HABP2

protein-coding

hyaluronan binding protein 2

Gene summary

This gene encodes a member of the peptidase S1 family of serine proteases. The encoded preproprotein is secreted by hepatocytes and proteolytically processed to generate heavy and light chains that form the mature heterodimer. Further autoproteolysis leads to smaller, inactive peptides. This extracellular protease binds hyaluronic acid and may play a role in the coagulation and fibrinolysis systems. Mutations in this gene are associated with nonmedullary thyroid cancer and susceptibility to venous thromboembolism. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed. [provided by RefSeq, Jan 2016]

MANE transcript

NM_004132.5

Inheritance

ClinVar variants

U:140B:24

Top phenotype

Thyroid cancer, nonmedullary 5

gnomAD constraint

pLI —, LoF o/e 0.86

Max pathogenic AF

—

Genomic locus

chr10:113,550,837-113,589,602

External References & Databases

Ensembl (ENSG00000148702)

Transcript & Mutation Effects

hg38 • Region Span ~38.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

Clinical Genomic Database (CGD)

Thyroid cancer, nonmedullary 5AD

Manifestation: Oncologic

Intervention: Oncologic

Rationale: Individuals have been described as being susceptible to nonmedullary thyroid cancer, and awareness may allow early surveillance, diagnosis, and management

Refs: 26222560

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to HABP2 variants in ClinVar

6 Conditions Cataloged

not specifiedTotal: 119

Factor VII-activating protease marburg ITotal: 54

not providedTotal: 36

HABP2-related disorderTotal: 13

Thyroid cancer, nonmedullary, 5Total: 6

Thrombophilia due to thrombin defectTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004132.5. 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.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			11 clinvar	11 clinvar		22
missense			128 clinvar	12 clinvar		140
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar	1 clinvar		2
Total	0	0	140	24	0	164

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 25 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004132.5	RefSeq	NP_004123.1	13	MANE Select
ENST00000351270.4	Ensembl	ENSP00000277903.4	13	MANE Select
NM_001177660.3	RefSeq	NP_001171131.1	12	Standard
ENST00000542051.5	Ensembl	ENSP00000443283.1	12	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

proteolysis
cell adhesion

Molecular Function

serine-type endopeptidase activity
calcium ion binding
glycosaminoglycan binding

Cellular Component

extracellular region
extracellular space

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000351270
Coding exons: 13
Length: 38766
Individuals with no LoFs: 125050
Homozygous LoFs: 3
Heterozygous LoFs: 695
Defined: 125748
p: 0.00278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-1.43	385	314	1.23	0.0000160	3726
Missense (PolyPhen)		127	106.93	1.1876		1298
Synonymous	-1.34	140	121	1.16	0.00000683	997
Loss of Function	0.690	25	29.0	0.862	0.00000123	362

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00043	0.00043	rare
Latino/Admixed American	0.0041	0.0040	notable
Ashkenazi Jewish	0.0062	0.0062	notable
East Asian	0.00038	0.00038	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.0038	0.0038	notable
South Asian	0.00046	0.00046	rare
Other	0.0055	0.0056	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Cleaves the alpha-chain at multiple sites and the beta- chain between 'Lys-53' and 'Lys-54' but not the gamma-chain of fibrinogen and therefore does not initiate the formation of the fibrin clot and does not cause the fibrinolysis directly. It does not cleave (activate) prothrombin and plasminogen but converts the inactive single chain urinary plasminogen activator (pro- urokinase) to the active two chain form. Activates coagulation factor VII (PubMed:8827452, PubMed:10754382, PubMed:11217080). May function as a tumor suppressor negatively regulating cell proliferation and cell migration (PubMed:26222560). {ECO:0000269|PubMed:10754382, ECO:0000269|PubMed:11217080, ECO:0000269|PubMed:26222560, ECO:0000269|PubMed:8827452}.;
Disease: DISEASE: Thyroid cancer, non-medullary, 5 (NMTC5) [MIM:616535]: A form of non-medullary thyroid cancer (NMTC), a cancer characterized by tumors originating from the thyroid follicular cells. NMTCs represent approximately 95% of all cases of thyroid cancer and are classified into papillary, follicular, Hurthle cell, and anaplastic neoplasms. {ECO:0000269|PubMed:12578864, ECO:0000269|PubMed:26222560}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.109

Intolerance Scores

LoFtool: 0.123
RVIS EVS: -0.06
RVIS percentile EVS: 48.89

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0875

Gene Damage Prediction

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