GeneBe

POU1F1

protein-coding

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

Gene summary

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. [provided by RefSeq, Jul 2008]

Previous symbols:
  • PIT1

MANE transcript

NM_000306.4

Inheritance

AD, AR, SD

ClinVar variants

P:39U:58B:66

Top phenotype

Pituitary hormone deficiency, combined or isolated 1

gnomAD constraint

pLI —, LoF o/e 0.32

Max pathogenic AF

—

Genomic locus

chr3:87,259,404-87,276,584

External References & Databases

Ensembl (ENSG00000064835)NCBI Gene (5449)OMIM (173110)HGNC:9210GenCCUniProt (P28069)AlphaFoldClinVar (POU1F1)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~17.2 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

isolated growth hormone deficiency type IISUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0008250

Submitter: Orphanet

hypothyroidism due to deficient transcription factors involved in pituitary development or functionSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0016411

Submitter: Orphanet

pituitary hormone deficiency, combined, 1MODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0024464

Submitter: Ambry Genetics

pituitary hormone deficiency, combined, 1STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0024464

Submitter: Labcorp Genetics (formerly Invitae)

pituitary hormone deficiency, combined, 1STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0024464

Submitter: PanelApp Australia

pituitary hormone deficiency, combined, 1DEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0024464

Submitter: G2P

pituitary hormone deficiency, combined, 1STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0024464

Submitter: PanelApp Australia

pituitary hormone deficiency, combined, 1STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0024464

Submitter: Labcorp Genetics (formerly Invitae)

combined pituitary hormone deficiencies, genetic formSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0013099

Submitter: Orphanet

pituitary hormone deficiency, combined, 1DEFINITIVE

Inheritance Pattern: SD

Disease ID:MONDO:0024464

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Pituitary hormone deficiency, combined or isolated 1AD/AR

Manifestation: Cardiovascular; Endocrine

Intervention: Cardiovascular; Endocrine

Rationale: Individuals may manifest with central deficiency of multiple hormones, which can result in severe sequelae if untreated, and replacement therapy can be effective

Comments: A minority of individuals have been described with cardiac anomalies

Refs: 2634610; 1302000; 15928241; 16060904; 18059085; 19498317; 21316014; 21521297; 21722153; 22010633; 34270938Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to POU1F1 variants in ClinVar

7 Conditions Cataloged
not providedTotal: 178
Pituitary hormone deficiency, combined, 1Total: 48
not specifiedTotal: 36
Inborn genetic diseasesTotal: 33
POU1F1-related disorderTotal: 8
Combined pituitary hormone deficiencies, genetic formTotal: 7
Leber congenital amaurosis 5Total: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000306.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
1
clinvar
63
clinvar
 64
missense
6
clinvar
8
clinvar
56
clinvar
3
clinvar
 73
nonsense
7
clinvar
1
clinvar
 8
start loss
1
clinvar
 1
frameshift
8
clinvar
3
clinvar
 11
splice donor/acceptor (+/-2bp)
1
clinvar
5
clinvar
 6
Total221758660163

Highest pathogenic variant AF is 0.000035949986

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 6 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_000306.4RefSeqNP_000297.16MANE Select
ENST00000350375.7EnsemblENSP00000263781.26MANE Select
NM_001122757.3RefSeqNP_001116229.16Standard
ENST00000344265.8EnsemblENSP00000342931.36Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
pou1f1Danio rerio

Structure: whole organism

Quality: decreased length

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Glucocorticoid receptor regulatory network

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

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

Cellular Component

  • chromatin
  • nucleus
  • transcription factor complex

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000344265
Coding exons
6
Length
17184
Individuals with no LoFs
125720
Homozygous LoFs
0
Heterozygous LoFs
18
Defined
125738
p
0.0000716
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense0.4571491660.9000.000008052075
Missense (PolyPhen)5959.4330.99272769
Synonymous-0.5326458.81.090.00000290607
Loss of Function2.46515.40.3248.93e-7178

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American00.0absent
Ashkenazi Jewish00.0absent
East Asian00.0absent
Finnish00.0absent
European (Non-Finnish)0.000130.00011rare
South Asian0.000160.00016rare
Other00.0absent

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec
0.288

Intolerance Scores

LoFtool
0.231
RVIS EVS
0.04
RVIS percentile EVS
56.92

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.754

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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