POU1F1

POU class 1 homeobox 1, the group of POU class homeoboxes and pseudogenes

Basic information

Region (hg38): 3:87259403-87276584

Previous symbols: [ "PIT1" ]

Links

ENSG00000064835 ∙ NCBI:5449 ∙ OMIM:173110 ∙ HGNC:9210 ∙ Uniprot:P28069 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• 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

Clinical Genomic Database

Source: CGD

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 ClinVar and linked to the POU1F1 gene.

• not provided (57 variants)
• Pituitary hormone deficiency, combined, 1 (32 variants)
• Combined Pituitary Hormone Deficiency, Recessive (15 variants)
• Inborn genetic diseases (10 variants)
• Frontotemporal dementia (7 variants)
• not specified (5 variants)
• Combined pituitary hormone deficiencies, genetic form (3 variants)
• POU1F1-related condition (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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			4	10		14
missense	2	4	18			24
nonsense	4					4
start loss			1			1
frameshift	3	2				5
inframe indel			1			1
splice donor/acceptor (+/-2bp)		1	1			2
splice region			1	5	1	7
non coding			9	8	3	20
Total	9	7	34	18	3

Highest pathogenic variant AF is 0.0000197

Variants in POU1F1

This is a list of pathogenic ClinVar variants found in the POU1F1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
3-87259649-T-C		Combined Pituitary Hormone Deficiency, Recessive • Pituitary hormone deficiency, combined, 1	Uncertain significance (Jan 13, 2018)
3-87259681-T-T		Frontotemporal dementia • Pituitary hormone deficiency, combined, 1	Benign (Jun 19, 2021)
3-87259711-GTAAA-G		Combined Pituitary Hormone Deficiency, Recessive	Uncertain significance (Jun 14, 2016)
3-87259746-C-CT		Combined Pituitary Hormone Deficiency, Recessive	Uncertain significance (Jun 14, 2016)
3-87259753-T-A		Pituitary hormone deficiency, combined, 1	Uncertain significance (Jan 13, 2018)
3-87259754-T-A		Combined Pituitary Hormone Deficiency, Recessive • Frontotemporal dementia • Pituitary hormone deficiency, combined, 1	Benign/Likely benign (Jun 19, 2021)
3-87259754-T-TA		Combined Pituitary Hormone Deficiency, Recessive • Frontotemporal dementia	Conflicting classifications of pathogenicity (Jun 14, 2016)
3-87259755-A-T		Combined Pituitary Hormone Deficiency, Recessive • Frontotemporal dementia • Pituitary hormone deficiency, combined, 1	Benign/Likely benign (Jun 19, 2021)
3-87259754-T-TAA		Combined Pituitary Hormone Deficiency, Recessive	Uncertain significance (Jun 14, 2016)
3-87259756-A-T		Frontotemporal dementia • Combined Pituitary Hormone Deficiency, Recessive • Pituitary hormone deficiency, combined, 1	Benign/Likely benign (Jun 20, 2021)
3-87259897-T-C			Likely benign (Nov 24, 2023)
3-87259899-T-G			Likely benign (May 05, 2023)
3-87259906-A-T			Likely benign (Jan 21, 2024)
3-87259909-A-G			Likely benign (Nov 17, 2023)
3-87259959-G-A		Pituitary hormone deficiency, combined, 1	Uncertain significance (Nov 16, 2016)
3-87259969-C-T			Likely benign (Jan 09, 2023)
3-87259973-C-G			Uncertain significance (Jun 06, 2017)
3-87259977-G-A			Likely pathogenic (Dec 19, 2023)
3-87259978-G-A			Likely benign (Jan 29, 2024)
3-87259982-CA-C			Pathogenic (Sep 06, 2023)
3-87259987-C-T			Pathogenic (Jun 27, 2023)
3-87259992-C-T		Inborn genetic diseases	Uncertain significance (Jan 17, 2024)
3-87259994-C-CT		Pituitary hormone deficiency, combined, 1	Pathogenic (Aug 01, 2005)
3-87259999-T-C			Likely benign (Jan 17, 2024)
3-87260022-C-A		Pituitary hormone deficiency, combined, 1	Pathogenic (Jun 01, 1995)

GnomAD

Source: gnomAD

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: dbNSFP

• 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