HP

haptoglobin, the group of Sushi domain containing

Basic information

Region (hg38): 16:72054505-72061055

Links

ENSG00000257017 ∙ NCBI:3240 ∙ OMIM:140100 ∙ HGNC:5141 ∙ Uniprot:P00738 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Anhaptoglobinemia; Hypohaptoglobinemia	AR	Hematologic	Variants may be important in specific situations (eg, related to transfusion)	Hematologic	9463309; 10666182; 14999562

ClinVar

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

• not_specified (51 variants)
• not_provided (12 variants)
• HP-related_disorder (4 variants)
• Anhaptoglobinemia (3 variants)
• HAPTOGLOBIN,_ALPHA-1,_FAST-SLOW_POLYMORPHISM (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HP gene is commonly pathogenic or not. These statistics are base on transcript: NM_000005143.5. 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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				9	3	12
missense			45	6	3	54
nonsense						0
start loss						0
frameshift			1			1
splice donor/acceptor (+/-2bp)						0
Total	0	0	46	15	6

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HP	protein_coding	protein_coding	ENST00000355906	7	6464

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000174	0.888	124771	0	28	124799	0.000112

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0135	212	213	0.997	0.0000116	2650
Missense in Polyphen		60	72.772	0.82449		856
Synonymous	-0.499	89	83.2	1.07	0.00000495	770
Loss of Function	1.51	10	16.7	0.600	7.98e-7	227

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000287	0.000287
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000557	0.0000557
Finnish	0.0000464	0.0000464
European (Non-Finnish)	0.000152	0.000150
Middle Eastern	0.0000557	0.0000557
South Asian	0.000131	0.000131
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: As a result of hemolysis, hemoglobin is found to accumulate in the kidney and is secreted in the urine. Haptoglobin captures, and combines with free plasma hemoglobin to allow hepatic recycling of heme iron and to prevent kidney damage. Haptoglobin also acts as an Antimicrobial; Antioxidant, has antibacterial activity and plays a role in modulating many aspects of the acute phase response. Hemoglobin/haptoglobin complexes are rapidely cleared by the macrophage CD163 scavenger receptor expressed on the surface of liver Kupfer cells through an endocytic lysosomal degradation pathway. {ECO:0000269|PubMed:21248165}.
• Disease: DISEASE: Anhaptoglobinemia (AHP) [MIM:614081]: A condition characterized by the absence of the serum glycoprotein haptoglobin. Serum levels of haptoglobin vary among normal persons: levels are low in the neonatal period and in the elderly, differ by population, and can be influenced by environmental factors, such as infection. Secondary hypohaptoglobinemia can occur as a consequence of hemolysis, during which haptoglobin binds to free hemoglobin. Congenital haptoglobin deficiency is a risk factor for anaphylactic non-hemolytic transfusion reactions. {ECO:0000269|PubMed:14999562}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Neutrophil degranulation;Vesicle-mediated transport;Innate Immune System;Immune System;Scavenging of heme from plasma;Binding and Uptake of Ligands by Scavenger Receptors (Consensus)

Recessive Scores

• pRec: 0.841

Intolerance Scores

• loftool: 0.235
• rvis_EVS: -0.8
• rvis_percentile_EVS: 12.24

Haploinsufficiency Scores

• hipred: N
• hipred_score: 0.194
• ghis: 0.491

Essentials

• essential_gene_CRISPR: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.839

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Hp
• Phenotype: liver/biliary 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); 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); hematopoietic system phenotype; neoplasm; immune system phenotype; renal/urinary system phenotype; cellular phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: acute inflammatory response;proteolysis;receptor-mediated endocytosis;defense response;acute-phase response;response to organic substance;positive regulation of cell death;response to hydrogen peroxide;defense response to bacterium;neutrophil degranulation;negative regulation of oxidoreductase activity;cellular oxidant detoxification;negative regulation of hydrogen peroxide catabolic process
• Cellular component: extracellular region;extracellular space;haptoglobin-hemoglobin complex;specific granule lumen;extracellular exosome;endocytic vesicle lumen;blood microparticle;tertiary granule lumen
• Molecular function: serine-type endopeptidase activity;protein binding;antioxidant activity;hemoglobin binding