction with lhx3 and pitx1. no effect on the interaction with elk1.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 299 (showing top): GOBP_PITUITARY_GLAND_DEVELOPMENT, PID_REG_GR_PATHWAY, GOBP_FOREBRAIN_DEVELOPMENT, MARTINEZ_RB1_TARGETS_DN, GOBP_HEAD_DEVELOPMENT, GOBP_DIENCEPHALON_DEVELOPMENT, POU3F2_02, GOBP_ENDOCRINE_SYSTEM_DEVELOPMENT, GOBP_ADENOHYPOPHYSIS_DEVELOPMENT, YATGNWAAT_OCT_C, MATZUK_CENTRAL_FOR_FEMALE_FERTILITY, GOMF_TRANSCRIPTION_FACTOR_BINDING, YOSHIMURA_MAPK8_TARGETS_UP, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, BROWNE_HCMV_INFECTION_48HR_UP

GO Biological Process (7): negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of DNA-templated transcription (GO:0006355), regulation of transcription by RNA polymerase II (GO:0006357), negative regulation of cell population proliferation (GO:0008285), adenohypophysis development (GO:0021984), positive regulation of transcription by RNA polymerase II (GO:0045944), positive regulation of DNA-templated transcription (GO:0045893)

GO Molecular Function (10): 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 activator activity, RNA polymerase II-specific (GO:0001228), DNA-binding transcription factor activity (GO:0003700), RNA polymerase II-specific DNA-binding transcription factor binding (GO:0061629), lncRNA binding (GO:0106222), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677), protein binding (GO:0005515), sequence-specific DNA binding (GO:0043565)

GO Cellular Component (4): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of transcription by RNA polymerase II	3
transcription by RNA polymerase II	3
regulation of DNA-templated transcription	3
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
cellular anatomical structure	3
DNA-templated transcription	2
negative regulation of DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
pituitary gland development	1
anatomical structure development	1
positive regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription activator activity	1
positive regulation of transcription by RNA polymerase II	1
transcription cis-regulatory region binding	1
transcription regulator activity	1
DNA-binding transcription factor binding	1
RNA binding	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
nucleic acid binding	1
binding	1
DNA binding	1
chromosome	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cytoplasm	1

Protein interactions and networks

STRING

1092 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
POU1F1	PROP1	O75360	971
POU1F1	HESX1	Q9UBX0	949
POU1F1	PRL	P01236	899
POU1F1	TSHB	P01222	893
POU1F1	LHX4	Q969G2	891
POU1F1	GHRHR	Q02643	869
POU1F1	LHX3	Q9UBR4	864
POU1F1	ZFHX3	Q15911	848
POU1F1	ESX1	Q8N693	783
POU1F1	PITX1	P78337	774
POU1F1	PITX2	Q99697	758
POU1F1	GHRH	P01286	739
POU1F1	TRH	P20396	735
POU1F1	TBX19	O60806	727
POU1F1	POMC	P01189	707

IntAct

40 interactions, top by confidence:

A	B	Type	Score
POU1F1	DDIT4L	psi-mi:“MI:0915”(physical association)	0.560
POU1F1	KRTAP10-8	psi-mi:“MI:0915”(physical association)	0.560
POU1F1	MSX2	psi-mi:“MI:0915”(physical association)	0.560
POU1F1	RAD54L2	psi-mi:“MI:0915”(physical association)	0.560
ARSA	POU1F1	psi-mi:“MI:0915”(physical association)	0.560
POU1F1	LASP1	psi-mi:“MI:0915”(physical association)	0.560
POU1F1	ARID5A	psi-mi:“MI:0915”(physical association)	0.560
POU1F1	KRTAP15-1	psi-mi:“MI:0915”(physical association)	0.560
POU1F1	UBE2I	psi-mi:“MI:0915”(physical association)	0.560
POU1F1	KRTAP6-1	psi-mi:“MI:0915”(physical association)	0.560
POU1F1	LHX4	psi-mi:“MI:0915”(physical association)	0.560
ETS1	POU1F1	psi-mi:“MI:0407”(direct interaction)	0.440
POU1F1	OPA1	psi-mi:“MI:0915”(physical association)	0.400
KIF5B	KLC1	psi-mi:“MI:0914”(association)	0.350
POU1F1	CDC42BPG	psi-mi:“MI:0914”(association)	0.350
POU1F1	LHX4	psi-mi:“MI:0915”(physical association)	0.000
POU1F1	KRTAP10-8	psi-mi:“MI:0915”(physical association)	0.000
POU1F1	MSX2	psi-mi:“MI:0915”(physical association)	0.000
POU1F1	LASP1	psi-mi:“MI:0915”(physical association)	0.000
POU1F1	ARID5A	psi-mi:“MI:0915”(physical association)	0.000
POU1F1	RAD54L2	psi-mi:“MI:0915”(physical association)	0.000
POU1F1	ARSA	psi-mi:“MI:0915”(physical association)	0.000
POU1F1	KRTAP15-1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (38): POU1F1 (Affinity Capture-MS), POU1F1 (Affinity Capture-MS), POU1F1 (Synthetic Lethality), POU1F1 (Two-hybrid), ARSA (Two-hybrid), UBE2I (Two-hybrid), MSX2 (Two-hybrid), LHX4 (Two-hybrid), RAD54L2 (Two-hybrid), KRTAP6-1 (Two-hybrid), KRTAP15-1 (Two-hybrid), KRTAP10-8 (Two-hybrid), ARID5A (Two-hybrid), NR3C1 (Reconstituted Complex), POU1F1 (Reconstituted Complex)

ESM2 similar proteins: A2RV29, A4QP16, B0JZ85, O15226, O48772, O74555, P10036, P10037, P24610, P28069, P43243, P43244, P79364, P79832, Q04788, Q09345, Q17339, Q28503, Q32NW2, Q3L1C9, Q569K4, Q5AED9, Q5PPV5, Q5R4W8, Q5XHY7, Q61324, Q63623, Q6AXX3, Q6DID3, Q6GLQ4, Q6PBT9, Q6Z358, Q750X2, Q78E60, Q8BXJ8, Q8BY02, Q8K310, Q8VD12, Q9D8C3, Q9DG12

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

6 interactions.

A	Effect	B	Mechanism
LHX4	“up-regulates quantity by expression”	POU1F1	“transcriptional regulation”
POU1F1	“up-regulates quantity by expression”	GH1	“transcriptional regulation”
CREBBP	“up-regulates activity”	POU1F1	binding
POU1F1	“up-regulates quantity by expression”	TSHB	“transcriptional regulation”
PITX1	“up-regulates activity”	POU1F1	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	27
Likely pathogenic	12
Uncertain significance	53
Likely benign	115
Benign	11

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
126542	NM_000306.4(POU1F1):c.665+1G>T	Pathogenic
1285381	NM_000306.4(POU1F1):c.143-69T>G	Pathogenic
1285382	NM_000306.4(POU1F1):c.143-66T>G	Pathogenic
1285384	NM_000306.4(POU1F1):c.143-71T>G	Pathogenic
1285385	NM_000306.4(POU1F1):c.143-68T>A	Pathogenic
13602	NM_000306.4(POU1F1):c.514C>T (p.Arg172Ter)	Pathogenic
13604	NM_000306.4(POU1F1):c.472G>C (p.Ala158Pro)	Pathogenic
13606	NM_000306.4(POU1F1):c.428G>A (p.Arg143Gln)	Pathogenic
13607	NM_000306.4(POU1F1):c.748G>T (p.Glu250Ter)	Pathogenic
13608	NM_000306.4(POU1F1):c.404T>G (p.Phe135Cys)	Pathogenic
13609	NM_000306.4(POU1F1):c.715C>T (p.Pro239Ser)	Pathogenic
13611	NM_000306.4(POU1F1):c.577T>C (p.Trp193Arg)	Pathogenic
13612	NM_000306.4(POU1F1):c.433A>T (p.Lys145Ter)	Pathogenic
13615	NM_000306.4(POU1F1):c.775dup (p.Arg259fs)	Pathogenic
13616	NM_000306.4(POU1F1):c.537C>G (p.Ser179Arg)	Pathogenic
2258706	NM_000306.4(POU1F1):c.427C>T (p.Arg143Ter)	Pathogenic
2696272	NM_000306.4(POU1F1):c.634_635del (p.Glu212fs)	Pathogenic
2730117	NM_000306.4(POU1F1):c.783G>A (p.Trp261Ter)	Pathogenic
2767156	NM_000306.4(POU1F1):c.7del (p.Cys3fs)	Pathogenic
2767806	NM_000306.4(POU1F1):c.495_496del (p.Phe165fs)	Pathogenic
2787075	NM_000306.4(POU1F1):c.23C>A (p.Ser8Ter)	Pathogenic
2790971	NM_000306.4(POU1F1):c.787del (p.Cys263fs)	Pathogenic
2846205	NM_000306.4(POU1F1):c.644_648del (p.Arg215fs)	Pathogenic
2879327	NM_000306.4(POU1F1):c.96_97delinsTT (p.Glu33Ter)	Pathogenic
3246956	NC_000003.11:g.(?87309044)(87313682_?)del	Pathogenic
3640342	NM_000306.4(POU1F1):c.658_661dup (p.Ile221fs)	Pathogenic
4292029	NM_000306.4(POU1F1):c.562_565del (p.Ala188fs)	Pathogenic
1183964	NM_000306.4(POU1F1):c.662T>C (p.Ile221Thr)	Likely pathogenic
13605	NM_000306.4(POU1F1):c.71C>T (p.Pro24Leu)	Likely pathogenic
13610	NM_000306.4(POU1F1):c.747del (p.Glu250fs)	Likely pathogenic

SpliceAI

1040 predictions. Top by Δscore:

Variant	Effect	Δscore
3:87260100:CAATG:C	acceptor_gain	1.0000
3:87260105:C:CC	acceptor_gain	1.0000
3:87260121:A:AC	acceptor_gain	1.0000
3:87260121:A:C	acceptor_gain	1.0000
3:87261267:GAATA:G	donor_loss	1.0000
3:87261268:AATAC:A	donor_loss	1.0000
3:87261269:ATAC:A	donor_loss	1.0000
3:87261272:CCT:C	donor_loss	1.0000
3:87261329:CAAAG:C	acceptor_gain	1.0000
3:87261331:AAGC:A	acceptor_loss	1.0000
3:87261332:AGC:A	acceptor_loss	1.0000
3:87261333:GCTA:G	acceptor_loss	1.0000
3:87261334:C:CA	acceptor_loss	1.0000
3:87261334:C:CC	acceptor_gain	1.0000
3:87262072:T:TA	donor_gain	1.0000
3:87262076:A:AC	donor_gain	1.0000
3:87262077:C:CC	donor_gain	1.0000
3:87262077:CTTG:C	donor_gain	1.0000
3:87262084:AGCTT:A	donor_gain	1.0000
3:87262085:G:C	donor_gain	1.0000
3:87262088:T:TA	donor_gain	1.0000
3:87262234:TC:T	acceptor_gain	1.0000
3:87262235:CC:C	acceptor_gain	1.0000
3:87262237:T:A	acceptor_loss	1.0000
3:87264305:A:AC	donor_gain	1.0000
3:87264306:C:CC	donor_gain	1.0000
3:87264509:CTAC:C	acceptor_gain	1.0000
3:87273471:T:C	acceptor_gain	1.0000
3:87273471:T:TC	acceptor_gain	1.0000
3:87273477:C:CT	acceptor_gain	1.0000

AlphaMissense

1918 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:87259966:T:A	R268S	1.000
3:87259966:T:G	R268S	1.000
3:87259969:C:A	Q267H	1.000
3:87259969:C:G	Q267H	1.000
3:87259970:T:G	Q267P	1.000
3:87259972:C:A	R266S	1.000
3:87259972:C:G	R266S	1.000
3:87259973:C:A	R266M	1.000
3:87259973:C:G	R266T	1.000
3:87259974:T:C	R266G	1.000
3:87259976:C:G	R265P	1.000
3:87259977:G:C	R265G	1.000
3:87259978:G:C	N264K	1.000
3:87259978:G:T	N264K	1.000
3:87259979:T:A	N264I	1.000
3:87259979:T:G	N264T	1.000
3:87259980:T:C	N264D	1.000
3:87259980:T:G	N264H	1.000
3:87259981:G:C	C263W	1.000
3:87259982:C:A	C263F	1.000
3:87259982:C:T	C263Y	1.000
3:87259983:A:G	C263R	1.000
3:87259984:A:C	F262L	1.000
3:87259984:A:T	F262L	1.000
3:87259985:A:C	F262C	1.000
3:87259985:A:G	F262S	1.000
3:87259986:A:C	F262V	1.000
3:87259986:A:G	F262L	1.000
3:87259986:A:T	F262I	1.000
3:87259987:C:A	W261C	1.000

dbSNP variants (sampled 300 via entrez): RS1000010334 (3:87265347 G>A), RS1000136619 (3:87270745 T>C), RS1000190392 (3:87273877 T>C), RS1000224816 (3:87274125 G>A,T), RS1000235489 (3:87270421 G>A,T), RS1000449076 (3:87268903 G>C), RS1000478058 (3:87261927 A>G), RS1000523699 (3:87260679 A>C), RS1000714533 (3:87267275 T>C), RS1000738244 (3:87267455 C>A,T), RS1000777526 (3:87268560 T>C), RS1000838866 (3:87271875 G>A,C), RS1000948832 (3:87277730 TG>T), RS1000974384 (3:87260471 G>A), RS1001141354 (3:87278578 G>A,T)

Disease associations

OMIM: gene MIM:173110 | disease phenotypes: MIM:613038, MIM:604537

GenCC curated gene-disease

Disease	Classification	Inheritance
pituitary hormone deficiency, combined, 1	Definitive	Semidominant
hypothyroidism due to deficient transcription factors involved in pituitary development or function	Supportive	Autosomal dominant
isolated growth hormone deficiency type II	Supportive	Autosomal dominant
combined pituitary hormone deficiencies, genetic form	Supportive	Autosomal dominant

Mondo (5): pituitary hormone deficiency, combined, 1 (MONDO:0024464), combined pituitary hormone deficiencies, genetic form (MONDO:0013099), Leber congenital amaurosis 5 (MONDO:0011473), hypothyroidism due to deficient transcription factors involved in pituitary development or function (MONDO:0016411), isolated growth hormone deficiency type II (MONDO:0008250)

Orphanet (2): Combined pituitary hormone deficiencies, genetic forms (Orphanet:95494), Leber congenital amaurosis (Orphanet:65)

HPO phenotypes

98 total (30 of 98 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000044	Hypogonadotropic hypogonadism
HP:0000141	Amenorrhea
HP:0000158	Macroglossia
HP:0000270	Delayed cranial suture closure
HP:0000272	Malar flattening
HP:0000282	Facial edema
HP:0000407	Sensorineural hearing impairment
HP:0000457	Depressed nasal ridge
HP:0000463	Anteverted nares
HP:0000470	Short neck
HP:0000478	Abnormality of the eye
HP:0000490	Deeply set eye
HP:0000609	Optic nerve hypoplasia
HP:0000789	Infertility
HP:0000821	Hypothyroidism
HP:0000823	Delayed puberty
HP:0000824	Decreased response to growth hormone stimulation test
HP:0000839	Pituitary dwarfism
HP:0000871	Panhypopituitarism
HP:0000938	Osteopenia
HP:0000952	Jaundice
HP:0001161	Hand polydactyly
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001254	Lethargy
HP:0001265	Hyporeflexia
HP:0001274	Agenesis of corpus callosum

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST002541_49	Menarche (age at onset)	3.000000e-16
GCST002682_4	Tourette’s syndrome or obsessive-compulsive disorder	4.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004703	age at menarche

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
C536602	Amaurosis congenita of Leber, type 5 (supp.)
C562704	Isolated Growth Hormone Deficiency, Type II (supp.)
C567803	Pituitary Hormone Deficiency, Combined, 1 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

7 total (human), top 7 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
propionaldehyde	decreases expression	1
VX-agent	increases expression	1
manganese chloride	increases expression	1
CGP 52608	affects binding, increases reaction	1
Air Pollutants	increases expression	1
Manganese	increases expression	1
Silicon Dioxide	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03655223	Not specified	ENROLLING_BY_INVITATION	Early Check: Expanded Screening in Newborns
NCT05687474	Not specified	COMPLETED	Baby Detect : Genomic Newborn Screening
NCT05616793	PHASE1/PHASE2	RECRUITING	Safety and Tolerability Subretinal OPGx-001 for LCA5-Associated Inherited Retinal Degeneration (LCA5-IRD) and Non-interventional Arm With Untreated Patients