POU1F1
POU class 1 homeobox 1, the group of POU class homeoboxes and pseudogenes
Basic information
Region (hg38): 3:87259404-87276584
Previous symbols: [ "PIT1" ]
Links
Phenotypes
GenCC
Source:
- pituitary hormone deficiency, combined, 1 (Definitive), mode of inheritance: AR
- pituitary hormone deficiency, combined, 1 (Definitive), mode of inheritance: Semidominant
- combined pituitary hormone deficiencies, genetic form (Supportive), mode of inheritance: AD
- hypothyroidism due to deficient transcription factors involved in pituitary development or function (Supportive), mode of inheritance: AD
- isolated growth hormone deficiency type II (Supportive), mode of inheritance: AD
- pituitary hormone deficiency, combined, 1 (Strong), mode of inheritance: AR
- pituitary hormone deficiency, combined, 1 (Strong), mode of inheritance: AD
- pituitary hormone deficiency, combined, 1 (Moderate), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Pituitary hormone deficiency, combined or isolated 1 | AD/AR | Cardiovascular; Endocrine | Individuals may manifest with central deficiency of multiple hormones, which can result in severe sequelae if untreated, and replacement therapy can be effective | Cardiovascular; Endocrine | 2634610; 1302000; 15928241; 16060904; 18059085; 19498317; 21316014; 21521297; 21722153; 22010633; 34270938 |
| A minority of individuals have been described with cardiac anomalies |
ClinVar
This is a list of variants' phenotypes submitted to
- not_provided (168 variants)
- Pituitary_hormone_deficiency,_combined,_1 (44 variants)
- Inborn_genetic_diseases (26 variants)
- not_specified (20 variants)
- POU1F1-related_disorder (8 variants)
- Combined_Pituitary_Hormone_Deficiency,_Recessive (7 variants)
- Combined_pituitary_hormone_deficiencies,_genetic_form (6 variants)
- Frontotemporal_dementia (2 variants)
- Leber_congenital_amaurosis_5 (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the POU1F1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000306.4. Only rare variants are included in the table.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 61 | 62 | ||||
| missense | 38 | 55 | ||||
| nonsense | 8 | |||||
| start loss | 1 | 1 | ||||
| frameshift | 9 | |||||
| splice donor/acceptor (+/-2bp) | 6 | |||||
| Total | 21 | 16 | 40 | 64 | 0 |
Highest pathogenic variant AF is 0.00003595
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| POU1F1 | protein_coding | protein_coding | ENST00000344265 | 6 | 17184 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.0450 | 0.950 | 125720 | 0 | 18 | 125738 | 0.0000716 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.457 | 149 | 166 | 0.900 | 0.00000805 | 2075 |
| Missense in Polyphen | 59 | 59.433 | 0.99272 | 769 | ||
| Synonymous | -0.532 | 64 | 58.8 | 1.09 | 0.00000290 | 607 |
| Loss of Function | 2.46 | 5 | 15.4 | 0.324 | 8.93e-7 | 178 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.000125 | 0.000114 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.000163 | 0.000163 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- 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 (PubMed:22010633, PubMed:26612202). {ECO:0000269|PubMed:22010633, ECO:0000269|PubMed:26612202}.;
- Disease
- DISEASE: 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 mental retardation along with short stature. {ECO:0000269|PubMed:11297581, ECO:0000269|PubMed:1472057, ECO:0000269|PubMed:1509262, ECO:0000269|PubMed:1509263, ECO:0000269|PubMed:15928241, ECO:0000269|PubMed:16968807, ECO:0000269|PubMed:22010633, ECO:0000269|PubMed:26612202, ECO:0000269|PubMed:7852536, ECO:0000269|PubMed:8768831, ECO:0000269|PubMed:9485179, ECO:0000269|PubMed:9626142}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Glucocorticoid receptor regulatory network
(Consensus)
Recessive Scores
- pRec
- 0.288
Intolerance Scores
- loftool
- 0.231
- rvis_EVS
- 0.04
- rvis_percentile_EVS
- 56.92
Haploinsufficiency Scores
- pHI
- 0.200
- hipred
- Y
- hipred_score
- 0.817
- ghis
- 0.436
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.754
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Pou1f1
- Phenotype
- hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; pigmentation phenotype; immune system phenotype; skeleton phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hearing/vestibular/ear phenotype; craniofacial phenotype; growth/size/body region phenotype; endocrine/exocrine gland phenotype; homeostasis/metabolism phenotype; cellular phenotype;
Zebrafish Information Network
- Gene name
- pou1f1
- Affected structure
- whole organism
- Phenotype tag
- abnormal
- Phenotype quality
- decreased length
Gene ontology
- Biological process
- negative regulation of transcription by RNA polymerase II;cell fate specification;regulation of transcription, DNA-templated;transcription by RNA polymerase II;positive regulation of cell population proliferation;negative regulation of cell population proliferation;determination of adult lifespan;B cell differentiation;positive regulation of inositol trisphosphate biosynthetic process;positive regulation of multicellular organism growth;regulation of insulin-like growth factor receptor signaling pathway;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;somatotropin secreting cell development
- Cellular component
- chromatin;nucleus;transcription factor complex
- Molecular function
- RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;RNA polymerase II transcription factor binding;RNA polymerase II activating transcription factor binding;DNA-binding transcription activator activity, RNA polymerase II-specific;chromatin binding;DNA-binding transcription factor activity