PROP1

PROP paired-like homeobox 1, the group of PRD class homeoboxes and pseudogenes

Basic information

Region (hg38): 5:177992235-177996242

Links

ENSG00000175325 ∙ NCBI:5626 ∙ OMIM:601538 ∙ HGNC:9455 ∙ Uniprot:O75360 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• pituitary hormone deficiency, combined, 2 (Definitive), mode of inheritance: AR
• pituitary hormone deficiency, combined, 2 (Definitive), mode of inheritance: AR
• pituitary hormone deficiency, combined, 2 (Strong), mode of inheritance: AR
• pituitary hormone deficiency, combined, 2 (Strong), mode of inheritance: AR
• panhypopituitarism (Supportive), mode of inheritance: AR
• 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

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Pituitary hormone deficiency, combined, 2	AR	Endocrine	Hormone replacement therapy can be effective to treat multiple endocrinological deficiencies (eg, GH and thyroid hormone deficiency); Individuals may develop ACTH deficiency, and may require treatment including "stress dose steroids"; Medical interventions may be necessary to induce puberty	Endocrine	6046325; 745452; 9661653; 9768691; 9462743; 10084575; 920061; 11134108; 10634415; 11549674; 11549703; 15472175; 15531542; 20301521; 20381582; 20395664; 22024773; 22111336; 22286799

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PROP1 gene.

• not provided (17 variants)
• Pituitary hormone deficiency, combined, 2 (6 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PROP1 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			1	101	1	103
missense	2	3	28	3	3	39
nonsense	3	7	1			11
start loss	1	2				3
frameshift	10	14	2			26
inframe indel			3			3
splice donor/acceptor (+/-2bp)	2	5				7
splice region				9	1	10
non coding			7	20	10	37
Total	18	31	42	124	14

Highest pathogenic variant AF is 0.0000131

Variants in PROP1

This is a list of pathogenic ClinVar variants found in the PROP1 region.

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

Position	Type	Phenotype	Significance	ClinVar
5-177992241-G-A		Pituitary hormone deficiency, combined, 2	Uncertain significance (Jan 13, 2018)
5-177992275-A-T		Pituitary hormone deficiency, combined, 2	Uncertain significance (Jan 13, 2018)
5-177992290-G-A		Pituitary hormone deficiency, combined, 2	Benign (Jan 12, 2018)
5-177992355-C-T		Pituitary hormone deficiency, combined, 2	Benign (Jan 12, 2018)
5-177992586-A-G		Pituitary hormone deficiency, combined, 2	Benign (Sep 22, 2018)
5-177992589-G-A			Likely benign (Apr 09, 2021)
5-177992657-C-T		Pituitary hormone deficiency, combined, 2	Conflicting classifications of pathogenicity (Nov 08, 2018)
5-177992672-G-A		Pituitary hormone deficiency, combined, 2	Uncertain significance (Jan 12, 2018)
5-177992719-G-C			Uncertain significance (Jun 28, 2022)
5-177992735-G-A		Inborn genetic diseases	Uncertain significance (Oct 20, 2024)
5-177992737-C-CT		Pituitary hormone deficiency, combined, 2	Uncertain significance (May 26, 2017)
5-177992745-G-T			Likely benign (Jul 23, 2022)
5-177992754-A-C			Likely benign (Nov 18, 2021)
5-177992754-A-G			Conflicting classifications of pathogenicity (Apr 27, 2020)
5-177992754-A-T			Likely benign (Nov 04, 2020)
5-177992756-G-C		Inborn genetic diseases	Uncertain significance (Aug 14, 2024)
5-177992757-G-A			Likely benign (Dec 24, 2020)
5-177992758-G-T		PROP1-related disorder	Uncertain significance (Jan 25, 2024)
5-177992760-T-C			Likely benign (Sep 29, 2023)
5-177992760-T-G		not specified • Pituitary hormone deficiency, combined, 2	Conflicting classifications of pathogenicity (Jan 12, 2018)
5-177992760-TG-T		Pituitary hormone deficiency, combined, 2	Likely pathogenic (Jul 16, 2023)
5-177992760-T-TG		Pituitary hormone deficiency, combined, 2	Conflicting classifications of pathogenicity (Nov 19, 2022)
5-177992761-G-A		not specified	Uncertain significance (Sep 25, 2024)
5-177992763-G-A			Likely benign (Jan 31, 2020)
5-177992766-G-A		Pituitary hormone deficiency, combined, 2	Likely benign (Jan 24, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PROP1	protein_coding	protein_coding	ENST00000308304	3	4008

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0877	0.875	125675	0	73	125748	0.000290

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.248	130	138	0.941	0.00000883	1416
Missense in Polyphen		50	44.389	1.1264		423
Synonymous	-0.570	60	54.6	1.10	0.00000314	494
Loss of Function	1.78	3	8.63	0.348	6.40e-7	73

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000293	0.000293
Ashkenazi Jewish	0.000198	0.000198
East Asian	0.00	0.00
Finnish	0.0000926	0.0000924
European (Non-Finnish)	0.000513	0.000501
Middle Eastern	0.00	0.00
South Asian	0.0000997	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Possibly involved in the ontogenesis of pituitary gonadotropes, as well as somatotropes, lactotropes and caudomedial thyrotropes.

Intolerance Scores

• loftool: 0.253
• rvis_EVS: 0.28
• rvis_percentile_EVS: 71.27

Haploinsufficiency Scores

• pHI: 0.0996
• hipred: N
• hipred_score: 0.212
• ghis: 0.412

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.488

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Prop1
• Phenotype: homeostasis/metabolism phenotype; growth/size/body region phenotype; endocrine/exocrine gland phenotype; respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); 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); reproductive 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)

Zebrafish Information Network

• Gene name: prop1
• Affected structure: prolactin secreting cell
• Phenotype tag: abnormal
• Phenotype quality: spatial pattern

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;blood vessel development;central nervous system development;dorsal/ventral pattern formation;cell migration;hypothalamus cell differentiation;negative regulation of apoptotic process;positive regulation of transcription by RNA polymerase II;hypophysis morphogenesis;canonical Wnt signaling pathway;somatotropin secreting cell differentiation
• Cellular component: nucleus;transcription factor complex
• Molecular function: RNA polymerase II distal enhancer sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription repressor activity, RNA polymerase II-specific;DNA-binding transcription activator activity, RNA polymerase II-specific;chromatin binding;protein binding;beta-catenin binding;protein C-terminus binding