HPGD

15-hydroxyprostaglandin dehydrogenase, the group of Short chain dehydrogenase/reductase superfamily

Basic information

Region (hg38): 4:174490174-174523154

Links

ENSG00000164120 ∙ NCBI:3248 ∙ OMIM:601688 ∙ HGNC:5154 ∙ Uniprot:P15428 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hypertrophic osteoarthropathy, primary, autosomal recessive, 1 (Definitive), mode of inheritance: AR
• hypertrophic osteoarthropathy, primary, autosomal recessive, 1 (Strong), mode of inheritance: AR
• cranio-osteoarthropathy (Supportive), mode of inheritance: AR
• pachydermoperiostosis (Supportive), mode of inheritance: AR
• isolated congenital digital clubbing (Supportive), mode of inheritance: AD
• isolated congenital digital clubbing (Limited), mode of inheritance: Unknown
• hypertrophic osteoarthropathy, primary, autosomal recessive, 1 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hypertrophic osteoarthropathy, primary, autosomal recessive 1	AR	Musculoskeletal	Medical treatment (eg, with sulfasalazine, methotrexate) has been described as beneficial related to joint manifestations	Musculoskeletal	9402870; 17551338; 17285282; 18500342; 18805827; 19306095; 19568269; 20299379; 20406614; 21426412; 24533558

ClinVar

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

• not provided (88 variants)
• Hypertrophic osteoarthropathy, primary, autosomal recessive, 1 (74 variants)
• Isolated congenital digital clubbing (68 variants)
• Inborn genetic diseases (9 variants)
• Isolated congenital digital clubbing;Hypertrophic osteoarthropathy, primary, autosomal recessive, 1 (4 variants)
• not specified (2 variants)
• Cranioosteoarthropathy (1 variants)
• HPGD-Related Disorders (1 variants)
• HPGD-related condition (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HPGD 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	3	4	8
missense	1	1	35	4	1	42
nonsense	1					1
start loss						0
frameshift	5	1				6
inframe indel			1			1
splice donor/acceptor (+/-2bp)	4					4
splice region			5	3		8
non coding			37	16	23	76
Total	11	2	74	23	28

Highest pathogenic variant AF is 0.000138

Variants in HPGD

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

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

Position	Type	Phenotype	Significance	ClinVar
4-174490230-G-A		Isolated congenital digital clubbing • Hypertrophic osteoarthropathy, primary, autosomal recessive, 1	Benign (Jan 13, 2018)
4-174490230-GC-AT		Hypertrophic osteoarthropathy, primary, autosomal recessive, 1 • Isolated congenital digital clubbing	Uncertain significance (Jun 14, 2016)
4-174490231-C-T		Isolated congenital digital clubbing • Hypertrophic osteoarthropathy, primary, autosomal recessive, 1	Benign (Jan 13, 2018)
4-174490313-T-C		Isolated congenital digital clubbing • Hypertrophic osteoarthropathy, primary, autosomal recessive, 1	Likely benign (Jan 12, 2018)
4-174490338-T-A		Hypertrophic osteoarthropathy, primary, autosomal recessive, 1 • Isolated congenital digital clubbing	Uncertain significance (Jan 12, 2018)
4-174490362-T-C		Isolated congenital digital clubbing • Hypertrophic osteoarthropathy, primary, autosomal recessive, 1	Uncertain significance (Jan 13, 2018)
4-174490372-T-C		Isolated congenital digital clubbing • Hypertrophic osteoarthropathy, primary, autosomal recessive, 1	Uncertain significance (Jan 13, 2018)
4-174490400-G-A		Hypertrophic osteoarthropathy, primary, autosomal recessive, 1 • Isolated congenital digital clubbing	Uncertain significance (Jan 13, 2018)
4-174490442-T-C		Isolated congenital digital clubbing • Hypertrophic osteoarthropathy, primary, autosomal recessive, 1	Likely benign (Jan 12, 2018)
4-174490445-T-C		Hypertrophic osteoarthropathy, primary, autosomal recessive, 1 • Isolated congenital digital clubbing	Uncertain significance (Jun 14, 2016)
4-174490478-G-A		Hypertrophic osteoarthropathy, primary, autosomal recessive, 1 • Isolated congenital digital clubbing	Uncertain significance (Jan 12, 2018)
4-174490506-G-A		Isolated congenital digital clubbing • Hypertrophic osteoarthropathy, primary, autosomal recessive, 1	Uncertain significance (Jan 13, 2018)
4-174490556-A-C		Hypertrophic osteoarthropathy, primary, autosomal recessive, 1 • Isolated congenital digital clubbing	Uncertain significance (Jan 12, 2018)
4-174490710-C-T		Hypertrophic osteoarthropathy, primary, autosomal recessive, 1 • Isolated congenital digital clubbing	Uncertain significance (Jan 13, 2018)
4-174490753-T-G		Hypertrophic osteoarthropathy, primary, autosomal recessive, 1 • Isolated congenital digital clubbing	Uncertain significance (Jan 13, 2018)
4-174490802-A-G		Isolated congenital digital clubbing • Hypertrophic osteoarthropathy, primary, autosomal recessive, 1	Benign (Jan 12, 2018)
4-174490825-G-A		Hypertrophic osteoarthropathy, primary, autosomal recessive, 1 • Isolated congenital digital clubbing	Uncertain significance (Jan 12, 2018)
4-174490890-C-T		Hypertrophic osteoarthropathy, primary, autosomal recessive, 1 • Isolated congenital digital clubbing	Likely benign (Jan 12, 2018)
4-174490912-A-T		Hypertrophic osteoarthropathy, primary, autosomal recessive, 1 • Isolated congenital digital clubbing	Uncertain significance (Jan 12, 2018)
4-174490988-A-G		Isolated congenital digital clubbing • Hypertrophic osteoarthropathy, primary, autosomal recessive, 1	Uncertain significance (Jan 13, 2018)
4-174491015-G-A		Hypertrophic osteoarthropathy, primary, autosomal recessive, 1 • Isolated congenital digital clubbing	Uncertain significance (Jan 13, 2018)
4-174491042-T-C		Isolated congenital digital clubbing • Hypertrophic osteoarthropathy, primary, autosomal recessive, 1	Uncertain significance (Jan 12, 2018)
4-174491137-A-G		Isolated congenital digital clubbing • Hypertrophic osteoarthropathy, primary, autosomal recessive, 1	Uncertain significance (Jan 13, 2018)
4-174491157-AT-A		Hypertrophic osteoarthropathy, primary, autosomal recessive, 1 • Isolated congenital digital clubbing	Uncertain significance (Jun 14, 2016)
4-174491207-T-C		Hypertrophic osteoarthropathy, primary, autosomal recessive, 1 • Isolated congenital digital clubbing	Uncertain significance (Jan 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HPGD	protein_coding	protein_coding	ENST00000296522	7	32978

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000144	0.654	125661	0	87	125748	0.000346

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.119	145	141	1.03	0.00000657	1740
Missense in Polyphen		55	56.309	0.97675		646
Synonymous	1.01	41	50.1	0.819	0.00000244	493
Loss of Function	0.930	9	12.6	0.717	5.28e-7	165

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000181	0.000181
Ashkenazi Jewish	0.00	0.00
East Asian	0.00109	0.00109
Finnish	0.000278	0.000277
European (Non-Finnish)	0.000476	0.000475
Middle Eastern	0.00109	0.00109
South Asian	0.0000988	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Prostaglandin inactivation. Contributes to the regulation of events that are under the control of prostaglandin levels. Catalyzes the NAD-dependent dehydrogenation of lipoxin A4 to form 15-oxo-lipoxin A4. Inhibits in vivo proliferation of colon cancer cells. {ECO:0000269|PubMed:10837478, ECO:0000269|PubMed:15574495, ECO:0000269|PubMed:16828555}.
• Disease: DISEASE: Hypertrophic osteoarthropathy, primary, autosomal recessive, 1 (PHOAR1) [MIM:259100]: A disease characterized by digital clubbing, periostosis, acroosteolysis, painful joint enlargement, and variable features of pachydermia that include thickened facial skin and a thickened scalp. Other developmental anomalies include delayed closure of the cranial sutures and congenital heart disease. {ECO:0000269|PubMed:18500342}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Cranioosteoarthropathy (COA) [MIM:259100]: A form of osteoarthropathy characterized by swelling of the joints, digital clubbing, hyperhidrosis, delayed closure of the fontanels, periostosis, and variable patent ductus arteriosus. Pachydermia is not a prominent feature. {ECO:0000269|PubMed:18500342}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Isolated congenital nail clubbing (ICNC) [MIM:119900]: A rare genodermatosis characterized by enlargement of the nail plate and terminal segments of the fingers and toes, resulting from proliferation of the connective tissues between the nail matrix and the distal phalanx. It is usually symmetrical and bilateral (in some cases unilateral). In nail clubbing usually the distal end of the nail matrix is relatively high compared to the proximal end, while the nail plate is complete but its dimensions and diameter more or less vary in comparison to normal. There may be different fingers and toes involved to varying degrees. Some fingers or toes are spared, but the thumbs are almost always involved. {ECO:0000269|PubMed:18805827}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Transcriptional misregulation in cancer - Homo sapiens (human);Prostaglandin Synthesis and Regulation;Metabolism of lipids;Synthesis of Prostaglandins (PG) and Thromboxanes (TX);Arachidonic acid metabolism;Synthesis of Lipoxins (LX);Metabolism;Biosynthesis of E-series 18(S)-resolvins;Biosynthesis of EPA-derived SPMs;Biosynthesis of D-series resolvins;Biosynthesis of DHA-derived SPMs;Biosynthesis of specialized proresolving mediators (SPMs);Fatty acid metabolism;Prostaglandin formation from arachidonate;Prostaglandin formation from dihomo gama-linoleic acid;Arachidonic acid metabolism (Consensus)

Recessive Scores

• pRec: 0.232

Intolerance Scores

• loftool: 0.311
• rvis_EVS: -0.21
• rvis_percentile_EVS: 38.58

Haploinsufficiency Scores

• pHI: 0.574
• hipred: N
• hipred_score: 0.350
• ghis: 0.485

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.164

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Hpgd
• Phenotype: cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); 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; endocrine/exocrine gland phenotype; homeostasis/metabolism phenotype; cellular phenotype

Gene ontology

• Biological process: kidney development;prostaglandin metabolic process;transforming growth factor beta receptor signaling pathway;female pregnancy;parturition;lipoxygenase pathway;ovulation;response to estradiol;response to lipopolysaccharide;long-chain fatty acid biosynthetic process;positive regulation of apoptotic process;response to ethanol;negative regulation of cell cycle;oxidation-reduction process;thrombin-activated receptor signaling pathway;ductus arteriosus closure;positive regulation of vascular smooth muscle cell proliferation;lipoxin biosynthetic process
• Cellular component: nucleoplasm;cytoplasm;cytosol;basolateral plasma membrane;extracellular exosome
• Molecular function: catalytic activity;prostaglandin E receptor activity;15-hydroxyprostaglandin dehydrogenase (NAD+) activity;protein homodimerization activity;NAD binding;NAD+ binding